Closing thoughts: Implications of the findings from the National Allergy Survey Assessing Limitations for the management of allergic rhinitis in America

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Closing thoughts: Implications of the findings from the National Allergy Survey Assessing Limitations for the management of allergic rhinitis in America
 

Authors of papers presented in this Supplement met in person at the 2011 Annual Meeting of the American College of Allergy, Asthma & Immunology to further discuss the clinical, social, and economic implications of the findings from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC. This paper represents an edited transcript of their discussion.

Given the recent changes in US health care, how should the results of the NASAL 2010 survey be used to inform current practice? What about the role of other health care professionals and what are the cost implications of the survey findings?

Dr. Hadley: Firstly, it is important to note that there were improvements in the design of the NASAL 2010 survey compared to its 2006 predecessor. More importantly, although some of the 2010 information was a little bit different, we found that the majority of patients still suffer from their symptoms, and that the symptoms are predominant and bothersome. Allergic rhinitis bothers their sleep; it bothers their work and daily activities. In other words, we have not really seen any difference in achieving a reduction of the patients’ symptoms from 2006 to 2010.

Dr. Meltzer: Looking at this issue more globally, I think that the lack of change has a great deal to do with the public not understanding what “health” is. The World Health Organization (WHO) definition of health is there should be no problems with physical, social, emotional, or mental well-being. Individuals often do not appreciate how healthy they could be, and thus do not have a reference point. The NASAL survey clearly shows that most nasal allergy sufferers are not aware of an appropriate respiratory health goal and, further, they are not cognizant of the magnitude of their disease due to their allergic rhinitis. I believe the patients are not the only ones who are unaware; I think many clinicians are also not aware of the extent of their patients’ morbidity. A current problem is that there is not enough assumption of responsibility; patients are not taking enough responsibility for their health, clinicians are not adequately managing these patients, and—despite the suggested health care reforms—there does not appear to be in the foreseeable future a system that is going to alter these conditions.

Dr. Stoloff: For example, many family physicians only ask the question “How are you (with respect to this topic)?” and patients often say they are fine, and that’s the end of the dialogue. But consequences of this type of discussion are that costs of health care continue due to the lack of health. So the person misses work or the person’s job performance is less than it would be because they don’t recognize what their health could be if they were properly treated. As far as they’re concerned, this situation has been going on year after year, and it is only when they are really bad that they know they should be somewhat better. Even then, most people do not fully appreciate what is achievable because no one in the health care system has ever told them, “You should be able to sleep through the night and wake up feeling well. You should be able to go to work. You should be able to participate in athletic, recreational venues to be healthy.” No one has brought that up, and as long as this situation continues, the cost for the patient, his or her family, and health care will continue to increase.

Dr. Hadley: One of the things that I see as an otolaryngologist is that there is also often a missed diagnosis. Everybody who comes in to see me tells me: “Doctor, I have ‘sinus’.” I think most of them are simply unaware of that fact that their nasal congestion plays a role in developing their sinus symptoms. So there is general unawareness of the importance of treating nasal allergies in the lay public, as well as in primary care physicians who have to deal with these patients. Going to issues of cost, I think that patients are seeing the economy go down, and this means that they don’t want to spend a lot of money on their health care. They have a lot of other worries, and I think this is playing a role in how we have to deal with our patients.

 

 

Dr. Stoloff: People need to understand that the cost of not spending money to be healthy has a consequence that is sometimes the greater cost of being unhealthy—cost in terms of morbidity, cost in terms of missed days from work, absenteeism, presenteeism, poor ability to function in the usual domains of physical, social, emotional, and mental.

Dr. Hadley: That’s what the public just does not understand. We have not achieved the goal of informing the lay public and practitioners about how effective management can get these patients better, reduce their costs, and enable patients to go back to work and their activities.

What should be done to better act on the challenges highlighted by these important surveys? Is there a need to increase the awareness of allergic rhinitis among health care providers?

Dr. Meltzer: If we’re not making progress then we have to make some changes. It seems to me that education could drive change. The public needs to better understand that it is not insignificant to have an inflammatory process called allergic rhinitis. Allergic rhinitis is clearly underestimated in terms of its burden. It is too often unrecognized or ignored as an inconsequential problem. It is important that the person who has allergic rhinitis does not disregard the burden of disease. The NASAL survey reports that allergic rhinitis affects the ability to sleep well in 40 of patients. We know that allergic rhinitis also compromises people’s activities and we know that they are not as productive when they’re at work. We also know there are many comorbidities—asthma in particular, and sinusitis, otitis, conjunctivitis are other common associated conditions. Patients and clinicians need to be educated to appreciate the significant morbidity associated with allergic rhinitis, and that nasal allergies need attention and effective control.

Dr. Hadley: One of the things that we all see is patients not always getting important information about the medications that they take; there is a walk-in to the grocery store and the pharmacy shelves are filled with medications that are over-the-counter. The problem is there is not enough education about what the benefits are and what the side effects are of all those medications. There is also a lot of direct to consumer advertising—radio, television, etc., that also leads to misconceptions about the benefits of some of these medications. Patients are somewhat aware that they have a problem, but they just don’t know where to go. From the health care provider perspective, the emphasis is on treating the major problems—diabetes, hypertension—and rhinitis is considered a minor problem. So I don’t think we are educating our patients well enough. And I think that is a misconception and misunderstanding, which should be corrected.

Dr. Stoloff: Most physicians will see on their schedule a brief description of what problems their upcoming patients have. In primary care, the person filling the schedule will often say that the patient with nasal symptoms has sinusitis, which overwhelmingly it is not. That is an “easy” quick visit and the typical conversation is “Here, take this pill—if you’ve tried that pill, then take this nasal inhaler—and if you didn’t like this one I’ve got another sample for you. And then we’ll figure out which one is going to be on your list, what is covered by your insurance, and what’s the generic.” There is very little discussion about the type of impairment suffered and the overall burden on the individual. Importantly, that burden is often substantial, especially if nasal allergy symptoms were the primary reason for the office visit.

In primary care, people can have a multitude of other conditions, and allergic rhinitis is down at the bottom of the list. For example, the patient may be a hypertensive diabetic who also has seasonal allergic rhinitis. So by the time a family doctor gets to discuss allergic rhinitis, the office visit time is over and it is easier for the physician to just give a medication. But when the presence of allergic rhinitis has an enormous influence on the other diseases as far as activity, sleep, fatigue, depression, all the other emotional components, as well as physical components, that the survey highlighted—that really needs to be brought to the attention of both the patient and the health care provider to spend the appropriate time discussing it. Because it will influence care in everything else the person does.

How would you work up a patient who you might consider as potentially having allergic rhinitis?

Dr. Meltzer: When physicians view their schedule, a word or phrase supposedly informs them in advance of the patient’s condition. In reality, every patient is different and, moreover, patients with allergic rhinitis vary over the course of days, months and years in their symptomatology. So when I evaluate a patient for rhinitis and their chief complaint is “I’m having problems with my nose,” I first find out the full range of symptoms, and which symptom is for them the most bothersome (most often it will turn out to be congestion). Secondly, I would find out whether the symptoms are intermittent, or persistent. If they are fairly persistent, this informs me about somewhat of their severity, which is another very important consideration. Thirdly, I would try to find out what are the triggers for the symptoms such as non-allergic precipitants (eg, climate changes, tobacco smoke, and other environmental pollutants), or specific allergen triggers (eg, pets, springtime pollens). I would also ask about any comorbid conditions because if they are having more than just nasal symptoms that expands what I am going to need to address. I need to know all of those things before I make a treatment plan. If the disease is intermittent and mild or not very bothersome, then I am going to initiate a modest management plan. If their allergic rhinitis is more problematic, then I will need to educate the patient about what they have, why they have it and what to do about it. The patient and I will need to agree about our expectations of treatment. We are going to have an action plan for the short-term as well as a plan for follow-up visits to see if in fact our initial plan is successful. Again, the specifics will depend upon the individual patient.

 

 

Dr. Hadley: Many patients come in to an ENT clinic with an inappropriate initial diagnosis, predominantly with sinus disease, and some of them actually have come in with inappropriately obtained CT scans of the paranasal sinuses because they were presumed to have a chronic sinus infection. Most importantly, many of them have come in with inappropriately administered multiple different courses of antibiotics, which is of concern to me. So I agree with Dr. Meltzer in the need to understand the history of the patient’s symptoms—whether they are intermittent or persistent. I also obtain a family history, which helps me to work out whether the patient has an allergic tendency or not. I also have to look back and see what medications have been tried, what has worked (and not worked) in the past. The timing of the medications is really important, and the patient’s own perceptions about whether they want a medication that is going to be beneficial, or whether they want a simple remedy also plays a role. Also, let’s not forget what Dr. Meltzer also talked about—environmental controls that can be helpful to reduce the patient’s symptomatology as well.

Dr. Stoloff: From my perspective, I’m always impressed how a simple explanation of what allergy actually is, in terms of definition and measurement, creates a totally different dialogue with the patient. When my patients come in, they are often past the point of just administering a medicine, and trying others if it didn’t work—especially now there are so many generic over-the-counter products in oral antihistamines available. As a consequence, I really want to talk to them about what is going on— what is the family history, what is the seasonality of the components. I live at a fairly substantial altitude with little or no humidity, so some of the environmental issues that are very clear in San Diego where Dr. Meltzer practices have no role in my patients. However, some of the people I’ve seen have come in with pages of an expensive serum test that shows positive for certain items that have no influence on the patient’s current environment.

Patient history has to guide our workup. Dr. Hadley’s point about family history was important; we look to document what in fact are the causes. If we can figure out what is pushing the disease forward, maybe we can prevent some of those problems or at least lessen them. The history also helps in diagnosis. If we find by their history they’re overusing topical decongestants, that’s important. If we find they’re using their intranasal spray in the wrong way, that’s important. After obtaining the patient history, we then need to individualize our workup based on physical examination. It is important to look in the nose; if we find they have mechanical problems that’s additional information. Certainly allergic specific testing can be helpful, but it has to be targeted based on the location and based on the patient’s story.

Dr. Meltzer: We also need to target treatment. As Dr. Hadley mentioned, we need to know what has and hasn’t worked in the past and what are the contributing mechanism of the rhinitis for a given patient—is it only allergic, is it infectious, is it nonspecific irritants, is it mechanical, or is it a mixture of all of these. Pharmacologic therapy can be stepped up or stepped down depending upon the patient’s progress. And immunotherapy is certainly an appropriate choice in patients who have more severe disease and/or who are not responding adequately. Individualization is the key in terms of management.

Dr. Hadley: There is a clear need for the identification of and appropriate care of patients who need further management. As clinicians, we glean from patients’ history when they have symptoms and when we can appropriately add to the pharmacological management other therapies that would be beneficial in helping patients control their environment a little bit better during specific times of the year. Some patients do need additional treatment at certain times of the year. For example, whereas patients with intermittent symptoms only need to be treated for a short period of time each year, other patients are plagued with year-round symptoms. So we have to gauge those patients appropriately.

Dr. Stoloff: Another point is that at times comanagement with an allergist or otolaryngologist will be beneficial to the patient. But the primary care physician has to recognize that and it takes time to have that discussion. Unfortunately, because allergic rhinitis is often trivialized (from a health care provider’s point of view), physicians do not step back to see how much of a burden this disease is for that individual. This lessens the opportunity to gain effective consultation in the specific fields, and therefore lessens the opportunity for better health for the patient.

 

 

How do current guidelines influence your current treatment practice? Which guidelines are useful?

Dr. Meltzer: The ARIA guidelines originate from a WHO program, initiated in 1999, to create an international appreciation of the morbidity associated with allergic rhinitis. They borrowed from the NIH guidelines for asthma, the classification concept of intermittent and persistent and rating of the disease into mild, moderate, and severe categories. I think that this is clinically more relevant than the FDA classifications of seasonal and perennial allergic rhinitis. If a person suffers symptoms when they visit a family member with cats for 2 weeks over Christmas—then that’s an intermittent problem. It is not really a “perennial” problem in terms of the allergen. The FDA view may be appropriate for approval of medications, but from the management standpoint of patients, classifications of persistent, intermittent and mild, moderate or severe are much more useful. Indeed US guidelines now also use these classifications.

The name ARIA actually stands for Allergic Rhinitis Impact on Asthma, and the impact on asthma was a key driver for the WHO program. ARIA recognized the concept of the unified airway and the consequence that having inflammation in one area of the airway created for other parts of the airway. The guidelines highlighted the recommendation to evaluate patients with allergic rhinitis for lower airway disease (be it with a pulmonary function or at least a good history), and conversely for patients with lower airway disease to check for an upper airway history of problems as well. This is important because there is crosstalk, and we should be managing the whole airway—reducing inflammation in all of it.

Dr. Stoloff: From my viewpoint, very few of my peers are aware of ARIA and what it recommends. Similarly, many of them are not aware of the differences between the FDA classification and clinical guidelines. They simply do not know that the field is moving away from using seasonal and perennial terminology and towards a redefinition in terms of severity, frequency, and intensity.

Dr. Hadley: I agree that the awareness of the ARIA guidelines in general medical communities is low. We should point outthat the American Academy of Asthma, Allergy & Immunology (AAAAI) did publish practice parameters for rhinitis in 2008 and those have made a lot of sense as they give a practitioner a stepwise process to look at whether the symptoms are intermittent versus persistent, the degree of severity, and then makes recommendations on the types of medication that can be of clinical benefit to the patient. These guidelines are much more useful to the primary care physician.

Dr. Stoloff: Speaking as an author of both the ARIA and the AAAAI practice parameters, one of the major problems is that my colleagues in primary care do not routinely read the journals where the guidelines are published. Thus, the information is not disseminated and consequently not incorporated into their clinical practice. If presented and disseminated properly, guidelines should influence the way clinicians look at these health care issues, for the patient’s benefit, for cost benefit, and for improving their practice, gaining better out come for everyone.

Dr. Meltzer: I think there are some common concepts that have been incorporated into each of the guidelines discussed. Firstly, we need to classify people by severity. Secondly, we need to appreciate that people with upper airway disease (including allergic rhinitis), often have involvement of other areas of the respiratory tract. In other words we need to consider the comorbidities of the associated diseases. Thirdly, once we appreciate the magnitude of the problems, the patient together with the clinician needs to establish goals. Fourthly, there are step recommendations; if the symptoms are mild or intermittent, less management is needed. If the symptoms are moderate to severe, and/or persistent, more intensive management is required. There are also defined therapeutic steps as to when one might include immunotherapy as part of the regimen. Finally, patients should be monitored as part of the long-term management of this chronic condition.

The ultimate goal is control—control based on what the patient’s goals were when defined during their discussions with their clinician. If we incorporate those basic five concepts into our clinical practice—it will be good for the upper airway, good for the lower airway, and good for long-term health.

Given the range of products available at present for allergic rhinitis, what criteria influence your choice of product?

Dr. Hadley: The problem is that our patients have problems that they do not consider allergic rhinitis as serious, compared to conditions such as hypertension or diabetes. However, they still have a problem that significantly influences their life. As far as the range of products, many of them have already been on an oral antihistamine and many have used and abused decongestant therapy, which is over-the-counter or now behind-the-counter that they have to ask for. Patients often try to first alleviate their symptoms with some of these products, and by the time the come to see me as a specialist they have already usually started on something already, and I have to look and determine whether or not they would be acceptable to use a more advanced product.

 

 

The topical nasal steroid is the pure anti-inflammatory product. We use this to treat the inflammatory state of the patient, recognizing that allergic rhinitis is an inflammatory problem. Antihistamines can reduce some of the symptoms but not as effectively as some of the topical nasal steroids. Added to that patients obviously have a preference to use a single product that they can use once per day, for most Americans this would ideally mean taking a pill, but unfortunately that’s not the best product for them. Our challenge is to change their attitudes and beliefs about appropriate treatment of these problems.

Dr. Meltzer: As an allergist I tend to think about allergic disease not only in terms of what is, but how did it get there. It is important to understand allergic rhinitis as an inflammatory process that involves numerous mediators, cytokines, and inflammatory cells. Oral antihistamines block only one of the mediators; they have no effect on cytokines or inflammatory cells or any of the other mediators. As such, while they can help with itchy noses, sneezing and runny noses, they do not help with congestion— which is the most bothersome and the most frequent symptom. Likewise, anticholinergics only help with runny nose, and are not effective against nasal itch, sneeze or congestion. Most people with allergic rhinitis have chronic disease, and topical decongestants should not be used for prolonged periods of time. Oral decongestants have dose-related side effects and the doses required to effectively reduce congestion increase the risks of irritability, diffculty sleeping and nervousness. Leukotriene modifiers are at best minimal to modest improvers of symptoms. Thus, the intranasal corticosteroids (because of their broad based mechanisms of action) are currently considered to be the best monotherapies.

However, when prescribing intranasal corticosteroids, there are a number of important considerations. First, we should ensure the patient is administering the spray properly in terms of the technique. In addition, there may be some patient preference in terms of whether an individual prefers an aerosol formulation or an aqueous formulation. There may also be issues in regard to cost and related to the availability of different agents on a formulary. Indeed, managed care limitations have been problematic for many of us who take care of patients. Furthermore, we certainly need to monitor that patients adhere to their regimen. I find in my practice that most people do not start taking their medication prior to a season; they wait until they’re in the midst of the worst time of their symptomatology and then expect an immediate treatment effect. I try to explain to them, that allergic rhinitis is an ongoing process, a fire, and if effective therapy is established and maintained early on, then the fire can be kept under control and the outcome will be far better than trying to deal with it when there is a flare-up of the major symptoms. This is a communication issue. Every person may have a different view and we need to come to an understanding of each individuals’ viewpoint (what their goals of treatment are). We are not going to be able to force a patient to stick with a particular treatment. It’s about educating them and encouraging them to take responsibility. I tell them “when you leave my office, you’re the one who has allergic rhinitis and I recommend you take the medication. However, you make the decisions.”

Dr. Hadley: We also must not forget that inappropriate patient comprehension and knowledge can also be problematic. Some patients take their medication too late, or perhaps too long, and they have side effects. Side effects can increase the burden of their disease and impact on their ability to perform well at work or school or play.

Dr. Stoloff: Yes, in primary care, especially when treating the older population who have hypertension, one often sees patients take decongestants, and one realizes the multitude of side effects associated with them. And, as Dr. Hadley says, very few patients are aware that their medications are causing these problems.

There are basically three key aspects related to patient communication. Firstly, patient education; we need to ensure our patients are aware of what they have, why they have it and what they can do about it. Secondly, there needs to be ongoing communication between the patient and the clinician to ensure availability of questions and availability of goal setting. Thirdly, patients should have realistic expectations, because when patients revisit we can assess if we have met their expectations or if adjustments in management are needed.

 

 

Dr. Hadley: I agree. Better awareness of the disease burden will improve the patient-clinician discussion and thereby improve the patient-physician relationship. This will enable physicians to better guide their patients through proposed treatment plans.

Another important topic is patient preference. We have discussed that most patients would like a pill that has no side effects or that they can take once a day, perhaps once a week, or a patch that they don’t have to deal with. Unfortunately, we need to recognize that such a medication does not yet exist. Patients who have a problem with the inflammatory process should be seen by the clinician and steered toward the most effective medication, and I personally believe that the topical nasal steroids are the best choice to reduce the inflammatory process as much as possible. There are new aerosol formulations of topical nasal steroids that will bring more treatment options for allergic rhinitis.

Dr. Meltzer: We should also note that these new developments with regards to new delivery systems address expanding patient choice. There are also a number of combination agents and biologics in development that may also improve pharmacotherapeutic outcomes. Advances in immunotherapy will also help treat the basic cause of allergic disease. I think many of these options will become available within the next few years.

Dr. Stoloff: I concur. The other point that we have made, and I think it’s important to reiterate, allergic rhinitis is not in a silo. It is associated with, for most of the population, comorbid diseases. When clinicians look for comorbidities, they often gain a far better appreciation of the value of treating the allergic rhinitis and therefore improving their outcome for other health issues such as asthma. But this needs to be taken in the context of communicating with the patient, always taking patient needs and goals into consideration, and working within the economic health care system that we now face.

Author and Disclosure Information

Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

James A. Hadley, MD
James A. Hadley, MD, has served on the advisory board for Meda Pharmaceuticals, Teva Pharmaceuticals, and Merck.

Eli O. Meltzer, MD
Eli O. Meltzer, MD, has received grant/research support from and served as a consultant/advisor and a speaker for Alcon, Sunovion/Sepracor, and Teva Pharmaceuticals. Dr. Meltzer has received grant/research support and served as a consultant/advisor for Astra Zeneca, Boehringer Ingelheim, and Procter & Gamble. He has served as a consultant/advisor and a speaker for Dey and Merck. He has received grant/research support from Amgen, Apotex, GlaxoSmithKline, HRA, MedImmune, Novartis, and Schering-Plough. He has served as a consultant/advisor for Alexza, Bausch & Lomb, Forest, ISTA Pharmaceuticals, Johnson & Johnson, Kalypsys, Meda, ONO, Optinase, and Rady Children’s Hospital San Diego. He has served as a speaker for Allergists for Israel, American College

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Author and Disclosure Information

Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

James A. Hadley, MD
James A. Hadley, MD, has served on the advisory board for Meda Pharmaceuticals, Teva Pharmaceuticals, and Merck.

Eli O. Meltzer, MD
Eli O. Meltzer, MD, has received grant/research support from and served as a consultant/advisor and a speaker for Alcon, Sunovion/Sepracor, and Teva Pharmaceuticals. Dr. Meltzer has received grant/research support and served as a consultant/advisor for Astra Zeneca, Boehringer Ingelheim, and Procter & Gamble. He has served as a consultant/advisor and a speaker for Dey and Merck. He has received grant/research support from Amgen, Apotex, GlaxoSmithKline, HRA, MedImmune, Novartis, and Schering-Plough. He has served as a consultant/advisor for Alexza, Bausch & Lomb, Forest, ISTA Pharmaceuticals, Johnson & Johnson, Kalypsys, Meda, ONO, Optinase, and Rady Children’s Hospital San Diego. He has served as a speaker for Allergists for Israel, American College

Author and Disclosure Information

Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

James A. Hadley, MD
James A. Hadley, MD, has served on the advisory board for Meda Pharmaceuticals, Teva Pharmaceuticals, and Merck.

Eli O. Meltzer, MD
Eli O. Meltzer, MD, has received grant/research support from and served as a consultant/advisor and a speaker for Alcon, Sunovion/Sepracor, and Teva Pharmaceuticals. Dr. Meltzer has received grant/research support and served as a consultant/advisor for Astra Zeneca, Boehringer Ingelheim, and Procter & Gamble. He has served as a consultant/advisor and a speaker for Dey and Merck. He has received grant/research support from Amgen, Apotex, GlaxoSmithKline, HRA, MedImmune, Novartis, and Schering-Plough. He has served as a consultant/advisor for Alexza, Bausch & Lomb, Forest, ISTA Pharmaceuticals, Johnson & Johnson, Kalypsys, Meda, ONO, Optinase, and Rady Children’s Hospital San Diego. He has served as a speaker for Allergists for Israel, American College

 

Authors of papers presented in this Supplement met in person at the 2011 Annual Meeting of the American College of Allergy, Asthma & Immunology to further discuss the clinical, social, and economic implications of the findings from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC. This paper represents an edited transcript of their discussion.

Given the recent changes in US health care, how should the results of the NASAL 2010 survey be used to inform current practice? What about the role of other health care professionals and what are the cost implications of the survey findings?

Dr. Hadley: Firstly, it is important to note that there were improvements in the design of the NASAL 2010 survey compared to its 2006 predecessor. More importantly, although some of the 2010 information was a little bit different, we found that the majority of patients still suffer from their symptoms, and that the symptoms are predominant and bothersome. Allergic rhinitis bothers their sleep; it bothers their work and daily activities. In other words, we have not really seen any difference in achieving a reduction of the patients’ symptoms from 2006 to 2010.

Dr. Meltzer: Looking at this issue more globally, I think that the lack of change has a great deal to do with the public not understanding what “health” is. The World Health Organization (WHO) definition of health is there should be no problems with physical, social, emotional, or mental well-being. Individuals often do not appreciate how healthy they could be, and thus do not have a reference point. The NASAL survey clearly shows that most nasal allergy sufferers are not aware of an appropriate respiratory health goal and, further, they are not cognizant of the magnitude of their disease due to their allergic rhinitis. I believe the patients are not the only ones who are unaware; I think many clinicians are also not aware of the extent of their patients’ morbidity. A current problem is that there is not enough assumption of responsibility; patients are not taking enough responsibility for their health, clinicians are not adequately managing these patients, and—despite the suggested health care reforms—there does not appear to be in the foreseeable future a system that is going to alter these conditions.

Dr. Stoloff: For example, many family physicians only ask the question “How are you (with respect to this topic)?” and patients often say they are fine, and that’s the end of the dialogue. But consequences of this type of discussion are that costs of health care continue due to the lack of health. So the person misses work or the person’s job performance is less than it would be because they don’t recognize what their health could be if they were properly treated. As far as they’re concerned, this situation has been going on year after year, and it is only when they are really bad that they know they should be somewhat better. Even then, most people do not fully appreciate what is achievable because no one in the health care system has ever told them, “You should be able to sleep through the night and wake up feeling well. You should be able to go to work. You should be able to participate in athletic, recreational venues to be healthy.” No one has brought that up, and as long as this situation continues, the cost for the patient, his or her family, and health care will continue to increase.

Dr. Hadley: One of the things that I see as an otolaryngologist is that there is also often a missed diagnosis. Everybody who comes in to see me tells me: “Doctor, I have ‘sinus’.” I think most of them are simply unaware of that fact that their nasal congestion plays a role in developing their sinus symptoms. So there is general unawareness of the importance of treating nasal allergies in the lay public, as well as in primary care physicians who have to deal with these patients. Going to issues of cost, I think that patients are seeing the economy go down, and this means that they don’t want to spend a lot of money on their health care. They have a lot of other worries, and I think this is playing a role in how we have to deal with our patients.

 

 

Dr. Stoloff: People need to understand that the cost of not spending money to be healthy has a consequence that is sometimes the greater cost of being unhealthy—cost in terms of morbidity, cost in terms of missed days from work, absenteeism, presenteeism, poor ability to function in the usual domains of physical, social, emotional, and mental.

Dr. Hadley: That’s what the public just does not understand. We have not achieved the goal of informing the lay public and practitioners about how effective management can get these patients better, reduce their costs, and enable patients to go back to work and their activities.

What should be done to better act on the challenges highlighted by these important surveys? Is there a need to increase the awareness of allergic rhinitis among health care providers?

Dr. Meltzer: If we’re not making progress then we have to make some changes. It seems to me that education could drive change. The public needs to better understand that it is not insignificant to have an inflammatory process called allergic rhinitis. Allergic rhinitis is clearly underestimated in terms of its burden. It is too often unrecognized or ignored as an inconsequential problem. It is important that the person who has allergic rhinitis does not disregard the burden of disease. The NASAL survey reports that allergic rhinitis affects the ability to sleep well in 40 of patients. We know that allergic rhinitis also compromises people’s activities and we know that they are not as productive when they’re at work. We also know there are many comorbidities—asthma in particular, and sinusitis, otitis, conjunctivitis are other common associated conditions. Patients and clinicians need to be educated to appreciate the significant morbidity associated with allergic rhinitis, and that nasal allergies need attention and effective control.

Dr. Hadley: One of the things that we all see is patients not always getting important information about the medications that they take; there is a walk-in to the grocery store and the pharmacy shelves are filled with medications that are over-the-counter. The problem is there is not enough education about what the benefits are and what the side effects are of all those medications. There is also a lot of direct to consumer advertising—radio, television, etc., that also leads to misconceptions about the benefits of some of these medications. Patients are somewhat aware that they have a problem, but they just don’t know where to go. From the health care provider perspective, the emphasis is on treating the major problems—diabetes, hypertension—and rhinitis is considered a minor problem. So I don’t think we are educating our patients well enough. And I think that is a misconception and misunderstanding, which should be corrected.

Dr. Stoloff: Most physicians will see on their schedule a brief description of what problems their upcoming patients have. In primary care, the person filling the schedule will often say that the patient with nasal symptoms has sinusitis, which overwhelmingly it is not. That is an “easy” quick visit and the typical conversation is “Here, take this pill—if you’ve tried that pill, then take this nasal inhaler—and if you didn’t like this one I’ve got another sample for you. And then we’ll figure out which one is going to be on your list, what is covered by your insurance, and what’s the generic.” There is very little discussion about the type of impairment suffered and the overall burden on the individual. Importantly, that burden is often substantial, especially if nasal allergy symptoms were the primary reason for the office visit.

In primary care, people can have a multitude of other conditions, and allergic rhinitis is down at the bottom of the list. For example, the patient may be a hypertensive diabetic who also has seasonal allergic rhinitis. So by the time a family doctor gets to discuss allergic rhinitis, the office visit time is over and it is easier for the physician to just give a medication. But when the presence of allergic rhinitis has an enormous influence on the other diseases as far as activity, sleep, fatigue, depression, all the other emotional components, as well as physical components, that the survey highlighted—that really needs to be brought to the attention of both the patient and the health care provider to spend the appropriate time discussing it. Because it will influence care in everything else the person does.

How would you work up a patient who you might consider as potentially having allergic rhinitis?

Dr. Meltzer: When physicians view their schedule, a word or phrase supposedly informs them in advance of the patient’s condition. In reality, every patient is different and, moreover, patients with allergic rhinitis vary over the course of days, months and years in their symptomatology. So when I evaluate a patient for rhinitis and their chief complaint is “I’m having problems with my nose,” I first find out the full range of symptoms, and which symptom is for them the most bothersome (most often it will turn out to be congestion). Secondly, I would find out whether the symptoms are intermittent, or persistent. If they are fairly persistent, this informs me about somewhat of their severity, which is another very important consideration. Thirdly, I would try to find out what are the triggers for the symptoms such as non-allergic precipitants (eg, climate changes, tobacco smoke, and other environmental pollutants), or specific allergen triggers (eg, pets, springtime pollens). I would also ask about any comorbid conditions because if they are having more than just nasal symptoms that expands what I am going to need to address. I need to know all of those things before I make a treatment plan. If the disease is intermittent and mild or not very bothersome, then I am going to initiate a modest management plan. If their allergic rhinitis is more problematic, then I will need to educate the patient about what they have, why they have it and what to do about it. The patient and I will need to agree about our expectations of treatment. We are going to have an action plan for the short-term as well as a plan for follow-up visits to see if in fact our initial plan is successful. Again, the specifics will depend upon the individual patient.

 

 

Dr. Hadley: Many patients come in to an ENT clinic with an inappropriate initial diagnosis, predominantly with sinus disease, and some of them actually have come in with inappropriately obtained CT scans of the paranasal sinuses because they were presumed to have a chronic sinus infection. Most importantly, many of them have come in with inappropriately administered multiple different courses of antibiotics, which is of concern to me. So I agree with Dr. Meltzer in the need to understand the history of the patient’s symptoms—whether they are intermittent or persistent. I also obtain a family history, which helps me to work out whether the patient has an allergic tendency or not. I also have to look back and see what medications have been tried, what has worked (and not worked) in the past. The timing of the medications is really important, and the patient’s own perceptions about whether they want a medication that is going to be beneficial, or whether they want a simple remedy also plays a role. Also, let’s not forget what Dr. Meltzer also talked about—environmental controls that can be helpful to reduce the patient’s symptomatology as well.

Dr. Stoloff: From my perspective, I’m always impressed how a simple explanation of what allergy actually is, in terms of definition and measurement, creates a totally different dialogue with the patient. When my patients come in, they are often past the point of just administering a medicine, and trying others if it didn’t work—especially now there are so many generic over-the-counter products in oral antihistamines available. As a consequence, I really want to talk to them about what is going on— what is the family history, what is the seasonality of the components. I live at a fairly substantial altitude with little or no humidity, so some of the environmental issues that are very clear in San Diego where Dr. Meltzer practices have no role in my patients. However, some of the people I’ve seen have come in with pages of an expensive serum test that shows positive for certain items that have no influence on the patient’s current environment.

Patient history has to guide our workup. Dr. Hadley’s point about family history was important; we look to document what in fact are the causes. If we can figure out what is pushing the disease forward, maybe we can prevent some of those problems or at least lessen them. The history also helps in diagnosis. If we find by their history they’re overusing topical decongestants, that’s important. If we find they’re using their intranasal spray in the wrong way, that’s important. After obtaining the patient history, we then need to individualize our workup based on physical examination. It is important to look in the nose; if we find they have mechanical problems that’s additional information. Certainly allergic specific testing can be helpful, but it has to be targeted based on the location and based on the patient’s story.

Dr. Meltzer: We also need to target treatment. As Dr. Hadley mentioned, we need to know what has and hasn’t worked in the past and what are the contributing mechanism of the rhinitis for a given patient—is it only allergic, is it infectious, is it nonspecific irritants, is it mechanical, or is it a mixture of all of these. Pharmacologic therapy can be stepped up or stepped down depending upon the patient’s progress. And immunotherapy is certainly an appropriate choice in patients who have more severe disease and/or who are not responding adequately. Individualization is the key in terms of management.

Dr. Hadley: There is a clear need for the identification of and appropriate care of patients who need further management. As clinicians, we glean from patients’ history when they have symptoms and when we can appropriately add to the pharmacological management other therapies that would be beneficial in helping patients control their environment a little bit better during specific times of the year. Some patients do need additional treatment at certain times of the year. For example, whereas patients with intermittent symptoms only need to be treated for a short period of time each year, other patients are plagued with year-round symptoms. So we have to gauge those patients appropriately.

Dr. Stoloff: Another point is that at times comanagement with an allergist or otolaryngologist will be beneficial to the patient. But the primary care physician has to recognize that and it takes time to have that discussion. Unfortunately, because allergic rhinitis is often trivialized (from a health care provider’s point of view), physicians do not step back to see how much of a burden this disease is for that individual. This lessens the opportunity to gain effective consultation in the specific fields, and therefore lessens the opportunity for better health for the patient.

 

 

How do current guidelines influence your current treatment practice? Which guidelines are useful?

Dr. Meltzer: The ARIA guidelines originate from a WHO program, initiated in 1999, to create an international appreciation of the morbidity associated with allergic rhinitis. They borrowed from the NIH guidelines for asthma, the classification concept of intermittent and persistent and rating of the disease into mild, moderate, and severe categories. I think that this is clinically more relevant than the FDA classifications of seasonal and perennial allergic rhinitis. If a person suffers symptoms when they visit a family member with cats for 2 weeks over Christmas—then that’s an intermittent problem. It is not really a “perennial” problem in terms of the allergen. The FDA view may be appropriate for approval of medications, but from the management standpoint of patients, classifications of persistent, intermittent and mild, moderate or severe are much more useful. Indeed US guidelines now also use these classifications.

The name ARIA actually stands for Allergic Rhinitis Impact on Asthma, and the impact on asthma was a key driver for the WHO program. ARIA recognized the concept of the unified airway and the consequence that having inflammation in one area of the airway created for other parts of the airway. The guidelines highlighted the recommendation to evaluate patients with allergic rhinitis for lower airway disease (be it with a pulmonary function or at least a good history), and conversely for patients with lower airway disease to check for an upper airway history of problems as well. This is important because there is crosstalk, and we should be managing the whole airway—reducing inflammation in all of it.

Dr. Stoloff: From my viewpoint, very few of my peers are aware of ARIA and what it recommends. Similarly, many of them are not aware of the differences between the FDA classification and clinical guidelines. They simply do not know that the field is moving away from using seasonal and perennial terminology and towards a redefinition in terms of severity, frequency, and intensity.

Dr. Hadley: I agree that the awareness of the ARIA guidelines in general medical communities is low. We should point outthat the American Academy of Asthma, Allergy & Immunology (AAAAI) did publish practice parameters for rhinitis in 2008 and those have made a lot of sense as they give a practitioner a stepwise process to look at whether the symptoms are intermittent versus persistent, the degree of severity, and then makes recommendations on the types of medication that can be of clinical benefit to the patient. These guidelines are much more useful to the primary care physician.

Dr. Stoloff: Speaking as an author of both the ARIA and the AAAAI practice parameters, one of the major problems is that my colleagues in primary care do not routinely read the journals where the guidelines are published. Thus, the information is not disseminated and consequently not incorporated into their clinical practice. If presented and disseminated properly, guidelines should influence the way clinicians look at these health care issues, for the patient’s benefit, for cost benefit, and for improving their practice, gaining better out come for everyone.

Dr. Meltzer: I think there are some common concepts that have been incorporated into each of the guidelines discussed. Firstly, we need to classify people by severity. Secondly, we need to appreciate that people with upper airway disease (including allergic rhinitis), often have involvement of other areas of the respiratory tract. In other words we need to consider the comorbidities of the associated diseases. Thirdly, once we appreciate the magnitude of the problems, the patient together with the clinician needs to establish goals. Fourthly, there are step recommendations; if the symptoms are mild or intermittent, less management is needed. If the symptoms are moderate to severe, and/or persistent, more intensive management is required. There are also defined therapeutic steps as to when one might include immunotherapy as part of the regimen. Finally, patients should be monitored as part of the long-term management of this chronic condition.

The ultimate goal is control—control based on what the patient’s goals were when defined during their discussions with their clinician. If we incorporate those basic five concepts into our clinical practice—it will be good for the upper airway, good for the lower airway, and good for long-term health.

Given the range of products available at present for allergic rhinitis, what criteria influence your choice of product?

Dr. Hadley: The problem is that our patients have problems that they do not consider allergic rhinitis as serious, compared to conditions such as hypertension or diabetes. However, they still have a problem that significantly influences their life. As far as the range of products, many of them have already been on an oral antihistamine and many have used and abused decongestant therapy, which is over-the-counter or now behind-the-counter that they have to ask for. Patients often try to first alleviate their symptoms with some of these products, and by the time the come to see me as a specialist they have already usually started on something already, and I have to look and determine whether or not they would be acceptable to use a more advanced product.

 

 

The topical nasal steroid is the pure anti-inflammatory product. We use this to treat the inflammatory state of the patient, recognizing that allergic rhinitis is an inflammatory problem. Antihistamines can reduce some of the symptoms but not as effectively as some of the topical nasal steroids. Added to that patients obviously have a preference to use a single product that they can use once per day, for most Americans this would ideally mean taking a pill, but unfortunately that’s not the best product for them. Our challenge is to change their attitudes and beliefs about appropriate treatment of these problems.

Dr. Meltzer: As an allergist I tend to think about allergic disease not only in terms of what is, but how did it get there. It is important to understand allergic rhinitis as an inflammatory process that involves numerous mediators, cytokines, and inflammatory cells. Oral antihistamines block only one of the mediators; they have no effect on cytokines or inflammatory cells or any of the other mediators. As such, while they can help with itchy noses, sneezing and runny noses, they do not help with congestion— which is the most bothersome and the most frequent symptom. Likewise, anticholinergics only help with runny nose, and are not effective against nasal itch, sneeze or congestion. Most people with allergic rhinitis have chronic disease, and topical decongestants should not be used for prolonged periods of time. Oral decongestants have dose-related side effects and the doses required to effectively reduce congestion increase the risks of irritability, diffculty sleeping and nervousness. Leukotriene modifiers are at best minimal to modest improvers of symptoms. Thus, the intranasal corticosteroids (because of their broad based mechanisms of action) are currently considered to be the best monotherapies.

However, when prescribing intranasal corticosteroids, there are a number of important considerations. First, we should ensure the patient is administering the spray properly in terms of the technique. In addition, there may be some patient preference in terms of whether an individual prefers an aerosol formulation or an aqueous formulation. There may also be issues in regard to cost and related to the availability of different agents on a formulary. Indeed, managed care limitations have been problematic for many of us who take care of patients. Furthermore, we certainly need to monitor that patients adhere to their regimen. I find in my practice that most people do not start taking their medication prior to a season; they wait until they’re in the midst of the worst time of their symptomatology and then expect an immediate treatment effect. I try to explain to them, that allergic rhinitis is an ongoing process, a fire, and if effective therapy is established and maintained early on, then the fire can be kept under control and the outcome will be far better than trying to deal with it when there is a flare-up of the major symptoms. This is a communication issue. Every person may have a different view and we need to come to an understanding of each individuals’ viewpoint (what their goals of treatment are). We are not going to be able to force a patient to stick with a particular treatment. It’s about educating them and encouraging them to take responsibility. I tell them “when you leave my office, you’re the one who has allergic rhinitis and I recommend you take the medication. However, you make the decisions.”

Dr. Hadley: We also must not forget that inappropriate patient comprehension and knowledge can also be problematic. Some patients take their medication too late, or perhaps too long, and they have side effects. Side effects can increase the burden of their disease and impact on their ability to perform well at work or school or play.

Dr. Stoloff: Yes, in primary care, especially when treating the older population who have hypertension, one often sees patients take decongestants, and one realizes the multitude of side effects associated with them. And, as Dr. Hadley says, very few patients are aware that their medications are causing these problems.

There are basically three key aspects related to patient communication. Firstly, patient education; we need to ensure our patients are aware of what they have, why they have it and what they can do about it. Secondly, there needs to be ongoing communication between the patient and the clinician to ensure availability of questions and availability of goal setting. Thirdly, patients should have realistic expectations, because when patients revisit we can assess if we have met their expectations or if adjustments in management are needed.

 

 

Dr. Hadley: I agree. Better awareness of the disease burden will improve the patient-clinician discussion and thereby improve the patient-physician relationship. This will enable physicians to better guide their patients through proposed treatment plans.

Another important topic is patient preference. We have discussed that most patients would like a pill that has no side effects or that they can take once a day, perhaps once a week, or a patch that they don’t have to deal with. Unfortunately, we need to recognize that such a medication does not yet exist. Patients who have a problem with the inflammatory process should be seen by the clinician and steered toward the most effective medication, and I personally believe that the topical nasal steroids are the best choice to reduce the inflammatory process as much as possible. There are new aerosol formulations of topical nasal steroids that will bring more treatment options for allergic rhinitis.

Dr. Meltzer: We should also note that these new developments with regards to new delivery systems address expanding patient choice. There are also a number of combination agents and biologics in development that may also improve pharmacotherapeutic outcomes. Advances in immunotherapy will also help treat the basic cause of allergic disease. I think many of these options will become available within the next few years.

Dr. Stoloff: I concur. The other point that we have made, and I think it’s important to reiterate, allergic rhinitis is not in a silo. It is associated with, for most of the population, comorbid diseases. When clinicians look for comorbidities, they often gain a far better appreciation of the value of treating the allergic rhinitis and therefore improving their outcome for other health issues such as asthma. But this needs to be taken in the context of communicating with the patient, always taking patient needs and goals into consideration, and working within the economic health care system that we now face.

 

Authors of papers presented in this Supplement met in person at the 2011 Annual Meeting of the American College of Allergy, Asthma & Immunology to further discuss the clinical, social, and economic implications of the findings from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC. This paper represents an edited transcript of their discussion.

Given the recent changes in US health care, how should the results of the NASAL 2010 survey be used to inform current practice? What about the role of other health care professionals and what are the cost implications of the survey findings?

Dr. Hadley: Firstly, it is important to note that there were improvements in the design of the NASAL 2010 survey compared to its 2006 predecessor. More importantly, although some of the 2010 information was a little bit different, we found that the majority of patients still suffer from their symptoms, and that the symptoms are predominant and bothersome. Allergic rhinitis bothers their sleep; it bothers their work and daily activities. In other words, we have not really seen any difference in achieving a reduction of the patients’ symptoms from 2006 to 2010.

Dr. Meltzer: Looking at this issue more globally, I think that the lack of change has a great deal to do with the public not understanding what “health” is. The World Health Organization (WHO) definition of health is there should be no problems with physical, social, emotional, or mental well-being. Individuals often do not appreciate how healthy they could be, and thus do not have a reference point. The NASAL survey clearly shows that most nasal allergy sufferers are not aware of an appropriate respiratory health goal and, further, they are not cognizant of the magnitude of their disease due to their allergic rhinitis. I believe the patients are not the only ones who are unaware; I think many clinicians are also not aware of the extent of their patients’ morbidity. A current problem is that there is not enough assumption of responsibility; patients are not taking enough responsibility for their health, clinicians are not adequately managing these patients, and—despite the suggested health care reforms—there does not appear to be in the foreseeable future a system that is going to alter these conditions.

Dr. Stoloff: For example, many family physicians only ask the question “How are you (with respect to this topic)?” and patients often say they are fine, and that’s the end of the dialogue. But consequences of this type of discussion are that costs of health care continue due to the lack of health. So the person misses work or the person’s job performance is less than it would be because they don’t recognize what their health could be if they were properly treated. As far as they’re concerned, this situation has been going on year after year, and it is only when they are really bad that they know they should be somewhat better. Even then, most people do not fully appreciate what is achievable because no one in the health care system has ever told them, “You should be able to sleep through the night and wake up feeling well. You should be able to go to work. You should be able to participate in athletic, recreational venues to be healthy.” No one has brought that up, and as long as this situation continues, the cost for the patient, his or her family, and health care will continue to increase.

Dr. Hadley: One of the things that I see as an otolaryngologist is that there is also often a missed diagnosis. Everybody who comes in to see me tells me: “Doctor, I have ‘sinus’.” I think most of them are simply unaware of that fact that their nasal congestion plays a role in developing their sinus symptoms. So there is general unawareness of the importance of treating nasal allergies in the lay public, as well as in primary care physicians who have to deal with these patients. Going to issues of cost, I think that patients are seeing the economy go down, and this means that they don’t want to spend a lot of money on their health care. They have a lot of other worries, and I think this is playing a role in how we have to deal with our patients.

 

 

Dr. Stoloff: People need to understand that the cost of not spending money to be healthy has a consequence that is sometimes the greater cost of being unhealthy—cost in terms of morbidity, cost in terms of missed days from work, absenteeism, presenteeism, poor ability to function in the usual domains of physical, social, emotional, and mental.

Dr. Hadley: That’s what the public just does not understand. We have not achieved the goal of informing the lay public and practitioners about how effective management can get these patients better, reduce their costs, and enable patients to go back to work and their activities.

What should be done to better act on the challenges highlighted by these important surveys? Is there a need to increase the awareness of allergic rhinitis among health care providers?

Dr. Meltzer: If we’re not making progress then we have to make some changes. It seems to me that education could drive change. The public needs to better understand that it is not insignificant to have an inflammatory process called allergic rhinitis. Allergic rhinitis is clearly underestimated in terms of its burden. It is too often unrecognized or ignored as an inconsequential problem. It is important that the person who has allergic rhinitis does not disregard the burden of disease. The NASAL survey reports that allergic rhinitis affects the ability to sleep well in 40 of patients. We know that allergic rhinitis also compromises people’s activities and we know that they are not as productive when they’re at work. We also know there are many comorbidities—asthma in particular, and sinusitis, otitis, conjunctivitis are other common associated conditions. Patients and clinicians need to be educated to appreciate the significant morbidity associated with allergic rhinitis, and that nasal allergies need attention and effective control.

Dr. Hadley: One of the things that we all see is patients not always getting important information about the medications that they take; there is a walk-in to the grocery store and the pharmacy shelves are filled with medications that are over-the-counter. The problem is there is not enough education about what the benefits are and what the side effects are of all those medications. There is also a lot of direct to consumer advertising—radio, television, etc., that also leads to misconceptions about the benefits of some of these medications. Patients are somewhat aware that they have a problem, but they just don’t know where to go. From the health care provider perspective, the emphasis is on treating the major problems—diabetes, hypertension—and rhinitis is considered a minor problem. So I don’t think we are educating our patients well enough. And I think that is a misconception and misunderstanding, which should be corrected.

Dr. Stoloff: Most physicians will see on their schedule a brief description of what problems their upcoming patients have. In primary care, the person filling the schedule will often say that the patient with nasal symptoms has sinusitis, which overwhelmingly it is not. That is an “easy” quick visit and the typical conversation is “Here, take this pill—if you’ve tried that pill, then take this nasal inhaler—and if you didn’t like this one I’ve got another sample for you. And then we’ll figure out which one is going to be on your list, what is covered by your insurance, and what’s the generic.” There is very little discussion about the type of impairment suffered and the overall burden on the individual. Importantly, that burden is often substantial, especially if nasal allergy symptoms were the primary reason for the office visit.

In primary care, people can have a multitude of other conditions, and allergic rhinitis is down at the bottom of the list. For example, the patient may be a hypertensive diabetic who also has seasonal allergic rhinitis. So by the time a family doctor gets to discuss allergic rhinitis, the office visit time is over and it is easier for the physician to just give a medication. But when the presence of allergic rhinitis has an enormous influence on the other diseases as far as activity, sleep, fatigue, depression, all the other emotional components, as well as physical components, that the survey highlighted—that really needs to be brought to the attention of both the patient and the health care provider to spend the appropriate time discussing it. Because it will influence care in everything else the person does.

How would you work up a patient who you might consider as potentially having allergic rhinitis?

Dr. Meltzer: When physicians view their schedule, a word or phrase supposedly informs them in advance of the patient’s condition. In reality, every patient is different and, moreover, patients with allergic rhinitis vary over the course of days, months and years in their symptomatology. So when I evaluate a patient for rhinitis and their chief complaint is “I’m having problems with my nose,” I first find out the full range of symptoms, and which symptom is for them the most bothersome (most often it will turn out to be congestion). Secondly, I would find out whether the symptoms are intermittent, or persistent. If they are fairly persistent, this informs me about somewhat of their severity, which is another very important consideration. Thirdly, I would try to find out what are the triggers for the symptoms such as non-allergic precipitants (eg, climate changes, tobacco smoke, and other environmental pollutants), or specific allergen triggers (eg, pets, springtime pollens). I would also ask about any comorbid conditions because if they are having more than just nasal symptoms that expands what I am going to need to address. I need to know all of those things before I make a treatment plan. If the disease is intermittent and mild or not very bothersome, then I am going to initiate a modest management plan. If their allergic rhinitis is more problematic, then I will need to educate the patient about what they have, why they have it and what to do about it. The patient and I will need to agree about our expectations of treatment. We are going to have an action plan for the short-term as well as a plan for follow-up visits to see if in fact our initial plan is successful. Again, the specifics will depend upon the individual patient.

 

 

Dr. Hadley: Many patients come in to an ENT clinic with an inappropriate initial diagnosis, predominantly with sinus disease, and some of them actually have come in with inappropriately obtained CT scans of the paranasal sinuses because they were presumed to have a chronic sinus infection. Most importantly, many of them have come in with inappropriately administered multiple different courses of antibiotics, which is of concern to me. So I agree with Dr. Meltzer in the need to understand the history of the patient’s symptoms—whether they are intermittent or persistent. I also obtain a family history, which helps me to work out whether the patient has an allergic tendency or not. I also have to look back and see what medications have been tried, what has worked (and not worked) in the past. The timing of the medications is really important, and the patient’s own perceptions about whether they want a medication that is going to be beneficial, or whether they want a simple remedy also plays a role. Also, let’s not forget what Dr. Meltzer also talked about—environmental controls that can be helpful to reduce the patient’s symptomatology as well.

Dr. Stoloff: From my perspective, I’m always impressed how a simple explanation of what allergy actually is, in terms of definition and measurement, creates a totally different dialogue with the patient. When my patients come in, they are often past the point of just administering a medicine, and trying others if it didn’t work—especially now there are so many generic over-the-counter products in oral antihistamines available. As a consequence, I really want to talk to them about what is going on— what is the family history, what is the seasonality of the components. I live at a fairly substantial altitude with little or no humidity, so some of the environmental issues that are very clear in San Diego where Dr. Meltzer practices have no role in my patients. However, some of the people I’ve seen have come in with pages of an expensive serum test that shows positive for certain items that have no influence on the patient’s current environment.

Patient history has to guide our workup. Dr. Hadley’s point about family history was important; we look to document what in fact are the causes. If we can figure out what is pushing the disease forward, maybe we can prevent some of those problems or at least lessen them. The history also helps in diagnosis. If we find by their history they’re overusing topical decongestants, that’s important. If we find they’re using their intranasal spray in the wrong way, that’s important. After obtaining the patient history, we then need to individualize our workup based on physical examination. It is important to look in the nose; if we find they have mechanical problems that’s additional information. Certainly allergic specific testing can be helpful, but it has to be targeted based on the location and based on the patient’s story.

Dr. Meltzer: We also need to target treatment. As Dr. Hadley mentioned, we need to know what has and hasn’t worked in the past and what are the contributing mechanism of the rhinitis for a given patient—is it only allergic, is it infectious, is it nonspecific irritants, is it mechanical, or is it a mixture of all of these. Pharmacologic therapy can be stepped up or stepped down depending upon the patient’s progress. And immunotherapy is certainly an appropriate choice in patients who have more severe disease and/or who are not responding adequately. Individualization is the key in terms of management.

Dr. Hadley: There is a clear need for the identification of and appropriate care of patients who need further management. As clinicians, we glean from patients’ history when they have symptoms and when we can appropriately add to the pharmacological management other therapies that would be beneficial in helping patients control their environment a little bit better during specific times of the year. Some patients do need additional treatment at certain times of the year. For example, whereas patients with intermittent symptoms only need to be treated for a short period of time each year, other patients are plagued with year-round symptoms. So we have to gauge those patients appropriately.

Dr. Stoloff: Another point is that at times comanagement with an allergist or otolaryngologist will be beneficial to the patient. But the primary care physician has to recognize that and it takes time to have that discussion. Unfortunately, because allergic rhinitis is often trivialized (from a health care provider’s point of view), physicians do not step back to see how much of a burden this disease is for that individual. This lessens the opportunity to gain effective consultation in the specific fields, and therefore lessens the opportunity for better health for the patient.

 

 

How do current guidelines influence your current treatment practice? Which guidelines are useful?

Dr. Meltzer: The ARIA guidelines originate from a WHO program, initiated in 1999, to create an international appreciation of the morbidity associated with allergic rhinitis. They borrowed from the NIH guidelines for asthma, the classification concept of intermittent and persistent and rating of the disease into mild, moderate, and severe categories. I think that this is clinically more relevant than the FDA classifications of seasonal and perennial allergic rhinitis. If a person suffers symptoms when they visit a family member with cats for 2 weeks over Christmas—then that’s an intermittent problem. It is not really a “perennial” problem in terms of the allergen. The FDA view may be appropriate for approval of medications, but from the management standpoint of patients, classifications of persistent, intermittent and mild, moderate or severe are much more useful. Indeed US guidelines now also use these classifications.

The name ARIA actually stands for Allergic Rhinitis Impact on Asthma, and the impact on asthma was a key driver for the WHO program. ARIA recognized the concept of the unified airway and the consequence that having inflammation in one area of the airway created for other parts of the airway. The guidelines highlighted the recommendation to evaluate patients with allergic rhinitis for lower airway disease (be it with a pulmonary function or at least a good history), and conversely for patients with lower airway disease to check for an upper airway history of problems as well. This is important because there is crosstalk, and we should be managing the whole airway—reducing inflammation in all of it.

Dr. Stoloff: From my viewpoint, very few of my peers are aware of ARIA and what it recommends. Similarly, many of them are not aware of the differences between the FDA classification and clinical guidelines. They simply do not know that the field is moving away from using seasonal and perennial terminology and towards a redefinition in terms of severity, frequency, and intensity.

Dr. Hadley: I agree that the awareness of the ARIA guidelines in general medical communities is low. We should point outthat the American Academy of Asthma, Allergy & Immunology (AAAAI) did publish practice parameters for rhinitis in 2008 and those have made a lot of sense as they give a practitioner a stepwise process to look at whether the symptoms are intermittent versus persistent, the degree of severity, and then makes recommendations on the types of medication that can be of clinical benefit to the patient. These guidelines are much more useful to the primary care physician.

Dr. Stoloff: Speaking as an author of both the ARIA and the AAAAI practice parameters, one of the major problems is that my colleagues in primary care do not routinely read the journals where the guidelines are published. Thus, the information is not disseminated and consequently not incorporated into their clinical practice. If presented and disseminated properly, guidelines should influence the way clinicians look at these health care issues, for the patient’s benefit, for cost benefit, and for improving their practice, gaining better out come for everyone.

Dr. Meltzer: I think there are some common concepts that have been incorporated into each of the guidelines discussed. Firstly, we need to classify people by severity. Secondly, we need to appreciate that people with upper airway disease (including allergic rhinitis), often have involvement of other areas of the respiratory tract. In other words we need to consider the comorbidities of the associated diseases. Thirdly, once we appreciate the magnitude of the problems, the patient together with the clinician needs to establish goals. Fourthly, there are step recommendations; if the symptoms are mild or intermittent, less management is needed. If the symptoms are moderate to severe, and/or persistent, more intensive management is required. There are also defined therapeutic steps as to when one might include immunotherapy as part of the regimen. Finally, patients should be monitored as part of the long-term management of this chronic condition.

The ultimate goal is control—control based on what the patient’s goals were when defined during their discussions with their clinician. If we incorporate those basic five concepts into our clinical practice—it will be good for the upper airway, good for the lower airway, and good for long-term health.

Given the range of products available at present for allergic rhinitis, what criteria influence your choice of product?

Dr. Hadley: The problem is that our patients have problems that they do not consider allergic rhinitis as serious, compared to conditions such as hypertension or diabetes. However, they still have a problem that significantly influences their life. As far as the range of products, many of them have already been on an oral antihistamine and many have used and abused decongestant therapy, which is over-the-counter or now behind-the-counter that they have to ask for. Patients often try to first alleviate their symptoms with some of these products, and by the time the come to see me as a specialist they have already usually started on something already, and I have to look and determine whether or not they would be acceptable to use a more advanced product.

 

 

The topical nasal steroid is the pure anti-inflammatory product. We use this to treat the inflammatory state of the patient, recognizing that allergic rhinitis is an inflammatory problem. Antihistamines can reduce some of the symptoms but not as effectively as some of the topical nasal steroids. Added to that patients obviously have a preference to use a single product that they can use once per day, for most Americans this would ideally mean taking a pill, but unfortunately that’s not the best product for them. Our challenge is to change their attitudes and beliefs about appropriate treatment of these problems.

Dr. Meltzer: As an allergist I tend to think about allergic disease not only in terms of what is, but how did it get there. It is important to understand allergic rhinitis as an inflammatory process that involves numerous mediators, cytokines, and inflammatory cells. Oral antihistamines block only one of the mediators; they have no effect on cytokines or inflammatory cells or any of the other mediators. As such, while they can help with itchy noses, sneezing and runny noses, they do not help with congestion— which is the most bothersome and the most frequent symptom. Likewise, anticholinergics only help with runny nose, and are not effective against nasal itch, sneeze or congestion. Most people with allergic rhinitis have chronic disease, and topical decongestants should not be used for prolonged periods of time. Oral decongestants have dose-related side effects and the doses required to effectively reduce congestion increase the risks of irritability, diffculty sleeping and nervousness. Leukotriene modifiers are at best minimal to modest improvers of symptoms. Thus, the intranasal corticosteroids (because of their broad based mechanisms of action) are currently considered to be the best monotherapies.

However, when prescribing intranasal corticosteroids, there are a number of important considerations. First, we should ensure the patient is administering the spray properly in terms of the technique. In addition, there may be some patient preference in terms of whether an individual prefers an aerosol formulation or an aqueous formulation. There may also be issues in regard to cost and related to the availability of different agents on a formulary. Indeed, managed care limitations have been problematic for many of us who take care of patients. Furthermore, we certainly need to monitor that patients adhere to their regimen. I find in my practice that most people do not start taking their medication prior to a season; they wait until they’re in the midst of the worst time of their symptomatology and then expect an immediate treatment effect. I try to explain to them, that allergic rhinitis is an ongoing process, a fire, and if effective therapy is established and maintained early on, then the fire can be kept under control and the outcome will be far better than trying to deal with it when there is a flare-up of the major symptoms. This is a communication issue. Every person may have a different view and we need to come to an understanding of each individuals’ viewpoint (what their goals of treatment are). We are not going to be able to force a patient to stick with a particular treatment. It’s about educating them and encouraging them to take responsibility. I tell them “when you leave my office, you’re the one who has allergic rhinitis and I recommend you take the medication. However, you make the decisions.”

Dr. Hadley: We also must not forget that inappropriate patient comprehension and knowledge can also be problematic. Some patients take their medication too late, or perhaps too long, and they have side effects. Side effects can increase the burden of their disease and impact on their ability to perform well at work or school or play.

Dr. Stoloff: Yes, in primary care, especially when treating the older population who have hypertension, one often sees patients take decongestants, and one realizes the multitude of side effects associated with them. And, as Dr. Hadley says, very few patients are aware that their medications are causing these problems.

There are basically three key aspects related to patient communication. Firstly, patient education; we need to ensure our patients are aware of what they have, why they have it and what they can do about it. Secondly, there needs to be ongoing communication between the patient and the clinician to ensure availability of questions and availability of goal setting. Thirdly, patients should have realistic expectations, because when patients revisit we can assess if we have met their expectations or if adjustments in management are needed.

 

 

Dr. Hadley: I agree. Better awareness of the disease burden will improve the patient-clinician discussion and thereby improve the patient-physician relationship. This will enable physicians to better guide their patients through proposed treatment plans.

Another important topic is patient preference. We have discussed that most patients would like a pill that has no side effects or that they can take once a day, perhaps once a week, or a patch that they don’t have to deal with. Unfortunately, we need to recognize that such a medication does not yet exist. Patients who have a problem with the inflammatory process should be seen by the clinician and steered toward the most effective medication, and I personally believe that the topical nasal steroids are the best choice to reduce the inflammatory process as much as possible. There are new aerosol formulations of topical nasal steroids that will bring more treatment options for allergic rhinitis.

Dr. Meltzer: We should also note that these new developments with regards to new delivery systems address expanding patient choice. There are also a number of combination agents and biologics in development that may also improve pharmacotherapeutic outcomes. Advances in immunotherapy will also help treat the basic cause of allergic disease. I think many of these options will become available within the next few years.

Dr. Stoloff: I concur. The other point that we have made, and I think it’s important to reiterate, allergic rhinitis is not in a silo. It is associated with, for most of the population, comorbid diseases. When clinicians look for comorbidities, they often gain a far better appreciation of the value of treating the allergic rhinitis and therefore improving their outcome for other health issues such as asthma. But this needs to be taken in the context of communicating with the patient, always taking patient needs and goals into consideration, and working within the economic health care system that we now face.

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Closing thoughts: Implications of the findings from the National Allergy Survey Assessing Limitations for the management of allergic rhinitis in America

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Closing thoughts: Implications of the findings from the National Allergy Survey Assessing Limitations for the management of allergic rhinitis in America

 

Authors of papers presented in this Supplement met in person at the 2011 Annual Meeting of the American College of Allergy, Asthma & Immunology to further discuss the clinical, social, and economic implications of the findings from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC. This paper represents an edited transcript of their discussion.

Given the recent changes in US health care, how should the results of the NASAL 2010 survey be used to inform current practice? What about the role of other health care professionals and what are the cost implications of the survey findings?

Dr. Hadley: Firstly, it is important to note that there were improvements in the design of the NASAL 2010 survey compared to its 2006 predecessor. More importantly, although some of the 2010 information was a little bit different, we found that the majority of patients still suffer from their symptoms, and that the symptoms are predominant and bothersome. Allergic rhinitis bothers their sleep; it bothers their work and daily activities. In other words, we have not really seen any difference in achieving a reduction of the patients’ symptoms from 2006 to 2010.

Dr. Meltzer: Looking at this issue more globally, I think that the lack of change has a great deal to do with the public not understanding what “health” is. The World Health Organization (WHO) definition of health is there should be no problems with physical, social, emotional, or mental well-being. Individuals often do not appreciate how healthy they could be, and thus do not have a reference point. The NASAL survey clearly shows that most nasal allergy sufferers are not aware of an appropriate respiratory health goal and, further, they are not cognizant of the magnitude of their disease due to their allergic rhinitis. I believe the patients are not the only ones who are unaware; I think many clinicians are also not aware of the extent of their patients’ morbidity. A current problem is that there is not enough assumption of responsibility; patients are not taking enough responsibility for their health, clinicians are not adequately managing these patients, and—despite the suggested health care reforms—there does not appear to be in the foreseeable future a system that is going to alter these conditions.

Dr. Stoloff: For example, many family physicians only ask the question “How are you (with respect to this topic)?” and patients often say they are fine, and that’s the end of the dialogue. But consequences of this type of discussion are that costs of health care continue due to the lack of health. So the person misses work or the person’s job performance is less than it would be because they don’t recognize what their health could be if they were properly treated. As far as they’re concerned, this situation has been going on year after year, and it is only when they are really bad that they know they should be somewhat better. Even then, most people do not fully appreciate what is achievable because no one in the health care system has ever told them, “You should be able to sleep through the night and wake up feeling well. You should be able to go to work. You should be able to participate in athletic, recreational venues to be healthy.” No one has brought that up, and as long as this situation continues, the cost for the patient, his or her family, and health care will continue to increase.

Dr. Hadley: One of the things that I see as an otolaryngologist is that there is also often a missed diagnosis. Everybody who comes in to see me tells me: “Doctor, I have ‘sinus’.” I think most of them are simply unaware of that fact that their nasal congestion plays a role in developing their sinus symptoms. So there is general unawareness of the importance of treating nasal allergies in the lay public, as well as in primary care physicians who have to deal with these patients. Going to issues of cost, I think that patients are seeing the economy go down, and this means that they don’t want to spend a lot of money on their health care. They have a lot of other worries, and I think this is playing a role in how we have to deal with our patients.

 

 

Dr. Stoloff: People need to understand that the cost of not spending money to be healthy has a consequence that is sometimes the greater cost of being unhealthy—cost in terms of morbidity, cost in terms of missed days from work, absenteeism, presenteeism, poor ability to function in the usual domains of physical, social, emotional, and mental.

Dr. Hadley: That’s what the public just does not understand. We have not achieved the goal of informing the lay public and practitioners about how effective management can get these patients better, reduce their costs, and enable patients to go back to work and their activities.

What should be done to better act on the challenges highlighted by these important surveys? Is there a need to increase the awareness of allergic rhinitis among health care providers?

Dr. Meltzer: If we’re not making progress then we have to make some changes. It seems to me that education could drive change. The public needs to better understand that it is not insignificant to have an inflammatory process called allergic rhinitis. Allergic rhinitis is clearly underestimated in terms of its burden. It is too often unrecognized or ignored as an inconsequential problem. It is important that the person who has allergic rhinitis does not disregard the burden of disease. The NASAL survey reports that allergic rhinitis affects the ability to sleep well in 40 of patients. We know that allergic rhinitis also compromises people’s activities and we know that they are not as productive when they’re at work. We also know there are many comorbidities—asthma in particular, and sinusitis, otitis, conjunctivitis are other common associated conditions. Patients and clinicians need to be educated to appreciate the significant morbidity associated with allergic rhinitis, and that nasal allergies need attention and effective control.

Dr. Hadley: One of the things that we all see is patients not always getting important information about the medications that they take; there is a walk-in to the grocery store and the pharmacy shelves are filled with medications that are over-the-counter. The problem is there is not enough education about what the benefits are and what the side effects are of all those medications. There is also a lot of direct to consumer advertising—radio, television, etc., that also leads to misconceptions about the benefits of some of these medications. Patients are somewhat aware that they have a problem, but they just don’t know where to go. From the health care provider perspective, the emphasis is on treating the major problems—diabetes, hypertension—and rhinitis is considered a minor problem. So I don’t think we are educating our patients well enough. And I think that is a misconception and misunderstanding, which should be corrected.

Dr. Stoloff: Most physicians will see on their schedule a brief description of what problems their upcoming patients have. In primary care, the person filling the schedule will often say that the patient with nasal symptoms has sinusitis, which overwhelmingly it is not. That is an “easy” quick visit and the typical conversation is “Here, take this pill—if you’ve tried that pill, then take this nasal inhaler—and if you didn’t like this one I’ve got another sample for you. And then we’ll figure out which one is going to be on your list, what is covered by your insurance, and what’s the generic.” There is very little discussion about the type of impairment suffered and the overall burden on the individual. Importantly, that burden is often substantial, especially if nasal allergy symptoms were the primary reason for the office visit.

In primary care, people can have a multitude of other conditions, and allergic rhinitis is down at the bottom of the list. For example, the patient may be a hypertensive diabetic who also has seasonal allergic rhinitis. So by the time a family doctor gets to discuss allergic rhinitis, the office visit time is over and it is easier for the physician to just give a medication. But when the presence of allergic rhinitis has an enormous influence on the other diseases as far as activity, sleep, fatigue, depression, all the other emotional components, as well as physical components, that the survey highlighted—that really needs to be brought to the attention of both the patient and the health care provider to spend the appropriate time discussing it. Because it will influence care in everything else the person does.

How would you work up a patient who you might consider as potentially having allergic rhinitis?

Dr. Meltzer: When physicians view their schedule, a word or phrase supposedly informs them in advance of the patient’s condition. In reality, every patient is different and, moreover, patients with allergic rhinitis vary over the course of days, months and years in their symptomatology. So when I evaluate a patient for rhinitis and their chief complaint is “I’m having problems with my nose,” I first find out the full range of symptoms, and which symptom is for them the most bothersome (most often it will turn out to be congestion). Secondly, I would find out whether the symptoms are intermittent, or persistent. If they are fairly persistent, this informs me about somewhat of their severity, which is another very important consideration. Thirdly, I would try to find out what are the triggers for the symptoms such as non-allergic precipitants (eg, climate changes, tobacco smoke, and other environmental pollutants), or specific allergen triggers (eg, pets, springtime pollens). I would also ask about any comorbid conditions because if they are having more than just nasal symptoms that expands what I am going to need to address. I need to know all of those things before I make a treatment plan. If the disease is intermittent and mild or not very bothersome, then I am going to initiate a modest management plan. If their allergic rhinitis is more problematic, then I will need to educate the patient about what they have, why they have it and what to do about it. The patient and I will need to agree about our expectations of treatment. We are going to have an action plan for the short-term as well as a plan for follow-up visits to see if in fact our initial plan is successful. Again, the specifics will depend upon the individual patient.

 

 

Dr. Hadley: Many patients come in to an ENT clinic with an inappropriate initial diagnosis, predominantly with sinus disease, and some of them actually have come in with inappropriately obtained CT scans of the paranasal sinuses because they were presumed to have a chronic sinus infection. Most importantly, many of them have come in with inappropriately administered multiple different courses of antibiotics, which is of concern to me. So I agree with Dr. Meltzer in the need to understand the history of the patient’s symptoms—whether they are intermittent or persistent. I also obtain a family history, which helps me to work out whether the patient has an allergic tendency or not. I also have to look back and see what medications have been tried, what has worked (and not worked) in the past. The timing of the medications is really important, and the patient’s own perceptions about whether they want a medication that is going to be beneficial, or whether they want a simple remedy also plays a role. Also, let’s not forget what Dr. Meltzer also talked about—environmental controls that can be helpful to reduce the patient’s symptomatology as well.

Dr. Stoloff: From my perspective, I’m always impressed how a simple explanation of what allergy actually is, in terms of definition and measurement, creates a totally different dialogue with the patient. When my patients come in, they are often past the point of just administering a medicine, and trying others if it didn’t work—especially now there are so many generic over-the-counter products in oral antihistamines available. As a consequence, I really want to talk to them about what is going on— what is the family history, what is the seasonality of the components. I live at a fairly substantial altitude with little or no humidity, so some of the environmental issues that are very clear in San Diego where Dr. Meltzer practices have no role in my patients. However, some of the people I’ve seen have come in with pages of an expensive serum test that shows positive for certain items that have no influence on the patient’s current environment.

Patient history has to guide our workup. Dr. Hadley’s point about family history was important; we look to document what in fact are the causes. If we can figure out what is pushing the disease forward, maybe we can prevent some of those problems or at least lessen them. The history also helps in diagnosis. If we find by their history they’re overusing topical decongestants, that’s important. If we find they’re using their intranasal spray in the wrong way, that’s important. After obtaining the patient history, we then need to individualize our workup based on physical examination. It is important to look in the nose; if we find they have mechanical problems that’s additional information. Certainly allergic specific testing can be helpful, but it has to be targeted based on the location and based on the patient’s story.

Dr. Meltzer: We also need to target treatment. As Dr. Hadley mentioned, we need to know what has and hasn’t worked in the past and what are the contributing mechanism of the rhinitis for a given patient—is it only allergic, is it infectious, is it nonspecific irritants, is it mechanical, or is it a mixture of all of these. Pharmacologic therapy can be stepped up or stepped down depending upon the patient’s progress. And immunotherapy is certainly an appropriate choice in patients who have more severe disease and/or who are not responding adequately. Individualization is the key in terms of management.

Dr. Hadley: There is a clear need for the identification of and appropriate care of patients who need further management. As clinicians, we glean from patients’ history when they have symptoms and when we can appropriately add to the pharmacological management other therapies that would be beneficial in helping patients control their environment a little bit better during specific times of the year. Some patients do need additional treatment at certain times of the year. For example, whereas patients with intermittent symptoms only need to be treated for a short period of time each year, other patients are plagued with year-round symptoms. So we have to gauge those patients appropriately.

Dr. Stoloff: Another point is that at times comanagement with an allergist or otolaryngologist will be beneficial to the patient. But the primary care physician has to recognize that and it takes time to have that discussion. Unfortunately, because allergic rhinitis is often trivialized (from a health care provider’s point of view), physicians do not step back to see how much of a burden this disease is for that individual. This lessens the opportunity to gain effective consultation in the specific fields, and therefore lessens the opportunity for better health for the patient.

 

 

How do current guidelines influence your current treatment practice? Which guidelines are useful?

Dr. Meltzer: The ARIA guidelines originate from a WHO program, initiated in 1999, to create an international appreciation of the morbidity associated with allergic rhinitis. They borrowed from the NIH guidelines for asthma, the classification concept of intermittent and persistent and rating of the disease into mild, moderate, and severe categories. I think that this is clinically more relevant than the FDA classifications of seasonal and perennial allergic rhinitis. If a person suffers symptoms when they visit a family member with cats for 2 weeks over Christmas—then that’s an intermittent problem. It is not really a “perennial” problem in terms of the allergen. The FDA view may be appropriate for approval of medications, but from the management standpoint of patients, classifications of persistent, intermittent and mild, moderate or severe are much more useful. Indeed US guidelines now also use these classifications.

The name ARIA actually stands for Allergic Rhinitis Impact on Asthma, and the impact on asthma was a key driver for the WHO program. ARIA recognized the concept of the unified airway and the consequence that having inflammation in one area of the airway created for other parts of the airway. The guidelines highlighted the recommendation to evaluate patients with allergic rhinitis for lower airway disease (be it with a pulmonary function or at least a good history), and conversely for patients with lower airway disease to check for an upper airway history of problems as well. This is important because there is crosstalk, and we should be managing the whole airway—reducing inflammation in all of it.

Dr. Stoloff: From my viewpoint, very few of my peers are aware of ARIA and what it recommends. Similarly, many of them are not aware of the differences between the FDA classification and clinical guidelines. They simply do not know that the field is moving away from using seasonal and perennial terminology and towards a redefinition in terms of severity, frequency, and intensity.

Dr. Hadley: I agree that the awareness of the ARIA guidelines in general medical communities is low. We should point outthat the American Academy of Asthma, Allergy & Immunology (AAAAI) did publish practice parameters for rhinitis in 2008 and those have made a lot of sense as they give a practitioner a stepwise process to look at whether the symptoms are intermittent versus persistent, the degree of severity, and then makes recommendations on the types of medication that can be of clinical benefit to the patient. These guidelines are much more useful to the primary care physician.

Dr. Stoloff: Speaking as an author of both the ARIA and the AAAAI practice parameters, one of the major problems is that my colleagues in primary care do not routinely read the journals where the guidelines are published. Thus, the information is not disseminated and consequently not incorporated into their clinical practice. If presented and disseminated properly, guidelines should influence the way clinicians look at these health care issues, for the patient’s benefit, for cost benefit, and for improving their practice, gaining better out come for everyone.

Dr. Meltzer: I think there are some common concepts that have been incorporated into each of the guidelines discussed. Firstly, we need to classify people by severity. Secondly, we need to appreciate that people with upper airway disease (including allergic rhinitis), often have involvement of other areas of the respiratory tract. In other words we need to consider the comorbidities of the associated diseases. Thirdly, once we appreciate the magnitude of the problems, the patient together with the clinician needs to establish goals. Fourthly, there are step recommendations; if the symptoms are mild or intermittent, less management is needed. If the symptoms are moderate to severe, and/or persistent, more intensive management is required. There are also defined therapeutic steps as to when one might include immunotherapy as part of the regimen. Finally, patients should be monitored as part of the long-term management of this chronic condition.

The ultimate goal is control—control based on what the patient’s goals were when defined during their discussions with their clinician. If we incorporate those basic five concepts into our clinical practice—it will be good for the upper airway, good for the lower airway, and good for long-term health.

Given the range of products available at present for allergic rhinitis, what criteria influence your choice of product?

Dr. Hadley: The problem is that our patients have problems that they do not consider allergic rhinitis as serious, compared to conditions such as hypertension or diabetes. However, they still have a problem that significantly influences their life. As far as the range of products, many of them have already been on an oral antihistamine and many have used and abused decongestant therapy, which is over-the-counter or now behind-the-counter that they have to ask for. Patients often try to first alleviate their symptoms with some of these products, and by the time the come to see me as a specialist they have already usually started on something already, and I have to look and determine whether or not they would be acceptable to use a more advanced product.

 

 

The topical nasal steroid is the pure anti-inflammatory product. We use this to treat the inflammatory state of the patient, recognizing that allergic rhinitis is an inflammatory problem. Antihistamines can reduce some of the symptoms but not as effectively as some of the topical nasal steroids. Added to that patients obviously have a preference to use a single product that they can use once per day, for most Americans this would ideally mean taking a pill, but unfortunately that’s not the best product for them. Our challenge is to change their attitudes and beliefs about appropriate treatment of these problems.

Dr. Meltzer: As an allergist I tend to think about allergic disease not only in terms of what is, but how did it get there. It is important to understand allergic rhinitis as an inflammatory process that involves numerous mediators, cytokines, and inflammatory cells. Oral antihistamines block only one of the mediators; they have no effect on cytokines or inflammatory cells or any of the other mediators. As such, while they can help with itchy noses, sneezing and runny noses, they do not help with congestion— which is the most bothersome and the most frequent symptom. Likewise, anticholinergics only help with runny nose, and are not effective against nasal itch, sneeze or congestion. Most people with allergic rhinitis have chronic disease, and topical decongestants should not be used for prolonged periods of time. Oral decongestants have dose-related side effects and the doses required to effectively reduce congestion increase the risks of irritability, diffculty sleeping and nervousness. Leukotriene modifiers are at best minimal to modest improvers of symptoms. Thus, the intranasal corticosteroids (because of their broad based mechanisms of action) are currently considered to be the best monotherapies.

However, when prescribing intranasal corticosteroids, there are a number of important considerations. First, we should ensure the patient is administering the spray properly in terms of the technique. In addition, there may be some patient preference in terms of whether an individual prefers an aerosol formulation or an aqueous formulation. There may also be issues in regard to cost and related to the availability of different agents on a formulary. Indeed, managed care limitations have been problematic for many of us who take care of patients. Furthermore, we certainly need to monitor that patients adhere to their regimen. I find in my practice that most people do not start taking their medication prior to a season; they wait until they’re in the midst of the worst time of their symptomatology and then expect an immediate treatment effect. I try to explain to them, that allergic rhinitis is an ongoing process, a fire, and if effective therapy is established and maintained early on, then the fire can be kept under control and the outcome will be far better than trying to deal with it when there is a flare-up of the major symptoms. This is a communication issue. Every person may have a different view and we need to come to an understanding of each individuals’ viewpoint (what their goals of treatment are). We are not going to be able to force a patient to stick with a particular treatment. It’s about educating them and encouraging them to take responsibility. I tell them “when you leave my office, you’re the one who has allergic rhinitis and I recommend you take the medication. However, you make the decisions.”

Dr. Hadley: We also must not forget that inappropriate patient comprehension and knowledge can also be problematic. Some patients take their medication too late, or perhaps too long, and they have side effects. Side effects can increase the burden of their disease and impact on their ability to perform well at work or school or play.

Dr. Stoloff: Yes, in primary care, especially when treating the older population who have hypertension, one often sees patients take decongestants, and one realizes the multitude of side effects associated with them. And, as Dr. Hadley says, very few patients are aware that their medications are causing these problems.

There are basically three key aspects related to patient communication. Firstly, patient education; we need to ensure our patients are aware of what they have, why they have it and what they can do about it. Secondly, there needs to be ongoing communication between the patient and the clinician to ensure availability of questions and availability of goal setting. Thirdly, patients should have realistic expectations, because when patients revisit we can assess if we have met their expectations or if adjustments in management are needed.

 

 

Dr. Hadley: I agree. Better awareness of the disease burden will improve the patient-clinician discussion and thereby improve the patient-physician relationship. This will enable physicians to better guide their patients through proposed treatment plans.

Another important topic is patient preference. We have discussed that most patients would like a pill that has no side effects or that they can take once a day, perhaps once a week, or a patch that they don’t have to deal with. Unfortunately, we need to recognize that such a medication does not yet exist. Patients who have a problem with the inflammatory process should be seen by the clinician and steered toward the most effective medication, and I personally believe that the topical nasal steroids are the best choice to reduce the inflammatory process as much as possible. There are new aerosol formulations of topical nasal steroids that will bring more treatment options for allergic rhinitis.

Dr. Meltzer: We should also note that these new developments with regards to new delivery systems address expanding patient choice. There are also a number of combination agents and biologics in development that may also improve pharmacotherapeutic outcomes. Advances in immunotherapy will also help treat the basic cause of allergic disease. I think many of these options will become available within the next few years.

Dr. Stoloff: I concur. The other point that we have made, and I think it’s important to reiterate, allergic rhinitis is not in a silo. It is associated with, for most of the population, comorbid diseases. When clinicians look for comorbidities, they often gain a far better appreciation of the value of treating the allergic rhinitis and therefore improving their outcome for other health issues such as asthma. But this needs to be taken in the context of communicating with the patient, always taking patient needs and goals into consideration, and working within the economic health care system that we now face.

Author and Disclosure Information

 

Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

James A. Hadley, MD
James A. Hadley, MD, has served on the advisory board for Meda Pharmaceuticals, Teva Pharmaceuticals, and Merck.

Eli O. Meltzer, MD
Eli O. Meltzer, MD, has received grant/research support from and served as a consultant/advisor and a speaker for Alcon, Sunovion/Sepracor, and Teva Pharmaceuticals. Dr. Meltzer has received grant/research support and served as a consultant/advisor for Astra Zeneca, Boehringer Ingelheim, and Procter & Gamble. He has served as a consultant/advisor and a speaker for Dey and Merck. He has received grant/research support from Amgen, Apotex, GlaxoSmithKline, HRA, MedImmune, Novartis, and Schering-Plough. He has served as a consultant/advisor for Alexza, Bausch & Lomb, Forest, ISTA Pharmaceuticals, Johnson & Johnson, Kalypsys, Meda, ONO, Optinase, and Rady Children’s Hospital San Diego. He has served as a speaker for Allergists for Israel, American College

Issue
The Journal of Family Practice - 61(02)
Publications
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S23-S28
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Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

James A. Hadley, MD
James A. Hadley, MD, has served on the advisory board for Meda Pharmaceuticals, Teva Pharmaceuticals, and Merck.

Eli O. Meltzer, MD
Eli O. Meltzer, MD, has received grant/research support from and served as a consultant/advisor and a speaker for Alcon, Sunovion/Sepracor, and Teva Pharmaceuticals. Dr. Meltzer has received grant/research support and served as a consultant/advisor for Astra Zeneca, Boehringer Ingelheim, and Procter & Gamble. He has served as a consultant/advisor and a speaker for Dey and Merck. He has received grant/research support from Amgen, Apotex, GlaxoSmithKline, HRA, MedImmune, Novartis, and Schering-Plough. He has served as a consultant/advisor for Alexza, Bausch & Lomb, Forest, ISTA Pharmaceuticals, Johnson & Johnson, Kalypsys, Meda, ONO, Optinase, and Rady Children’s Hospital San Diego. He has served as a speaker for Allergists for Israel, American College

Author and Disclosure Information

 

Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

James A. Hadley, MD
James A. Hadley, MD, has served on the advisory board for Meda Pharmaceuticals, Teva Pharmaceuticals, and Merck.

Eli O. Meltzer, MD
Eli O. Meltzer, MD, has received grant/research support from and served as a consultant/advisor and a speaker for Alcon, Sunovion/Sepracor, and Teva Pharmaceuticals. Dr. Meltzer has received grant/research support and served as a consultant/advisor for Astra Zeneca, Boehringer Ingelheim, and Procter & Gamble. He has served as a consultant/advisor and a speaker for Dey and Merck. He has received grant/research support from Amgen, Apotex, GlaxoSmithKline, HRA, MedImmune, Novartis, and Schering-Plough. He has served as a consultant/advisor for Alexza, Bausch & Lomb, Forest, ISTA Pharmaceuticals, Johnson & Johnson, Kalypsys, Meda, ONO, Optinase, and Rady Children’s Hospital San Diego. He has served as a speaker for Allergists for Israel, American College

 

Authors of papers presented in this Supplement met in person at the 2011 Annual Meeting of the American College of Allergy, Asthma & Immunology to further discuss the clinical, social, and economic implications of the findings from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC. This paper represents an edited transcript of their discussion.

Given the recent changes in US health care, how should the results of the NASAL 2010 survey be used to inform current practice? What about the role of other health care professionals and what are the cost implications of the survey findings?

Dr. Hadley: Firstly, it is important to note that there were improvements in the design of the NASAL 2010 survey compared to its 2006 predecessor. More importantly, although some of the 2010 information was a little bit different, we found that the majority of patients still suffer from their symptoms, and that the symptoms are predominant and bothersome. Allergic rhinitis bothers their sleep; it bothers their work and daily activities. In other words, we have not really seen any difference in achieving a reduction of the patients’ symptoms from 2006 to 2010.

Dr. Meltzer: Looking at this issue more globally, I think that the lack of change has a great deal to do with the public not understanding what “health” is. The World Health Organization (WHO) definition of health is there should be no problems with physical, social, emotional, or mental well-being. Individuals often do not appreciate how healthy they could be, and thus do not have a reference point. The NASAL survey clearly shows that most nasal allergy sufferers are not aware of an appropriate respiratory health goal and, further, they are not cognizant of the magnitude of their disease due to their allergic rhinitis. I believe the patients are not the only ones who are unaware; I think many clinicians are also not aware of the extent of their patients’ morbidity. A current problem is that there is not enough assumption of responsibility; patients are not taking enough responsibility for their health, clinicians are not adequately managing these patients, and—despite the suggested health care reforms—there does not appear to be in the foreseeable future a system that is going to alter these conditions.

Dr. Stoloff: For example, many family physicians only ask the question “How are you (with respect to this topic)?” and patients often say they are fine, and that’s the end of the dialogue. But consequences of this type of discussion are that costs of health care continue due to the lack of health. So the person misses work or the person’s job performance is less than it would be because they don’t recognize what their health could be if they were properly treated. As far as they’re concerned, this situation has been going on year after year, and it is only when they are really bad that they know they should be somewhat better. Even then, most people do not fully appreciate what is achievable because no one in the health care system has ever told them, “You should be able to sleep through the night and wake up feeling well. You should be able to go to work. You should be able to participate in athletic, recreational venues to be healthy.” No one has brought that up, and as long as this situation continues, the cost for the patient, his or her family, and health care will continue to increase.

Dr. Hadley: One of the things that I see as an otolaryngologist is that there is also often a missed diagnosis. Everybody who comes in to see me tells me: “Doctor, I have ‘sinus’.” I think most of them are simply unaware of that fact that their nasal congestion plays a role in developing their sinus symptoms. So there is general unawareness of the importance of treating nasal allergies in the lay public, as well as in primary care physicians who have to deal with these patients. Going to issues of cost, I think that patients are seeing the economy go down, and this means that they don’t want to spend a lot of money on their health care. They have a lot of other worries, and I think this is playing a role in how we have to deal with our patients.

 

 

Dr. Stoloff: People need to understand that the cost of not spending money to be healthy has a consequence that is sometimes the greater cost of being unhealthy—cost in terms of morbidity, cost in terms of missed days from work, absenteeism, presenteeism, poor ability to function in the usual domains of physical, social, emotional, and mental.

Dr. Hadley: That’s what the public just does not understand. We have not achieved the goal of informing the lay public and practitioners about how effective management can get these patients better, reduce their costs, and enable patients to go back to work and their activities.

What should be done to better act on the challenges highlighted by these important surveys? Is there a need to increase the awareness of allergic rhinitis among health care providers?

Dr. Meltzer: If we’re not making progress then we have to make some changes. It seems to me that education could drive change. The public needs to better understand that it is not insignificant to have an inflammatory process called allergic rhinitis. Allergic rhinitis is clearly underestimated in terms of its burden. It is too often unrecognized or ignored as an inconsequential problem. It is important that the person who has allergic rhinitis does not disregard the burden of disease. The NASAL survey reports that allergic rhinitis affects the ability to sleep well in 40 of patients. We know that allergic rhinitis also compromises people’s activities and we know that they are not as productive when they’re at work. We also know there are many comorbidities—asthma in particular, and sinusitis, otitis, conjunctivitis are other common associated conditions. Patients and clinicians need to be educated to appreciate the significant morbidity associated with allergic rhinitis, and that nasal allergies need attention and effective control.

Dr. Hadley: One of the things that we all see is patients not always getting important information about the medications that they take; there is a walk-in to the grocery store and the pharmacy shelves are filled with medications that are over-the-counter. The problem is there is not enough education about what the benefits are and what the side effects are of all those medications. There is also a lot of direct to consumer advertising—radio, television, etc., that also leads to misconceptions about the benefits of some of these medications. Patients are somewhat aware that they have a problem, but they just don’t know where to go. From the health care provider perspective, the emphasis is on treating the major problems—diabetes, hypertension—and rhinitis is considered a minor problem. So I don’t think we are educating our patients well enough. And I think that is a misconception and misunderstanding, which should be corrected.

Dr. Stoloff: Most physicians will see on their schedule a brief description of what problems their upcoming patients have. In primary care, the person filling the schedule will often say that the patient with nasal symptoms has sinusitis, which overwhelmingly it is not. That is an “easy” quick visit and the typical conversation is “Here, take this pill—if you’ve tried that pill, then take this nasal inhaler—and if you didn’t like this one I’ve got another sample for you. And then we’ll figure out which one is going to be on your list, what is covered by your insurance, and what’s the generic.” There is very little discussion about the type of impairment suffered and the overall burden on the individual. Importantly, that burden is often substantial, especially if nasal allergy symptoms were the primary reason for the office visit.

In primary care, people can have a multitude of other conditions, and allergic rhinitis is down at the bottom of the list. For example, the patient may be a hypertensive diabetic who also has seasonal allergic rhinitis. So by the time a family doctor gets to discuss allergic rhinitis, the office visit time is over and it is easier for the physician to just give a medication. But when the presence of allergic rhinitis has an enormous influence on the other diseases as far as activity, sleep, fatigue, depression, all the other emotional components, as well as physical components, that the survey highlighted—that really needs to be brought to the attention of both the patient and the health care provider to spend the appropriate time discussing it. Because it will influence care in everything else the person does.

How would you work up a patient who you might consider as potentially having allergic rhinitis?

Dr. Meltzer: When physicians view their schedule, a word or phrase supposedly informs them in advance of the patient’s condition. In reality, every patient is different and, moreover, patients with allergic rhinitis vary over the course of days, months and years in their symptomatology. So when I evaluate a patient for rhinitis and their chief complaint is “I’m having problems with my nose,” I first find out the full range of symptoms, and which symptom is for them the most bothersome (most often it will turn out to be congestion). Secondly, I would find out whether the symptoms are intermittent, or persistent. If they are fairly persistent, this informs me about somewhat of their severity, which is another very important consideration. Thirdly, I would try to find out what are the triggers for the symptoms such as non-allergic precipitants (eg, climate changes, tobacco smoke, and other environmental pollutants), or specific allergen triggers (eg, pets, springtime pollens). I would also ask about any comorbid conditions because if they are having more than just nasal symptoms that expands what I am going to need to address. I need to know all of those things before I make a treatment plan. If the disease is intermittent and mild or not very bothersome, then I am going to initiate a modest management plan. If their allergic rhinitis is more problematic, then I will need to educate the patient about what they have, why they have it and what to do about it. The patient and I will need to agree about our expectations of treatment. We are going to have an action plan for the short-term as well as a plan for follow-up visits to see if in fact our initial plan is successful. Again, the specifics will depend upon the individual patient.

 

 

Dr. Hadley: Many patients come in to an ENT clinic with an inappropriate initial diagnosis, predominantly with sinus disease, and some of them actually have come in with inappropriately obtained CT scans of the paranasal sinuses because they were presumed to have a chronic sinus infection. Most importantly, many of them have come in with inappropriately administered multiple different courses of antibiotics, which is of concern to me. So I agree with Dr. Meltzer in the need to understand the history of the patient’s symptoms—whether they are intermittent or persistent. I also obtain a family history, which helps me to work out whether the patient has an allergic tendency or not. I also have to look back and see what medications have been tried, what has worked (and not worked) in the past. The timing of the medications is really important, and the patient’s own perceptions about whether they want a medication that is going to be beneficial, or whether they want a simple remedy also plays a role. Also, let’s not forget what Dr. Meltzer also talked about—environmental controls that can be helpful to reduce the patient’s symptomatology as well.

Dr. Stoloff: From my perspective, I’m always impressed how a simple explanation of what allergy actually is, in terms of definition and measurement, creates a totally different dialogue with the patient. When my patients come in, they are often past the point of just administering a medicine, and trying others if it didn’t work—especially now there are so many generic over-the-counter products in oral antihistamines available. As a consequence, I really want to talk to them about what is going on— what is the family history, what is the seasonality of the components. I live at a fairly substantial altitude with little or no humidity, so some of the environmental issues that are very clear in San Diego where Dr. Meltzer practices have no role in my patients. However, some of the people I’ve seen have come in with pages of an expensive serum test that shows positive for certain items that have no influence on the patient’s current environment.

Patient history has to guide our workup. Dr. Hadley’s point about family history was important; we look to document what in fact are the causes. If we can figure out what is pushing the disease forward, maybe we can prevent some of those problems or at least lessen them. The history also helps in diagnosis. If we find by their history they’re overusing topical decongestants, that’s important. If we find they’re using their intranasal spray in the wrong way, that’s important. After obtaining the patient history, we then need to individualize our workup based on physical examination. It is important to look in the nose; if we find they have mechanical problems that’s additional information. Certainly allergic specific testing can be helpful, but it has to be targeted based on the location and based on the patient’s story.

Dr. Meltzer: We also need to target treatment. As Dr. Hadley mentioned, we need to know what has and hasn’t worked in the past and what are the contributing mechanism of the rhinitis for a given patient—is it only allergic, is it infectious, is it nonspecific irritants, is it mechanical, or is it a mixture of all of these. Pharmacologic therapy can be stepped up or stepped down depending upon the patient’s progress. And immunotherapy is certainly an appropriate choice in patients who have more severe disease and/or who are not responding adequately. Individualization is the key in terms of management.

Dr. Hadley: There is a clear need for the identification of and appropriate care of patients who need further management. As clinicians, we glean from patients’ history when they have symptoms and when we can appropriately add to the pharmacological management other therapies that would be beneficial in helping patients control their environment a little bit better during specific times of the year. Some patients do need additional treatment at certain times of the year. For example, whereas patients with intermittent symptoms only need to be treated for a short period of time each year, other patients are plagued with year-round symptoms. So we have to gauge those patients appropriately.

Dr. Stoloff: Another point is that at times comanagement with an allergist or otolaryngologist will be beneficial to the patient. But the primary care physician has to recognize that and it takes time to have that discussion. Unfortunately, because allergic rhinitis is often trivialized (from a health care provider’s point of view), physicians do not step back to see how much of a burden this disease is for that individual. This lessens the opportunity to gain effective consultation in the specific fields, and therefore lessens the opportunity for better health for the patient.

 

 

How do current guidelines influence your current treatment practice? Which guidelines are useful?

Dr. Meltzer: The ARIA guidelines originate from a WHO program, initiated in 1999, to create an international appreciation of the morbidity associated with allergic rhinitis. They borrowed from the NIH guidelines for asthma, the classification concept of intermittent and persistent and rating of the disease into mild, moderate, and severe categories. I think that this is clinically more relevant than the FDA classifications of seasonal and perennial allergic rhinitis. If a person suffers symptoms when they visit a family member with cats for 2 weeks over Christmas—then that’s an intermittent problem. It is not really a “perennial” problem in terms of the allergen. The FDA view may be appropriate for approval of medications, but from the management standpoint of patients, classifications of persistent, intermittent and mild, moderate or severe are much more useful. Indeed US guidelines now also use these classifications.

The name ARIA actually stands for Allergic Rhinitis Impact on Asthma, and the impact on asthma was a key driver for the WHO program. ARIA recognized the concept of the unified airway and the consequence that having inflammation in one area of the airway created for other parts of the airway. The guidelines highlighted the recommendation to evaluate patients with allergic rhinitis for lower airway disease (be it with a pulmonary function or at least a good history), and conversely for patients with lower airway disease to check for an upper airway history of problems as well. This is important because there is crosstalk, and we should be managing the whole airway—reducing inflammation in all of it.

Dr. Stoloff: From my viewpoint, very few of my peers are aware of ARIA and what it recommends. Similarly, many of them are not aware of the differences between the FDA classification and clinical guidelines. They simply do not know that the field is moving away from using seasonal and perennial terminology and towards a redefinition in terms of severity, frequency, and intensity.

Dr. Hadley: I agree that the awareness of the ARIA guidelines in general medical communities is low. We should point outthat the American Academy of Asthma, Allergy & Immunology (AAAAI) did publish practice parameters for rhinitis in 2008 and those have made a lot of sense as they give a practitioner a stepwise process to look at whether the symptoms are intermittent versus persistent, the degree of severity, and then makes recommendations on the types of medication that can be of clinical benefit to the patient. These guidelines are much more useful to the primary care physician.

Dr. Stoloff: Speaking as an author of both the ARIA and the AAAAI practice parameters, one of the major problems is that my colleagues in primary care do not routinely read the journals where the guidelines are published. Thus, the information is not disseminated and consequently not incorporated into their clinical practice. If presented and disseminated properly, guidelines should influence the way clinicians look at these health care issues, for the patient’s benefit, for cost benefit, and for improving their practice, gaining better out come for everyone.

Dr. Meltzer: I think there are some common concepts that have been incorporated into each of the guidelines discussed. Firstly, we need to classify people by severity. Secondly, we need to appreciate that people with upper airway disease (including allergic rhinitis), often have involvement of other areas of the respiratory tract. In other words we need to consider the comorbidities of the associated diseases. Thirdly, once we appreciate the magnitude of the problems, the patient together with the clinician needs to establish goals. Fourthly, there are step recommendations; if the symptoms are mild or intermittent, less management is needed. If the symptoms are moderate to severe, and/or persistent, more intensive management is required. There are also defined therapeutic steps as to when one might include immunotherapy as part of the regimen. Finally, patients should be monitored as part of the long-term management of this chronic condition.

The ultimate goal is control—control based on what the patient’s goals were when defined during their discussions with their clinician. If we incorporate those basic five concepts into our clinical practice—it will be good for the upper airway, good for the lower airway, and good for long-term health.

Given the range of products available at present for allergic rhinitis, what criteria influence your choice of product?

Dr. Hadley: The problem is that our patients have problems that they do not consider allergic rhinitis as serious, compared to conditions such as hypertension or diabetes. However, they still have a problem that significantly influences their life. As far as the range of products, many of them have already been on an oral antihistamine and many have used and abused decongestant therapy, which is over-the-counter or now behind-the-counter that they have to ask for. Patients often try to first alleviate their symptoms with some of these products, and by the time the come to see me as a specialist they have already usually started on something already, and I have to look and determine whether or not they would be acceptable to use a more advanced product.

 

 

The topical nasal steroid is the pure anti-inflammatory product. We use this to treat the inflammatory state of the patient, recognizing that allergic rhinitis is an inflammatory problem. Antihistamines can reduce some of the symptoms but not as effectively as some of the topical nasal steroids. Added to that patients obviously have a preference to use a single product that they can use once per day, for most Americans this would ideally mean taking a pill, but unfortunately that’s not the best product for them. Our challenge is to change their attitudes and beliefs about appropriate treatment of these problems.

Dr. Meltzer: As an allergist I tend to think about allergic disease not only in terms of what is, but how did it get there. It is important to understand allergic rhinitis as an inflammatory process that involves numerous mediators, cytokines, and inflammatory cells. Oral antihistamines block only one of the mediators; they have no effect on cytokines or inflammatory cells or any of the other mediators. As such, while they can help with itchy noses, sneezing and runny noses, they do not help with congestion— which is the most bothersome and the most frequent symptom. Likewise, anticholinergics only help with runny nose, and are not effective against nasal itch, sneeze or congestion. Most people with allergic rhinitis have chronic disease, and topical decongestants should not be used for prolonged periods of time. Oral decongestants have dose-related side effects and the doses required to effectively reduce congestion increase the risks of irritability, diffculty sleeping and nervousness. Leukotriene modifiers are at best minimal to modest improvers of symptoms. Thus, the intranasal corticosteroids (because of their broad based mechanisms of action) are currently considered to be the best monotherapies.

However, when prescribing intranasal corticosteroids, there are a number of important considerations. First, we should ensure the patient is administering the spray properly in terms of the technique. In addition, there may be some patient preference in terms of whether an individual prefers an aerosol formulation or an aqueous formulation. There may also be issues in regard to cost and related to the availability of different agents on a formulary. Indeed, managed care limitations have been problematic for many of us who take care of patients. Furthermore, we certainly need to monitor that patients adhere to their regimen. I find in my practice that most people do not start taking their medication prior to a season; they wait until they’re in the midst of the worst time of their symptomatology and then expect an immediate treatment effect. I try to explain to them, that allergic rhinitis is an ongoing process, a fire, and if effective therapy is established and maintained early on, then the fire can be kept under control and the outcome will be far better than trying to deal with it when there is a flare-up of the major symptoms. This is a communication issue. Every person may have a different view and we need to come to an understanding of each individuals’ viewpoint (what their goals of treatment are). We are not going to be able to force a patient to stick with a particular treatment. It’s about educating them and encouraging them to take responsibility. I tell them “when you leave my office, you’re the one who has allergic rhinitis and I recommend you take the medication. However, you make the decisions.”

Dr. Hadley: We also must not forget that inappropriate patient comprehension and knowledge can also be problematic. Some patients take their medication too late, or perhaps too long, and they have side effects. Side effects can increase the burden of their disease and impact on their ability to perform well at work or school or play.

Dr. Stoloff: Yes, in primary care, especially when treating the older population who have hypertension, one often sees patients take decongestants, and one realizes the multitude of side effects associated with them. And, as Dr. Hadley says, very few patients are aware that their medications are causing these problems.

There are basically three key aspects related to patient communication. Firstly, patient education; we need to ensure our patients are aware of what they have, why they have it and what they can do about it. Secondly, there needs to be ongoing communication between the patient and the clinician to ensure availability of questions and availability of goal setting. Thirdly, patients should have realistic expectations, because when patients revisit we can assess if we have met their expectations or if adjustments in management are needed.

 

 

Dr. Hadley: I agree. Better awareness of the disease burden will improve the patient-clinician discussion and thereby improve the patient-physician relationship. This will enable physicians to better guide their patients through proposed treatment plans.

Another important topic is patient preference. We have discussed that most patients would like a pill that has no side effects or that they can take once a day, perhaps once a week, or a patch that they don’t have to deal with. Unfortunately, we need to recognize that such a medication does not yet exist. Patients who have a problem with the inflammatory process should be seen by the clinician and steered toward the most effective medication, and I personally believe that the topical nasal steroids are the best choice to reduce the inflammatory process as much as possible. There are new aerosol formulations of topical nasal steroids that will bring more treatment options for allergic rhinitis.

Dr. Meltzer: We should also note that these new developments with regards to new delivery systems address expanding patient choice. There are also a number of combination agents and biologics in development that may also improve pharmacotherapeutic outcomes. Advances in immunotherapy will also help treat the basic cause of allergic disease. I think many of these options will become available within the next few years.

Dr. Stoloff: I concur. The other point that we have made, and I think it’s important to reiterate, allergic rhinitis is not in a silo. It is associated with, for most of the population, comorbid diseases. When clinicians look for comorbidities, they often gain a far better appreciation of the value of treating the allergic rhinitis and therefore improving their outcome for other health issues such as asthma. But this needs to be taken in the context of communicating with the patient, always taking patient needs and goals into consideration, and working within the economic health care system that we now face.

 

Authors of papers presented in this Supplement met in person at the 2011 Annual Meeting of the American College of Allergy, Asthma & Immunology to further discuss the clinical, social, and economic implications of the findings from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC. This paper represents an edited transcript of their discussion.

Given the recent changes in US health care, how should the results of the NASAL 2010 survey be used to inform current practice? What about the role of other health care professionals and what are the cost implications of the survey findings?

Dr. Hadley: Firstly, it is important to note that there were improvements in the design of the NASAL 2010 survey compared to its 2006 predecessor. More importantly, although some of the 2010 information was a little bit different, we found that the majority of patients still suffer from their symptoms, and that the symptoms are predominant and bothersome. Allergic rhinitis bothers their sleep; it bothers their work and daily activities. In other words, we have not really seen any difference in achieving a reduction of the patients’ symptoms from 2006 to 2010.

Dr. Meltzer: Looking at this issue more globally, I think that the lack of change has a great deal to do with the public not understanding what “health” is. The World Health Organization (WHO) definition of health is there should be no problems with physical, social, emotional, or mental well-being. Individuals often do not appreciate how healthy they could be, and thus do not have a reference point. The NASAL survey clearly shows that most nasal allergy sufferers are not aware of an appropriate respiratory health goal and, further, they are not cognizant of the magnitude of their disease due to their allergic rhinitis. I believe the patients are not the only ones who are unaware; I think many clinicians are also not aware of the extent of their patients’ morbidity. A current problem is that there is not enough assumption of responsibility; patients are not taking enough responsibility for their health, clinicians are not adequately managing these patients, and—despite the suggested health care reforms—there does not appear to be in the foreseeable future a system that is going to alter these conditions.

Dr. Stoloff: For example, many family physicians only ask the question “How are you (with respect to this topic)?” and patients often say they are fine, and that’s the end of the dialogue. But consequences of this type of discussion are that costs of health care continue due to the lack of health. So the person misses work or the person’s job performance is less than it would be because they don’t recognize what their health could be if they were properly treated. As far as they’re concerned, this situation has been going on year after year, and it is only when they are really bad that they know they should be somewhat better. Even then, most people do not fully appreciate what is achievable because no one in the health care system has ever told them, “You should be able to sleep through the night and wake up feeling well. You should be able to go to work. You should be able to participate in athletic, recreational venues to be healthy.” No one has brought that up, and as long as this situation continues, the cost for the patient, his or her family, and health care will continue to increase.

Dr. Hadley: One of the things that I see as an otolaryngologist is that there is also often a missed diagnosis. Everybody who comes in to see me tells me: “Doctor, I have ‘sinus’.” I think most of them are simply unaware of that fact that their nasal congestion plays a role in developing their sinus symptoms. So there is general unawareness of the importance of treating nasal allergies in the lay public, as well as in primary care physicians who have to deal with these patients. Going to issues of cost, I think that patients are seeing the economy go down, and this means that they don’t want to spend a lot of money on their health care. They have a lot of other worries, and I think this is playing a role in how we have to deal with our patients.

 

 

Dr. Stoloff: People need to understand that the cost of not spending money to be healthy has a consequence that is sometimes the greater cost of being unhealthy—cost in terms of morbidity, cost in terms of missed days from work, absenteeism, presenteeism, poor ability to function in the usual domains of physical, social, emotional, and mental.

Dr. Hadley: That’s what the public just does not understand. We have not achieved the goal of informing the lay public and practitioners about how effective management can get these patients better, reduce their costs, and enable patients to go back to work and their activities.

What should be done to better act on the challenges highlighted by these important surveys? Is there a need to increase the awareness of allergic rhinitis among health care providers?

Dr. Meltzer: If we’re not making progress then we have to make some changes. It seems to me that education could drive change. The public needs to better understand that it is not insignificant to have an inflammatory process called allergic rhinitis. Allergic rhinitis is clearly underestimated in terms of its burden. It is too often unrecognized or ignored as an inconsequential problem. It is important that the person who has allergic rhinitis does not disregard the burden of disease. The NASAL survey reports that allergic rhinitis affects the ability to sleep well in 40 of patients. We know that allergic rhinitis also compromises people’s activities and we know that they are not as productive when they’re at work. We also know there are many comorbidities—asthma in particular, and sinusitis, otitis, conjunctivitis are other common associated conditions. Patients and clinicians need to be educated to appreciate the significant morbidity associated with allergic rhinitis, and that nasal allergies need attention and effective control.

Dr. Hadley: One of the things that we all see is patients not always getting important information about the medications that they take; there is a walk-in to the grocery store and the pharmacy shelves are filled with medications that are over-the-counter. The problem is there is not enough education about what the benefits are and what the side effects are of all those medications. There is also a lot of direct to consumer advertising—radio, television, etc., that also leads to misconceptions about the benefits of some of these medications. Patients are somewhat aware that they have a problem, but they just don’t know where to go. From the health care provider perspective, the emphasis is on treating the major problems—diabetes, hypertension—and rhinitis is considered a minor problem. So I don’t think we are educating our patients well enough. And I think that is a misconception and misunderstanding, which should be corrected.

Dr. Stoloff: Most physicians will see on their schedule a brief description of what problems their upcoming patients have. In primary care, the person filling the schedule will often say that the patient with nasal symptoms has sinusitis, which overwhelmingly it is not. That is an “easy” quick visit and the typical conversation is “Here, take this pill—if you’ve tried that pill, then take this nasal inhaler—and if you didn’t like this one I’ve got another sample for you. And then we’ll figure out which one is going to be on your list, what is covered by your insurance, and what’s the generic.” There is very little discussion about the type of impairment suffered and the overall burden on the individual. Importantly, that burden is often substantial, especially if nasal allergy symptoms were the primary reason for the office visit.

In primary care, people can have a multitude of other conditions, and allergic rhinitis is down at the bottom of the list. For example, the patient may be a hypertensive diabetic who also has seasonal allergic rhinitis. So by the time a family doctor gets to discuss allergic rhinitis, the office visit time is over and it is easier for the physician to just give a medication. But when the presence of allergic rhinitis has an enormous influence on the other diseases as far as activity, sleep, fatigue, depression, all the other emotional components, as well as physical components, that the survey highlighted—that really needs to be brought to the attention of both the patient and the health care provider to spend the appropriate time discussing it. Because it will influence care in everything else the person does.

How would you work up a patient who you might consider as potentially having allergic rhinitis?

Dr. Meltzer: When physicians view their schedule, a word or phrase supposedly informs them in advance of the patient’s condition. In reality, every patient is different and, moreover, patients with allergic rhinitis vary over the course of days, months and years in their symptomatology. So when I evaluate a patient for rhinitis and their chief complaint is “I’m having problems with my nose,” I first find out the full range of symptoms, and which symptom is for them the most bothersome (most often it will turn out to be congestion). Secondly, I would find out whether the symptoms are intermittent, or persistent. If they are fairly persistent, this informs me about somewhat of their severity, which is another very important consideration. Thirdly, I would try to find out what are the triggers for the symptoms such as non-allergic precipitants (eg, climate changes, tobacco smoke, and other environmental pollutants), or specific allergen triggers (eg, pets, springtime pollens). I would also ask about any comorbid conditions because if they are having more than just nasal symptoms that expands what I am going to need to address. I need to know all of those things before I make a treatment plan. If the disease is intermittent and mild or not very bothersome, then I am going to initiate a modest management plan. If their allergic rhinitis is more problematic, then I will need to educate the patient about what they have, why they have it and what to do about it. The patient and I will need to agree about our expectations of treatment. We are going to have an action plan for the short-term as well as a plan for follow-up visits to see if in fact our initial plan is successful. Again, the specifics will depend upon the individual patient.

 

 

Dr. Hadley: Many patients come in to an ENT clinic with an inappropriate initial diagnosis, predominantly with sinus disease, and some of them actually have come in with inappropriately obtained CT scans of the paranasal sinuses because they were presumed to have a chronic sinus infection. Most importantly, many of them have come in with inappropriately administered multiple different courses of antibiotics, which is of concern to me. So I agree with Dr. Meltzer in the need to understand the history of the patient’s symptoms—whether they are intermittent or persistent. I also obtain a family history, which helps me to work out whether the patient has an allergic tendency or not. I also have to look back and see what medications have been tried, what has worked (and not worked) in the past. The timing of the medications is really important, and the patient’s own perceptions about whether they want a medication that is going to be beneficial, or whether they want a simple remedy also plays a role. Also, let’s not forget what Dr. Meltzer also talked about—environmental controls that can be helpful to reduce the patient’s symptomatology as well.

Dr. Stoloff: From my perspective, I’m always impressed how a simple explanation of what allergy actually is, in terms of definition and measurement, creates a totally different dialogue with the patient. When my patients come in, they are often past the point of just administering a medicine, and trying others if it didn’t work—especially now there are so many generic over-the-counter products in oral antihistamines available. As a consequence, I really want to talk to them about what is going on— what is the family history, what is the seasonality of the components. I live at a fairly substantial altitude with little or no humidity, so some of the environmental issues that are very clear in San Diego where Dr. Meltzer practices have no role in my patients. However, some of the people I’ve seen have come in with pages of an expensive serum test that shows positive for certain items that have no influence on the patient’s current environment.

Patient history has to guide our workup. Dr. Hadley’s point about family history was important; we look to document what in fact are the causes. If we can figure out what is pushing the disease forward, maybe we can prevent some of those problems or at least lessen them. The history also helps in diagnosis. If we find by their history they’re overusing topical decongestants, that’s important. If we find they’re using their intranasal spray in the wrong way, that’s important. After obtaining the patient history, we then need to individualize our workup based on physical examination. It is important to look in the nose; if we find they have mechanical problems that’s additional information. Certainly allergic specific testing can be helpful, but it has to be targeted based on the location and based on the patient’s story.

Dr. Meltzer: We also need to target treatment. As Dr. Hadley mentioned, we need to know what has and hasn’t worked in the past and what are the contributing mechanism of the rhinitis for a given patient—is it only allergic, is it infectious, is it nonspecific irritants, is it mechanical, or is it a mixture of all of these. Pharmacologic therapy can be stepped up or stepped down depending upon the patient’s progress. And immunotherapy is certainly an appropriate choice in patients who have more severe disease and/or who are not responding adequately. Individualization is the key in terms of management.

Dr. Hadley: There is a clear need for the identification of and appropriate care of patients who need further management. As clinicians, we glean from patients’ history when they have symptoms and when we can appropriately add to the pharmacological management other therapies that would be beneficial in helping patients control their environment a little bit better during specific times of the year. Some patients do need additional treatment at certain times of the year. For example, whereas patients with intermittent symptoms only need to be treated for a short period of time each year, other patients are plagued with year-round symptoms. So we have to gauge those patients appropriately.

Dr. Stoloff: Another point is that at times comanagement with an allergist or otolaryngologist will be beneficial to the patient. But the primary care physician has to recognize that and it takes time to have that discussion. Unfortunately, because allergic rhinitis is often trivialized (from a health care provider’s point of view), physicians do not step back to see how much of a burden this disease is for that individual. This lessens the opportunity to gain effective consultation in the specific fields, and therefore lessens the opportunity for better health for the patient.

 

 

How do current guidelines influence your current treatment practice? Which guidelines are useful?

Dr. Meltzer: The ARIA guidelines originate from a WHO program, initiated in 1999, to create an international appreciation of the morbidity associated with allergic rhinitis. They borrowed from the NIH guidelines for asthma, the classification concept of intermittent and persistent and rating of the disease into mild, moderate, and severe categories. I think that this is clinically more relevant than the FDA classifications of seasonal and perennial allergic rhinitis. If a person suffers symptoms when they visit a family member with cats for 2 weeks over Christmas—then that’s an intermittent problem. It is not really a “perennial” problem in terms of the allergen. The FDA view may be appropriate for approval of medications, but from the management standpoint of patients, classifications of persistent, intermittent and mild, moderate or severe are much more useful. Indeed US guidelines now also use these classifications.

The name ARIA actually stands for Allergic Rhinitis Impact on Asthma, and the impact on asthma was a key driver for the WHO program. ARIA recognized the concept of the unified airway and the consequence that having inflammation in one area of the airway created for other parts of the airway. The guidelines highlighted the recommendation to evaluate patients with allergic rhinitis for lower airway disease (be it with a pulmonary function or at least a good history), and conversely for patients with lower airway disease to check for an upper airway history of problems as well. This is important because there is crosstalk, and we should be managing the whole airway—reducing inflammation in all of it.

Dr. Stoloff: From my viewpoint, very few of my peers are aware of ARIA and what it recommends. Similarly, many of them are not aware of the differences between the FDA classification and clinical guidelines. They simply do not know that the field is moving away from using seasonal and perennial terminology and towards a redefinition in terms of severity, frequency, and intensity.

Dr. Hadley: I agree that the awareness of the ARIA guidelines in general medical communities is low. We should point outthat the American Academy of Asthma, Allergy & Immunology (AAAAI) did publish practice parameters for rhinitis in 2008 and those have made a lot of sense as they give a practitioner a stepwise process to look at whether the symptoms are intermittent versus persistent, the degree of severity, and then makes recommendations on the types of medication that can be of clinical benefit to the patient. These guidelines are much more useful to the primary care physician.

Dr. Stoloff: Speaking as an author of both the ARIA and the AAAAI practice parameters, one of the major problems is that my colleagues in primary care do not routinely read the journals where the guidelines are published. Thus, the information is not disseminated and consequently not incorporated into their clinical practice. If presented and disseminated properly, guidelines should influence the way clinicians look at these health care issues, for the patient’s benefit, for cost benefit, and for improving their practice, gaining better out come for everyone.

Dr. Meltzer: I think there are some common concepts that have been incorporated into each of the guidelines discussed. Firstly, we need to classify people by severity. Secondly, we need to appreciate that people with upper airway disease (including allergic rhinitis), often have involvement of other areas of the respiratory tract. In other words we need to consider the comorbidities of the associated diseases. Thirdly, once we appreciate the magnitude of the problems, the patient together with the clinician needs to establish goals. Fourthly, there are step recommendations; if the symptoms are mild or intermittent, less management is needed. If the symptoms are moderate to severe, and/or persistent, more intensive management is required. There are also defined therapeutic steps as to when one might include immunotherapy as part of the regimen. Finally, patients should be monitored as part of the long-term management of this chronic condition.

The ultimate goal is control—control based on what the patient’s goals were when defined during their discussions with their clinician. If we incorporate those basic five concepts into our clinical practice—it will be good for the upper airway, good for the lower airway, and good for long-term health.

Given the range of products available at present for allergic rhinitis, what criteria influence your choice of product?

Dr. Hadley: The problem is that our patients have problems that they do not consider allergic rhinitis as serious, compared to conditions such as hypertension or diabetes. However, they still have a problem that significantly influences their life. As far as the range of products, many of them have already been on an oral antihistamine and many have used and abused decongestant therapy, which is over-the-counter or now behind-the-counter that they have to ask for. Patients often try to first alleviate their symptoms with some of these products, and by the time the come to see me as a specialist they have already usually started on something already, and I have to look and determine whether or not they would be acceptable to use a more advanced product.

 

 

The topical nasal steroid is the pure anti-inflammatory product. We use this to treat the inflammatory state of the patient, recognizing that allergic rhinitis is an inflammatory problem. Antihistamines can reduce some of the symptoms but not as effectively as some of the topical nasal steroids. Added to that patients obviously have a preference to use a single product that they can use once per day, for most Americans this would ideally mean taking a pill, but unfortunately that’s not the best product for them. Our challenge is to change their attitudes and beliefs about appropriate treatment of these problems.

Dr. Meltzer: As an allergist I tend to think about allergic disease not only in terms of what is, but how did it get there. It is important to understand allergic rhinitis as an inflammatory process that involves numerous mediators, cytokines, and inflammatory cells. Oral antihistamines block only one of the mediators; they have no effect on cytokines or inflammatory cells or any of the other mediators. As such, while they can help with itchy noses, sneezing and runny noses, they do not help with congestion— which is the most bothersome and the most frequent symptom. Likewise, anticholinergics only help with runny nose, and are not effective against nasal itch, sneeze or congestion. Most people with allergic rhinitis have chronic disease, and topical decongestants should not be used for prolonged periods of time. Oral decongestants have dose-related side effects and the doses required to effectively reduce congestion increase the risks of irritability, diffculty sleeping and nervousness. Leukotriene modifiers are at best minimal to modest improvers of symptoms. Thus, the intranasal corticosteroids (because of their broad based mechanisms of action) are currently considered to be the best monotherapies.

However, when prescribing intranasal corticosteroids, there are a number of important considerations. First, we should ensure the patient is administering the spray properly in terms of the technique. In addition, there may be some patient preference in terms of whether an individual prefers an aerosol formulation or an aqueous formulation. There may also be issues in regard to cost and related to the availability of different agents on a formulary. Indeed, managed care limitations have been problematic for many of us who take care of patients. Furthermore, we certainly need to monitor that patients adhere to their regimen. I find in my practice that most people do not start taking their medication prior to a season; they wait until they’re in the midst of the worst time of their symptomatology and then expect an immediate treatment effect. I try to explain to them, that allergic rhinitis is an ongoing process, a fire, and if effective therapy is established and maintained early on, then the fire can be kept under control and the outcome will be far better than trying to deal with it when there is a flare-up of the major symptoms. This is a communication issue. Every person may have a different view and we need to come to an understanding of each individuals’ viewpoint (what their goals of treatment are). We are not going to be able to force a patient to stick with a particular treatment. It’s about educating them and encouraging them to take responsibility. I tell them “when you leave my office, you’re the one who has allergic rhinitis and I recommend you take the medication. However, you make the decisions.”

Dr. Hadley: We also must not forget that inappropriate patient comprehension and knowledge can also be problematic. Some patients take their medication too late, or perhaps too long, and they have side effects. Side effects can increase the burden of their disease and impact on their ability to perform well at work or school or play.

Dr. Stoloff: Yes, in primary care, especially when treating the older population who have hypertension, one often sees patients take decongestants, and one realizes the multitude of side effects associated with them. And, as Dr. Hadley says, very few patients are aware that their medications are causing these problems.

There are basically three key aspects related to patient communication. Firstly, patient education; we need to ensure our patients are aware of what they have, why they have it and what they can do about it. Secondly, there needs to be ongoing communication between the patient and the clinician to ensure availability of questions and availability of goal setting. Thirdly, patients should have realistic expectations, because when patients revisit we can assess if we have met their expectations or if adjustments in management are needed.

 

 

Dr. Hadley: I agree. Better awareness of the disease burden will improve the patient-clinician discussion and thereby improve the patient-physician relationship. This will enable physicians to better guide their patients through proposed treatment plans.

Another important topic is patient preference. We have discussed that most patients would like a pill that has no side effects or that they can take once a day, perhaps once a week, or a patch that they don’t have to deal with. Unfortunately, we need to recognize that such a medication does not yet exist. Patients who have a problem with the inflammatory process should be seen by the clinician and steered toward the most effective medication, and I personally believe that the topical nasal steroids are the best choice to reduce the inflammatory process as much as possible. There are new aerosol formulations of topical nasal steroids that will bring more treatment options for allergic rhinitis.

Dr. Meltzer: We should also note that these new developments with regards to new delivery systems address expanding patient choice. There are also a number of combination agents and biologics in development that may also improve pharmacotherapeutic outcomes. Advances in immunotherapy will also help treat the basic cause of allergic disease. I think many of these options will become available within the next few years.

Dr. Stoloff: I concur. The other point that we have made, and I think it’s important to reiterate, allergic rhinitis is not in a silo. It is associated with, for most of the population, comorbid diseases. When clinicians look for comorbidities, they often gain a far better appreciation of the value of treating the allergic rhinitis and therefore improving their outcome for other health issues such as asthma. But this needs to be taken in the context of communicating with the patient, always taking patient needs and goals into consideration, and working within the economic health care system that we now face.

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Closing thoughts: Implications of the findings from the National Allergy Survey Assessing Limitations for the management of allergic rhinitis in America
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Introduction

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Introduction
 

Today, virtually all physicians working in primary care will have a significant caseload of patients with allergic rhinitis (AR). Yet, many physicians still regard AR as a relatively unimportant “nuisance” illness and only treat the symptoms on an as-needed basis. Likewise, many patients do not realize that effective treatments are available that can help control their condition and assume that they just have to live with their symptoms. However, the incidence of AR has grown dramatically in recent years, and it is associated with significant morbidity.1 For example, as well as experiencing troublesome nasal symptoms, patients with AR have an increased risk of suffering associated conditions such as asthma, rhinosinusitis, and chronic otitis media, which themselves increase morbidity and medical costs.2,3 It is also well known that AR has a significant impact on the quality of life of the sufferer,4 with days lost from work or school.5,6

Ten years ago, the Institute of Medicine published “Crossing the Quality Chasm,” which identified key weaknesses in the quality of American health care.7 Increasing patient-centered care was identified as one of the “six aims for improvement.” This meant that health care should respect and respond to patient preferences, needs, and values, and that patient values should guide all clinical decisions. In 2006, the Allergies in America: A Landmark Survey of Nasal Allergy Sufferers was conducted to assess how well we manage our patients who have nasal allergies.8 At the time, it was the largest and most comprehensive national survey of patients with AR and the health care providers who treat them. The survey revealed a number of truths. It highlighted that AR was not just a seasonal problem and that more than half of patients suffered symptoms throughout the year.9 It showed that, at their peak, nasal allergy symptoms left patients feeling tired, miserable, and irritable and, for most patients in the survey, decreased their performance at work. Importantly, the survey also uncovered gaps in communication between physician and patient. For example, fewer than half of patients who had seen a physician reported following his or her instructions on the management and treatment of AR.9

Five years after the landmark survey was conducted, we wanted to see how the treatment of nasal allergies had progressed in America. This supplement presents results from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC, which included many of the same questions as the earlier survey. NASAL provided an up-to-date assessment of patient and provider perspectives concerning AR and nasal allergies in the United States (US). It included a national sample of 400 persons aged ≥18 years who had been diagnosed with AR, nasal allergies, or hay fever, and had experienced nasal allergy symptoms or taken medication for their condition in the past 12 months. To determine the burden of disease of AR, a telephone survey was conducted among a national probability sample of 522 adults sampled by random-digit dialing. This parallel survey of the general adult US population yielded a subsample of 400 persons aged ≥18 years who did not currently have nasal allergies. The comparison of the 2 samples of adults with and without nasal allergies provided a new and unique measure of the impact of nasal allergies on the health and lifestyle of patients. Finally, another parallel survey was conducted among 250 health care practitioners who saw patients with nasal allergies.

NASAL was the first survey of its kind to include the full range of health care practitioners involved in the management of nasal allergies. It included 100 physicians in adult primary care specialties (family medicine and internal medicine), 100 specialists (allergy and otolaryngology), and 50 nurse practitioners and physician assistants.

The purpose of NASAL was to describe the symptoms, burden of disease, and treatment of AR. The articles in this supplement report new data from NASAL showing the significant impact AR has on quality of life, the comorbidities associated with AR, and the oft-forgotten patient perspective. During the preparation of these articles, the most common phrase from our authors was, “Don’t get me started…” Each author has passionate views on the current treatment of nasal allergies in America, and these are shared in the roundtable discussion presented at the end of the supplement.

References

1. Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Global Allergy and Asthma European Network; Grading of Recommendations Assessment Development and Evaluation Working Group Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126(3):466-476.

2. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004;24(1):19-43.

3. Meltzer EO, Szwarcberg J, Pill MW. Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway. J Manag Care Pharm. 2004;10(4):310-317.

4. Meltzer EO, Nathan R, Derebery J, et al. Sleep, quality of life, and productivity impact of nasal symptoms in the United States: Findings from the Burden of Rhinitis in America survey. Allergy Asthma Proc. 2009;30(3):244-254.

5. Lamb CE, Ratner PH, Johnson CE, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203-1210.

6. Schoenwetter WF, Dupclay L, Jr, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin. 2004;20(3):305-317.

7. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.

8. Meltzer EO. Introduction: how can we improve the treatment of allergic rhinitis? Allergy Asthma Proc. 2007;28(suppl 1):S2-S3.

9. Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4-S10.

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Today, virtually all physicians working in primary care will have a significant caseload of patients with allergic rhinitis (AR). Yet, many physicians still regard AR as a relatively unimportant “nuisance” illness and only treat the symptoms on an as-needed basis. Likewise, many patients do not realize that effective treatments are available that can help control their condition and assume that they just have to live with their symptoms. However, the incidence of AR has grown dramatically in recent years, and it is associated with significant morbidity.1 For example, as well as experiencing troublesome nasal symptoms, patients with AR have an increased risk of suffering associated conditions such as asthma, rhinosinusitis, and chronic otitis media, which themselves increase morbidity and medical costs.2,3 It is also well known that AR has a significant impact on the quality of life of the sufferer,4 with days lost from work or school.5,6

Ten years ago, the Institute of Medicine published “Crossing the Quality Chasm,” which identified key weaknesses in the quality of American health care.7 Increasing patient-centered care was identified as one of the “six aims for improvement.” This meant that health care should respect and respond to patient preferences, needs, and values, and that patient values should guide all clinical decisions. In 2006, the Allergies in America: A Landmark Survey of Nasal Allergy Sufferers was conducted to assess how well we manage our patients who have nasal allergies.8 At the time, it was the largest and most comprehensive national survey of patients with AR and the health care providers who treat them. The survey revealed a number of truths. It highlighted that AR was not just a seasonal problem and that more than half of patients suffered symptoms throughout the year.9 It showed that, at their peak, nasal allergy symptoms left patients feeling tired, miserable, and irritable and, for most patients in the survey, decreased their performance at work. Importantly, the survey also uncovered gaps in communication between physician and patient. For example, fewer than half of patients who had seen a physician reported following his or her instructions on the management and treatment of AR.9

Five years after the landmark survey was conducted, we wanted to see how the treatment of nasal allergies had progressed in America. This supplement presents results from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC, which included many of the same questions as the earlier survey. NASAL provided an up-to-date assessment of patient and provider perspectives concerning AR and nasal allergies in the United States (US). It included a national sample of 400 persons aged ≥18 years who had been diagnosed with AR, nasal allergies, or hay fever, and had experienced nasal allergy symptoms or taken medication for their condition in the past 12 months. To determine the burden of disease of AR, a telephone survey was conducted among a national probability sample of 522 adults sampled by random-digit dialing. This parallel survey of the general adult US population yielded a subsample of 400 persons aged ≥18 years who did not currently have nasal allergies. The comparison of the 2 samples of adults with and without nasal allergies provided a new and unique measure of the impact of nasal allergies on the health and lifestyle of patients. Finally, another parallel survey was conducted among 250 health care practitioners who saw patients with nasal allergies.

NASAL was the first survey of its kind to include the full range of health care practitioners involved in the management of nasal allergies. It included 100 physicians in adult primary care specialties (family medicine and internal medicine), 100 specialists (allergy and otolaryngology), and 50 nurse practitioners and physician assistants.

The purpose of NASAL was to describe the symptoms, burden of disease, and treatment of AR. The articles in this supplement report new data from NASAL showing the significant impact AR has on quality of life, the comorbidities associated with AR, and the oft-forgotten patient perspective. During the preparation of these articles, the most common phrase from our authors was, “Don’t get me started…” Each author has passionate views on the current treatment of nasal allergies in America, and these are shared in the roundtable discussion presented at the end of the supplement.

 

Today, virtually all physicians working in primary care will have a significant caseload of patients with allergic rhinitis (AR). Yet, many physicians still regard AR as a relatively unimportant “nuisance” illness and only treat the symptoms on an as-needed basis. Likewise, many patients do not realize that effective treatments are available that can help control their condition and assume that they just have to live with their symptoms. However, the incidence of AR has grown dramatically in recent years, and it is associated with significant morbidity.1 For example, as well as experiencing troublesome nasal symptoms, patients with AR have an increased risk of suffering associated conditions such as asthma, rhinosinusitis, and chronic otitis media, which themselves increase morbidity and medical costs.2,3 It is also well known that AR has a significant impact on the quality of life of the sufferer,4 with days lost from work or school.5,6

Ten years ago, the Institute of Medicine published “Crossing the Quality Chasm,” which identified key weaknesses in the quality of American health care.7 Increasing patient-centered care was identified as one of the “six aims for improvement.” This meant that health care should respect and respond to patient preferences, needs, and values, and that patient values should guide all clinical decisions. In 2006, the Allergies in America: A Landmark Survey of Nasal Allergy Sufferers was conducted to assess how well we manage our patients who have nasal allergies.8 At the time, it was the largest and most comprehensive national survey of patients with AR and the health care providers who treat them. The survey revealed a number of truths. It highlighted that AR was not just a seasonal problem and that more than half of patients suffered symptoms throughout the year.9 It showed that, at their peak, nasal allergy symptoms left patients feeling tired, miserable, and irritable and, for most patients in the survey, decreased their performance at work. Importantly, the survey also uncovered gaps in communication between physician and patient. For example, fewer than half of patients who had seen a physician reported following his or her instructions on the management and treatment of AR.9

Five years after the landmark survey was conducted, we wanted to see how the treatment of nasal allergies had progressed in America. This supplement presents results from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC, which included many of the same questions as the earlier survey. NASAL provided an up-to-date assessment of patient and provider perspectives concerning AR and nasal allergies in the United States (US). It included a national sample of 400 persons aged ≥18 years who had been diagnosed with AR, nasal allergies, or hay fever, and had experienced nasal allergy symptoms or taken medication for their condition in the past 12 months. To determine the burden of disease of AR, a telephone survey was conducted among a national probability sample of 522 adults sampled by random-digit dialing. This parallel survey of the general adult US population yielded a subsample of 400 persons aged ≥18 years who did not currently have nasal allergies. The comparison of the 2 samples of adults with and without nasal allergies provided a new and unique measure of the impact of nasal allergies on the health and lifestyle of patients. Finally, another parallel survey was conducted among 250 health care practitioners who saw patients with nasal allergies.

NASAL was the first survey of its kind to include the full range of health care practitioners involved in the management of nasal allergies. It included 100 physicians in adult primary care specialties (family medicine and internal medicine), 100 specialists (allergy and otolaryngology), and 50 nurse practitioners and physician assistants.

The purpose of NASAL was to describe the symptoms, burden of disease, and treatment of AR. The articles in this supplement report new data from NASAL showing the significant impact AR has on quality of life, the comorbidities associated with AR, and the oft-forgotten patient perspective. During the preparation of these articles, the most common phrase from our authors was, “Don’t get me started…” Each author has passionate views on the current treatment of nasal allergies in America, and these are shared in the roundtable discussion presented at the end of the supplement.

References

1. Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Global Allergy and Asthma European Network; Grading of Recommendations Assessment Development and Evaluation Working Group Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126(3):466-476.

2. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004;24(1):19-43.

3. Meltzer EO, Szwarcberg J, Pill MW. Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway. J Manag Care Pharm. 2004;10(4):310-317.

4. Meltzer EO, Nathan R, Derebery J, et al. Sleep, quality of life, and productivity impact of nasal symptoms in the United States: Findings from the Burden of Rhinitis in America survey. Allergy Asthma Proc. 2009;30(3):244-254.

5. Lamb CE, Ratner PH, Johnson CE, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203-1210.

6. Schoenwetter WF, Dupclay L, Jr, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin. 2004;20(3):305-317.

7. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.

8. Meltzer EO. Introduction: how can we improve the treatment of allergic rhinitis? Allergy Asthma Proc. 2007;28(suppl 1):S2-S3.

9. Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4-S10.

References

1. Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Global Allergy and Asthma European Network; Grading of Recommendations Assessment Development and Evaluation Working Group Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126(3):466-476.

2. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004;24(1):19-43.

3. Meltzer EO, Szwarcberg J, Pill MW. Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway. J Manag Care Pharm. 2004;10(4):310-317.

4. Meltzer EO, Nathan R, Derebery J, et al. Sleep, quality of life, and productivity impact of nasal symptoms in the United States: Findings from the Burden of Rhinitis in America survey. Allergy Asthma Proc. 2009;30(3):244-254.

5. Lamb CE, Ratner PH, Johnson CE, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203-1210.

6. Schoenwetter WF, Dupclay L, Jr, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin. 2004;20(3):305-317.

7. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.

8. Meltzer EO. Introduction: how can we improve the treatment of allergic rhinitis? Allergy Asthma Proc. 2007;28(suppl 1):S2-S3.

9. Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4-S10.

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Today, virtually all physicians working in primary care will have a significant caseload of patients with allergic rhinitis (AR). Yet, many physicians still regard AR as a relatively unimportant “nuisance” illness and only treat the symptoms on an as-needed basis. Likewise, many patients do not realize that effective treatments are available that can help control their condition and assume that they just have to live with their symptoms. However, the incidence of AR has grown dramatically in recent years, and it is associated with significant morbidity.1 For example, as well as experiencing troublesome nasal symptoms, patients with AR have an increased risk of suffering associated conditions such as asthma, rhinosinusitis, and chronic otitis media, which themselves increase morbidity and medical costs.2,3 It is also well known that AR has a significant impact on the quality of life of the sufferer,4 with days lost from work or school.5,6

Ten years ago, the Institute of Medicine published “Crossing the Quality Chasm,” which identified key weaknesses in the quality of American health care.7 Increasing patient-centered care was identified as one of the “six aims for improvement.” This meant that health care should respect and respond to patient preferences, needs, and values, and that patient values should guide all clinical decisions. In 2006, the Allergies in America: A Landmark Survey of Nasal Allergy Sufferers was conducted to assess how well we manage our patients who have nasal allergies.8 At the time, it was the largest and most comprehensive national survey of patients with AR and the health care providers who treat them. The survey revealed a number of truths. It highlighted that AR was not just a seasonal problem and that more than half of patients suffered symptoms throughout the year.9 It showed that, at their peak, nasal allergy symptoms left patients feeling tired, miserable, and irritable and, for most patients in the survey, decreased their performance at work. Importantly, the survey also uncovered gaps in communication between physician and patient. For example, fewer than half of patients who had seen a physician reported following his or her instructions on the management and treatment of AR.9

Five years after the landmark survey was conducted, we wanted to see how the treatment of nasal allergies had progressed in America. This supplement presents results from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC, which included many of the same questions as the earlier survey. NASAL provided an up-to-date assessment of patient and provider perspectives concerning AR and nasal allergies in the United States (US). It included a national sample of 400 persons aged ≥18 years who had been diagnosed with AR, nasal allergies, or hay fever, and had experienced nasal allergy symptoms or taken medication for their condition in the past 12 months. To determine the burden of disease of AR, a telephone survey was conducted among a national probability sample of 522 adults sampled by random-digit dialing. This parallel survey of the general adult US population yielded a subsample of 400 persons aged ≥18 years who did not currently have nasal allergies. The comparison of the 2 samples of adults with and without nasal allergies provided a new and unique measure of the impact of nasal allergies on the health and lifestyle of patients. Finally, another parallel survey was conducted among 250 health care practitioners who saw patients with nasal allergies.

NASAL was the first survey of its kind to include the full range of health care practitioners involved in the management of nasal allergies. It included 100 physicians in adult primary care specialties (family medicine and internal medicine), 100 specialists (allergy and otolaryngology), and 50 nurse practitioners and physician assistants.

The purpose of NASAL was to describe the symptoms, burden of disease, and treatment of AR. The articles in this supplement report new data from NASAL showing the significant impact AR has on quality of life, the comorbidities associated with AR, and the oft-forgotten patient perspective. During the preparation of these articles, the most common phrase from our authors was, “Don’t get me started…” Each author has passionate views on the current treatment of nasal allergies in America, and these are shared in the roundtable discussion presented at the end of the supplement.

References

 

1. Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Global Allergy and Asthma European Network; Grading of Recommendations Assessment Development and Evaluation Working Group Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126(3):466-476.

2. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004;24(1):19-43.

3. Meltzer EO, Szwarcberg J, Pill MW. Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway. J Manag Care Pharm. 2004;10(4):310-317.

4. Meltzer EO, Nathan R, Derebery J, et al. Sleep, quality of life, and productivity impact of nasal symptoms in the United States: Findings from the Burden of Rhinitis in America survey. Allergy Asthma Proc. 2009;30(3):244-254.

5. Lamb CE, Ratner PH, Johnson CE, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203-1210.

6. Schoenwetter WF, Dupclay L, Jr, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin. 2004;20(3):305-317.

7. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.

8. Meltzer EO. Introduction: how can we improve the treatment of allergic rhinitis? Allergy Asthma Proc. 2007;28(suppl 1):S2-S3.

9. Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4-S10.

Author and Disclosure Information

 

Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

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Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

Author and Disclosure Information

 

Stuart W. Stoloff, MD
Stuart W. Stoloff, MD, has served as a consultant/advisor and on the advisory board for Teva Pharmaceuticals. Dr. Stoloff has served as a consultant/advisor for Alcon, AstraZeneca, and Merck.

 

Today, virtually all physicians working in primary care will have a significant caseload of patients with allergic rhinitis (AR). Yet, many physicians still regard AR as a relatively unimportant “nuisance” illness and only treat the symptoms on an as-needed basis. Likewise, many patients do not realize that effective treatments are available that can help control their condition and assume that they just have to live with their symptoms. However, the incidence of AR has grown dramatically in recent years, and it is associated with significant morbidity.1 For example, as well as experiencing troublesome nasal symptoms, patients with AR have an increased risk of suffering associated conditions such as asthma, rhinosinusitis, and chronic otitis media, which themselves increase morbidity and medical costs.2,3 It is also well known that AR has a significant impact on the quality of life of the sufferer,4 with days lost from work or school.5,6

Ten years ago, the Institute of Medicine published “Crossing the Quality Chasm,” which identified key weaknesses in the quality of American health care.7 Increasing patient-centered care was identified as one of the “six aims for improvement.” This meant that health care should respect and respond to patient preferences, needs, and values, and that patient values should guide all clinical decisions. In 2006, the Allergies in America: A Landmark Survey of Nasal Allergy Sufferers was conducted to assess how well we manage our patients who have nasal allergies.8 At the time, it was the largest and most comprehensive national survey of patients with AR and the health care providers who treat them. The survey revealed a number of truths. It highlighted that AR was not just a seasonal problem and that more than half of patients suffered symptoms throughout the year.9 It showed that, at their peak, nasal allergy symptoms left patients feeling tired, miserable, and irritable and, for most patients in the survey, decreased their performance at work. Importantly, the survey also uncovered gaps in communication between physician and patient. For example, fewer than half of patients who had seen a physician reported following his or her instructions on the management and treatment of AR.9

Five years after the landmark survey was conducted, we wanted to see how the treatment of nasal allergies had progressed in America. This supplement presents results from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC, which included many of the same questions as the earlier survey. NASAL provided an up-to-date assessment of patient and provider perspectives concerning AR and nasal allergies in the United States (US). It included a national sample of 400 persons aged ≥18 years who had been diagnosed with AR, nasal allergies, or hay fever, and had experienced nasal allergy symptoms or taken medication for their condition in the past 12 months. To determine the burden of disease of AR, a telephone survey was conducted among a national probability sample of 522 adults sampled by random-digit dialing. This parallel survey of the general adult US population yielded a subsample of 400 persons aged ≥18 years who did not currently have nasal allergies. The comparison of the 2 samples of adults with and without nasal allergies provided a new and unique measure of the impact of nasal allergies on the health and lifestyle of patients. Finally, another parallel survey was conducted among 250 health care practitioners who saw patients with nasal allergies.

NASAL was the first survey of its kind to include the full range of health care practitioners involved in the management of nasal allergies. It included 100 physicians in adult primary care specialties (family medicine and internal medicine), 100 specialists (allergy and otolaryngology), and 50 nurse practitioners and physician assistants.

The purpose of NASAL was to describe the symptoms, burden of disease, and treatment of AR. The articles in this supplement report new data from NASAL showing the significant impact AR has on quality of life, the comorbidities associated with AR, and the oft-forgotten patient perspective. During the preparation of these articles, the most common phrase from our authors was, “Don’t get me started…” Each author has passionate views on the current treatment of nasal allergies in America, and these are shared in the roundtable discussion presented at the end of the supplement.

 

Today, virtually all physicians working in primary care will have a significant caseload of patients with allergic rhinitis (AR). Yet, many physicians still regard AR as a relatively unimportant “nuisance” illness and only treat the symptoms on an as-needed basis. Likewise, many patients do not realize that effective treatments are available that can help control their condition and assume that they just have to live with their symptoms. However, the incidence of AR has grown dramatically in recent years, and it is associated with significant morbidity.1 For example, as well as experiencing troublesome nasal symptoms, patients with AR have an increased risk of suffering associated conditions such as asthma, rhinosinusitis, and chronic otitis media, which themselves increase morbidity and medical costs.2,3 It is also well known that AR has a significant impact on the quality of life of the sufferer,4 with days lost from work or school.5,6

Ten years ago, the Institute of Medicine published “Crossing the Quality Chasm,” which identified key weaknesses in the quality of American health care.7 Increasing patient-centered care was identified as one of the “six aims for improvement.” This meant that health care should respect and respond to patient preferences, needs, and values, and that patient values should guide all clinical decisions. In 2006, the Allergies in America: A Landmark Survey of Nasal Allergy Sufferers was conducted to assess how well we manage our patients who have nasal allergies.8 At the time, it was the largest and most comprehensive national survey of patients with AR and the health care providers who treat them. The survey revealed a number of truths. It highlighted that AR was not just a seasonal problem and that more than half of patients suffered symptoms throughout the year.9 It showed that, at their peak, nasal allergy symptoms left patients feeling tired, miserable, and irritable and, for most patients in the survey, decreased their performance at work. Importantly, the survey also uncovered gaps in communication between physician and patient. For example, fewer than half of patients who had seen a physician reported following his or her instructions on the management and treatment of AR.9

Five years after the landmark survey was conducted, we wanted to see how the treatment of nasal allergies had progressed in America. This supplement presents results from the Nasal Allergy Survey Assessing Limitations (NASAL; www.nasalsurvey.com), a study sponsored by Teva Respiratory, LLC, which included many of the same questions as the earlier survey. NASAL provided an up-to-date assessment of patient and provider perspectives concerning AR and nasal allergies in the United States (US). It included a national sample of 400 persons aged ≥18 years who had been diagnosed with AR, nasal allergies, or hay fever, and had experienced nasal allergy symptoms or taken medication for their condition in the past 12 months. To determine the burden of disease of AR, a telephone survey was conducted among a national probability sample of 522 adults sampled by random-digit dialing. This parallel survey of the general adult US population yielded a subsample of 400 persons aged ≥18 years who did not currently have nasal allergies. The comparison of the 2 samples of adults with and without nasal allergies provided a new and unique measure of the impact of nasal allergies on the health and lifestyle of patients. Finally, another parallel survey was conducted among 250 health care practitioners who saw patients with nasal allergies.

NASAL was the first survey of its kind to include the full range of health care practitioners involved in the management of nasal allergies. It included 100 physicians in adult primary care specialties (family medicine and internal medicine), 100 specialists (allergy and otolaryngology), and 50 nurse practitioners and physician assistants.

The purpose of NASAL was to describe the symptoms, burden of disease, and treatment of AR. The articles in this supplement report new data from NASAL showing the significant impact AR has on quality of life, the comorbidities associated with AR, and the oft-forgotten patient perspective. During the preparation of these articles, the most common phrase from our authors was, “Don’t get me started…” Each author has passionate views on the current treatment of nasal allergies in America, and these are shared in the roundtable discussion presented at the end of the supplement.

References

 

1. Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Global Allergy and Asthma European Network; Grading of Recommendations Assessment Development and Evaluation Working Group Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126(3):466-476.

2. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004;24(1):19-43.

3. Meltzer EO, Szwarcberg J, Pill MW. Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway. J Manag Care Pharm. 2004;10(4):310-317.

4. Meltzer EO, Nathan R, Derebery J, et al. Sleep, quality of life, and productivity impact of nasal symptoms in the United States: Findings from the Burden of Rhinitis in America survey. Allergy Asthma Proc. 2009;30(3):244-254.

5. Lamb CE, Ratner PH, Johnson CE, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203-1210.

6. Schoenwetter WF, Dupclay L, Jr, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin. 2004;20(3):305-317.

7. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.

8. Meltzer EO. Introduction: how can we improve the treatment of allergic rhinitis? Allergy Asthma Proc. 2007;28(suppl 1):S2-S3.

9. Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4-S10.

References

 

1. Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Global Allergy and Asthma European Network; Grading of Recommendations Assessment Development and Evaluation Working Group Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126(3):466-476.

2. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004;24(1):19-43.

3. Meltzer EO, Szwarcberg J, Pill MW. Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway. J Manag Care Pharm. 2004;10(4):310-317.

4. Meltzer EO, Nathan R, Derebery J, et al. Sleep, quality of life, and productivity impact of nasal symptoms in the United States: Findings from the Burden of Rhinitis in America survey. Allergy Asthma Proc. 2009;30(3):244-254.

5. Lamb CE, Ratner PH, Johnson CE, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203-1210.

6. Schoenwetter WF, Dupclay L, Jr, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin. 2004;20(3):305-317.

7. Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.

8. Meltzer EO. Introduction: how can we improve the treatment of allergic rhinitis? Allergy Asthma Proc. 2007;28(suppl 1):S2-S3.

9. Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4-S10.

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Practice recommendations

 

  • Assess asthma severity before initiating treatment; monitor asthma control to guide adjustments in therapy using measures of impairment (B) and risk (C) (National Heart, Lung, and Blood Institute [NHLBI] and National Asthma Education and Prevention Program [NAEPP] third expert panel report [EPR-3]).
  • Base treatment decisions on recommendations specific to each age group (0-4 years, 5-11 years, and ≥12 years) (A).
  • Use spirometry in patients ≥5 years of age to diagnose asthma, classify severity, and assess control (C).
  • Provide each patient with a written asthma action plan with instructions for daily disease management, as well as identification of, and response to, worsening symptoms (B).

EPR-3 evidence categories:

 

  1. Randomized, controlled trials (RCTs), rich body of data
  2. RCTs, limited body of data
  3. Nonrandomized trials and observational studies
  4. Panel consensus judgment

JJ, a 4-year-old boy, was taken to an urgent care clinic 3 times last winter for “recurrent bronchitis” and given a 7-day course of prednisone and antibiotics at each visit. His mother reports that “his colds always seem to go to his chest” and his skin is always dry. She was given a nebulizer and albuterol for use when JJ begins wheezing, which often happens when he has a cold, plays vigorously, or visits a friend who has cats.

JJ is one of approximately 6.7 million children—and 22.9 million US residents—who have asthma.1 To help guide the care of patients like JJ, the National Heart, Lung, and Blood Institute (NHLBI) and National Asthma Education and Prevention Program (NAEPP) released the third expert panel report (EPR-3) in 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm, the EPR-3 provides the most comprehensive evidence-based guidance for the diagnosis and management of asthma to date.2

The guidelines were an invaluable resource for JJ’s family physician, who referred to them to categorize the severity of JJ’s asthma as “mild persistent.” In initiating treatment, JJ’s physician relied on specific recommendations for children 0 to 4 years of age to prescribe low-dose inhaled corticosteroids (ICS). Without the new guidelines, which underscore the safety of controller medication for young children, JJ’s physician would likely have been reluctant to place a 4-year-old on ICS.

This review highlights the EPR-3’s key recommendations to encourage widespread implementation by family physicians.

The EPR-3: What’s changed

The 2007 guidelines:
Recommend assessing asthma severity before starting treatment and assessing asthma control to guide adjustments in treatment.
Address both severity and control in terms of impairment and risk.
Feature 3 age breakdowns (0-4 years, 5-11 years, and ≥12 years) and a 6-step approach to asthma management.
Make it easier to individualize and adjust treatment.

What’s changed?

There’s a new paradigm

The 2007 update to guidelines released in 1997 and 2002 reflects a paradigm shift in the overall approach to asthma management. The change in focus addresses the highly variable nature of asthma2 and the recognition that asthma severity and asthma control are distinct concepts serving different functions in clinical practice.

Severity and control in 2 domains. Asthma severity—a measure of the intrinsic intensity of the disease process—is ideally assessed before initiating treatment. In contrast, asthma control is monitored over time to guide adjustments to therapy. The guidelines call for assessing severity and control within the domains of:

 

  • impairment, based on asthma symptoms (identified by patient or caregiver recall of the past 2-4 weeks), quality of life, and functional limitations; and
  • risk, of asthma exacerbations, progressive decline in pulmonary function (or reduced lung growth in children), or adverse events. Predictors of increased risk for exacerbations or death include persistent and/or severe airflow obstruction; at least 2 visits to the emergency department or hospitalizations for asthma within the past year; and a history of intubation or admission to intensive care, especially within the past 5 years.

 

The specific criteria for determining asthma severity and assessing asthma control are detailed in FIGURES 1 AND 2, respectively. Because treatment affects impairment and risk differently, this dual assessment helps ensure that therapeutic interventions minimize all manifestations of asthma as much as possible.

More steps and age-specific interventions. The EPR-3’s stepwise approach to asthma therapy has gone from 4 steps to 6, and the recommended treatments, as well as the levels of severity and criteria for assessing control that guide them, are now divided into 3 age groups: 0 to 4 years, 5 to 11 years, and ≥12 years (FIGURE 3). The previous guidelines, issued in 2002, divided treatment recommendations into 2 age groups: ≤5 years and >5 years. The EPR-3’s expansion makes it easier for physicians to initiate, individualize, and adjust treatment.

FIGURE 1
Classifying asthma severity and initiating therapy in children, adolescents, and adults


EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroids; NA, not applicable; OCS, oral corticosteroids; SABA, short-acting β2-adrenergic agonist.
*Normal FEV1/FVC values are defined according to age: 8–9 years (85%), 20–39 years (80%), 40–59 years (75%), 60–80 years (70%).
For treatment purposes, children with at least 2 exacerbations (eg, requiring urgent, unscheduled care; hospitalization; or intensive care unit admission) or adolescents/adults with at least 2 exacerbations requiring OCS in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

FIGURE 2
Assessing asthma control and adjusting therapy


ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; ATAQ, Asthma Therapy Assessment Questionnaire; EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; N/A, not applicable; OCS, oral corticosteroids; SABA, short-acting β2-adrenergic agonist.
*ACQ values of 0.76 to 1.4 are indeterminate regarding well-controlled asthma.
For treatment purposes, children with at least 2 exacerbations (eg, requiring urgent, unscheduled care; hospitalization; or intensive care unit admission) or adolescents/adults with at least 2 exacerbations requiring OCS in the past year may be considered the same as patients who have asthma that is not well controlled, even in the absence of impairment levels consistent with that classification.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

FIGURE 3
Stepwise approach for managing asthma


EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, long-acting β2-adrenergic agonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; PRN, as needed; SABA, short-acting β2-adrenergic agonist.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

 

 

Putting guidelines into practice begins with the history

A detailed medical history and a physical examination focusing on the upper respiratory tract, chest, and skin are needed to arrive at an asthma diagnosis. JJ’s physician asked his mother to describe recent symptoms and inquired about comorbid conditions that can aggravate asthma. He also identified viral respiratory infections, environmental causes, and activity as precipitating factors.

In considering an asthma diagnosis, try to determine the presence of episodic symptoms of airflow obstruction or bronchial hyperresponsiveness, as well as airflow obstruction that is at least partly reversible (an increase in forced expiratory volume in 1 second [FEV1] of >200 mL and ≥12% from baseline or an increase of ≥10% of predicted FEV1), and to exclude alternative diagnoses.

EPR-3 emphasizes spirometry

Recognizing that patients’ perception of airflow obstruction is highly variable and that pulmonary function measures do not always correlate directly with symptoms,3,4 the EPR-3 recommends spirometry for patients ≥5 years of age, both before and after bronchodilation. In addition to helping to confirm an asthma diagnosis, spirometry is the preferred measure of pulmonary function in classifying severity, because peak expiratory flow (PEF) testing has not proven reliable.5,6

 

Objective measurement of pulmonary function is difficult to obtain in children <5 years of age. If diagnosis remains uncertain for patients in this age group, a therapeutic trial of medication is recommended. In JJ’s case, however, 3 courses of oral corticosteroids (OCS) in less than 6 months were indicative of persistent asthma.

Spirometry is often underutilized. For patients ≥5 years of age, spirometry is a vital tool, but often underutilized in family practice. A recent study by Yawn and colleagues found that family physicians made changes in the management of approximately half of the asthma patients who underwent spirometry.7 (Information about spirometry training is available through the National Institute for Occupational Safety and Health at http://www.cdc.gov/niosh.) Referral to a specialist is recommended if the physician has difficulty making a differential diagnosis or is unable to perform spirometry on a patient who presents with atypical signs and symptoms of asthma.

What is the patient’s level of severity?

In patients who are not yet receiving long-term controller therapy, severity level is based on an assessment of impairment and risk (FIGURE 1). For patients who are already receiving treatment, severity is determined by the minimum pharmacologic therapy needed to maintain asthma control.

The severity classification—intermittent asthma or persistent asthma that is mild, moderate, or severe—is determined by the most severe category in which any feature occurs. (In children, FEV1/FVC [forced vital capacity] ratio has been shown to be a more sensitive determinant of severity than FEV1,4 which may be more useful in predicting exacerbations.8)

Asthma management: Preferred and alternative Tx

The recommended stepwise interventions include both preferred therapies (evidence-based) and alternative treatments (listed alphabetically in FIGURE 3 because there is insufficient evidence to rank them). The additional steps and age categories support the goal of using the least possible medication needed to maintain good control and minimize the potential for adverse events.

In initiating treatment, select the step that corresponds to the level of severity in the bottom row of FIGURE 1; to adjust medications, determine the patient’s level of asthma control and follow the corresponding guidance in the bottom row of FIGURE 2.

Inhaled corticosteroids remain the bedrock of therapy

ICS, the most potent and consistently effective long-term controller therapy, remain the foundation of therapy for patients of all ages who have persistent asthma. (Evidence: A).

Several of the age-based recommendations follow, with a focus on preferred treatments:

Children 0 to 4 years of age

 

  • The guidelines recommend low-dose ICS at Step 2 (Evidence: A) and medium-dose ICS at Step 3 (Evidence: D), as inhaled corticosteroids have been shown to reduce impairment and risk in this age group.9-16 The potential risk is generally limited to a small reduction in growth velocity during the first year of treatment, and offset by the benefits of therapy.15,16
  • Add a long-acting β2-adrenergic agonist (LABA) or montelukast to medium-dose ICS therapy at Step 4 rather than increasing the ICS dose (Evidence: D) to avoid the risk of side effects associated with high-dose ICS. Montelukast has demonstrated efficacy in children 2 to 5 years of age with persistent asthma.17
  • Recommendations for preferred therapy at Steps 5 (high-dose ICS + LABA or montelukast) and 6 (Step 5 therapy + OCS) are based on expert panel judgment (Evidence: D). When severe persistent asthma warrants Step 6 therapy, start with a 2-week course of the lowest possible dose of OCS to confirm reversibility.
  • In this age group, a therapeutic trial with close monitoring is recommended for patients whose asthma is not well controlled. If there is no response in 4 to 6 weeks, consider alternative therapies or diagnoses (Evidence: D).
 

 

 

Children 5 to 11 years of age

 

  • For Step 3 therapy, the guidelines recommend either low-dose ICS plus a LABA, leukotriene receptor antagonist (LTRA), or theophylline; or medium-dose ICS (Evidence: B). Treatment decisions at Step 3 depend on whether impairment or risk is the chief concern, as well as on safety considerations.
  • For Steps 4 and 5, ICS (medium dose for Step 5 and high dose for Step 6) plus a LABA is preferred, based on studies of patients ≥12 years of age (Evidence: B). Step 6 builds on Step 5, adding an OCS to the LABA/ICS combination (Evidence: D).
  • If theophylline is prescribed—a viable option if cost and adherence to inhaled medications are key concerns—serum levels must be closely monitored because of the risk of toxicity.
  • Closely monitor and be prepared to identify and respond to anaphylaxis in a child at Step 2, 3, or 4 who is receiving allergen immunotherapy.

Adolescents ≥12 years of age and adults

 

  • There are 2 preferred Step 3 treatments: Low-dose ICS plus a LABA, or medium-dose ICS. The combination therapy has shown greater improvement in impairment24,25 and risk24-26 compared with the higher dose of ICS.
  • Preferred treatments at Steps 4, 5, and 6 are the same as those for children ages 5 to 11 years, with one exception: Subcutaneous anti-IgE therapy (omalizumab) may be added to the regimen at Steps 5 and 6 for adolescents and adults with severe persistent allergic asthma to reduce the risk of exacerbations.27

 

Weigh the benefits and risks of therapy

Safety is a key consideration for all asthma patients. Carefully weigh the benefits and risks of therapy, including the rare but potential risk of life-threatening or fatal exacerbations with daily LABA therapy28 and systemic effects with higher doses of ICS.23 Patients who begin receiving oral corticosteroids require close monitoring, regardless of age.

Regular reassessment and monitoring are critical

 

Schedule visits at 2- to 6-week intervals for those who are starting therapy or require a step up to achieve or regain asthma control. After control is achieved, reassess at least every 1 to 6 months. Measures of asthma control are the same as those used to assess severity, with the addition of validated multidimensional questionnaires (eg, Asthma Control Test [ACT])29 to gauge impairment.

JJ’s physician scheduled a follow-up visit in 4 weeks, at which time he did a reassessment based on a physical exam and symptom recall. Finding JJ’s asthma to be well controlled, the physician asked the boy’s mother to bring him back to the office in 2 months, or earlier if symptoms recurred.

TABLE W1
Asthma education resources

 

Allergy & Asthma Network Mothers of Asthmatics
2751 Prosperity Avenue, Suite 150
Fairfax, VA 22030
www.breatherville.org
(800) 878-4403 or (703) 641-9595
Asthma and Allergy Foundation of America
1233 20th Street, NW, Suite 402
Washington, DC 20036
www.aafa.org
(800) 727-8462
American Academy of Allergy,
Asthma, and Immunology
555 East Wells Street, Suite 1100
Milwaukee, WI 53202-3823
www.aaaai.org
(414) 272-6071
Centers for Disease Control and Prevention
1600 Clifton Road
Atlanta, GA 30333
www.cdc.gov
(800) 311-3435
American Association for Respiratory Care
9125 North macArthur boulevard, Suite 100
Irving, TX 75063
www.aarc.org
(972) 243-2272
Food Allergy & Anaphylaxis Network
11781 lee Jackson Highway, Suite 160
Fairfax, VA 22033
www.foodallergy.org
(800) 929-4040
American College of Allergy, Asthma, and Immunology
85 West Algonquin road, Suite 550
Arlington Heights, IL 60005
www.acaai.org
(800) 842-7777 or (847) 427-1200
National Heart, Lung, and Blood Institute Information Center
P.O. Box 30105
Bethesda, MD 20824-0105
www.nhlbi.nih.gov
(301) 592-8573
American Lung Association
61 Broadway
New York, NY 10006
www.lungusa.org
(800) 586-4872
National Jewish Medical and Research Center (Lung Line)
1400 Jackson Street
Denver, CO 80206
www.njc.org
(800) 222-lUNG
Association of Asthma Educators
1215 Anthony Avenue
Columbia, SC 29201
www.asthmaeducators.org
(888) 988-7747
US Environmental Protection Agency
National Center for Environmental Publications
P.O. Box 42419
Cincinnati, OH 45242-0419
www.airnow.gov
(800) 490-9198

Does your patient require a step down or step up?

A step down is recommended for patients whose asthma is well controlled for 3 months or more. Reduce the dose of ICS gradually, about 25% to 50% every 3 months, because deterioration in asthma control is highly variable. Review adherence and medication administration technique with patients whose asthma is not well controlled, and consider a step up in treatment. If an alternative treatment is used but does not result in an adequate response, it should be discontinued and the preferred treatment used before stepping up. Refer patients to an asthma specialist if their asthma does not respond to these adjustments.

 

 

Partner with patients for optimal care

The EPR-3 recommends the integration of patient education into all aspects of asthma care. To forge an active partnership, identify and address concerns about the condition and its treatment and involve the patient and family in developing treatment goals and making treatment decisions. If the patient is old enough, encourage self-monitoring and management.

The EPR-3 recommends that physicians give every patient a written asthma action plan that addresses individual symptoms and/or PEF measurements and includes instructions for self-management. Daily PEF monitoring can be useful in identifying early changes in the disease state and evaluating response to changes in therapy. It is ideal for those who have moderate to severe persistent asthma, difficulty recognizing signs of exacerbations, or a history of severe exacerbations.

Correspondence
Stuart W. Stoloff, MD, Clinical Professor, Department of Family and Community Medicine, University of Nevada–Reno, 1200 Mountain Street, Suite 220, Carson City, NV 89703; drstoloff@sbcglobal.net.

References

 

1. National Center for Health Statistics. Fast stats A to Z. Available at: www.cdc.gov/nchs/fastats/asthma.htm. Accessed August 1, 2008.

2. National Heart, Lung, and Blood Institute (NHLBI). National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. Bethesda, MD: NHLBI; August 2007. NIH publication no. 07-4051. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed July 17, 2008.

3. Stout JW, Visness CM, Enright P, et al. Classification of asthma severity in children: the contribution of pulmonary function testing. Arch Pediatr Adolesc Med. 2006;160:844-850.

4. Bacharier LB, Strunk RC, Mauger D, et al. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med. 2004;170:426-432.

5. Eid N, Yandell B, Howell L, Eddy M, Sheikh S. Can children with asthma? Pediatrics. 2000;105:354-358.

6. Llewellin P, Sawyer G, Lewis S, et al. The relationship between FEV1 and PEF in the assessment of the severity of airways obstruction. Respirology. 2002;7:333-337.

7. Yawn BP, Enright PL, Lemanske RF, Jr, et al. Spirometry can be done in family physicians’ offices and alters clinical decisions in management of asthma and COPD. Chest. 2007;132:1162-1168.

8. Fuhlbrigge AL, Kitch BT, Paltiel AD, et al. FEV1 is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol. 2001;107:61-67.

9. Roorda RJ, Mezei G, Bisgaard H, Maden C. Response of preschool children with asthma symptoms to fluticasone propionate. J Allergy Clin Immunol. 2001;108:540-546.

10. Baker JW, Mellon M, Wald J, Welch M, Cruz-Rivera M, Walton-Bowen K. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics. 1999;103:414-421.

11. Kemp JP, Skoner DP, Szefler SJ, Walton-Bowen K, Cruz-Rivera M, Smith JA. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol. 1999;83:231-239.

12. Shapiro G, Mendelson L, Kraemer MJ, Cruz-Rivera M, Walton-Bowen K, Smith JA. Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma. J Allergy Clin Immunol. 1998;102:789-796.

13. Bisgaard H, Gillies J, Groenewald M, Maden C. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med. 1999;160:126-131.

14. Szefler SJ, Eigen H. Budesonide inhalation suspension: a nebulized corticosteroid for persistent asthma. J Allergy Clin Immunol. 2002;109:730-742.

15. Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354:1985-1997.

16. Bisgaard H, Allen D, Milanowski J, Kalev I, Willits L, Davies P. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1 to 3 years with recurrent wheezing. Pediatrics. 2004;113:e87-e94.

17. Knorr B, Franchi LM, Bisgaard H, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 2001;108:e48.-

18. Russell G, Williams DA, Weller P, Price JF. Salmeterol xinafoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol. 1995;75:423-428.

19. Zimmerman B, D’Urzo A, Bérubé D. Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma. Pediatr Pulmonol. 2004;37:122-127.

20. Simons FE, Villa JR, Lee BW, et al. Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study. J Pediatr. 2001;138:694-698.

21. Shapiro G, Bronsky EA, LaForce CF, et al. Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. J Pediatr. 1998;132:976-982.

22. Pauwels RA, Lofdahl C-G, Postma DS, et al. for the Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med. 1997;337:1405-1411.

23. Tattersfield AE, Harrison TW, Hubbard RB, Mortimer K. Safety of inhaled corticosteroids. Proc Am Thorac Soc. 2004;1:171-175.

24. Bateman ED, Boushey HA, Bousquet J, et al. For the GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170:836-844.

25. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med. 2001;164:1392-1397.

26. Masoli M, Weatherall M, Holt S, Beasley R. Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma. Thorax. 2005;60:730-734.

27. Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Fox H. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest. 2004;125:1378-1386.

28. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. For the SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26.

29. Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113:59-65.

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Stuart W. Stoloff, MD
Department of Family and Community Medicine, University of Nevada—Reno

Dr. Stoloff served on the panel that issued the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma

Dr. Stoloff discloses that he serves as a consultant to Adelphi Publishing, Alcon, AstraZeneca LP, Dey, Dyson, Genentech, GlaxoSmithKline, Merck & Co., Novartis, Pfizer, Schering-Plough, and Teva Pharmaceutical Industries. He is on the speakers’ bureau of Alcon, AstraZeneca LP, Dey, Genentech, GlaxoSmithKline, Novartis, Schering-Plough, and Teva Pharmaceutical Industries.

Dr. Stoloff received writing assistance from Cynthia Gobbel, PhD, at Scientific Connexions, Newtown, PA, funded by AstraZeneca LP.

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Stuart W. Stoloff, MD
Department of Family and Community Medicine, University of Nevada—Reno

Dr. Stoloff served on the panel that issued the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma

Dr. Stoloff discloses that he serves as a consultant to Adelphi Publishing, Alcon, AstraZeneca LP, Dey, Dyson, Genentech, GlaxoSmithKline, Merck & Co., Novartis, Pfizer, Schering-Plough, and Teva Pharmaceutical Industries. He is on the speakers’ bureau of Alcon, AstraZeneca LP, Dey, Genentech, GlaxoSmithKline, Novartis, Schering-Plough, and Teva Pharmaceutical Industries.

Dr. Stoloff received writing assistance from Cynthia Gobbel, PhD, at Scientific Connexions, Newtown, PA, funded by AstraZeneca LP.

Author and Disclosure Information

 

Stuart W. Stoloff, MD
Department of Family and Community Medicine, University of Nevada—Reno

Dr. Stoloff served on the panel that issued the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma

Dr. Stoloff discloses that he serves as a consultant to Adelphi Publishing, Alcon, AstraZeneca LP, Dey, Dyson, Genentech, GlaxoSmithKline, Merck & Co., Novartis, Pfizer, Schering-Plough, and Teva Pharmaceutical Industries. He is on the speakers’ bureau of Alcon, AstraZeneca LP, Dey, Genentech, GlaxoSmithKline, Novartis, Schering-Plough, and Teva Pharmaceutical Industries.

Dr. Stoloff received writing assistance from Cynthia Gobbel, PhD, at Scientific Connexions, Newtown, PA, funded by AstraZeneca LP.

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Practice recommendations

 

  • Assess asthma severity before initiating treatment; monitor asthma control to guide adjustments in therapy using measures of impairment (B) and risk (C) (National Heart, Lung, and Blood Institute [NHLBI] and National Asthma Education and Prevention Program [NAEPP] third expert panel report [EPR-3]).
  • Base treatment decisions on recommendations specific to each age group (0-4 years, 5-11 years, and ≥12 years) (A).
  • Use spirometry in patients ≥5 years of age to diagnose asthma, classify severity, and assess control (C).
  • Provide each patient with a written asthma action plan with instructions for daily disease management, as well as identification of, and response to, worsening symptoms (B).

EPR-3 evidence categories:

 

  1. Randomized, controlled trials (RCTs), rich body of data
  2. RCTs, limited body of data
  3. Nonrandomized trials and observational studies
  4. Panel consensus judgment

JJ, a 4-year-old boy, was taken to an urgent care clinic 3 times last winter for “recurrent bronchitis” and given a 7-day course of prednisone and antibiotics at each visit. His mother reports that “his colds always seem to go to his chest” and his skin is always dry. She was given a nebulizer and albuterol for use when JJ begins wheezing, which often happens when he has a cold, plays vigorously, or visits a friend who has cats.

JJ is one of approximately 6.7 million children—and 22.9 million US residents—who have asthma.1 To help guide the care of patients like JJ, the National Heart, Lung, and Blood Institute (NHLBI) and National Asthma Education and Prevention Program (NAEPP) released the third expert panel report (EPR-3) in 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm, the EPR-3 provides the most comprehensive evidence-based guidance for the diagnosis and management of asthma to date.2

The guidelines were an invaluable resource for JJ’s family physician, who referred to them to categorize the severity of JJ’s asthma as “mild persistent.” In initiating treatment, JJ’s physician relied on specific recommendations for children 0 to 4 years of age to prescribe low-dose inhaled corticosteroids (ICS). Without the new guidelines, which underscore the safety of controller medication for young children, JJ’s physician would likely have been reluctant to place a 4-year-old on ICS.

This review highlights the EPR-3’s key recommendations to encourage widespread implementation by family physicians.

The EPR-3: What’s changed

The 2007 guidelines:
Recommend assessing asthma severity before starting treatment and assessing asthma control to guide adjustments in treatment.
Address both severity and control in terms of impairment and risk.
Feature 3 age breakdowns (0-4 years, 5-11 years, and ≥12 years) and a 6-step approach to asthma management.
Make it easier to individualize and adjust treatment.

What’s changed?

There’s a new paradigm

The 2007 update to guidelines released in 1997 and 2002 reflects a paradigm shift in the overall approach to asthma management. The change in focus addresses the highly variable nature of asthma2 and the recognition that asthma severity and asthma control are distinct concepts serving different functions in clinical practice.

Severity and control in 2 domains. Asthma severity—a measure of the intrinsic intensity of the disease process—is ideally assessed before initiating treatment. In contrast, asthma control is monitored over time to guide adjustments to therapy. The guidelines call for assessing severity and control within the domains of:

 

  • impairment, based on asthma symptoms (identified by patient or caregiver recall of the past 2-4 weeks), quality of life, and functional limitations; and
  • risk, of asthma exacerbations, progressive decline in pulmonary function (or reduced lung growth in children), or adverse events. Predictors of increased risk for exacerbations or death include persistent and/or severe airflow obstruction; at least 2 visits to the emergency department or hospitalizations for asthma within the past year; and a history of intubation or admission to intensive care, especially within the past 5 years.

 

The specific criteria for determining asthma severity and assessing asthma control are detailed in FIGURES 1 AND 2, respectively. Because treatment affects impairment and risk differently, this dual assessment helps ensure that therapeutic interventions minimize all manifestations of asthma as much as possible.

More steps and age-specific interventions. The EPR-3’s stepwise approach to asthma therapy has gone from 4 steps to 6, and the recommended treatments, as well as the levels of severity and criteria for assessing control that guide them, are now divided into 3 age groups: 0 to 4 years, 5 to 11 years, and ≥12 years (FIGURE 3). The previous guidelines, issued in 2002, divided treatment recommendations into 2 age groups: ≤5 years and >5 years. The EPR-3’s expansion makes it easier for physicians to initiate, individualize, and adjust treatment.

FIGURE 1
Classifying asthma severity and initiating therapy in children, adolescents, and adults


EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroids; NA, not applicable; OCS, oral corticosteroids; SABA, short-acting β2-adrenergic agonist.
*Normal FEV1/FVC values are defined according to age: 8–9 years (85%), 20–39 years (80%), 40–59 years (75%), 60–80 years (70%).
For treatment purposes, children with at least 2 exacerbations (eg, requiring urgent, unscheduled care; hospitalization; or intensive care unit admission) or adolescents/adults with at least 2 exacerbations requiring OCS in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

FIGURE 2
Assessing asthma control and adjusting therapy


ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; ATAQ, Asthma Therapy Assessment Questionnaire; EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; N/A, not applicable; OCS, oral corticosteroids; SABA, short-acting β2-adrenergic agonist.
*ACQ values of 0.76 to 1.4 are indeterminate regarding well-controlled asthma.
For treatment purposes, children with at least 2 exacerbations (eg, requiring urgent, unscheduled care; hospitalization; or intensive care unit admission) or adolescents/adults with at least 2 exacerbations requiring OCS in the past year may be considered the same as patients who have asthma that is not well controlled, even in the absence of impairment levels consistent with that classification.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

FIGURE 3
Stepwise approach for managing asthma


EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, long-acting β2-adrenergic agonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; PRN, as needed; SABA, short-acting β2-adrenergic agonist.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

 

 

Putting guidelines into practice begins with the history

A detailed medical history and a physical examination focusing on the upper respiratory tract, chest, and skin are needed to arrive at an asthma diagnosis. JJ’s physician asked his mother to describe recent symptoms and inquired about comorbid conditions that can aggravate asthma. He also identified viral respiratory infections, environmental causes, and activity as precipitating factors.

In considering an asthma diagnosis, try to determine the presence of episodic symptoms of airflow obstruction or bronchial hyperresponsiveness, as well as airflow obstruction that is at least partly reversible (an increase in forced expiratory volume in 1 second [FEV1] of >200 mL and ≥12% from baseline or an increase of ≥10% of predicted FEV1), and to exclude alternative diagnoses.

EPR-3 emphasizes spirometry

Recognizing that patients’ perception of airflow obstruction is highly variable and that pulmonary function measures do not always correlate directly with symptoms,3,4 the EPR-3 recommends spirometry for patients ≥5 years of age, both before and after bronchodilation. In addition to helping to confirm an asthma diagnosis, spirometry is the preferred measure of pulmonary function in classifying severity, because peak expiratory flow (PEF) testing has not proven reliable.5,6

 

Objective measurement of pulmonary function is difficult to obtain in children <5 years of age. If diagnosis remains uncertain for patients in this age group, a therapeutic trial of medication is recommended. In JJ’s case, however, 3 courses of oral corticosteroids (OCS) in less than 6 months were indicative of persistent asthma.

Spirometry is often underutilized. For patients ≥5 years of age, spirometry is a vital tool, but often underutilized in family practice. A recent study by Yawn and colleagues found that family physicians made changes in the management of approximately half of the asthma patients who underwent spirometry.7 (Information about spirometry training is available through the National Institute for Occupational Safety and Health at http://www.cdc.gov/niosh.) Referral to a specialist is recommended if the physician has difficulty making a differential diagnosis or is unable to perform spirometry on a patient who presents with atypical signs and symptoms of asthma.

What is the patient’s level of severity?

In patients who are not yet receiving long-term controller therapy, severity level is based on an assessment of impairment and risk (FIGURE 1). For patients who are already receiving treatment, severity is determined by the minimum pharmacologic therapy needed to maintain asthma control.

The severity classification—intermittent asthma or persistent asthma that is mild, moderate, or severe—is determined by the most severe category in which any feature occurs. (In children, FEV1/FVC [forced vital capacity] ratio has been shown to be a more sensitive determinant of severity than FEV1,4 which may be more useful in predicting exacerbations.8)

Asthma management: Preferred and alternative Tx

The recommended stepwise interventions include both preferred therapies (evidence-based) and alternative treatments (listed alphabetically in FIGURE 3 because there is insufficient evidence to rank them). The additional steps and age categories support the goal of using the least possible medication needed to maintain good control and minimize the potential for adverse events.

In initiating treatment, select the step that corresponds to the level of severity in the bottom row of FIGURE 1; to adjust medications, determine the patient’s level of asthma control and follow the corresponding guidance in the bottom row of FIGURE 2.

Inhaled corticosteroids remain the bedrock of therapy

ICS, the most potent and consistently effective long-term controller therapy, remain the foundation of therapy for patients of all ages who have persistent asthma. (Evidence: A).

Several of the age-based recommendations follow, with a focus on preferred treatments:

Children 0 to 4 years of age

 

  • The guidelines recommend low-dose ICS at Step 2 (Evidence: A) and medium-dose ICS at Step 3 (Evidence: D), as inhaled corticosteroids have been shown to reduce impairment and risk in this age group.9-16 The potential risk is generally limited to a small reduction in growth velocity during the first year of treatment, and offset by the benefits of therapy.15,16
  • Add a long-acting β2-adrenergic agonist (LABA) or montelukast to medium-dose ICS therapy at Step 4 rather than increasing the ICS dose (Evidence: D) to avoid the risk of side effects associated with high-dose ICS. Montelukast has demonstrated efficacy in children 2 to 5 years of age with persistent asthma.17
  • Recommendations for preferred therapy at Steps 5 (high-dose ICS + LABA or montelukast) and 6 (Step 5 therapy + OCS) are based on expert panel judgment (Evidence: D). When severe persistent asthma warrants Step 6 therapy, start with a 2-week course of the lowest possible dose of OCS to confirm reversibility.
  • In this age group, a therapeutic trial with close monitoring is recommended for patients whose asthma is not well controlled. If there is no response in 4 to 6 weeks, consider alternative therapies or diagnoses (Evidence: D).
 

 

 

Children 5 to 11 years of age

 

  • For Step 3 therapy, the guidelines recommend either low-dose ICS plus a LABA, leukotriene receptor antagonist (LTRA), or theophylline; or medium-dose ICS (Evidence: B). Treatment decisions at Step 3 depend on whether impairment or risk is the chief concern, as well as on safety considerations.
  • For Steps 4 and 5, ICS (medium dose for Step 5 and high dose for Step 6) plus a LABA is preferred, based on studies of patients ≥12 years of age (Evidence: B). Step 6 builds on Step 5, adding an OCS to the LABA/ICS combination (Evidence: D).
  • If theophylline is prescribed—a viable option if cost and adherence to inhaled medications are key concerns—serum levels must be closely monitored because of the risk of toxicity.
  • Closely monitor and be prepared to identify and respond to anaphylaxis in a child at Step 2, 3, or 4 who is receiving allergen immunotherapy.

Adolescents ≥12 years of age and adults

 

  • There are 2 preferred Step 3 treatments: Low-dose ICS plus a LABA, or medium-dose ICS. The combination therapy has shown greater improvement in impairment24,25 and risk24-26 compared with the higher dose of ICS.
  • Preferred treatments at Steps 4, 5, and 6 are the same as those for children ages 5 to 11 years, with one exception: Subcutaneous anti-IgE therapy (omalizumab) may be added to the regimen at Steps 5 and 6 for adolescents and adults with severe persistent allergic asthma to reduce the risk of exacerbations.27

 

Weigh the benefits and risks of therapy

Safety is a key consideration for all asthma patients. Carefully weigh the benefits and risks of therapy, including the rare but potential risk of life-threatening or fatal exacerbations with daily LABA therapy28 and systemic effects with higher doses of ICS.23 Patients who begin receiving oral corticosteroids require close monitoring, regardless of age.

Regular reassessment and monitoring are critical

 

Schedule visits at 2- to 6-week intervals for those who are starting therapy or require a step up to achieve or regain asthma control. After control is achieved, reassess at least every 1 to 6 months. Measures of asthma control are the same as those used to assess severity, with the addition of validated multidimensional questionnaires (eg, Asthma Control Test [ACT])29 to gauge impairment.

JJ’s physician scheduled a follow-up visit in 4 weeks, at which time he did a reassessment based on a physical exam and symptom recall. Finding JJ’s asthma to be well controlled, the physician asked the boy’s mother to bring him back to the office in 2 months, or earlier if symptoms recurred.

TABLE W1
Asthma education resources

 

Allergy & Asthma Network Mothers of Asthmatics
2751 Prosperity Avenue, Suite 150
Fairfax, VA 22030
www.breatherville.org
(800) 878-4403 or (703) 641-9595
Asthma and Allergy Foundation of America
1233 20th Street, NW, Suite 402
Washington, DC 20036
www.aafa.org
(800) 727-8462
American Academy of Allergy,
Asthma, and Immunology
555 East Wells Street, Suite 1100
Milwaukee, WI 53202-3823
www.aaaai.org
(414) 272-6071
Centers for Disease Control and Prevention
1600 Clifton Road
Atlanta, GA 30333
www.cdc.gov
(800) 311-3435
American Association for Respiratory Care
9125 North macArthur boulevard, Suite 100
Irving, TX 75063
www.aarc.org
(972) 243-2272
Food Allergy & Anaphylaxis Network
11781 lee Jackson Highway, Suite 160
Fairfax, VA 22033
www.foodallergy.org
(800) 929-4040
American College of Allergy, Asthma, and Immunology
85 West Algonquin road, Suite 550
Arlington Heights, IL 60005
www.acaai.org
(800) 842-7777 or (847) 427-1200
National Heart, Lung, and Blood Institute Information Center
P.O. Box 30105
Bethesda, MD 20824-0105
www.nhlbi.nih.gov
(301) 592-8573
American Lung Association
61 Broadway
New York, NY 10006
www.lungusa.org
(800) 586-4872
National Jewish Medical and Research Center (Lung Line)
1400 Jackson Street
Denver, CO 80206
www.njc.org
(800) 222-lUNG
Association of Asthma Educators
1215 Anthony Avenue
Columbia, SC 29201
www.asthmaeducators.org
(888) 988-7747
US Environmental Protection Agency
National Center for Environmental Publications
P.O. Box 42419
Cincinnati, OH 45242-0419
www.airnow.gov
(800) 490-9198

Does your patient require a step down or step up?

A step down is recommended for patients whose asthma is well controlled for 3 months or more. Reduce the dose of ICS gradually, about 25% to 50% every 3 months, because deterioration in asthma control is highly variable. Review adherence and medication administration technique with patients whose asthma is not well controlled, and consider a step up in treatment. If an alternative treatment is used but does not result in an adequate response, it should be discontinued and the preferred treatment used before stepping up. Refer patients to an asthma specialist if their asthma does not respond to these adjustments.

 

 

Partner with patients for optimal care

The EPR-3 recommends the integration of patient education into all aspects of asthma care. To forge an active partnership, identify and address concerns about the condition and its treatment and involve the patient and family in developing treatment goals and making treatment decisions. If the patient is old enough, encourage self-monitoring and management.

The EPR-3 recommends that physicians give every patient a written asthma action plan that addresses individual symptoms and/or PEF measurements and includes instructions for self-management. Daily PEF monitoring can be useful in identifying early changes in the disease state and evaluating response to changes in therapy. It is ideal for those who have moderate to severe persistent asthma, difficulty recognizing signs of exacerbations, or a history of severe exacerbations.

Correspondence
Stuart W. Stoloff, MD, Clinical Professor, Department of Family and Community Medicine, University of Nevada–Reno, 1200 Mountain Street, Suite 220, Carson City, NV 89703; drstoloff@sbcglobal.net.

 

Practice recommendations

 

  • Assess asthma severity before initiating treatment; monitor asthma control to guide adjustments in therapy using measures of impairment (B) and risk (C) (National Heart, Lung, and Blood Institute [NHLBI] and National Asthma Education and Prevention Program [NAEPP] third expert panel report [EPR-3]).
  • Base treatment decisions on recommendations specific to each age group (0-4 years, 5-11 years, and ≥12 years) (A).
  • Use spirometry in patients ≥5 years of age to diagnose asthma, classify severity, and assess control (C).
  • Provide each patient with a written asthma action plan with instructions for daily disease management, as well as identification of, and response to, worsening symptoms (B).

EPR-3 evidence categories:

 

  1. Randomized, controlled trials (RCTs), rich body of data
  2. RCTs, limited body of data
  3. Nonrandomized trials and observational studies
  4. Panel consensus judgment

JJ, a 4-year-old boy, was taken to an urgent care clinic 3 times last winter for “recurrent bronchitis” and given a 7-day course of prednisone and antibiotics at each visit. His mother reports that “his colds always seem to go to his chest” and his skin is always dry. She was given a nebulizer and albuterol for use when JJ begins wheezing, which often happens when he has a cold, plays vigorously, or visits a friend who has cats.

JJ is one of approximately 6.7 million children—and 22.9 million US residents—who have asthma.1 To help guide the care of patients like JJ, the National Heart, Lung, and Blood Institute (NHLBI) and National Asthma Education and Prevention Program (NAEPP) released the third expert panel report (EPR-3) in 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm, the EPR-3 provides the most comprehensive evidence-based guidance for the diagnosis and management of asthma to date.2

The guidelines were an invaluable resource for JJ’s family physician, who referred to them to categorize the severity of JJ’s asthma as “mild persistent.” In initiating treatment, JJ’s physician relied on specific recommendations for children 0 to 4 years of age to prescribe low-dose inhaled corticosteroids (ICS). Without the new guidelines, which underscore the safety of controller medication for young children, JJ’s physician would likely have been reluctant to place a 4-year-old on ICS.

This review highlights the EPR-3’s key recommendations to encourage widespread implementation by family physicians.

The EPR-3: What’s changed

The 2007 guidelines:
Recommend assessing asthma severity before starting treatment and assessing asthma control to guide adjustments in treatment.
Address both severity and control in terms of impairment and risk.
Feature 3 age breakdowns (0-4 years, 5-11 years, and ≥12 years) and a 6-step approach to asthma management.
Make it easier to individualize and adjust treatment.

What’s changed?

There’s a new paradigm

The 2007 update to guidelines released in 1997 and 2002 reflects a paradigm shift in the overall approach to asthma management. The change in focus addresses the highly variable nature of asthma2 and the recognition that asthma severity and asthma control are distinct concepts serving different functions in clinical practice.

Severity and control in 2 domains. Asthma severity—a measure of the intrinsic intensity of the disease process—is ideally assessed before initiating treatment. In contrast, asthma control is monitored over time to guide adjustments to therapy. The guidelines call for assessing severity and control within the domains of:

 

  • impairment, based on asthma symptoms (identified by patient or caregiver recall of the past 2-4 weeks), quality of life, and functional limitations; and
  • risk, of asthma exacerbations, progressive decline in pulmonary function (or reduced lung growth in children), or adverse events. Predictors of increased risk for exacerbations or death include persistent and/or severe airflow obstruction; at least 2 visits to the emergency department or hospitalizations for asthma within the past year; and a history of intubation or admission to intensive care, especially within the past 5 years.

 

The specific criteria for determining asthma severity and assessing asthma control are detailed in FIGURES 1 AND 2, respectively. Because treatment affects impairment and risk differently, this dual assessment helps ensure that therapeutic interventions minimize all manifestations of asthma as much as possible.

More steps and age-specific interventions. The EPR-3’s stepwise approach to asthma therapy has gone from 4 steps to 6, and the recommended treatments, as well as the levels of severity and criteria for assessing control that guide them, are now divided into 3 age groups: 0 to 4 years, 5 to 11 years, and ≥12 years (FIGURE 3). The previous guidelines, issued in 2002, divided treatment recommendations into 2 age groups: ≤5 years and >5 years. The EPR-3’s expansion makes it easier for physicians to initiate, individualize, and adjust treatment.

FIGURE 1
Classifying asthma severity and initiating therapy in children, adolescents, and adults


EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroids; NA, not applicable; OCS, oral corticosteroids; SABA, short-acting β2-adrenergic agonist.
*Normal FEV1/FVC values are defined according to age: 8–9 years (85%), 20–39 years (80%), 40–59 years (75%), 60–80 years (70%).
For treatment purposes, children with at least 2 exacerbations (eg, requiring urgent, unscheduled care; hospitalization; or intensive care unit admission) or adolescents/adults with at least 2 exacerbations requiring OCS in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

FIGURE 2
Assessing asthma control and adjusting therapy


ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; ATAQ, Asthma Therapy Assessment Questionnaire; EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; N/A, not applicable; OCS, oral corticosteroids; SABA, short-acting β2-adrenergic agonist.
*ACQ values of 0.76 to 1.4 are indeterminate regarding well-controlled asthma.
For treatment purposes, children with at least 2 exacerbations (eg, requiring urgent, unscheduled care; hospitalization; or intensive care unit admission) or adolescents/adults with at least 2 exacerbations requiring OCS in the past year may be considered the same as patients who have asthma that is not well controlled, even in the absence of impairment levels consistent with that classification.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

FIGURE 3
Stepwise approach for managing asthma


EIB, exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, long-acting β2-adrenergic agonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; PRN, as needed; SABA, short-acting β2-adrenergic agonist.
Adapted from: National Heart, Lung, and Blood Institute (NHLBI).2

 

 

Putting guidelines into practice begins with the history

A detailed medical history and a physical examination focusing on the upper respiratory tract, chest, and skin are needed to arrive at an asthma diagnosis. JJ’s physician asked his mother to describe recent symptoms and inquired about comorbid conditions that can aggravate asthma. He also identified viral respiratory infections, environmental causes, and activity as precipitating factors.

In considering an asthma diagnosis, try to determine the presence of episodic symptoms of airflow obstruction or bronchial hyperresponsiveness, as well as airflow obstruction that is at least partly reversible (an increase in forced expiratory volume in 1 second [FEV1] of >200 mL and ≥12% from baseline or an increase of ≥10% of predicted FEV1), and to exclude alternative diagnoses.

EPR-3 emphasizes spirometry

Recognizing that patients’ perception of airflow obstruction is highly variable and that pulmonary function measures do not always correlate directly with symptoms,3,4 the EPR-3 recommends spirometry for patients ≥5 years of age, both before and after bronchodilation. In addition to helping to confirm an asthma diagnosis, spirometry is the preferred measure of pulmonary function in classifying severity, because peak expiratory flow (PEF) testing has not proven reliable.5,6

 

Objective measurement of pulmonary function is difficult to obtain in children <5 years of age. If diagnosis remains uncertain for patients in this age group, a therapeutic trial of medication is recommended. In JJ’s case, however, 3 courses of oral corticosteroids (OCS) in less than 6 months were indicative of persistent asthma.

Spirometry is often underutilized. For patients ≥5 years of age, spirometry is a vital tool, but often underutilized in family practice. A recent study by Yawn and colleagues found that family physicians made changes in the management of approximately half of the asthma patients who underwent spirometry.7 (Information about spirometry training is available through the National Institute for Occupational Safety and Health at http://www.cdc.gov/niosh.) Referral to a specialist is recommended if the physician has difficulty making a differential diagnosis or is unable to perform spirometry on a patient who presents with atypical signs and symptoms of asthma.

What is the patient’s level of severity?

In patients who are not yet receiving long-term controller therapy, severity level is based on an assessment of impairment and risk (FIGURE 1). For patients who are already receiving treatment, severity is determined by the minimum pharmacologic therapy needed to maintain asthma control.

The severity classification—intermittent asthma or persistent asthma that is mild, moderate, or severe—is determined by the most severe category in which any feature occurs. (In children, FEV1/FVC [forced vital capacity] ratio has been shown to be a more sensitive determinant of severity than FEV1,4 which may be more useful in predicting exacerbations.8)

Asthma management: Preferred and alternative Tx

The recommended stepwise interventions include both preferred therapies (evidence-based) and alternative treatments (listed alphabetically in FIGURE 3 because there is insufficient evidence to rank them). The additional steps and age categories support the goal of using the least possible medication needed to maintain good control and minimize the potential for adverse events.

In initiating treatment, select the step that corresponds to the level of severity in the bottom row of FIGURE 1; to adjust medications, determine the patient’s level of asthma control and follow the corresponding guidance in the bottom row of FIGURE 2.

Inhaled corticosteroids remain the bedrock of therapy

ICS, the most potent and consistently effective long-term controller therapy, remain the foundation of therapy for patients of all ages who have persistent asthma. (Evidence: A).

Several of the age-based recommendations follow, with a focus on preferred treatments:

Children 0 to 4 years of age

 

  • The guidelines recommend low-dose ICS at Step 2 (Evidence: A) and medium-dose ICS at Step 3 (Evidence: D), as inhaled corticosteroids have been shown to reduce impairment and risk in this age group.9-16 The potential risk is generally limited to a small reduction in growth velocity during the first year of treatment, and offset by the benefits of therapy.15,16
  • Add a long-acting β2-adrenergic agonist (LABA) or montelukast to medium-dose ICS therapy at Step 4 rather than increasing the ICS dose (Evidence: D) to avoid the risk of side effects associated with high-dose ICS. Montelukast has demonstrated efficacy in children 2 to 5 years of age with persistent asthma.17
  • Recommendations for preferred therapy at Steps 5 (high-dose ICS + LABA or montelukast) and 6 (Step 5 therapy + OCS) are based on expert panel judgment (Evidence: D). When severe persistent asthma warrants Step 6 therapy, start with a 2-week course of the lowest possible dose of OCS to confirm reversibility.
  • In this age group, a therapeutic trial with close monitoring is recommended for patients whose asthma is not well controlled. If there is no response in 4 to 6 weeks, consider alternative therapies or diagnoses (Evidence: D).
 

 

 

Children 5 to 11 years of age

 

  • For Step 3 therapy, the guidelines recommend either low-dose ICS plus a LABA, leukotriene receptor antagonist (LTRA), or theophylline; or medium-dose ICS (Evidence: B). Treatment decisions at Step 3 depend on whether impairment or risk is the chief concern, as well as on safety considerations.
  • For Steps 4 and 5, ICS (medium dose for Step 5 and high dose for Step 6) plus a LABA is preferred, based on studies of patients ≥12 years of age (Evidence: B). Step 6 builds on Step 5, adding an OCS to the LABA/ICS combination (Evidence: D).
  • If theophylline is prescribed—a viable option if cost and adherence to inhaled medications are key concerns—serum levels must be closely monitored because of the risk of toxicity.
  • Closely monitor and be prepared to identify and respond to anaphylaxis in a child at Step 2, 3, or 4 who is receiving allergen immunotherapy.

Adolescents ≥12 years of age and adults

 

  • There are 2 preferred Step 3 treatments: Low-dose ICS plus a LABA, or medium-dose ICS. The combination therapy has shown greater improvement in impairment24,25 and risk24-26 compared with the higher dose of ICS.
  • Preferred treatments at Steps 4, 5, and 6 are the same as those for children ages 5 to 11 years, with one exception: Subcutaneous anti-IgE therapy (omalizumab) may be added to the regimen at Steps 5 and 6 for adolescents and adults with severe persistent allergic asthma to reduce the risk of exacerbations.27

 

Weigh the benefits and risks of therapy

Safety is a key consideration for all asthma patients. Carefully weigh the benefits and risks of therapy, including the rare but potential risk of life-threatening or fatal exacerbations with daily LABA therapy28 and systemic effects with higher doses of ICS.23 Patients who begin receiving oral corticosteroids require close monitoring, regardless of age.

Regular reassessment and monitoring are critical

 

Schedule visits at 2- to 6-week intervals for those who are starting therapy or require a step up to achieve or regain asthma control. After control is achieved, reassess at least every 1 to 6 months. Measures of asthma control are the same as those used to assess severity, with the addition of validated multidimensional questionnaires (eg, Asthma Control Test [ACT])29 to gauge impairment.

JJ’s physician scheduled a follow-up visit in 4 weeks, at which time he did a reassessment based on a physical exam and symptom recall. Finding JJ’s asthma to be well controlled, the physician asked the boy’s mother to bring him back to the office in 2 months, or earlier if symptoms recurred.

TABLE W1
Asthma education resources

 

Allergy & Asthma Network Mothers of Asthmatics
2751 Prosperity Avenue, Suite 150
Fairfax, VA 22030
www.breatherville.org
(800) 878-4403 or (703) 641-9595
Asthma and Allergy Foundation of America
1233 20th Street, NW, Suite 402
Washington, DC 20036
www.aafa.org
(800) 727-8462
American Academy of Allergy,
Asthma, and Immunology
555 East Wells Street, Suite 1100
Milwaukee, WI 53202-3823
www.aaaai.org
(414) 272-6071
Centers for Disease Control and Prevention
1600 Clifton Road
Atlanta, GA 30333
www.cdc.gov
(800) 311-3435
American Association for Respiratory Care
9125 North macArthur boulevard, Suite 100
Irving, TX 75063
www.aarc.org
(972) 243-2272
Food Allergy & Anaphylaxis Network
11781 lee Jackson Highway, Suite 160
Fairfax, VA 22033
www.foodallergy.org
(800) 929-4040
American College of Allergy, Asthma, and Immunology
85 West Algonquin road, Suite 550
Arlington Heights, IL 60005
www.acaai.org
(800) 842-7777 or (847) 427-1200
National Heart, Lung, and Blood Institute Information Center
P.O. Box 30105
Bethesda, MD 20824-0105
www.nhlbi.nih.gov
(301) 592-8573
American Lung Association
61 Broadway
New York, NY 10006
www.lungusa.org
(800) 586-4872
National Jewish Medical and Research Center (Lung Line)
1400 Jackson Street
Denver, CO 80206
www.njc.org
(800) 222-lUNG
Association of Asthma Educators
1215 Anthony Avenue
Columbia, SC 29201
www.asthmaeducators.org
(888) 988-7747
US Environmental Protection Agency
National Center for Environmental Publications
P.O. Box 42419
Cincinnati, OH 45242-0419
www.airnow.gov
(800) 490-9198

Does your patient require a step down or step up?

A step down is recommended for patients whose asthma is well controlled for 3 months or more. Reduce the dose of ICS gradually, about 25% to 50% every 3 months, because deterioration in asthma control is highly variable. Review adherence and medication administration technique with patients whose asthma is not well controlled, and consider a step up in treatment. If an alternative treatment is used but does not result in an adequate response, it should be discontinued and the preferred treatment used before stepping up. Refer patients to an asthma specialist if their asthma does not respond to these adjustments.

 

 

Partner with patients for optimal care

The EPR-3 recommends the integration of patient education into all aspects of asthma care. To forge an active partnership, identify and address concerns about the condition and its treatment and involve the patient and family in developing treatment goals and making treatment decisions. If the patient is old enough, encourage self-monitoring and management.

The EPR-3 recommends that physicians give every patient a written asthma action plan that addresses individual symptoms and/or PEF measurements and includes instructions for self-management. Daily PEF monitoring can be useful in identifying early changes in the disease state and evaluating response to changes in therapy. It is ideal for those who have moderate to severe persistent asthma, difficulty recognizing signs of exacerbations, or a history of severe exacerbations.

Correspondence
Stuart W. Stoloff, MD, Clinical Professor, Department of Family and Community Medicine, University of Nevada–Reno, 1200 Mountain Street, Suite 220, Carson City, NV 89703; drstoloff@sbcglobal.net.

References

 

1. National Center for Health Statistics. Fast stats A to Z. Available at: www.cdc.gov/nchs/fastats/asthma.htm. Accessed August 1, 2008.

2. National Heart, Lung, and Blood Institute (NHLBI). National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. Bethesda, MD: NHLBI; August 2007. NIH publication no. 07-4051. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed July 17, 2008.

3. Stout JW, Visness CM, Enright P, et al. Classification of asthma severity in children: the contribution of pulmonary function testing. Arch Pediatr Adolesc Med. 2006;160:844-850.

4. Bacharier LB, Strunk RC, Mauger D, et al. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med. 2004;170:426-432.

5. Eid N, Yandell B, Howell L, Eddy M, Sheikh S. Can children with asthma? Pediatrics. 2000;105:354-358.

6. Llewellin P, Sawyer G, Lewis S, et al. The relationship between FEV1 and PEF in the assessment of the severity of airways obstruction. Respirology. 2002;7:333-337.

7. Yawn BP, Enright PL, Lemanske RF, Jr, et al. Spirometry can be done in family physicians’ offices and alters clinical decisions in management of asthma and COPD. Chest. 2007;132:1162-1168.

8. Fuhlbrigge AL, Kitch BT, Paltiel AD, et al. FEV1 is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol. 2001;107:61-67.

9. Roorda RJ, Mezei G, Bisgaard H, Maden C. Response of preschool children with asthma symptoms to fluticasone propionate. J Allergy Clin Immunol. 2001;108:540-546.

10. Baker JW, Mellon M, Wald J, Welch M, Cruz-Rivera M, Walton-Bowen K. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics. 1999;103:414-421.

11. Kemp JP, Skoner DP, Szefler SJ, Walton-Bowen K, Cruz-Rivera M, Smith JA. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol. 1999;83:231-239.

12. Shapiro G, Mendelson L, Kraemer MJ, Cruz-Rivera M, Walton-Bowen K, Smith JA. Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma. J Allergy Clin Immunol. 1998;102:789-796.

13. Bisgaard H, Gillies J, Groenewald M, Maden C. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med. 1999;160:126-131.

14. Szefler SJ, Eigen H. Budesonide inhalation suspension: a nebulized corticosteroid for persistent asthma. J Allergy Clin Immunol. 2002;109:730-742.

15. Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354:1985-1997.

16. Bisgaard H, Allen D, Milanowski J, Kalev I, Willits L, Davies P. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1 to 3 years with recurrent wheezing. Pediatrics. 2004;113:e87-e94.

17. Knorr B, Franchi LM, Bisgaard H, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 2001;108:e48.-

18. Russell G, Williams DA, Weller P, Price JF. Salmeterol xinafoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol. 1995;75:423-428.

19. Zimmerman B, D’Urzo A, Bérubé D. Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma. Pediatr Pulmonol. 2004;37:122-127.

20. Simons FE, Villa JR, Lee BW, et al. Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study. J Pediatr. 2001;138:694-698.

21. Shapiro G, Bronsky EA, LaForce CF, et al. Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. J Pediatr. 1998;132:976-982.

22. Pauwels RA, Lofdahl C-G, Postma DS, et al. for the Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med. 1997;337:1405-1411.

23. Tattersfield AE, Harrison TW, Hubbard RB, Mortimer K. Safety of inhaled corticosteroids. Proc Am Thorac Soc. 2004;1:171-175.

24. Bateman ED, Boushey HA, Bousquet J, et al. For the GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170:836-844.

25. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med. 2001;164:1392-1397.

26. Masoli M, Weatherall M, Holt S, Beasley R. Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma. Thorax. 2005;60:730-734.

27. Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Fox H. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest. 2004;125:1378-1386.

28. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. For the SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26.

29. Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113:59-65.

References

 

1. National Center for Health Statistics. Fast stats A to Z. Available at: www.cdc.gov/nchs/fastats/asthma.htm. Accessed August 1, 2008.

2. National Heart, Lung, and Blood Institute (NHLBI). National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. Bethesda, MD: NHLBI; August 2007. NIH publication no. 07-4051. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed July 17, 2008.

3. Stout JW, Visness CM, Enright P, et al. Classification of asthma severity in children: the contribution of pulmonary function testing. Arch Pediatr Adolesc Med. 2006;160:844-850.

4. Bacharier LB, Strunk RC, Mauger D, et al. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med. 2004;170:426-432.

5. Eid N, Yandell B, Howell L, Eddy M, Sheikh S. Can children with asthma? Pediatrics. 2000;105:354-358.

6. Llewellin P, Sawyer G, Lewis S, et al. The relationship between FEV1 and PEF in the assessment of the severity of airways obstruction. Respirology. 2002;7:333-337.

7. Yawn BP, Enright PL, Lemanske RF, Jr, et al. Spirometry can be done in family physicians’ offices and alters clinical decisions in management of asthma and COPD. Chest. 2007;132:1162-1168.

8. Fuhlbrigge AL, Kitch BT, Paltiel AD, et al. FEV1 is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol. 2001;107:61-67.

9. Roorda RJ, Mezei G, Bisgaard H, Maden C. Response of preschool children with asthma symptoms to fluticasone propionate. J Allergy Clin Immunol. 2001;108:540-546.

10. Baker JW, Mellon M, Wald J, Welch M, Cruz-Rivera M, Walton-Bowen K. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics. 1999;103:414-421.

11. Kemp JP, Skoner DP, Szefler SJ, Walton-Bowen K, Cruz-Rivera M, Smith JA. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Ann Allergy Asthma Immunol. 1999;83:231-239.

12. Shapiro G, Mendelson L, Kraemer MJ, Cruz-Rivera M, Walton-Bowen K, Smith JA. Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma. J Allergy Clin Immunol. 1998;102:789-796.

13. Bisgaard H, Gillies J, Groenewald M, Maden C. The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med. 1999;160:126-131.

14. Szefler SJ, Eigen H. Budesonide inhalation suspension: a nebulized corticosteroid for persistent asthma. J Allergy Clin Immunol. 2002;109:730-742.

15. Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354:1985-1997.

16. Bisgaard H, Allen D, Milanowski J, Kalev I, Willits L, Davies P. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1 to 3 years with recurrent wheezing. Pediatrics. 2004;113:e87-e94.

17. Knorr B, Franchi LM, Bisgaard H, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 2001;108:e48.-

18. Russell G, Williams DA, Weller P, Price JF. Salmeterol xinafoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol. 1995;75:423-428.

19. Zimmerman B, D’Urzo A, Bérubé D. Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma. Pediatr Pulmonol. 2004;37:122-127.

20. Simons FE, Villa JR, Lee BW, et al. Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study. J Pediatr. 2001;138:694-698.

21. Shapiro G, Bronsky EA, LaForce CF, et al. Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. J Pediatr. 1998;132:976-982.

22. Pauwels RA, Lofdahl C-G, Postma DS, et al. for the Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med. 1997;337:1405-1411.

23. Tattersfield AE, Harrison TW, Hubbard RB, Mortimer K. Safety of inhaled corticosteroids. Proc Am Thorac Soc. 2004;1:171-175.

24. Bateman ED, Boushey HA, Bousquet J, et al. For the GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170:836-844.

25. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med. 2001;164:1392-1397.

26. Masoli M, Weatherall M, Holt S, Beasley R. Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma. Thorax. 2005;60:730-734.

27. Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Fox H. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest. 2004;125:1378-1386.

28. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. For the SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26.

29. Nathan RA, Sorkness CA, Kosinski M, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113:59-65.

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Changes in recommended treatments for mild and moderate asthma

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Changes in recommended treatments for mild and moderate asthma

 

Practice recommendations

 

  • Every patient with persistent asthma, regardless of disease severity, should use a daily controller medication.
  • Consider an inhaled corticosteroid (ICS) first when choosing controller medications for long-term treatment of mild, moderate, and severe persistent asthma in adults and children. Leukotriene modifiers, cromolyn, and nedocromil may be considered as alternative, not preferred, controller medications for patients with persistent asthma.
  • Long-acting β2-adrenergic agonists should not be used as monotherapy.
  • Long-term use of ICSs within labeled doses is safe for children in terms of growth, bone mineral density, and adrenal function; nonetheless, asthma should be monitored and ICS therapy stepped down to the lowest effective dose.
  • Low-to medium-dose ICSs are not associated with the development of cataracts or glaucoma in children, but high cumulative lifetime doses may slightly increase the prevalence of cataracts in adults and elderly patients.
  • ICSs are recommended for use in pregnant women with asthma; budesonide is the only ICS rated Pregnancy Category B.

Consider an adult with the following characteristics. To which disease severity would you assign this patient’s asthma?

 

  • Forced expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF) ≥80%
  • PEF variability 20%–30%
  • Daytime symptoms less than once a day
  • Nighttime symptoms more than 1 night a week.

This patient is said to have moderate persistent asthma based on nighttime symptoms. An accurate classification of a patient’s asthma is the foundation for selecting an appropriate treatment strategy.

In 2002 the National Asthma Education and Prevention Program (NAEPP) updated select topics1from its 1997 Guidelines for the Diagnosis and Management of Asthma.2 These evidence-based revisions to the stepwise approach to asthma management were made following a systematic review of the literature (see Search function).

 

Search function

A comprehensive search of Medline and EMBASE databases was performed to identify controlled clinical studies relevant to each topic that were published (in English or foreign languages with English abstracts) from 1980 through August 2000. The search included studies published before 1980 if referenced in the post-1980 literature. Studies that did not include control groups were excluded, except for those reporting adverse effects of ICSs. Studies that met the study selection criteria established for each topic were included in a systematic review of the evidence. An expert panel reviewed the evidence, along with additional literature published since August 2000, and reached a consensus on whether the evidence supported 1997 guideline recommendations or indicated a need for revision. Writing committees were then assigned to developed position statements for each topic. The level of evidence for included studies was rated based on the system of Jadad and colleagues,3 where A = randomized controlled trials, rich body of data; B = randomized controlled trials, limited data; C = nonrandomized trials and observational studies; D = panel consensus judgment.

This article reviews the 2002 NAEPP recommendations for the use of controller medications for asthma, including:

 

  • Relative effectiveness of inhaled corticosteroids (ICSs) versus other controller medications
  • Safety of long-term ICS use in children
  • Potential benefits of early ICS treatment.

We emphasize mild and moderate persistent asthma because the recommended treatments for these levels of severity have been most affected by the recent guideline changes. We also discuss a recent change by the US Food and Drug Administration (FDA) in its pregnancy category rating for an ICS.

2002 Stepwise approach to asthma management

New criteria for classifying asthma severity

The NAEPP classifies asthma severity according to symptoms and lung function in adults and children older than 5 years, and symptoms in children 5 years and younger.1 Persistent asthma is classified as mild, moderate, or severe according to the feature of greatest severity.

Asthma severity should be assigned according to symptoms before treatment.1 Because it is difficult to predict which infants and young children who wheeze with acute viral upper respiratory infection will go on to develop persistent asthma, new criteria have been detailed to help distinguish these children from those with transient wheeze (Table 1).1,4

TABLE 1
Criteria for children with intermittent wheeze

 

Infants and young children meeting these criteria should receive controller therapy for asthma:
  • Significant exacerbations that occur <6 weeks apart
  • ≥4 episodes of wheeze in the past year lasting >1 day and affecting sleep,
AND presence of risk factors for development of persistent asthma:
  • Atopic dermatitis or parental asthma,
  • OR 2 of the following:
  • – Diagnosis of allergic rhinitis
  • – >4% peripheral blood eosinophilia
  • – Wheezing apart from colds

Choosing pharmacologic treatment according to asthma classification

Quick-relief medications, which include the short-acting β2-agonists (SABAs), are taken as needed to promptly reverse acute airflow obstruction and relieve accompanying symptoms.2

Asthma controller medications (ie, ICSs, cromolyn sodium, long-acting β2-adrenergic-agonists [LABAs], leukotriene modifiers, nedocromil, and theophylline) are used daily to achieve and maintain long-term control of persistent asthma. All patients with persistent asthma, regardless of disease severity, should use a daily controller. Criteria for determining asthma severity and updated recommendations for the use of controller treatment in mild and moderate persistent asthma are presented in the Figure.3,5 Levels of evidence justifying NAEPP treatment recommendations are shown in Table 2.

 

 

For use in children. Asthma controller medications approved for use in children younger than 5 years include the fluticasone dry-powder inhalers (Flovent, Rotadisk, and Flovent Diskus), which are approved for children as young as 4 years (Flovent Diskus is not yet commercially available), and nebulized budesonide inhalation suspension (Pulmicort Respules), which is approved for children as young as 12 months.

The LABAs formoterol (Foradil) and salmeterol (Serevent Diskus) are approved for children as young as 5 and 4 years, respectively. Cromolyn sodium nebulizer solution is approved for children as young as 2 years, and theophylline is available for use at any age.

Based on safety and extrapolation of efficacy data in older patients, the oral granule formulation of the leukotriene receptor antagonist (LTRA) montelukast (Singulair) is approved for children as young as 1 year, and the chewable tablets are approved for children 2 to 5 years of age. Zafirlukast (Accolate) is approved for use in children 5 years and older.

New recommendations for mild persistent asthma. Recommendations for the treatment of mild and moderate persistent asthma have changed considerably from the 1997 guidelines. ICSs are now the preferred controller medications, based on greater efficacy. The updated guidelines no longer recommend an initial trial of cromolyn or nedocromil for the treatment of mild persistent asthma; these agents, along with the leukotriene modifiers and slow-release theophylline, are now considered alternatives to low-dose ICSs for adults and children older than 5 years with mild persistent disease (Figure).

According to the NAEPP update, daily low-dose ICS treatment also is preferred for the control of mild persistent asthma in preschool children. As in older children, cromolyn and nedocromil are no longer considered appropriate initial treatments for infants and children 5 years and younger. Cromolyn is considered an alternative controller, whereas nedocromil is no longer recommended for use.

New recommendations for moderate persistent asthma. For adults and children older than 5 years with moderate persistent asthma, revision to the guidelines involved recommendation of a low- to medium-dose ICS plus a LABA as the preferred controller treatment (Figure). Comparative low, medium, and high daily doses for ICSs are shown in Table 3 .1

For preschool children, preferred controller treatments for moderate persistent asthma include low-dose ICSs plus a LABA, or increasing ICSs within the medium-dose range (Figure). Recommendations for the use of LABAs as add-on therapy in this age group are based on extrapolation of data from older patients, since therapy with an ICS/LABA combination has not been adequately studied in children younger than 5 years. Four studies included in the NAEPP evaluation showed clear benefit of medium-dose ICSs in this age group, supporting the use of medium-dose ICSs as a preferred option.6-9 LABAs are not recommended for use without an ICS, and the only ICS/LABA combination product currently available has been FDA approved only for patients aged 12 years and older.

TABLE 2
Levels of evidence for NAEPP assessments*

 

MedicationNAEPP assessmentSOR*
ICSPreferred treatment for children of all ages with persistent asthmaA (A)
SABAICSs improve asthma control compared with as-needed SABAsA (A)
Cromolyn/nedocromilFor use as alternative, not preferred, treatment of mild persistent asthma in children of all ages (cromolyn) or children >5 years of age (nedocromil)A (A)
LABAFor use with ICSs as the preferred combination treatment for moderate and severe persistent asthma in children >5 years of ageA (A)
For use as a preferred option for combination treatment in children 5 years of ageB (B)
Leukotriene modifierFor use as alternative, not preferred, treatment of mild persistent asthma and as ICS adjunct in moderate persistent asthmaB (B)
TheophyllineFor use as an alternative ICS add-on in moderate or severe persistent asthma if serum concentrations are monitoredD (D)
Not considered an alternative controller for young children with mild persistent asthma due to potential adverse effects in infants with frequent febrile illnesses
*Highest level of evidence available is reported. Strengths of recommendation are based on the method of Jadad et al.3 Strength of evidence based on the Oxford Center for Evidence-Based Medicine5 is in parentheses. SOR, strength of recommendation; NAEPP, National Asthma Education and Prevention Program; ICS, inhaled corticosteroid; SABA, short-acting β2-adrenergic agonist; LABA, long-acting β2-adrenergic agonist.

TABLE 3
Estimated comparative daily doses for inhaled corticosteroids*

 

DrugLow daily doseMedium daily doseHigh daily dose
AdultChildAdultChildAdultChild
Beclomethasone CFC 42 or 84 μg/puff168–504 μg84–336 μg504–840 μg336–672 μg>840 μg>672 μg
Beclomethasone HFA 40 or 80 μg/puff80–240 μg80–160 μg240–480 μg160–320 μg>480 μg>320 μg
Budesonide DPI 200 μg/inhalation200–600 μg200–400 μg600–1200 μg400–800 μg>1200 μg>800 μg
Budesonide inhalation suspension for nebulization (child dose)0.5mg1.0 mg2.0 mg
Fluticasone MDI 44, 110, or 220 μg/puff88–264 μg88–176 μg264–660 μg176–440 μg>660 μg>440 μg
Fluticasone DPI 50, 100, or 250 μg/inhalation100–300 μg100–200 μg300–600 μg200–400 μg>600 μg>400 μg
Triamcinolone acetonide 100 μg/puff400–1000 μg400–800 μg1000–2000 μg800–1200 μg>2000 μg>1200 μg
*The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to therapy. This updated comparative dose chart is based on review of recently published clinical trials involving more than 5000 patients and published reviews. Some doses may be outside package labeling, especially in the high-dose range.
Children 12 years of age.
CFC, chlorofluorocarbon; HFA, hydrofluoroalkane; DPI, dry-powder inhaler; MDI, metered-dose inhaler.

FIGURE
Updated National Asthma Education and Prevention Program recommendations for long-term controller treatment in mild and moderate persistent asthma

 

 

Topics in the management of asthma in children

Recognizing the need for continual appraisal of the benefits and risks of asthma medications in children, the NAEPP Expert Panel considered new studies comparing the effectiveness of ICS monotherapy with that of as-needed SABAs and other controllers used as monotherapy in children with mild or moderate persistent asthma. In addition, the safety of long-term ICS use in children was evaluated based on vertical growth, bone mineral density, ocular toxicity, and adrenal suppression.

Effectiveness of ICSs compared with other asthma medications

Short-acting β2-adrenergic agonists. Eight studies met the eligibility criteria for evaluating the effectiveness of ICSs versus as-needed SABAs.6,10-16 Six studies (4 involving budesonide) in children 5 years and older showed that ICSs improve lung function and symptoms and reduce the need for emergency intervention compared with as-needed SABAs.1 Among all studies included in the NAEPP update, the Childhood Asthma Management Program (CAMP) Research Group Study,9 a placebo-controlled study of inhaled budesonide and nedocromil, contributed the most evidence. Studies with children 5 years and younger are limited to 2 small studies enrolling a total of 69 children.6,15 Consistent with studies of older children, these studies indicate that ICSs improve asthma control compared with as-needed SABAs.1

Cromolyn and nedocromil. Despite well-established safety profiles, cromolyn and nedocromil are no longer recommended as first-line therapy for children, even those with mild disease. New recommendations reflect the greater effectiveness of inhaled budesonide compared with nedocromil demonstrated in the CAMP study,10 and the lack of apparent benefit of cromolyn as maintenance treatment in childhood asthma reported by Tasche and colleagues in a systematic review of the literature.17

In the CAMP study, children 5 to 12 years of age receiving inhaled budesonide showed greater reductions in symptoms and albuterol use, lower rates of hospitalization and urgent care visits, and less need for additional asthma therapy and oral prednisone compared with placebo over 4 to 6 years of treatment.10 The marginal effectiveness of nedocromil demonstrated in the CAMP study mirrored that of cromolyn reported in the review of 24 randomized placebo-controlled studies by Tasche and colleagues.1,17

For children 5 years and younger, the NAEPP Expert Panel took into account 1 randomized placebo-controlled study conducted with children 2 to 5 years of age; it showed improvements in lung function, symptoms, and bronchial hyperre-activity with inhaled budesonide.9 Support for the new NAEPP recommendations preferring ICSs for preschool children is found in a more recent open-label study18 that showed greater symptom improvement and significantly lower rates of asthma exacerbations, urgent care visits, and oral prednisone use with budesonide inhalation suspension, compared with cromolyn sodium nebulizer solution (Intal Nebulizer Solution) in children 2 to 6 years of age with persistent asthma.

Leukotriene modifiers. The LTRAs zafir-lukast and montelukast are approved for use in children. According to the NAEPP Expert Panel, studies have shown only modest improvements in lung function and other asthma control outcomes with LTRA monotherapy in children as young as 6 and 2 years, respectively.1 Because studies comparing ICSs with LTRAs in children are lacking, findings of greater overall efficacy of ICSs in adults with persistent asthma have been extrapolated for use with children; clear superiority of ICSs versus LTRAs in most outcomes has resulted in the recommendation for ICSs as the preferred treatment for mild persistent asthma in children.

Long-acting β2-adrenergic agonists. There is no role for LABAs as monotherapy in asthma. No studies have compared the effectiveness of ICS versus LABA monotherapy in children younger than 5 years, and studies in older children have shown greater effectiveness of inhaled beclomethasone versus salmeterol.14,19 In the study by Verberne and colleagues, salmeterol monotherapy was associated with deterioration in FEV1.19 In a more recent study that included patients as young as 16 years, a switch from ICS to LABA treatment was associated with a significant increase in treatment failures and exacerbations.20

Theophylline. Only 1 study has compared outcomes with low-dose ICSs versus theophylline in adults and children.21 Although limited, the data support greater effectiveness of ICSs based on symptoms, bronchial hyperresponsiveness, and the need for β2-adrenergic agonists and oral corticosteroids.1

Safety of long-term ICS use in children

Systemic corticosteroids have the potential to suppress growth over the long term.2 Short-term growth studies with ICSs show an average reduction in growth velocity of 1 cm per year during the first year of treatment, but the CAMP study showed that initial reductions in growth velocity with inhaled budesonide were not maintained over a 4- to 6-year treatment period.1,10

Although catch-up growth was not observed in the CAMP study, Agertoft and Pedersen reported no effect of long-term treatment with inhaled budesonide (mean 9.2 years) on final adult height.22 Based on these long-term prospective studies of budesonide, showing only a transient reduction in growth velocity and attainment of expected final adult height, and retrospective studies including inhaled beclomethasone, the Expert Panel concluded that the ICS class is safe regarding growth effects.

 

 

According to the NAEPP Expert Panel, clinical study data for children monitored for up to 6 years strongly suggest that ICSs are safe when used at recommended doses (strength of recommendation: A).1 The panel could not rule out a potential cumulative effect of ICS use on some conditions, (eg, osteoporosis, cataracts, glaucoma) in adulthood, as sufficient long-term data are not available.

The panel did conclude that low- to medium-dose ICSs (Table 3) appear to have no serious adverse effects on bone mineral density in children.

Likewise, low- to medium-dose ICS use was not associated with the development of cataracts or glaucoma in children, although the potential for high cumulative lifetime doses of ICSs to slightly increase the prevalence of cataracts in adults and elderly patients was noted.

Strong evidence also indicates that ICS effects on adrenal function are usually clinically insignificant at low to medium doses; however, certain individuals may be at higher risk for hypothalam-ic pituitary adrenal axis effects while using conventional ICS doses.1

Although ICSs are safe when used within labeled dosing, it is still preferable to maintain doses at the lowest effective dose. In general, treatment should be reviewed every 1 to 6 months and doses reduced in a stepwise fashion when possible.1 For children showing a favorable response to treatment, a step down in dose should be considered, but not more frequently than every 3 months. If children show no clear response to treatment within 4 to 6 weeks, consider an alternative treatment or diagnosis.1

Safety of long-term ICS use in pregnant women

Uncontrolled asthma during pregnancy is associated with an increased risk of perinatal complications. 23 Since the consequences of not using asthma controllers during pregnancy can be worse than those with using them, daily controller treatment is recommended for all pregnant women with persistent asthma. 23

The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology previously recommended cromolyn as the treatment of choice for pregnant women with mild persistent asthma. ICSs were recommended for patients whose asthma was inadequately controlled with cromolyn. 24 Beclomethasone and budesonide were the ICSs of choice for pregnant women and those who might become pregnant, with a preference for budesonide when high-dose therapy was indicated.24

These recommendations predate the 2002 NAEPP recommendations for ICSs as preferred therapy in mild persistent asthma and the 2004 NAEPP recommendations for ICSs as the first-choice controller therapy for mild persistent asthma during pregnancy. 25 Among ICSs, one (inhaled budesonide) has an FDA Pregnancy Category B rating based on studies showing no risk in pregnant women. 26,27 All other ICSs are rated Pregnancy Category C.

Based on current evidence, it seems reasonable to consider whether budesonide should now be the preferred therapy for mild persistent asthma during pregnancy.

Effects of early treatment on asthma progression

The potential for early ICS intervention to prevent progression of mild or moderate persistent asthma was evaluated solely with data from children enrolled in the CAMP study. 10 The NAEPP Expert Panel concluded that CAMP study data do not support a progressive decline in lung function in children aged 5 to 12 years with mild or moderate persistent asthma, but do suggest that lung function decline is influenced by age of asthma onset.

According to the panel, CAMP data suggest that most deficits in lung function growth due to childhood asthma occur during the first 3 years of life. Preliminary results of the recent START study (Inhaled Steroid Treatment As Regular Therapy in Early Asthma), 28 conducted with 7165 corticosteroidnaïve patients 5 to 66 years of age with recent onset mild persistent asthma, did show a decline in lung function in patients with mild persistent disease.

Although improvements in prebronchodilator and postbronchodilator FEV1 were significant after 3 years of treatment with inhaled budes-onide, differences from placebo in both outcomes were greatest after the first year. When patients with mild persistent disease inhaled budesonide once daily in addition to normal treatment within 2 years of asthma onset,28 they enjoyed considerable protection from severe and life-threatening asthma exacerbations and overall greater asthma control.

 

Drug brand names

 

  • Budesonide • Pulmicort
  • Rhinocort Cromolyn • Intal
  • Fluticasone • Flovent
  • Formoterol • Foradil
  • Montelukast • Singulair
  • Nedocromil • Tilade
  • Salmeterol • Servent
  • Triamcinolone acetonide • Azmacort
  • Zafirlukast • Accolate

Corresponding author
Gregory J. Redding, MD, Children’s Hospital and Regional Medical Center, 4800 Sand Point Way, NE, Seattle, WA 98105-0371. E-mail: gredding@u.washington.edu.

References

 

1. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma. Update on selected topics–2002. J Allergy Clin Immunol 2002;110(5 suppl):S141-S219.

2. National Asthma Education and Prevention Program Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health; 1997. Publication 97;4051.-

3. Jadad AR, Moher M, Browman GP, Booker L, Sigouin C, Fuentes M, et al. Systematic reviews and meta-analyses on treatment of asthma: critical evaluation. BMJ 2000;320:537-540.

4. Castro-Rodríguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000;162:1403-1406.

5. Oxford Centre for Evidence-based Medicine Levels of Evidence Available atwww.cebm.net/levels_faq.asp . Accessed January 8, 2004.

6. Connett GJ, Warde C, Wooler E, Lenney W. Use of budes-onide in severe asthmatics aged 1–3 years. Arch Dis Child 1993;69:351-355.

7. de Blic J, Delacourt C, Le Bourgeois M, Mahut B, Ostinelli J, Caswell C, et al. Efficacy of nebulized budesonide in treatment of severe infantile asthma: a double-blind study. J Allergy Clin Immunol 1996;98:14-20.

8. Bisgaard H, Gillies J, Groenewald M, Maden C, . for an International Study Group The effect of inhaled fluticas-one propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med 1999;160:126-131.

9. Nielsen KG, Bisgaard H. The effect of inhaled budesonide on symptoms, lung function, and cold air and metha-choline responsiveness in 2- to 5-year–old asthmatic children. Am J Respir Crit Care Med 2000;162:1500-1506.

10. Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000;343:1054-1063.

11. Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994;88:373-381.

12. Hoekstra MO, Grol MH, Bouman K, Stijnen T, Koëter GH, Kauffman HF, et al. Fluticasone propionate in children with moderate asthma. Am J Respir Crit Care Med 1996;154:1039-1044.

13. Jónasson G, Carlsen K-H, Blomqvist P. Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Eur Respir J 1998;12:1099-1104.

14. Simons FER and the Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. N Engl J Med 1997;337:1659-1665.

15. Storr J, Lenney CA, Lenney W. Nebulized beclomethasone dipropionate in preschool asthma. Arch Dis Child 1986;61:270-273.

16. Van Essen-Zandvliet EE, Hughes MD, Waalkens HJ, Duiverman EJ, Pocock SJ, Kerrebijn KF. and the Dutch Chronic Non-Specific Lung Disease Study Group Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. Am Rev Respir Dis 1992;146:547-554.

17. Tasche MJA, Uijen JHJM, Bernsen RMD, de Jongste JC, van der Wouden JC. Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review. Thorax 2000;55:913-920.

18. Leflein JG, Szefler SJ, Murphy KR, Fitzpatrick S, Cruz-Rivera M, Miller CJ, et al. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Pediatrics 2002;109:866-872.

19. Verberne AAPH, Frost C, Duiverman EJ, Grol MH, Kerrebijn KF. and the Dutch Paediatric Asthma Study Group Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 1998;158:213-219.

20. Lazarus SC, Boushey HA, Fahy JV, Chinchilli VM, Lemanske RF Jr, Sorkness CA, , et al. for the Asthma Clinical Research Network of the National Heart Lung and Blood Institute. Long-acting 2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA 2001;285:2583-2593.

21. Reed CE, Offord KP, Nelson HS, Li JT, Tinkelman DG. and the American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group. Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild or moderate persistent asthma. J Allergy Clin Immunol 1998;101:14-23.

22. Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-1069.

23. National Asthma Education Program (NAEP). Report of the Working Group on Asthma and Pregnancy: Management of Asthma during Pregnancy. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health, 1993. NIH Publication No. 96-141593.

24. American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthmaand Immunology (ACAAI). The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475-480.

25. National Asthma Education and Prevention Program. NAEPP Expert Panel Report. Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment—Update 2004. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health. NIH Publication No. 04-5246. March 2004.

26. Källén B, Rydhstroem H, Äberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999;93:392-395.

27. Ericson A, Källén B. Use of drugs during pregnancy—unique Swedish registration method that can be improved. Information From the Swedish Medical Products Agency 1999;1:8-11.

28. Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen Y-Z, Ohlsson SV, et al. for the START Investigators Group. Early intervention with budesonide in mild persistent asthma. Lancet 2003;361:1071-1076.

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Practice recommendations

 

  • Every patient with persistent asthma, regardless of disease severity, should use a daily controller medication.
  • Consider an inhaled corticosteroid (ICS) first when choosing controller medications for long-term treatment of mild, moderate, and severe persistent asthma in adults and children. Leukotriene modifiers, cromolyn, and nedocromil may be considered as alternative, not preferred, controller medications for patients with persistent asthma.
  • Long-acting β2-adrenergic agonists should not be used as monotherapy.
  • Long-term use of ICSs within labeled doses is safe for children in terms of growth, bone mineral density, and adrenal function; nonetheless, asthma should be monitored and ICS therapy stepped down to the lowest effective dose.
  • Low-to medium-dose ICSs are not associated with the development of cataracts or glaucoma in children, but high cumulative lifetime doses may slightly increase the prevalence of cataracts in adults and elderly patients.
  • ICSs are recommended for use in pregnant women with asthma; budesonide is the only ICS rated Pregnancy Category B.

Consider an adult with the following characteristics. To which disease severity would you assign this patient’s asthma?

 

  • Forced expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF) ≥80%
  • PEF variability 20%–30%
  • Daytime symptoms less than once a day
  • Nighttime symptoms more than 1 night a week.

This patient is said to have moderate persistent asthma based on nighttime symptoms. An accurate classification of a patient’s asthma is the foundation for selecting an appropriate treatment strategy.

In 2002 the National Asthma Education and Prevention Program (NAEPP) updated select topics1from its 1997 Guidelines for the Diagnosis and Management of Asthma.2 These evidence-based revisions to the stepwise approach to asthma management were made following a systematic review of the literature (see Search function).

 

Search function

A comprehensive search of Medline and EMBASE databases was performed to identify controlled clinical studies relevant to each topic that were published (in English or foreign languages with English abstracts) from 1980 through August 2000. The search included studies published before 1980 if referenced in the post-1980 literature. Studies that did not include control groups were excluded, except for those reporting adverse effects of ICSs. Studies that met the study selection criteria established for each topic were included in a systematic review of the evidence. An expert panel reviewed the evidence, along with additional literature published since August 2000, and reached a consensus on whether the evidence supported 1997 guideline recommendations or indicated a need for revision. Writing committees were then assigned to developed position statements for each topic. The level of evidence for included studies was rated based on the system of Jadad and colleagues,3 where A = randomized controlled trials, rich body of data; B = randomized controlled trials, limited data; C = nonrandomized trials and observational studies; D = panel consensus judgment.

This article reviews the 2002 NAEPP recommendations for the use of controller medications for asthma, including:

 

  • Relative effectiveness of inhaled corticosteroids (ICSs) versus other controller medications
  • Safety of long-term ICS use in children
  • Potential benefits of early ICS treatment.

We emphasize mild and moderate persistent asthma because the recommended treatments for these levels of severity have been most affected by the recent guideline changes. We also discuss a recent change by the US Food and Drug Administration (FDA) in its pregnancy category rating for an ICS.

2002 Stepwise approach to asthma management

New criteria for classifying asthma severity

The NAEPP classifies asthma severity according to symptoms and lung function in adults and children older than 5 years, and symptoms in children 5 years and younger.1 Persistent asthma is classified as mild, moderate, or severe according to the feature of greatest severity.

Asthma severity should be assigned according to symptoms before treatment.1 Because it is difficult to predict which infants and young children who wheeze with acute viral upper respiratory infection will go on to develop persistent asthma, new criteria have been detailed to help distinguish these children from those with transient wheeze (Table 1).1,4

TABLE 1
Criteria for children with intermittent wheeze

 

Infants and young children meeting these criteria should receive controller therapy for asthma:
  • Significant exacerbations that occur <6 weeks apart
  • ≥4 episodes of wheeze in the past year lasting >1 day and affecting sleep,
AND presence of risk factors for development of persistent asthma:
  • Atopic dermatitis or parental asthma,
  • OR 2 of the following:
  • – Diagnosis of allergic rhinitis
  • – >4% peripheral blood eosinophilia
  • – Wheezing apart from colds

Choosing pharmacologic treatment according to asthma classification

Quick-relief medications, which include the short-acting β2-agonists (SABAs), are taken as needed to promptly reverse acute airflow obstruction and relieve accompanying symptoms.2

Asthma controller medications (ie, ICSs, cromolyn sodium, long-acting β2-adrenergic-agonists [LABAs], leukotriene modifiers, nedocromil, and theophylline) are used daily to achieve and maintain long-term control of persistent asthma. All patients with persistent asthma, regardless of disease severity, should use a daily controller. Criteria for determining asthma severity and updated recommendations for the use of controller treatment in mild and moderate persistent asthma are presented in the Figure.3,5 Levels of evidence justifying NAEPP treatment recommendations are shown in Table 2.

 

 

For use in children. Asthma controller medications approved for use in children younger than 5 years include the fluticasone dry-powder inhalers (Flovent, Rotadisk, and Flovent Diskus), which are approved for children as young as 4 years (Flovent Diskus is not yet commercially available), and nebulized budesonide inhalation suspension (Pulmicort Respules), which is approved for children as young as 12 months.

The LABAs formoterol (Foradil) and salmeterol (Serevent Diskus) are approved for children as young as 5 and 4 years, respectively. Cromolyn sodium nebulizer solution is approved for children as young as 2 years, and theophylline is available for use at any age.

Based on safety and extrapolation of efficacy data in older patients, the oral granule formulation of the leukotriene receptor antagonist (LTRA) montelukast (Singulair) is approved for children as young as 1 year, and the chewable tablets are approved for children 2 to 5 years of age. Zafirlukast (Accolate) is approved for use in children 5 years and older.

New recommendations for mild persistent asthma. Recommendations for the treatment of mild and moderate persistent asthma have changed considerably from the 1997 guidelines. ICSs are now the preferred controller medications, based on greater efficacy. The updated guidelines no longer recommend an initial trial of cromolyn or nedocromil for the treatment of mild persistent asthma; these agents, along with the leukotriene modifiers and slow-release theophylline, are now considered alternatives to low-dose ICSs for adults and children older than 5 years with mild persistent disease (Figure).

According to the NAEPP update, daily low-dose ICS treatment also is preferred for the control of mild persistent asthma in preschool children. As in older children, cromolyn and nedocromil are no longer considered appropriate initial treatments for infants and children 5 years and younger. Cromolyn is considered an alternative controller, whereas nedocromil is no longer recommended for use.

New recommendations for moderate persistent asthma. For adults and children older than 5 years with moderate persistent asthma, revision to the guidelines involved recommendation of a low- to medium-dose ICS plus a LABA as the preferred controller treatment (Figure). Comparative low, medium, and high daily doses for ICSs are shown in Table 3 .1

For preschool children, preferred controller treatments for moderate persistent asthma include low-dose ICSs plus a LABA, or increasing ICSs within the medium-dose range (Figure). Recommendations for the use of LABAs as add-on therapy in this age group are based on extrapolation of data from older patients, since therapy with an ICS/LABA combination has not been adequately studied in children younger than 5 years. Four studies included in the NAEPP evaluation showed clear benefit of medium-dose ICSs in this age group, supporting the use of medium-dose ICSs as a preferred option.6-9 LABAs are not recommended for use without an ICS, and the only ICS/LABA combination product currently available has been FDA approved only for patients aged 12 years and older.

TABLE 2
Levels of evidence for NAEPP assessments*

 

MedicationNAEPP assessmentSOR*
ICSPreferred treatment for children of all ages with persistent asthmaA (A)
SABAICSs improve asthma control compared with as-needed SABAsA (A)
Cromolyn/nedocromilFor use as alternative, not preferred, treatment of mild persistent asthma in children of all ages (cromolyn) or children >5 years of age (nedocromil)A (A)
LABAFor use with ICSs as the preferred combination treatment for moderate and severe persistent asthma in children >5 years of ageA (A)
For use as a preferred option for combination treatment in children 5 years of ageB (B)
Leukotriene modifierFor use as alternative, not preferred, treatment of mild persistent asthma and as ICS adjunct in moderate persistent asthmaB (B)
TheophyllineFor use as an alternative ICS add-on in moderate or severe persistent asthma if serum concentrations are monitoredD (D)
Not considered an alternative controller for young children with mild persistent asthma due to potential adverse effects in infants with frequent febrile illnesses
*Highest level of evidence available is reported. Strengths of recommendation are based on the method of Jadad et al.3 Strength of evidence based on the Oxford Center for Evidence-Based Medicine5 is in parentheses. SOR, strength of recommendation; NAEPP, National Asthma Education and Prevention Program; ICS, inhaled corticosteroid; SABA, short-acting β2-adrenergic agonist; LABA, long-acting β2-adrenergic agonist.

TABLE 3
Estimated comparative daily doses for inhaled corticosteroids*

 

DrugLow daily doseMedium daily doseHigh daily dose
AdultChildAdultChildAdultChild
Beclomethasone CFC 42 or 84 μg/puff168–504 μg84–336 μg504–840 μg336–672 μg>840 μg>672 μg
Beclomethasone HFA 40 or 80 μg/puff80–240 μg80–160 μg240–480 μg160–320 μg>480 μg>320 μg
Budesonide DPI 200 μg/inhalation200–600 μg200–400 μg600–1200 μg400–800 μg>1200 μg>800 μg
Budesonide inhalation suspension for nebulization (child dose)0.5mg1.0 mg2.0 mg
Fluticasone MDI 44, 110, or 220 μg/puff88–264 μg88–176 μg264–660 μg176–440 μg>660 μg>440 μg
Fluticasone DPI 50, 100, or 250 μg/inhalation100–300 μg100–200 μg300–600 μg200–400 μg>600 μg>400 μg
Triamcinolone acetonide 100 μg/puff400–1000 μg400–800 μg1000–2000 μg800–1200 μg>2000 μg>1200 μg
*The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to therapy. This updated comparative dose chart is based on review of recently published clinical trials involving more than 5000 patients and published reviews. Some doses may be outside package labeling, especially in the high-dose range.
Children 12 years of age.
CFC, chlorofluorocarbon; HFA, hydrofluoroalkane; DPI, dry-powder inhaler; MDI, metered-dose inhaler.

FIGURE
Updated National Asthma Education and Prevention Program recommendations for long-term controller treatment in mild and moderate persistent asthma

 

 

Topics in the management of asthma in children

Recognizing the need for continual appraisal of the benefits and risks of asthma medications in children, the NAEPP Expert Panel considered new studies comparing the effectiveness of ICS monotherapy with that of as-needed SABAs and other controllers used as monotherapy in children with mild or moderate persistent asthma. In addition, the safety of long-term ICS use in children was evaluated based on vertical growth, bone mineral density, ocular toxicity, and adrenal suppression.

Effectiveness of ICSs compared with other asthma medications

Short-acting β2-adrenergic agonists. Eight studies met the eligibility criteria for evaluating the effectiveness of ICSs versus as-needed SABAs.6,10-16 Six studies (4 involving budesonide) in children 5 years and older showed that ICSs improve lung function and symptoms and reduce the need for emergency intervention compared with as-needed SABAs.1 Among all studies included in the NAEPP update, the Childhood Asthma Management Program (CAMP) Research Group Study,9 a placebo-controlled study of inhaled budesonide and nedocromil, contributed the most evidence. Studies with children 5 years and younger are limited to 2 small studies enrolling a total of 69 children.6,15 Consistent with studies of older children, these studies indicate that ICSs improve asthma control compared with as-needed SABAs.1

Cromolyn and nedocromil. Despite well-established safety profiles, cromolyn and nedocromil are no longer recommended as first-line therapy for children, even those with mild disease. New recommendations reflect the greater effectiveness of inhaled budesonide compared with nedocromil demonstrated in the CAMP study,10 and the lack of apparent benefit of cromolyn as maintenance treatment in childhood asthma reported by Tasche and colleagues in a systematic review of the literature.17

In the CAMP study, children 5 to 12 years of age receiving inhaled budesonide showed greater reductions in symptoms and albuterol use, lower rates of hospitalization and urgent care visits, and less need for additional asthma therapy and oral prednisone compared with placebo over 4 to 6 years of treatment.10 The marginal effectiveness of nedocromil demonstrated in the CAMP study mirrored that of cromolyn reported in the review of 24 randomized placebo-controlled studies by Tasche and colleagues.1,17

For children 5 years and younger, the NAEPP Expert Panel took into account 1 randomized placebo-controlled study conducted with children 2 to 5 years of age; it showed improvements in lung function, symptoms, and bronchial hyperre-activity with inhaled budesonide.9 Support for the new NAEPP recommendations preferring ICSs for preschool children is found in a more recent open-label study18 that showed greater symptom improvement and significantly lower rates of asthma exacerbations, urgent care visits, and oral prednisone use with budesonide inhalation suspension, compared with cromolyn sodium nebulizer solution (Intal Nebulizer Solution) in children 2 to 6 years of age with persistent asthma.

Leukotriene modifiers. The LTRAs zafir-lukast and montelukast are approved for use in children. According to the NAEPP Expert Panel, studies have shown only modest improvements in lung function and other asthma control outcomes with LTRA monotherapy in children as young as 6 and 2 years, respectively.1 Because studies comparing ICSs with LTRAs in children are lacking, findings of greater overall efficacy of ICSs in adults with persistent asthma have been extrapolated for use with children; clear superiority of ICSs versus LTRAs in most outcomes has resulted in the recommendation for ICSs as the preferred treatment for mild persistent asthma in children.

Long-acting β2-adrenergic agonists. There is no role for LABAs as monotherapy in asthma. No studies have compared the effectiveness of ICS versus LABA monotherapy in children younger than 5 years, and studies in older children have shown greater effectiveness of inhaled beclomethasone versus salmeterol.14,19 In the study by Verberne and colleagues, salmeterol monotherapy was associated with deterioration in FEV1.19 In a more recent study that included patients as young as 16 years, a switch from ICS to LABA treatment was associated with a significant increase in treatment failures and exacerbations.20

Theophylline. Only 1 study has compared outcomes with low-dose ICSs versus theophylline in adults and children.21 Although limited, the data support greater effectiveness of ICSs based on symptoms, bronchial hyperresponsiveness, and the need for β2-adrenergic agonists and oral corticosteroids.1

Safety of long-term ICS use in children

Systemic corticosteroids have the potential to suppress growth over the long term.2 Short-term growth studies with ICSs show an average reduction in growth velocity of 1 cm per year during the first year of treatment, but the CAMP study showed that initial reductions in growth velocity with inhaled budesonide were not maintained over a 4- to 6-year treatment period.1,10

Although catch-up growth was not observed in the CAMP study, Agertoft and Pedersen reported no effect of long-term treatment with inhaled budesonide (mean 9.2 years) on final adult height.22 Based on these long-term prospective studies of budesonide, showing only a transient reduction in growth velocity and attainment of expected final adult height, and retrospective studies including inhaled beclomethasone, the Expert Panel concluded that the ICS class is safe regarding growth effects.

 

 

According to the NAEPP Expert Panel, clinical study data for children monitored for up to 6 years strongly suggest that ICSs are safe when used at recommended doses (strength of recommendation: A).1 The panel could not rule out a potential cumulative effect of ICS use on some conditions, (eg, osteoporosis, cataracts, glaucoma) in adulthood, as sufficient long-term data are not available.

The panel did conclude that low- to medium-dose ICSs (Table 3) appear to have no serious adverse effects on bone mineral density in children.

Likewise, low- to medium-dose ICS use was not associated with the development of cataracts or glaucoma in children, although the potential for high cumulative lifetime doses of ICSs to slightly increase the prevalence of cataracts in adults and elderly patients was noted.

Strong evidence also indicates that ICS effects on adrenal function are usually clinically insignificant at low to medium doses; however, certain individuals may be at higher risk for hypothalam-ic pituitary adrenal axis effects while using conventional ICS doses.1

Although ICSs are safe when used within labeled dosing, it is still preferable to maintain doses at the lowest effective dose. In general, treatment should be reviewed every 1 to 6 months and doses reduced in a stepwise fashion when possible.1 For children showing a favorable response to treatment, a step down in dose should be considered, but not more frequently than every 3 months. If children show no clear response to treatment within 4 to 6 weeks, consider an alternative treatment or diagnosis.1

Safety of long-term ICS use in pregnant women

Uncontrolled asthma during pregnancy is associated with an increased risk of perinatal complications. 23 Since the consequences of not using asthma controllers during pregnancy can be worse than those with using them, daily controller treatment is recommended for all pregnant women with persistent asthma. 23

The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology previously recommended cromolyn as the treatment of choice for pregnant women with mild persistent asthma. ICSs were recommended for patients whose asthma was inadequately controlled with cromolyn. 24 Beclomethasone and budesonide were the ICSs of choice for pregnant women and those who might become pregnant, with a preference for budesonide when high-dose therapy was indicated.24

These recommendations predate the 2002 NAEPP recommendations for ICSs as preferred therapy in mild persistent asthma and the 2004 NAEPP recommendations for ICSs as the first-choice controller therapy for mild persistent asthma during pregnancy. 25 Among ICSs, one (inhaled budesonide) has an FDA Pregnancy Category B rating based on studies showing no risk in pregnant women. 26,27 All other ICSs are rated Pregnancy Category C.

Based on current evidence, it seems reasonable to consider whether budesonide should now be the preferred therapy for mild persistent asthma during pregnancy.

Effects of early treatment on asthma progression

The potential for early ICS intervention to prevent progression of mild or moderate persistent asthma was evaluated solely with data from children enrolled in the CAMP study. 10 The NAEPP Expert Panel concluded that CAMP study data do not support a progressive decline in lung function in children aged 5 to 12 years with mild or moderate persistent asthma, but do suggest that lung function decline is influenced by age of asthma onset.

According to the panel, CAMP data suggest that most deficits in lung function growth due to childhood asthma occur during the first 3 years of life. Preliminary results of the recent START study (Inhaled Steroid Treatment As Regular Therapy in Early Asthma), 28 conducted with 7165 corticosteroidnaïve patients 5 to 66 years of age with recent onset mild persistent asthma, did show a decline in lung function in patients with mild persistent disease.

Although improvements in prebronchodilator and postbronchodilator FEV1 were significant after 3 years of treatment with inhaled budes-onide, differences from placebo in both outcomes were greatest after the first year. When patients with mild persistent disease inhaled budesonide once daily in addition to normal treatment within 2 years of asthma onset,28 they enjoyed considerable protection from severe and life-threatening asthma exacerbations and overall greater asthma control.

 

Drug brand names

 

  • Budesonide • Pulmicort
  • Rhinocort Cromolyn • Intal
  • Fluticasone • Flovent
  • Formoterol • Foradil
  • Montelukast • Singulair
  • Nedocromil • Tilade
  • Salmeterol • Servent
  • Triamcinolone acetonide • Azmacort
  • Zafirlukast • Accolate

Corresponding author
Gregory J. Redding, MD, Children’s Hospital and Regional Medical Center, 4800 Sand Point Way, NE, Seattle, WA 98105-0371. E-mail: gredding@u.washington.edu.

 

Practice recommendations

 

  • Every patient with persistent asthma, regardless of disease severity, should use a daily controller medication.
  • Consider an inhaled corticosteroid (ICS) first when choosing controller medications for long-term treatment of mild, moderate, and severe persistent asthma in adults and children. Leukotriene modifiers, cromolyn, and nedocromil may be considered as alternative, not preferred, controller medications for patients with persistent asthma.
  • Long-acting β2-adrenergic agonists should not be used as monotherapy.
  • Long-term use of ICSs within labeled doses is safe for children in terms of growth, bone mineral density, and adrenal function; nonetheless, asthma should be monitored and ICS therapy stepped down to the lowest effective dose.
  • Low-to medium-dose ICSs are not associated with the development of cataracts or glaucoma in children, but high cumulative lifetime doses may slightly increase the prevalence of cataracts in adults and elderly patients.
  • ICSs are recommended for use in pregnant women with asthma; budesonide is the only ICS rated Pregnancy Category B.

Consider an adult with the following characteristics. To which disease severity would you assign this patient’s asthma?

 

  • Forced expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF) ≥80%
  • PEF variability 20%–30%
  • Daytime symptoms less than once a day
  • Nighttime symptoms more than 1 night a week.

This patient is said to have moderate persistent asthma based on nighttime symptoms. An accurate classification of a patient’s asthma is the foundation for selecting an appropriate treatment strategy.

In 2002 the National Asthma Education and Prevention Program (NAEPP) updated select topics1from its 1997 Guidelines for the Diagnosis and Management of Asthma.2 These evidence-based revisions to the stepwise approach to asthma management were made following a systematic review of the literature (see Search function).

 

Search function

A comprehensive search of Medline and EMBASE databases was performed to identify controlled clinical studies relevant to each topic that were published (in English or foreign languages with English abstracts) from 1980 through August 2000. The search included studies published before 1980 if referenced in the post-1980 literature. Studies that did not include control groups were excluded, except for those reporting adverse effects of ICSs. Studies that met the study selection criteria established for each topic were included in a systematic review of the evidence. An expert panel reviewed the evidence, along with additional literature published since August 2000, and reached a consensus on whether the evidence supported 1997 guideline recommendations or indicated a need for revision. Writing committees were then assigned to developed position statements for each topic. The level of evidence for included studies was rated based on the system of Jadad and colleagues,3 where A = randomized controlled trials, rich body of data; B = randomized controlled trials, limited data; C = nonrandomized trials and observational studies; D = panel consensus judgment.

This article reviews the 2002 NAEPP recommendations for the use of controller medications for asthma, including:

 

  • Relative effectiveness of inhaled corticosteroids (ICSs) versus other controller medications
  • Safety of long-term ICS use in children
  • Potential benefits of early ICS treatment.

We emphasize mild and moderate persistent asthma because the recommended treatments for these levels of severity have been most affected by the recent guideline changes. We also discuss a recent change by the US Food and Drug Administration (FDA) in its pregnancy category rating for an ICS.

2002 Stepwise approach to asthma management

New criteria for classifying asthma severity

The NAEPP classifies asthma severity according to symptoms and lung function in adults and children older than 5 years, and symptoms in children 5 years and younger.1 Persistent asthma is classified as mild, moderate, or severe according to the feature of greatest severity.

Asthma severity should be assigned according to symptoms before treatment.1 Because it is difficult to predict which infants and young children who wheeze with acute viral upper respiratory infection will go on to develop persistent asthma, new criteria have been detailed to help distinguish these children from those with transient wheeze (Table 1).1,4

TABLE 1
Criteria for children with intermittent wheeze

 

Infants and young children meeting these criteria should receive controller therapy for asthma:
  • Significant exacerbations that occur <6 weeks apart
  • ≥4 episodes of wheeze in the past year lasting >1 day and affecting sleep,
AND presence of risk factors for development of persistent asthma:
  • Atopic dermatitis or parental asthma,
  • OR 2 of the following:
  • – Diagnosis of allergic rhinitis
  • – >4% peripheral blood eosinophilia
  • – Wheezing apart from colds

Choosing pharmacologic treatment according to asthma classification

Quick-relief medications, which include the short-acting β2-agonists (SABAs), are taken as needed to promptly reverse acute airflow obstruction and relieve accompanying symptoms.2

Asthma controller medications (ie, ICSs, cromolyn sodium, long-acting β2-adrenergic-agonists [LABAs], leukotriene modifiers, nedocromil, and theophylline) are used daily to achieve and maintain long-term control of persistent asthma. All patients with persistent asthma, regardless of disease severity, should use a daily controller. Criteria for determining asthma severity and updated recommendations for the use of controller treatment in mild and moderate persistent asthma are presented in the Figure.3,5 Levels of evidence justifying NAEPP treatment recommendations are shown in Table 2.

 

 

For use in children. Asthma controller medications approved for use in children younger than 5 years include the fluticasone dry-powder inhalers (Flovent, Rotadisk, and Flovent Diskus), which are approved for children as young as 4 years (Flovent Diskus is not yet commercially available), and nebulized budesonide inhalation suspension (Pulmicort Respules), which is approved for children as young as 12 months.

The LABAs formoterol (Foradil) and salmeterol (Serevent Diskus) are approved for children as young as 5 and 4 years, respectively. Cromolyn sodium nebulizer solution is approved for children as young as 2 years, and theophylline is available for use at any age.

Based on safety and extrapolation of efficacy data in older patients, the oral granule formulation of the leukotriene receptor antagonist (LTRA) montelukast (Singulair) is approved for children as young as 1 year, and the chewable tablets are approved for children 2 to 5 years of age. Zafirlukast (Accolate) is approved for use in children 5 years and older.

New recommendations for mild persistent asthma. Recommendations for the treatment of mild and moderate persistent asthma have changed considerably from the 1997 guidelines. ICSs are now the preferred controller medications, based on greater efficacy. The updated guidelines no longer recommend an initial trial of cromolyn or nedocromil for the treatment of mild persistent asthma; these agents, along with the leukotriene modifiers and slow-release theophylline, are now considered alternatives to low-dose ICSs for adults and children older than 5 years with mild persistent disease (Figure).

According to the NAEPP update, daily low-dose ICS treatment also is preferred for the control of mild persistent asthma in preschool children. As in older children, cromolyn and nedocromil are no longer considered appropriate initial treatments for infants and children 5 years and younger. Cromolyn is considered an alternative controller, whereas nedocromil is no longer recommended for use.

New recommendations for moderate persistent asthma. For adults and children older than 5 years with moderate persistent asthma, revision to the guidelines involved recommendation of a low- to medium-dose ICS plus a LABA as the preferred controller treatment (Figure). Comparative low, medium, and high daily doses for ICSs are shown in Table 3 .1

For preschool children, preferred controller treatments for moderate persistent asthma include low-dose ICSs plus a LABA, or increasing ICSs within the medium-dose range (Figure). Recommendations for the use of LABAs as add-on therapy in this age group are based on extrapolation of data from older patients, since therapy with an ICS/LABA combination has not been adequately studied in children younger than 5 years. Four studies included in the NAEPP evaluation showed clear benefit of medium-dose ICSs in this age group, supporting the use of medium-dose ICSs as a preferred option.6-9 LABAs are not recommended for use without an ICS, and the only ICS/LABA combination product currently available has been FDA approved only for patients aged 12 years and older.

TABLE 2
Levels of evidence for NAEPP assessments*

 

MedicationNAEPP assessmentSOR*
ICSPreferred treatment for children of all ages with persistent asthmaA (A)
SABAICSs improve asthma control compared with as-needed SABAsA (A)
Cromolyn/nedocromilFor use as alternative, not preferred, treatment of mild persistent asthma in children of all ages (cromolyn) or children >5 years of age (nedocromil)A (A)
LABAFor use with ICSs as the preferred combination treatment for moderate and severe persistent asthma in children >5 years of ageA (A)
For use as a preferred option for combination treatment in children 5 years of ageB (B)
Leukotriene modifierFor use as alternative, not preferred, treatment of mild persistent asthma and as ICS adjunct in moderate persistent asthmaB (B)
TheophyllineFor use as an alternative ICS add-on in moderate or severe persistent asthma if serum concentrations are monitoredD (D)
Not considered an alternative controller for young children with mild persistent asthma due to potential adverse effects in infants with frequent febrile illnesses
*Highest level of evidence available is reported. Strengths of recommendation are based on the method of Jadad et al.3 Strength of evidence based on the Oxford Center for Evidence-Based Medicine5 is in parentheses. SOR, strength of recommendation; NAEPP, National Asthma Education and Prevention Program; ICS, inhaled corticosteroid; SABA, short-acting β2-adrenergic agonist; LABA, long-acting β2-adrenergic agonist.

TABLE 3
Estimated comparative daily doses for inhaled corticosteroids*

 

DrugLow daily doseMedium daily doseHigh daily dose
AdultChildAdultChildAdultChild
Beclomethasone CFC 42 or 84 μg/puff168–504 μg84–336 μg504–840 μg336–672 μg>840 μg>672 μg
Beclomethasone HFA 40 or 80 μg/puff80–240 μg80–160 μg240–480 μg160–320 μg>480 μg>320 μg
Budesonide DPI 200 μg/inhalation200–600 μg200–400 μg600–1200 μg400–800 μg>1200 μg>800 μg
Budesonide inhalation suspension for nebulization (child dose)0.5mg1.0 mg2.0 mg
Fluticasone MDI 44, 110, or 220 μg/puff88–264 μg88–176 μg264–660 μg176–440 μg>660 μg>440 μg
Fluticasone DPI 50, 100, or 250 μg/inhalation100–300 μg100–200 μg300–600 μg200–400 μg>600 μg>400 μg
Triamcinolone acetonide 100 μg/puff400–1000 μg400–800 μg1000–2000 μg800–1200 μg>2000 μg>1200 μg
*The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to therapy. This updated comparative dose chart is based on review of recently published clinical trials involving more than 5000 patients and published reviews. Some doses may be outside package labeling, especially in the high-dose range.
Children 12 years of age.
CFC, chlorofluorocarbon; HFA, hydrofluoroalkane; DPI, dry-powder inhaler; MDI, metered-dose inhaler.

FIGURE
Updated National Asthma Education and Prevention Program recommendations for long-term controller treatment in mild and moderate persistent asthma

 

 

Topics in the management of asthma in children

Recognizing the need for continual appraisal of the benefits and risks of asthma medications in children, the NAEPP Expert Panel considered new studies comparing the effectiveness of ICS monotherapy with that of as-needed SABAs and other controllers used as monotherapy in children with mild or moderate persistent asthma. In addition, the safety of long-term ICS use in children was evaluated based on vertical growth, bone mineral density, ocular toxicity, and adrenal suppression.

Effectiveness of ICSs compared with other asthma medications

Short-acting β2-adrenergic agonists. Eight studies met the eligibility criteria for evaluating the effectiveness of ICSs versus as-needed SABAs.6,10-16 Six studies (4 involving budesonide) in children 5 years and older showed that ICSs improve lung function and symptoms and reduce the need for emergency intervention compared with as-needed SABAs.1 Among all studies included in the NAEPP update, the Childhood Asthma Management Program (CAMP) Research Group Study,9 a placebo-controlled study of inhaled budesonide and nedocromil, contributed the most evidence. Studies with children 5 years and younger are limited to 2 small studies enrolling a total of 69 children.6,15 Consistent with studies of older children, these studies indicate that ICSs improve asthma control compared with as-needed SABAs.1

Cromolyn and nedocromil. Despite well-established safety profiles, cromolyn and nedocromil are no longer recommended as first-line therapy for children, even those with mild disease. New recommendations reflect the greater effectiveness of inhaled budesonide compared with nedocromil demonstrated in the CAMP study,10 and the lack of apparent benefit of cromolyn as maintenance treatment in childhood asthma reported by Tasche and colleagues in a systematic review of the literature.17

In the CAMP study, children 5 to 12 years of age receiving inhaled budesonide showed greater reductions in symptoms and albuterol use, lower rates of hospitalization and urgent care visits, and less need for additional asthma therapy and oral prednisone compared with placebo over 4 to 6 years of treatment.10 The marginal effectiveness of nedocromil demonstrated in the CAMP study mirrored that of cromolyn reported in the review of 24 randomized placebo-controlled studies by Tasche and colleagues.1,17

For children 5 years and younger, the NAEPP Expert Panel took into account 1 randomized placebo-controlled study conducted with children 2 to 5 years of age; it showed improvements in lung function, symptoms, and bronchial hyperre-activity with inhaled budesonide.9 Support for the new NAEPP recommendations preferring ICSs for preschool children is found in a more recent open-label study18 that showed greater symptom improvement and significantly lower rates of asthma exacerbations, urgent care visits, and oral prednisone use with budesonide inhalation suspension, compared with cromolyn sodium nebulizer solution (Intal Nebulizer Solution) in children 2 to 6 years of age with persistent asthma.

Leukotriene modifiers. The LTRAs zafir-lukast and montelukast are approved for use in children. According to the NAEPP Expert Panel, studies have shown only modest improvements in lung function and other asthma control outcomes with LTRA monotherapy in children as young as 6 and 2 years, respectively.1 Because studies comparing ICSs with LTRAs in children are lacking, findings of greater overall efficacy of ICSs in adults with persistent asthma have been extrapolated for use with children; clear superiority of ICSs versus LTRAs in most outcomes has resulted in the recommendation for ICSs as the preferred treatment for mild persistent asthma in children.

Long-acting β2-adrenergic agonists. There is no role for LABAs as monotherapy in asthma. No studies have compared the effectiveness of ICS versus LABA monotherapy in children younger than 5 years, and studies in older children have shown greater effectiveness of inhaled beclomethasone versus salmeterol.14,19 In the study by Verberne and colleagues, salmeterol monotherapy was associated with deterioration in FEV1.19 In a more recent study that included patients as young as 16 years, a switch from ICS to LABA treatment was associated with a significant increase in treatment failures and exacerbations.20

Theophylline. Only 1 study has compared outcomes with low-dose ICSs versus theophylline in adults and children.21 Although limited, the data support greater effectiveness of ICSs based on symptoms, bronchial hyperresponsiveness, and the need for β2-adrenergic agonists and oral corticosteroids.1

Safety of long-term ICS use in children

Systemic corticosteroids have the potential to suppress growth over the long term.2 Short-term growth studies with ICSs show an average reduction in growth velocity of 1 cm per year during the first year of treatment, but the CAMP study showed that initial reductions in growth velocity with inhaled budesonide were not maintained over a 4- to 6-year treatment period.1,10

Although catch-up growth was not observed in the CAMP study, Agertoft and Pedersen reported no effect of long-term treatment with inhaled budesonide (mean 9.2 years) on final adult height.22 Based on these long-term prospective studies of budesonide, showing only a transient reduction in growth velocity and attainment of expected final adult height, and retrospective studies including inhaled beclomethasone, the Expert Panel concluded that the ICS class is safe regarding growth effects.

 

 

According to the NAEPP Expert Panel, clinical study data for children monitored for up to 6 years strongly suggest that ICSs are safe when used at recommended doses (strength of recommendation: A).1 The panel could not rule out a potential cumulative effect of ICS use on some conditions, (eg, osteoporosis, cataracts, glaucoma) in adulthood, as sufficient long-term data are not available.

The panel did conclude that low- to medium-dose ICSs (Table 3) appear to have no serious adverse effects on bone mineral density in children.

Likewise, low- to medium-dose ICS use was not associated with the development of cataracts or glaucoma in children, although the potential for high cumulative lifetime doses of ICSs to slightly increase the prevalence of cataracts in adults and elderly patients was noted.

Strong evidence also indicates that ICS effects on adrenal function are usually clinically insignificant at low to medium doses; however, certain individuals may be at higher risk for hypothalam-ic pituitary adrenal axis effects while using conventional ICS doses.1

Although ICSs are safe when used within labeled dosing, it is still preferable to maintain doses at the lowest effective dose. In general, treatment should be reviewed every 1 to 6 months and doses reduced in a stepwise fashion when possible.1 For children showing a favorable response to treatment, a step down in dose should be considered, but not more frequently than every 3 months. If children show no clear response to treatment within 4 to 6 weeks, consider an alternative treatment or diagnosis.1

Safety of long-term ICS use in pregnant women

Uncontrolled asthma during pregnancy is associated with an increased risk of perinatal complications. 23 Since the consequences of not using asthma controllers during pregnancy can be worse than those with using them, daily controller treatment is recommended for all pregnant women with persistent asthma. 23

The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology previously recommended cromolyn as the treatment of choice for pregnant women with mild persistent asthma. ICSs were recommended for patients whose asthma was inadequately controlled with cromolyn. 24 Beclomethasone and budesonide were the ICSs of choice for pregnant women and those who might become pregnant, with a preference for budesonide when high-dose therapy was indicated.24

These recommendations predate the 2002 NAEPP recommendations for ICSs as preferred therapy in mild persistent asthma and the 2004 NAEPP recommendations for ICSs as the first-choice controller therapy for mild persistent asthma during pregnancy. 25 Among ICSs, one (inhaled budesonide) has an FDA Pregnancy Category B rating based on studies showing no risk in pregnant women. 26,27 All other ICSs are rated Pregnancy Category C.

Based on current evidence, it seems reasonable to consider whether budesonide should now be the preferred therapy for mild persistent asthma during pregnancy.

Effects of early treatment on asthma progression

The potential for early ICS intervention to prevent progression of mild or moderate persistent asthma was evaluated solely with data from children enrolled in the CAMP study. 10 The NAEPP Expert Panel concluded that CAMP study data do not support a progressive decline in lung function in children aged 5 to 12 years with mild or moderate persistent asthma, but do suggest that lung function decline is influenced by age of asthma onset.

According to the panel, CAMP data suggest that most deficits in lung function growth due to childhood asthma occur during the first 3 years of life. Preliminary results of the recent START study (Inhaled Steroid Treatment As Regular Therapy in Early Asthma), 28 conducted with 7165 corticosteroidnaïve patients 5 to 66 years of age with recent onset mild persistent asthma, did show a decline in lung function in patients with mild persistent disease.

Although improvements in prebronchodilator and postbronchodilator FEV1 were significant after 3 years of treatment with inhaled budes-onide, differences from placebo in both outcomes were greatest after the first year. When patients with mild persistent disease inhaled budesonide once daily in addition to normal treatment within 2 years of asthma onset,28 they enjoyed considerable protection from severe and life-threatening asthma exacerbations and overall greater asthma control.

 

Drug brand names

 

  • Budesonide • Pulmicort
  • Rhinocort Cromolyn • Intal
  • Fluticasone • Flovent
  • Formoterol • Foradil
  • Montelukast • Singulair
  • Nedocromil • Tilade
  • Salmeterol • Servent
  • Triamcinolone acetonide • Azmacort
  • Zafirlukast • Accolate

Corresponding author
Gregory J. Redding, MD, Children’s Hospital and Regional Medical Center, 4800 Sand Point Way, NE, Seattle, WA 98105-0371. E-mail: gredding@u.washington.edu.

References

 

1. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma. Update on selected topics–2002. J Allergy Clin Immunol 2002;110(5 suppl):S141-S219.

2. National Asthma Education and Prevention Program Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health; 1997. Publication 97;4051.-

3. Jadad AR, Moher M, Browman GP, Booker L, Sigouin C, Fuentes M, et al. Systematic reviews and meta-analyses on treatment of asthma: critical evaluation. BMJ 2000;320:537-540.

4. Castro-Rodríguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000;162:1403-1406.

5. Oxford Centre for Evidence-based Medicine Levels of Evidence Available atwww.cebm.net/levels_faq.asp . Accessed January 8, 2004.

6. Connett GJ, Warde C, Wooler E, Lenney W. Use of budes-onide in severe asthmatics aged 1–3 years. Arch Dis Child 1993;69:351-355.

7. de Blic J, Delacourt C, Le Bourgeois M, Mahut B, Ostinelli J, Caswell C, et al. Efficacy of nebulized budesonide in treatment of severe infantile asthma: a double-blind study. J Allergy Clin Immunol 1996;98:14-20.

8. Bisgaard H, Gillies J, Groenewald M, Maden C, . for an International Study Group The effect of inhaled fluticas-one propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med 1999;160:126-131.

9. Nielsen KG, Bisgaard H. The effect of inhaled budesonide on symptoms, lung function, and cold air and metha-choline responsiveness in 2- to 5-year–old asthmatic children. Am J Respir Crit Care Med 2000;162:1500-1506.

10. Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000;343:1054-1063.

11. Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994;88:373-381.

12. Hoekstra MO, Grol MH, Bouman K, Stijnen T, Koëter GH, Kauffman HF, et al. Fluticasone propionate in children with moderate asthma. Am J Respir Crit Care Med 1996;154:1039-1044.

13. Jónasson G, Carlsen K-H, Blomqvist P. Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Eur Respir J 1998;12:1099-1104.

14. Simons FER and the Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. N Engl J Med 1997;337:1659-1665.

15. Storr J, Lenney CA, Lenney W. Nebulized beclomethasone dipropionate in preschool asthma. Arch Dis Child 1986;61:270-273.

16. Van Essen-Zandvliet EE, Hughes MD, Waalkens HJ, Duiverman EJ, Pocock SJ, Kerrebijn KF. and the Dutch Chronic Non-Specific Lung Disease Study Group Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. Am Rev Respir Dis 1992;146:547-554.

17. Tasche MJA, Uijen JHJM, Bernsen RMD, de Jongste JC, van der Wouden JC. Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review. Thorax 2000;55:913-920.

18. Leflein JG, Szefler SJ, Murphy KR, Fitzpatrick S, Cruz-Rivera M, Miller CJ, et al. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Pediatrics 2002;109:866-872.

19. Verberne AAPH, Frost C, Duiverman EJ, Grol MH, Kerrebijn KF. and the Dutch Paediatric Asthma Study Group Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 1998;158:213-219.

20. Lazarus SC, Boushey HA, Fahy JV, Chinchilli VM, Lemanske RF Jr, Sorkness CA, , et al. for the Asthma Clinical Research Network of the National Heart Lung and Blood Institute. Long-acting 2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA 2001;285:2583-2593.

21. Reed CE, Offord KP, Nelson HS, Li JT, Tinkelman DG. and the American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group. Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild or moderate persistent asthma. J Allergy Clin Immunol 1998;101:14-23.

22. Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-1069.

23. National Asthma Education Program (NAEP). Report of the Working Group on Asthma and Pregnancy: Management of Asthma during Pregnancy. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health, 1993. NIH Publication No. 96-141593.

24. American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthmaand Immunology (ACAAI). The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475-480.

25. National Asthma Education and Prevention Program. NAEPP Expert Panel Report. Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment—Update 2004. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health. NIH Publication No. 04-5246. March 2004.

26. Källén B, Rydhstroem H, Äberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999;93:392-395.

27. Ericson A, Källén B. Use of drugs during pregnancy—unique Swedish registration method that can be improved. Information From the Swedish Medical Products Agency 1999;1:8-11.

28. Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen Y-Z, Ohlsson SV, et al. for the START Investigators Group. Early intervention with budesonide in mild persistent asthma. Lancet 2003;361:1071-1076.

References

 

1. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma. Update on selected topics–2002. J Allergy Clin Immunol 2002;110(5 suppl):S141-S219.

2. National Asthma Education and Prevention Program Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health; 1997. Publication 97;4051.-

3. Jadad AR, Moher M, Browman GP, Booker L, Sigouin C, Fuentes M, et al. Systematic reviews and meta-analyses on treatment of asthma: critical evaluation. BMJ 2000;320:537-540.

4. Castro-Rodríguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000;162:1403-1406.

5. Oxford Centre for Evidence-based Medicine Levels of Evidence Available atwww.cebm.net/levels_faq.asp . Accessed January 8, 2004.

6. Connett GJ, Warde C, Wooler E, Lenney W. Use of budes-onide in severe asthmatics aged 1–3 years. Arch Dis Child 1993;69:351-355.

7. de Blic J, Delacourt C, Le Bourgeois M, Mahut B, Ostinelli J, Caswell C, et al. Efficacy of nebulized budesonide in treatment of severe infantile asthma: a double-blind study. J Allergy Clin Immunol 1996;98:14-20.

8. Bisgaard H, Gillies J, Groenewald M, Maden C, . for an International Study Group The effect of inhaled fluticas-one propionate in the treatment of young asthmatic children: a dose comparison study. Am J Respir Crit Care Med 1999;160:126-131.

9. Nielsen KG, Bisgaard H. The effect of inhaled budesonide on symptoms, lung function, and cold air and metha-choline responsiveness in 2- to 5-year–old asthmatic children. Am J Respir Crit Care Med 2000;162:1500-1506.

10. Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000;343:1054-1063.

11. Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994;88:373-381.

12. Hoekstra MO, Grol MH, Bouman K, Stijnen T, Koëter GH, Kauffman HF, et al. Fluticasone propionate in children with moderate asthma. Am J Respir Crit Care Med 1996;154:1039-1044.

13. Jónasson G, Carlsen K-H, Blomqvist P. Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Eur Respir J 1998;12:1099-1104.

14. Simons FER and the Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. N Engl J Med 1997;337:1659-1665.

15. Storr J, Lenney CA, Lenney W. Nebulized beclomethasone dipropionate in preschool asthma. Arch Dis Child 1986;61:270-273.

16. Van Essen-Zandvliet EE, Hughes MD, Waalkens HJ, Duiverman EJ, Pocock SJ, Kerrebijn KF. and the Dutch Chronic Non-Specific Lung Disease Study Group Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. Am Rev Respir Dis 1992;146:547-554.

17. Tasche MJA, Uijen JHJM, Bernsen RMD, de Jongste JC, van der Wouden JC. Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review. Thorax 2000;55:913-920.

18. Leflein JG, Szefler SJ, Murphy KR, Fitzpatrick S, Cruz-Rivera M, Miller CJ, et al. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Pediatrics 2002;109:866-872.

19. Verberne AAPH, Frost C, Duiverman EJ, Grol MH, Kerrebijn KF. and the Dutch Paediatric Asthma Study Group Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 1998;158:213-219.

20. Lazarus SC, Boushey HA, Fahy JV, Chinchilli VM, Lemanske RF Jr, Sorkness CA, , et al. for the Asthma Clinical Research Network of the National Heart Lung and Blood Institute. Long-acting 2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA 2001;285:2583-2593.

21. Reed CE, Offord KP, Nelson HS, Li JT, Tinkelman DG. and the American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group. Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild or moderate persistent asthma. J Allergy Clin Immunol 1998;101:14-23.

22. Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-1069.

23. National Asthma Education Program (NAEP). Report of the Working Group on Asthma and Pregnancy: Management of Asthma during Pregnancy. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health, 1993. NIH Publication No. 96-141593.

24. American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthmaand Immunology (ACAAI). The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475-480.

25. National Asthma Education and Prevention Program. NAEPP Expert Panel Report. Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment—Update 2004. Bethesda, Md: National Heart, Lung, and Blood Institute; National Institutes of Health. NIH Publication No. 04-5246. March 2004.

26. Källén B, Rydhstroem H, Äberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999;93:392-395.

27. Ericson A, Källén B. Use of drugs during pregnancy—unique Swedish registration method that can be improved. Information From the Swedish Medical Products Agency 1999;1:8-11.

28. Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen Y-Z, Ohlsson SV, et al. for the START Investigators Group. Early intervention with budesonide in mild persistent asthma. Lancet 2003;361:1071-1076.

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The Journal of Family Practice - 53(9)
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The Journal of Family Practice - 53(9)
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692-700
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