COPD

Researchers in Scotland have developed a risk calculator using a large electronic health records database that has shown a high reliability in predicting the risk of death for patients hospitalized for chronic occlusive pulmonary disease (COPD), providing another potential tool for improving postdischarge survival in these patients.

In a study published online in the journal Pharmacological Research, Pierpalo Pellicori, MD, and colleagues reported that a few variables, including prescriptions and laboratory data in routine EHRs, could help predict a patient’s risk of dying within 90 days after a hospital stay for COPD. Dr. Pellicori is a clinical cardiologist and research fellow at the Robertson Center for Biostatistics at the University of Glasgow.

“Identification of patients at high risk is valuable information for multidisciplinary teams,” Dr. Pellicori said in a written comment. “It allows the most vulnerable patients to be highlighted and prioritized for consideration of optimized value-based care, and for anticipatory care plan discussions.”

The retrospective cohort study analyzed EHR records of 17,973 patients who had an unplanned hospitalization for COPD in the Glasgow area from 2011 to 2017. The risk calculator model achieved a potential accuracy of 80%.

The study noted that, while a number of models have been developed to calculate the risk of exacerbations, inpatient death and prognosis in patients hospitalized for COPD, most of those models were based on cohorts of 1000 patients or less.

“Older age, male sex, and a longer hospital stay were important predictors of mortality in patients with COPD,” Dr. Pellicori said. “We also found that use of commonly prescribed medications such as digoxin identify patients with COPD more likely to die, perhaps because many have underlying heart failure, a highly prevalent but frequently missed diagnosis.”

He noted that heart failure and COPD share many risk factors, signs, and symptoms, such as smoking history, peripheral edema, and breathlessness. “Distinguishing between COPD and heart failure can be difficult, but is very important, as appropriate treatment for heart failure can improve a patient’s quality of life and survival substantially in many cases.”

The study also found that routinely collected and inexpensive blood markers – such as hemoglobin, neutrophil/lymphocyte ratio, serum chloride, urea, creatinine, and albumin – can also improve predictability of outcomes.

For example, the study found a linear increase in mortality of blood hemoglobin concentration less than 14 g/dL, but higher levels posed no greater risk. Higher white blood cell and neutrophil counts and lower lymphocyte and eosinophil counts were associated with a worse prognosis.

The study also found a linear increase in mortality with serum sodium less than 140 mmol/L or serum chloride less than 105 mmol/L –  but that higher concentrations of each were associated with a worse outcome.

“Interestingly,” Pellicori added, “social deprivation was not associated with mortality in this cohort.”

The final predictive model included age, sex, length of stay, and just nine other variables. “The model can be applied easily in clinical practice, even if electronic records are not available, because there are only 12 variables,” Dr. Pellicori said. “These could easily be entered manually into the risk calculator that we provide.”

“What is notable about this risk calculator is that it uses some of the techniques of machine learning, although it’s not specifically machine learning,” Angel Coz, MD, a pulmonologist at the Cleveland Clinic Respiratory Institute, said in an interview. “But it’s a retrospective data analysis, and actually by doing that it may catch some factors that we may not have necessarily paid attention to on a regular basis.”

While he called it a “well-done study,” Dr. Coz cautioned that “we have to be conservative in how to interpret and apply this because it is retrospective,” adding that future research should also use a prospective cohort.

For future consideration, Dr. Pellicori said that, while EHRs provide a “rich source” of data for such risk calculators, systems differ greatly across hospitals and health care systems and don’t link easily.

Future research would focus on validating the model in other large national datasets and seeing if machine learning can improve its predictability, Dr. Pellicori said. “Whether such models can provide a real-time, refined risk assessment for all patients in both primary or secondary care settings and improve the efficacy, efficiency, and quality of health care is our long-term goal.”

Dr. Pellicori and Dr. Coz disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers in Scotland have developed a risk calculator using a large electronic health records database that has shown a high reliability in predicting the risk of death for patients hospitalized for chronic occlusive pulmonary disease (COPD), providing another potential tool for improving postdischarge survival in these patients.

In a study published online in the journal Pharmacological Research, Pierpalo Pellicori, MD, and colleagues reported that a few variables, including prescriptions and laboratory data in routine EHRs, could help predict a patient’s risk of dying within 90 days after a hospital stay for COPD. Dr. Pellicori is a clinical cardiologist and research fellow at the Robertson Center for Biostatistics at the University of Glasgow.

“Identification of patients at high risk is valuable information for multidisciplinary teams,” Dr. Pellicori said in a written comment. “It allows the most vulnerable patients to be highlighted and prioritized for consideration of optimized value-based care, and for anticipatory care plan discussions.”

The retrospective cohort study analyzed EHR records of 17,973 patients who had an unplanned hospitalization for COPD in the Glasgow area from 2011 to 2017. The risk calculator model achieved a potential accuracy of 80%.

The study noted that, while a number of models have been developed to calculate the risk of exacerbations, inpatient death and prognosis in patients hospitalized for COPD, most of those models were based on cohorts of 1000 patients or less.

“Older age, male sex, and a longer hospital stay were important predictors of mortality in patients with COPD,” Dr. Pellicori said. “We also found that use of commonly prescribed medications such as digoxin identify patients with COPD more likely to die, perhaps because many have underlying heart failure, a highly prevalent but frequently missed diagnosis.”

He noted that heart failure and COPD share many risk factors, signs, and symptoms, such as smoking history, peripheral edema, and breathlessness. “Distinguishing between COPD and heart failure can be difficult, but is very important, as appropriate treatment for heart failure can improve a patient’s quality of life and survival substantially in many cases.”

The study also found that routinely collected and inexpensive blood markers – such as hemoglobin, neutrophil/lymphocyte ratio, serum chloride, urea, creatinine, and albumin – can also improve predictability of outcomes.

For example, the study found a linear increase in mortality of blood hemoglobin concentration less than 14 g/dL, but higher levels posed no greater risk. Higher white blood cell and neutrophil counts and lower lymphocyte and eosinophil counts were associated with a worse prognosis.

The study also found a linear increase in mortality with serum sodium less than 140 mmol/L or serum chloride less than 105 mmol/L –  but that higher concentrations of each were associated with a worse outcome.

“Interestingly,” Pellicori added, “social deprivation was not associated with mortality in this cohort.”

The final predictive model included age, sex, length of stay, and just nine other variables. “The model can be applied easily in clinical practice, even if electronic records are not available, because there are only 12 variables,” Dr. Pellicori said. “These could easily be entered manually into the risk calculator that we provide.”

“What is notable about this risk calculator is that it uses some of the techniques of machine learning, although it’s not specifically machine learning,” Angel Coz, MD, a pulmonologist at the Cleveland Clinic Respiratory Institute, said in an interview. “But it’s a retrospective data analysis, and actually by doing that it may catch some factors that we may not have necessarily paid attention to on a regular basis.”

While he called it a “well-done study,” Dr. Coz cautioned that “we have to be conservative in how to interpret and apply this because it is retrospective,” adding that future research should also use a prospective cohort.

For future consideration, Dr. Pellicori said that, while EHRs provide a “rich source” of data for such risk calculators, systems differ greatly across hospitals and health care systems and don’t link easily.

Future research would focus on validating the model in other large national datasets and seeing if machine learning can improve its predictability, Dr. Pellicori said. “Whether such models can provide a real-time, refined risk assessment for all patients in both primary or secondary care settings and improve the efficacy, efficiency, and quality of health care is our long-term goal.”

Dr. Pellicori and Dr. Coz disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers in Scotland have developed a risk calculator using a large electronic health records database that has shown a high reliability in predicting the risk of death for patients hospitalized for chronic occlusive pulmonary disease (COPD), providing another potential tool for improving postdischarge survival in these patients.

In a study published online in the journal Pharmacological Research, Pierpalo Pellicori, MD, and colleagues reported that a few variables, including prescriptions and laboratory data in routine EHRs, could help predict a patient’s risk of dying within 90 days after a hospital stay for COPD. Dr. Pellicori is a clinical cardiologist and research fellow at the Robertson Center for Biostatistics at the University of Glasgow.

“Identification of patients at high risk is valuable information for multidisciplinary teams,” Dr. Pellicori said in a written comment. “It allows the most vulnerable patients to be highlighted and prioritized for consideration of optimized value-based care, and for anticipatory care plan discussions.”

The retrospective cohort study analyzed EHR records of 17,973 patients who had an unplanned hospitalization for COPD in the Glasgow area from 2011 to 2017. The risk calculator model achieved a potential accuracy of 80%.

The study noted that, while a number of models have been developed to calculate the risk of exacerbations, inpatient death and prognosis in patients hospitalized for COPD, most of those models were based on cohorts of 1000 patients or less.

“Older age, male sex, and a longer hospital stay were important predictors of mortality in patients with COPD,” Dr. Pellicori said. “We also found that use of commonly prescribed medications such as digoxin identify patients with COPD more likely to die, perhaps because many have underlying heart failure, a highly prevalent but frequently missed diagnosis.”

He noted that heart failure and COPD share many risk factors, signs, and symptoms, such as smoking history, peripheral edema, and breathlessness. “Distinguishing between COPD and heart failure can be difficult, but is very important, as appropriate treatment for heart failure can improve a patient’s quality of life and survival substantially in many cases.”

The study also found that routinely collected and inexpensive blood markers – such as hemoglobin, neutrophil/lymphocyte ratio, serum chloride, urea, creatinine, and albumin – can also improve predictability of outcomes.

For example, the study found a linear increase in mortality of blood hemoglobin concentration less than 14 g/dL, but higher levels posed no greater risk. Higher white blood cell and neutrophil counts and lower lymphocyte and eosinophil counts were associated with a worse prognosis.

The study also found a linear increase in mortality with serum sodium less than 140 mmol/L or serum chloride less than 105 mmol/L –  but that higher concentrations of each were associated with a worse outcome.

“Interestingly,” Pellicori added, “social deprivation was not associated with mortality in this cohort.”

The final predictive model included age, sex, length of stay, and just nine other variables. “The model can be applied easily in clinical practice, even if electronic records are not available, because there are only 12 variables,” Dr. Pellicori said. “These could easily be entered manually into the risk calculator that we provide.”

“What is notable about this risk calculator is that it uses some of the techniques of machine learning, although it’s not specifically machine learning,” Angel Coz, MD, a pulmonologist at the Cleveland Clinic Respiratory Institute, said in an interview. “But it’s a retrospective data analysis, and actually by doing that it may catch some factors that we may not have necessarily paid attention to on a regular basis.”

While he called it a “well-done study,” Dr. Coz cautioned that “we have to be conservative in how to interpret and apply this because it is retrospective,” adding that future research should also use a prospective cohort.

For future consideration, Dr. Pellicori said that, while EHRs provide a “rich source” of data for such risk calculators, systems differ greatly across hospitals and health care systems and don’t link easily.

Future research would focus on validating the model in other large national datasets and seeing if machine learning can improve its predictability, Dr. Pellicori said. “Whether such models can provide a real-time, refined risk assessment for all patients in both primary or secondary care settings and improve the efficacy, efficiency, and quality of health care is our long-term goal.”

Dr. Pellicori and Dr. Coz disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Heavier smoking significantly increased mortality in adults with progressive fibrosing interstitial lung disease (PF-ILD), based on data from 377 individuals.

The negative impact of smoking on pulmonary diseases is well documented, but the specific impact on patients with PF-ILD has not been well studied, Mark Platenburg, MD, of St. Antonious Hospital, Nieuwegein, the Netherlands, and colleagues wrote in Respiratory Medicine .

GaryPhoto/ThinkStock

“Patients with PF-ILD or IPF [idiopathic pulmonary fibrosis] are prone to early mortality, indicating a need for prognostic [bio]marker studies for precision medicine,” they said.

The researchers identified adults older than 18 years with PF-ILD who were diagnosed at a single center. All study participants had at least 10% fibrosis, and showed either a decline of at least 10% in forced vital capacity, a 5.0%-9.9% relative FVC decline plus progressive respiratory symptoms and/or an increase in extent of fibrosis on subsequent high-resolution (HRCT progression), or progressive respiratory symptoms and HRCT progression over 24 months after ILD diagnosis.

Pack-years of smoking was a prognostic variable; the researchers also compared median transplant-free survival in heavy smokers and mild to moderate smokers. They also investigated the association between smoking quantity and emphysema in the study population.

Overall, the increased risk for mortality was 11%, 22%, and 44% in patients with 10, 20, and 40 pack-years of smoking, respectively.

Both the unadjusted and adjusted hazard ratio for pack-years were significant (1.014, P < .001 and 1.011, P = .022, respectively).

The median transplant-free survival of ever-smokers versus never-smokers with PF-ILD was 3.3 years versus 4.8 years; median transplant-free survival was 3.0 years for heavy smokers and 3.8 years for mild to moderate smokers. Similarly, median survival was 4.2 years in never-smokers versus 3.0 years in former smokers.

Emphysema was significantly more comment in heavy smokers, compared with never smokers and mild to moderate smokers (P < .001 for both).

“We observed a gradual decrease in survival starting from never to mild-moderate and subsequent heavy smokers supporting our finding that [pack-years] is an independent predictor for mortality in PF-ILD,” the researchers wrote. “This is an important message that clinicians could convey to their ILD patients, but also to patients at-risk for ILD.”

The study findings were limited by several factors, mainly the retrospective design, incomplete data for some patients, and lack of data on comorbidities, the researchers noted. However, the results strengthen the evidence for the detrimental effect of heavy smoking in PF-ILD, they said. Consequently, “efforts to reduce pack-years in those with, and at risk for, PF-ILD may translate into a survival benefit and should have high priority in clinical practice.”

The study was supported by grants from ZonMw TopZorg Care and TZO. The researchers had no financial conflicts to disclose.

Heavier smoking significantly increased mortality in adults with progressive fibrosing interstitial lung disease (PF-ILD), based on data from 377 individuals.

The negative impact of smoking on pulmonary diseases is well documented, but the specific impact on patients with PF-ILD has not been well studied, Mark Platenburg, MD, of St. Antonious Hospital, Nieuwegein, the Netherlands, and colleagues wrote in Respiratory Medicine .

GaryPhoto/ThinkStock

“Patients with PF-ILD or IPF [idiopathic pulmonary fibrosis] are prone to early mortality, indicating a need for prognostic [bio]marker studies for precision medicine,” they said.

The researchers identified adults older than 18 years with PF-ILD who were diagnosed at a single center. All study participants had at least 10% fibrosis, and showed either a decline of at least 10% in forced vital capacity, a 5.0%-9.9% relative FVC decline plus progressive respiratory symptoms and/or an increase in extent of fibrosis on subsequent high-resolution (HRCT progression), or progressive respiratory symptoms and HRCT progression over 24 months after ILD diagnosis.

Pack-years of smoking was a prognostic variable; the researchers also compared median transplant-free survival in heavy smokers and mild to moderate smokers. They also investigated the association between smoking quantity and emphysema in the study population.

Overall, the increased risk for mortality was 11%, 22%, and 44% in patients with 10, 20, and 40 pack-years of smoking, respectively.

Both the unadjusted and adjusted hazard ratio for pack-years were significant (1.014, P < .001 and 1.011, P = .022, respectively).

The median transplant-free survival of ever-smokers versus never-smokers with PF-ILD was 3.3 years versus 4.8 years; median transplant-free survival was 3.0 years for heavy smokers and 3.8 years for mild to moderate smokers. Similarly, median survival was 4.2 years in never-smokers versus 3.0 years in former smokers.

Emphysema was significantly more comment in heavy smokers, compared with never smokers and mild to moderate smokers (P < .001 for both).

“We observed a gradual decrease in survival starting from never to mild-moderate and subsequent heavy smokers supporting our finding that [pack-years] is an independent predictor for mortality in PF-ILD,” the researchers wrote. “This is an important message that clinicians could convey to their ILD patients, but also to patients at-risk for ILD.”

The study findings were limited by several factors, mainly the retrospective design, incomplete data for some patients, and lack of data on comorbidities, the researchers noted. However, the results strengthen the evidence for the detrimental effect of heavy smoking in PF-ILD, they said. Consequently, “efforts to reduce pack-years in those with, and at risk for, PF-ILD may translate into a survival benefit and should have high priority in clinical practice.”

The study was supported by grants from ZonMw TopZorg Care and TZO. The researchers had no financial conflicts to disclose.

Heavier smoking significantly increased mortality in adults with progressive fibrosing interstitial lung disease (PF-ILD), based on data from 377 individuals.

The negative impact of smoking on pulmonary diseases is well documented, but the specific impact on patients with PF-ILD has not been well studied, Mark Platenburg, MD, of St. Antonious Hospital, Nieuwegein, the Netherlands, and colleagues wrote in Respiratory Medicine .

GaryPhoto/ThinkStock

“Patients with PF-ILD or IPF [idiopathic pulmonary fibrosis] are prone to early mortality, indicating a need for prognostic [bio]marker studies for precision medicine,” they said.

The researchers identified adults older than 18 years with PF-ILD who were diagnosed at a single center. All study participants had at least 10% fibrosis, and showed either a decline of at least 10% in forced vital capacity, a 5.0%-9.9% relative FVC decline plus progressive respiratory symptoms and/or an increase in extent of fibrosis on subsequent high-resolution (HRCT progression), or progressive respiratory symptoms and HRCT progression over 24 months after ILD diagnosis.

Pack-years of smoking was a prognostic variable; the researchers also compared median transplant-free survival in heavy smokers and mild to moderate smokers. They also investigated the association between smoking quantity and emphysema in the study population.

Overall, the increased risk for mortality was 11%, 22%, and 44% in patients with 10, 20, and 40 pack-years of smoking, respectively.

Both the unadjusted and adjusted hazard ratio for pack-years were significant (1.014, P < .001 and 1.011, P = .022, respectively).

The median transplant-free survival of ever-smokers versus never-smokers with PF-ILD was 3.3 years versus 4.8 years; median transplant-free survival was 3.0 years for heavy smokers and 3.8 years for mild to moderate smokers. Similarly, median survival was 4.2 years in never-smokers versus 3.0 years in former smokers.

Emphysema was significantly more comment in heavy smokers, compared with never smokers and mild to moderate smokers (P < .001 for both).

“We observed a gradual decrease in survival starting from never to mild-moderate and subsequent heavy smokers supporting our finding that [pack-years] is an independent predictor for mortality in PF-ILD,” the researchers wrote. “This is an important message that clinicians could convey to their ILD patients, but also to patients at-risk for ILD.”

The study findings were limited by several factors, mainly the retrospective design, incomplete data for some patients, and lack of data on comorbidities, the researchers noted. However, the results strengthen the evidence for the detrimental effect of heavy smoking in PF-ILD, they said. Consequently, “efforts to reduce pack-years in those with, and at risk for, PF-ILD may translate into a survival benefit and should have high priority in clinical practice.”

The study was supported by grants from ZonMw TopZorg Care and TZO. The researchers had no financial conflicts to disclose.

Younger and older patients with severe chronic obstructive pulmonary disease have similar pulmonary and physical health limitations, based on data from 1,058 adults.

Although chronic obstructive pulmonary disease (COPD) generally appears in older patients, the prevalence among adults aged 45-55 years was 6.5% in 2014-2015, wrote Rosanne J.H.C.G. Beijers, PhD, of Maastricht (the Netherlands) University Medical Center, and colleagues. However, data on the early-onset COPD phenotype are limited. In particular, the extent to which younger patients with early-onset severe COPD experienced the same physical and mental health problems as older patients with similar degree of airflow limitation has not been examined, they said.

In a study published in Clinical Nutrition, the researchers analyzed data from adults with COPD who were referred for pulmonary rehabilitation at a single center between July 2013 and August 2018. Severe disease was defined as FEV1< 50%, and early onset was defined as younger than 55 years. The mean age difference between older and younger patient groups was 15.8 years.

The study population included 79 individuals with early-onset severe disease, 54 with early-onset mild to moderate disease, 158 older adults with severe disease, and 103 older adults with mild to moderate disease. The researchers compared disease markers including body composition, physical performance, and mental health between the groups. A significantly greater proportion of the early-onset group were women, compared to the older group (64% vs. 44%).

In comparing early-onset and older patients with severe COPD, the researchers found that clinical characteristics were similar for body composition, skeletal muscle index, fat percentage, and bone mineral content, and for physical performance factors including the percent predicted maximal work capacity (Wmax), 6-minute walk test, and isokinetic strength. However, a higher prevalence of depression appeared in the early-onset severe-disease patients, compared with the older severe-disease patients (51.9% vs. 32.7%; P = .029).

Although the prevalence of depression was not based on a clinical diagnosis, this finding should prompt health care professionals to pay more attention to psychosocial and emotional well-being in early-onset severe COPD patients, the researchers noted.

In comparing early-onset severe-disease patients and early-onset patients with mild to moderate disease, patients with early-onset severe COPD had significantly lower exercise performance, based on a 6-minute walk test and percent predicted Wmax. However, body composition and isokinetic muscle strength were not significantly different between both early-onset groups.

The findings were limited by several factors including the relatively small number of early-onset patients and the lack of data on whether older patients were diagnosed with severe COPD at a younger age, and more research using age and lung function at the time of diagnosis is needed, the researchers noted. However, the results highlight the importance of early identification of patients at risk for early-onset severe COPD, they said. “Within these individuals at risk, special attention should also be paid to the development of extrapulmonary disease manifestations such as exercise limitations, impaired body composition, and psychological and emotional problems,” the researchers said. “Subsequently, intervention strategies need to be applied that not only focus on the regular advice of quitting smoking but also include decreasing the exposure to air pollutants and promoting a healthy lifestyle including physical activity and a healthy diet,” they added.

The study received no outside funding. Lead author Dr. Beijers had no financial conflicts to disclose.

Younger and older patients with severe chronic obstructive pulmonary disease have similar pulmonary and physical health limitations, based on data from 1,058 adults.

Although chronic obstructive pulmonary disease (COPD) generally appears in older patients, the prevalence among adults aged 45-55 years was 6.5% in 2014-2015, wrote Rosanne J.H.C.G. Beijers, PhD, of Maastricht (the Netherlands) University Medical Center, and colleagues. However, data on the early-onset COPD phenotype are limited. In particular, the extent to which younger patients with early-onset severe COPD experienced the same physical and mental health problems as older patients with similar degree of airflow limitation has not been examined, they said.

In a study published in Clinical Nutrition, the researchers analyzed data from adults with COPD who were referred for pulmonary rehabilitation at a single center between July 2013 and August 2018. Severe disease was defined as FEV1< 50%, and early onset was defined as younger than 55 years. The mean age difference between older and younger patient groups was 15.8 years.

The study population included 79 individuals with early-onset severe disease, 54 with early-onset mild to moderate disease, 158 older adults with severe disease, and 103 older adults with mild to moderate disease. The researchers compared disease markers including body composition, physical performance, and mental health between the groups. A significantly greater proportion of the early-onset group were women, compared to the older group (64% vs. 44%).

In comparing early-onset and older patients with severe COPD, the researchers found that clinical characteristics were similar for body composition, skeletal muscle index, fat percentage, and bone mineral content, and for physical performance factors including the percent predicted maximal work capacity (Wmax), 6-minute walk test, and isokinetic strength. However, a higher prevalence of depression appeared in the early-onset severe-disease patients, compared with the older severe-disease patients (51.9% vs. 32.7%; P = .029).

Although the prevalence of depression was not based on a clinical diagnosis, this finding should prompt health care professionals to pay more attention to psychosocial and emotional well-being in early-onset severe COPD patients, the researchers noted.

In comparing early-onset severe-disease patients and early-onset patients with mild to moderate disease, patients with early-onset severe COPD had significantly lower exercise performance, based on a 6-minute walk test and percent predicted Wmax. However, body composition and isokinetic muscle strength were not significantly different between both early-onset groups.

The findings were limited by several factors including the relatively small number of early-onset patients and the lack of data on whether older patients were diagnosed with severe COPD at a younger age, and more research using age and lung function at the time of diagnosis is needed, the researchers noted. However, the results highlight the importance of early identification of patients at risk for early-onset severe COPD, they said. “Within these individuals at risk, special attention should also be paid to the development of extrapulmonary disease manifestations such as exercise limitations, impaired body composition, and psychological and emotional problems,” the researchers said. “Subsequently, intervention strategies need to be applied that not only focus on the regular advice of quitting smoking but also include decreasing the exposure to air pollutants and promoting a healthy lifestyle including physical activity and a healthy diet,” they added.

The study received no outside funding. Lead author Dr. Beijers had no financial conflicts to disclose.

Younger and older patients with severe chronic obstructive pulmonary disease have similar pulmonary and physical health limitations, based on data from 1,058 adults.

Although chronic obstructive pulmonary disease (COPD) generally appears in older patients, the prevalence among adults aged 45-55 years was 6.5% in 2014-2015, wrote Rosanne J.H.C.G. Beijers, PhD, of Maastricht (the Netherlands) University Medical Center, and colleagues. However, data on the early-onset COPD phenotype are limited. In particular, the extent to which younger patients with early-onset severe COPD experienced the same physical and mental health problems as older patients with similar degree of airflow limitation has not been examined, they said.

In a study published in Clinical Nutrition, the researchers analyzed data from adults with COPD who were referred for pulmonary rehabilitation at a single center between July 2013 and August 2018. Severe disease was defined as FEV1< 50%, and early onset was defined as younger than 55 years. The mean age difference between older and younger patient groups was 15.8 years.

The study population included 79 individuals with early-onset severe disease, 54 with early-onset mild to moderate disease, 158 older adults with severe disease, and 103 older adults with mild to moderate disease. The researchers compared disease markers including body composition, physical performance, and mental health between the groups. A significantly greater proportion of the early-onset group were women, compared to the older group (64% vs. 44%).

In comparing early-onset and older patients with severe COPD, the researchers found that clinical characteristics were similar for body composition, skeletal muscle index, fat percentage, and bone mineral content, and for physical performance factors including the percent predicted maximal work capacity (Wmax), 6-minute walk test, and isokinetic strength. However, a higher prevalence of depression appeared in the early-onset severe-disease patients, compared with the older severe-disease patients (51.9% vs. 32.7%; P = .029).

Although the prevalence of depression was not based on a clinical diagnosis, this finding should prompt health care professionals to pay more attention to psychosocial and emotional well-being in early-onset severe COPD patients, the researchers noted.

In comparing early-onset severe-disease patients and early-onset patients with mild to moderate disease, patients with early-onset severe COPD had significantly lower exercise performance, based on a 6-minute walk test and percent predicted Wmax. However, body composition and isokinetic muscle strength were not significantly different between both early-onset groups.

The findings were limited by several factors including the relatively small number of early-onset patients and the lack of data on whether older patients were diagnosed with severe COPD at a younger age, and more research using age and lung function at the time of diagnosis is needed, the researchers noted. However, the results highlight the importance of early identification of patients at risk for early-onset severe COPD, they said. “Within these individuals at risk, special attention should also be paid to the development of extrapulmonary disease manifestations such as exercise limitations, impaired body composition, and psychological and emotional problems,” the researchers said. “Subsequently, intervention strategies need to be applied that not only focus on the regular advice of quitting smoking but also include decreasing the exposure to air pollutants and promoting a healthy lifestyle including physical activity and a healthy diet,” they added.

The study received no outside funding. Lead author Dr. Beijers had no financial conflicts to disclose.

Patients with chronic obstructive pulmonary disease (COPD) who are both frail and who have poor lung function or dyspnea are at especially high risk of disability within 3 to 5 years as well as all-cause mortality years later, a prospective cohort study of community-dwelling adults has shown.

“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.

The study was published online Dec. 12 in the journal CHEST^®.

SLAS-1 and SLAS-2

Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.

Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.

Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.

Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
 

Frail or prefrail

Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.

This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.

Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.

Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
 

Frailty and mortality

Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.

“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.

Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.

Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
 

Frailty scoring system

Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.

The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.

The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.

A version of this article first appeared on Medscape.com.

Patients with chronic obstructive pulmonary disease (COPD) who are both frail and who have poor lung function or dyspnea are at especially high risk of disability within 3 to 5 years as well as all-cause mortality years later, a prospective cohort study of community-dwelling adults has shown.

“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.

The study was published online Dec. 12 in the journal CHEST^®.

SLAS-1 and SLAS-2

Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.

Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.

Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.

Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
 

Frail or prefrail

Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.

This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.

Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.

Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
 

Frailty and mortality

Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.

“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.

Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.

Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
 

Frailty scoring system

Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.

The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.

The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.

A version of this article first appeared on Medscape.com.

Patients with chronic obstructive pulmonary disease (COPD) who are both frail and who have poor lung function or dyspnea are at especially high risk of disability within 3 to 5 years as well as all-cause mortality years later, a prospective cohort study of community-dwelling adults has shown.

“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, MD, National University of Singapore, and colleagues explain.“Our results ... suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.

The study was published online Dec. 12 in the journal CHEST^®.

SLAS-1 and SLAS-2

Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2,804 participants 55 years of age and older from Sept. 2003 through Dec. 2004, while SLAS-2 recruited 3,270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3-5 years apart,” the investigators noted.

Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4,627 participants were eventually included in the analysis, of whom 1,162 patients had COPD and 3,465 patients did not. COPD was classified as mild if FEV1% was greater than or equal to 80%; moderate if FEV1% was greater than or equal to 50% to less than 80%, and severe if FEV1% was less than 50%.

Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefrail if they met one or two criteria.

Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.
 

Frail or prefrail

Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefrailty, while approximately 7% were classified as frail.

This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio of 1.86 (95% CI, 1.35-2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15-2.26), the investigators note.

Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04-2.08; 1.84-9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% less than 80% with either prefrailty, frailty, or dyspnea.

Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.
 

Frailty and mortality

Some 1,116 participants with COPD were followed for a mean of 2,981 days for mortality outcomes. Both FEV1% less than 50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio of 1.8 (95% CI, 1.24-2.68) compared to patients with an FEV1% greater than or equal to 80%. In combination with either FEV1% less than 80% or prefrailty/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.

“However, the mortality risk of participants with COPD was highest among those with FEV1% less than 80% and prefrailty/frailty,” the authors note, more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97-5.36). Interestingly, FEV1 less than 80% and prefrailty/frailty – both alone and in combination – were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.

Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.

Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.
 

Frailty scoring system

Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, Calif., noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told this news organization in an email.

The summary risk assessment tool developed and assessed is familiar: It carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits – frailty – can be codified and be part of a tool that is predictive of outcomes,” Dr. Gupta underscored.

The authors had no conflicts of interest to declare. Dr. Gupta disclosed that he is also an employee and shareholder at Genentech.

A version of this article first appeared on Medscape.com.

Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.

A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST^® authored by Charles R. Esther Jr. MD, PhD, and colleagues.

Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?

They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.

Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.

Addressing inflammation

“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the  patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,

The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.

The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
 

Study results

Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).

Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
 

Sputum tests needed

While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”

Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”

The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.

Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.

A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST^® authored by Charles R. Esther Jr. MD, PhD, and colleagues.

Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?

They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.

Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.

Addressing inflammation

“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the  patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,

The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.

The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
 

Study results

Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).

Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
 

Sputum tests needed

While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”

Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”

The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.

Examining sputum from patients with chronic obstructive pulmonary disease may help predict the course of the disease.

A mass spectrometric panel of biomarkers related to mucus hydration and inflammation examined in sputa showed elevated levels of metabolites from multiple pathways in patients with COPD. These correlated with sputum neutrophil counts and COPD exacerbations. In particular, sialic acid and hypoxanthine concentrations were strongly associated with disease severity, according to a study reported in the journal CHEST^® authored by Charles R. Esther Jr. MD, PhD, and colleagues.

Given that an improved understanding of the pathways associated with airway pathophysiology in COPD will identify new predictive biomarkers and novel therapeutic targets, Dr. Esther and colleagues posed the question: Which physiologic pathways are altered and predict exacerbations in the airways of subjects with COPD?

They noted that in persons with COPD – characterized by dominant small airway obstruction associated with airway inflammation – multiple inflammatory pathways, as well as indices of oxidative stress (including oxidized glutathione and 8-isoprostane), are elevated in sputum. Because inflammation is a challenging therapeutic target, identification of other biologic pathways involved in COPD pathogenesis could point to novel biomarkers and therapeutic targets.

Using this approach in cystic fibrosis (CF), the authors have previously identified small molecule metabolites correlated with airway inflammation. Findings from that research supported development of a mass spectrometric biomarker panel for simultaneous measurement of inflammatory markers coupled to biomarkers of mucus hydration. The researchers applied this technology to sputum supernatants collected through the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which included subjects with COPD, as well as relevant smoking and nonsmoking controls.

Addressing inflammation

“Inhaled steroids are really more effective for allergic inflammation as in asthma and less so for the neutrophilic inflammation that dominates in COPD. The challenge is that neutrophilic inflammation is also a key response to infection, and it’s really hard to find an anti-inflammatory that suppresses neutrophilic inflammation well enough to get clinical benefit but not so much that the  patient becomes vulnerable to infection. Lots of clinical trials of anti-inflammatories in cystic fibrosis or COPD have been stopped because treated subjects had more trouble with infection,” Dr. Esther stated in an interview,

The investigators analyzed cell-free sputum supernatants from 980 subjects, including samples from 77 healthy nonsmokers (NS), 341 ever-smokers with preserved spirometry (SPS), and 562 subjects with COPD (178 GOLD [Global Initiative for Chronic Obstructive Lung Disease]1, 303 GOLD 2, and 81 GOLD 3). Among the subjects with COPD, elevated biomarkers from multiple pathways correlated with sputum neutrophil counts.

The most significant analytes (at FDR [False Discovery Rate] 0.1) were sialic acid (a mucin marker), hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione, with sialic acid and hypoxanthine strongly associated with measures of disease severity. Elevation of sialic acid and hypoxanthine were associated with shorter time to exacerbation and improved prediction models of future exacerbations.
 

Study results

Sialic acid was elevated in all GOLD groups relative to NS healthy controls, with a 2.8-fold (0.44 log) increase in GOLD 2 and 3.7 fold (0.56 log) increase in GOLD 3 relative to NS. Sialic acid was also elevated in the most severe disease cohorts (GOLD 2 and GOLD 3) relative to smokers with preserved spirometry (SPS) and those with less severe disease (GOLD 1).

Because mucin secretion and inflammation are also related to the pathophysiology of pulmonary exacerbations, Dr. Esther and colleagues had hypothesized that sputum biomarkers would be predictive of future exacerbations. Within the full cohort, both sialic acid and hypoxanthine were significantly elevated in those who had multiple (two or more) pulmonary exacerbations relative to those who had none (P = .001). Similar, though less significant findings were observed for xanthine (P = .01), methylthioadenosine (P = .01), adenine (P = .01), and glutathione (P = .01).
 

Sputum tests needed

While tests still need to be developed, Dr. Esther noted in an interview that they would be based on well-established technologies commonly utilized in clinical laboratories. “Sputum biomarkers of mucus hydration and adenosine metabolism could help clinicians predict which patients with COPD are likely to experience multiple pulmonary exacerbations. Tests would be applied to patients with COPD at higher risk for exacerbations; for example, those who have low lung function or a history of prior exacerbations.”

Dr. Esther noted that these biomarkers could be helpful in developing novel therapies. “Using sialic acid to assess mucus concentrations is much easier than other methods, so it could help in developing mucolytic treatments. Also, adenosine metabolism represents a novel therapeutic target in COPD. Drugs that modify adenosine metabolism that have been approved for other diseases such as gout could be tested in COPD. As with mucus hydration, the biomarkers we identified (particularly hypoxanthine) could be utilized to make sure that novel therapies are having the intended impact on airway adenosine metabolism.”

The research was supported by SPIROMICS (funded by NIH and the COPD Foundation). Dr. Esther reported having no relevant disclosures.

Concomitant rhinosinusitis without nasal polyps (RSsNP) in patients with chronic obstructive pulmonary disease (COPD) is associated with a poorer, disease-specific, health-related quality of life (HRQoL), a Norwegian study is showing.

“Chronic rhinosinusitis has an impact on patients’ HRQoL,” lead author Marte Rystad Øie, Trondheim (Norway) University Hospital, said in an interview.

“We found that RSsNP in COPD was associated with more psychological issues, higher COPD symptom burden, and overall COPD-related HRQoL after adjusting for lung function, so RSsNP does have clinical relevance and [our findings] support previous studies that have suggested that rhinosinusitis should be recognized as a comorbidity in COPD,” she emphasized.

The study was published in the Nov. 1 issue of Respiratory Medicine.
 

Study sample

The study sample consisted of 90 patients with COPD and 93 control subjects, all age 40-80 years. “Generic HRQoL was measured with the Norwegian version of the SF-36v2 Health Survey Standard questionnaire,” the authors wrote, and responses were compared between patients with COPD and controls as well as between subgroups of patients who had COPD both with and without RSsNP.

Disease-specific HRQoL was assessed by the Sinonasal Outcome Test-22 (SNOT-22); the St. Georges Respiratory Questionnaire (SGRQ), and the COPD Assessment Test (CAT), and responses were again compared between patients who had COPD with and without RSsNP. In the COPD group, “severe” and “very severe” airflow obstruction was present in 56.5% of patients with RSsNP compared with 38.6% of patients without RSsNP, as Ms. Øie reported.

Furthermore, total SNOT-22 along with psychological subscale scores were both significantly higher in patients who had COPD with RSsNP than those without RSsNP. Among those with RSsNP, the mean value of the total SNOT-22 score was 36.8 whereas the mean value of the psychological subscale score was 22.6. Comparable mean values among patients who had COPD without RSsNP were 9.5 and 6.5, respectively (P < .05).

Total scores on the SGRQ were again significantly greater in patients who had COPD with RSsNP at a mean of 43.3 compared with a mean of 34 in those without RSsNP, investigators observe. Similarly, scores for the symptom and activity domains again on the SGRQ were significantly greater for patients who had COPD with RSsNP than those without nasal polyps. As for the total CAT score, once again it was significantly higher in patients who had COPD with RSsNP at a mean of 18.8 compared with a mean of 13.5 in those without RSsNP (P < .05).

Indeed, patients with RSsNP were four times more likely to have CAT scores indicating the condition was having a high or very high impact on their HRQoL compared with patients without RSsNP (P < .001). As the authors pointed out, having a high impact on HRQoL translates into patients having to stop their desired activities and having no good days in the week.

“This suggests that having RSsNP substantially adds to the activity limitation experienced by patients with COPD,” they emphasized. The authors also found that RSsNP was significantly associated with poorer physical functioning after adjusting for COPD as reflected by SF-36v2 findings, again suggesting that patients who had COPD with concomitant RSsNP have an additional limitation in activity and a heavier symptom burden.

As Ms. Øie explained, rhinosinusitis has two clinical phenotypes: that with nasal polyps and that without nasal polyps, the latter being twice as prevalent. In fact, rhinosinusitis with nasal polyps is associated with asthma, as she pointed out. Given, however, that rhinosinusitis without polyps is amenable to treatment with daily use of nasal steroids, it is possible to reduce the burden of symptoms and psychological stress associated with RSsNP in COPD.

Limitations of the study include the fact that investigators did not assess patients for the presence of any comorbidities that could contribute to poorer HRQoL in this patient population.

The study was funded by Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Concomitant rhinosinusitis without nasal polyps (RSsNP) in patients with chronic obstructive pulmonary disease (COPD) is associated with a poorer, disease-specific, health-related quality of life (HRQoL), a Norwegian study is showing.

“Chronic rhinosinusitis has an impact on patients’ HRQoL,” lead author Marte Rystad Øie, Trondheim (Norway) University Hospital, said in an interview.

“We found that RSsNP in COPD was associated with more psychological issues, higher COPD symptom burden, and overall COPD-related HRQoL after adjusting for lung function, so RSsNP does have clinical relevance and [our findings] support previous studies that have suggested that rhinosinusitis should be recognized as a comorbidity in COPD,” she emphasized.

The study was published in the Nov. 1 issue of Respiratory Medicine.
 

Study sample

The study sample consisted of 90 patients with COPD and 93 control subjects, all age 40-80 years. “Generic HRQoL was measured with the Norwegian version of the SF-36v2 Health Survey Standard questionnaire,” the authors wrote, and responses were compared between patients with COPD and controls as well as between subgroups of patients who had COPD both with and without RSsNP.

Disease-specific HRQoL was assessed by the Sinonasal Outcome Test-22 (SNOT-22); the St. Georges Respiratory Questionnaire (SGRQ), and the COPD Assessment Test (CAT), and responses were again compared between patients who had COPD with and without RSsNP. In the COPD group, “severe” and “very severe” airflow obstruction was present in 56.5% of patients with RSsNP compared with 38.6% of patients without RSsNP, as Ms. Øie reported.

Furthermore, total SNOT-22 along with psychological subscale scores were both significantly higher in patients who had COPD with RSsNP than those without RSsNP. Among those with RSsNP, the mean value of the total SNOT-22 score was 36.8 whereas the mean value of the psychological subscale score was 22.6. Comparable mean values among patients who had COPD without RSsNP were 9.5 and 6.5, respectively (P < .05).

Total scores on the SGRQ were again significantly greater in patients who had COPD with RSsNP at a mean of 43.3 compared with a mean of 34 in those without RSsNP, investigators observe. Similarly, scores for the symptom and activity domains again on the SGRQ were significantly greater for patients who had COPD with RSsNP than those without nasal polyps. As for the total CAT score, once again it was significantly higher in patients who had COPD with RSsNP at a mean of 18.8 compared with a mean of 13.5 in those without RSsNP (P < .05).

Indeed, patients with RSsNP were four times more likely to have CAT scores indicating the condition was having a high or very high impact on their HRQoL compared with patients without RSsNP (P < .001). As the authors pointed out, having a high impact on HRQoL translates into patients having to stop their desired activities and having no good days in the week.

“This suggests that having RSsNP substantially adds to the activity limitation experienced by patients with COPD,” they emphasized. The authors also found that RSsNP was significantly associated with poorer physical functioning after adjusting for COPD as reflected by SF-36v2 findings, again suggesting that patients who had COPD with concomitant RSsNP have an additional limitation in activity and a heavier symptom burden.

As Ms. Øie explained, rhinosinusitis has two clinical phenotypes: that with nasal polyps and that without nasal polyps, the latter being twice as prevalent. In fact, rhinosinusitis with nasal polyps is associated with asthma, as she pointed out. Given, however, that rhinosinusitis without polyps is amenable to treatment with daily use of nasal steroids, it is possible to reduce the burden of symptoms and psychological stress associated with RSsNP in COPD.

Limitations of the study include the fact that investigators did not assess patients for the presence of any comorbidities that could contribute to poorer HRQoL in this patient population.

The study was funded by Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Concomitant rhinosinusitis without nasal polyps (RSsNP) in patients with chronic obstructive pulmonary disease (COPD) is associated with a poorer, disease-specific, health-related quality of life (HRQoL), a Norwegian study is showing.

“Chronic rhinosinusitis has an impact on patients’ HRQoL,” lead author Marte Rystad Øie, Trondheim (Norway) University Hospital, said in an interview.

“We found that RSsNP in COPD was associated with more psychological issues, higher COPD symptom burden, and overall COPD-related HRQoL after adjusting for lung function, so RSsNP does have clinical relevance and [our findings] support previous studies that have suggested that rhinosinusitis should be recognized as a comorbidity in COPD,” she emphasized.

The study was published in the Nov. 1 issue of Respiratory Medicine.
 

Study sample

The study sample consisted of 90 patients with COPD and 93 control subjects, all age 40-80 years. “Generic HRQoL was measured with the Norwegian version of the SF-36v2 Health Survey Standard questionnaire,” the authors wrote, and responses were compared between patients with COPD and controls as well as between subgroups of patients who had COPD both with and without RSsNP.

Disease-specific HRQoL was assessed by the Sinonasal Outcome Test-22 (SNOT-22); the St. Georges Respiratory Questionnaire (SGRQ), and the COPD Assessment Test (CAT), and responses were again compared between patients who had COPD with and without RSsNP. In the COPD group, “severe” and “very severe” airflow obstruction was present in 56.5% of patients with RSsNP compared with 38.6% of patients without RSsNP, as Ms. Øie reported.

Furthermore, total SNOT-22 along with psychological subscale scores were both significantly higher in patients who had COPD with RSsNP than those without RSsNP. Among those with RSsNP, the mean value of the total SNOT-22 score was 36.8 whereas the mean value of the psychological subscale score was 22.6. Comparable mean values among patients who had COPD without RSsNP were 9.5 and 6.5, respectively (P < .05).

Total scores on the SGRQ were again significantly greater in patients who had COPD with RSsNP at a mean of 43.3 compared with a mean of 34 in those without RSsNP, investigators observe. Similarly, scores for the symptom and activity domains again on the SGRQ were significantly greater for patients who had COPD with RSsNP than those without nasal polyps. As for the total CAT score, once again it was significantly higher in patients who had COPD with RSsNP at a mean of 18.8 compared with a mean of 13.5 in those without RSsNP (P < .05).

Indeed, patients with RSsNP were four times more likely to have CAT scores indicating the condition was having a high or very high impact on their HRQoL compared with patients without RSsNP (P < .001). As the authors pointed out, having a high impact on HRQoL translates into patients having to stop their desired activities and having no good days in the week.

“This suggests that having RSsNP substantially adds to the activity limitation experienced by patients with COPD,” they emphasized. The authors also found that RSsNP was significantly associated with poorer physical functioning after adjusting for COPD as reflected by SF-36v2 findings, again suggesting that patients who had COPD with concomitant RSsNP have an additional limitation in activity and a heavier symptom burden.

As Ms. Øie explained, rhinosinusitis has two clinical phenotypes: that with nasal polyps and that without nasal polyps, the latter being twice as prevalent. In fact, rhinosinusitis with nasal polyps is associated with asthma, as she pointed out. Given, however, that rhinosinusitis without polyps is amenable to treatment with daily use of nasal steroids, it is possible to reduce the burden of symptoms and psychological stress associated with RSsNP in COPD.

Limitations of the study include the fact that investigators did not assess patients for the presence of any comorbidities that could contribute to poorer HRQoL in this patient population.

The study was funded by Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Dr Darcy Marciniuk, of the University of Saskatchewan in Saskatchewan, Canada, discusses essential abstracts in the management of patients with COPD presented at the American College of Chest Physicians' annual meeting, CHEST 2020, which was held virtually this year because of the coronavirus.

Dr Marciniuk reviews new data from a phase 3 ETHOS substudy evaluating lung function decline in patients receiving inhaled corticosteroid (ICS)-containing therapies vs non–ICS-containing therapies. He also discusses a retrospective cohort study using Medicare data from 2012-2017 evaluating the association of noninvasive ventilation at home with risk for death, hospitalizations, and emergency room visits.

Additionally, he highlights a multi-institutional, post hoc analysis of the phase 3 IMPACT trial to estimate cardiovascular event risk following acute exacerbation in patients with COPD.

From another post hoc analysis, this one from the SUMMIT trial comparing fluticasone, vilanterol, and ICS/LABA with placebo, Dr Marciniuk reports on an investigation of all-cause mortality and severe exacerbation risk in a subgroup of patients with a history of exacerbation.

Finally, he highlights a retrospective cohort study using data from the US 2015 Inpatient Sample, which compared outcomes of patients admitted to hospitals with COPD exacerbations with and without mobility impairment.

--

Darcy D. Marciniuk, MD, Master FCCP, Professor, Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, University of Saskatoon, Saskatoon, Saskatchewan, Canada.

Darcy D. Marciniuk, MD, Master FCCP, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: Alberta Lung Association; AstraZeneca; Boehringer Ingelheim; Canadian Foundation for Healthcare Improvement; GlaxoSmithKline; Heath Canada; Lung Association of Saskatchewan; Mylan; Novartis; Saskatchewan Ministry of Health; Saskatchewan Health Authority; Yukon Health and Social Services
Received research funding (managed by University of Saskatchewan) from: AstraZeneca; Boehringer Ingelheim; Canada Health Infoway; Canadian Institute of Health Research; GlaxoSmithKline; Grifols; Lung Association of Saskatchewan; Lung Health Institute of Canada; Novartis; Sanofi; Saskatchewan Health Research Foundation; Schering-Plough
Serve(s) as deputy editor of: CHEST Journal.

Dr Darcy Marciniuk, of the University of Saskatchewan in Saskatchewan, Canada, discusses essential abstracts in the management of patients with COPD presented at the American College of Chest Physicians' annual meeting, CHEST 2020, which was held virtually this year because of the coronavirus.

Dr Marciniuk reviews new data from a phase 3 ETHOS substudy evaluating lung function decline in patients receiving inhaled corticosteroid (ICS)-containing therapies vs non–ICS-containing therapies. He also discusses a retrospective cohort study using Medicare data from 2012-2017 evaluating the association of noninvasive ventilation at home with risk for death, hospitalizations, and emergency room visits.

Additionally, he highlights a multi-institutional, post hoc analysis of the phase 3 IMPACT trial to estimate cardiovascular event risk following acute exacerbation in patients with COPD.

From another post hoc analysis, this one from the SUMMIT trial comparing fluticasone, vilanterol, and ICS/LABA with placebo, Dr Marciniuk reports on an investigation of all-cause mortality and severe exacerbation risk in a subgroup of patients with a history of exacerbation.

Finally, he highlights a retrospective cohort study using data from the US 2015 Inpatient Sample, which compared outcomes of patients admitted to hospitals with COPD exacerbations with and without mobility impairment.

--

Darcy D. Marciniuk, MD, Master FCCP, Professor, Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, University of Saskatoon, Saskatoon, Saskatchewan, Canada.

Darcy D. Marciniuk, MD, Master FCCP, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: Alberta Lung Association; AstraZeneca; Boehringer Ingelheim; Canadian Foundation for Healthcare Improvement; GlaxoSmithKline; Heath Canada; Lung Association of Saskatchewan; Mylan; Novartis; Saskatchewan Ministry of Health; Saskatchewan Health Authority; Yukon Health and Social Services
Received research funding (managed by University of Saskatchewan) from: AstraZeneca; Boehringer Ingelheim; Canada Health Infoway; Canadian Institute of Health Research; GlaxoSmithKline; Grifols; Lung Association of Saskatchewan; Lung Health Institute of Canada; Novartis; Sanofi; Saskatchewan Health Research Foundation; Schering-Plough
Serve(s) as deputy editor of: CHEST Journal.

Dr Darcy Marciniuk, of the University of Saskatchewan in Saskatchewan, Canada, discusses essential abstracts in the management of patients with COPD presented at the American College of Chest Physicians' annual meeting, CHEST 2020, which was held virtually this year because of the coronavirus.

Dr Marciniuk reviews new data from a phase 3 ETHOS substudy evaluating lung function decline in patients receiving inhaled corticosteroid (ICS)-containing therapies vs non–ICS-containing therapies. He also discusses a retrospective cohort study using Medicare data from 2012-2017 evaluating the association of noninvasive ventilation at home with risk for death, hospitalizations, and emergency room visits.

Additionally, he highlights a multi-institutional, post hoc analysis of the phase 3 IMPACT trial to estimate cardiovascular event risk following acute exacerbation in patients with COPD.

From another post hoc analysis, this one from the SUMMIT trial comparing fluticasone, vilanterol, and ICS/LABA with placebo, Dr Marciniuk reports on an investigation of all-cause mortality and severe exacerbation risk in a subgroup of patients with a history of exacerbation.

Finally, he highlights a retrospective cohort study using data from the US 2015 Inpatient Sample, which compared outcomes of patients admitted to hospitals with COPD exacerbations with and without mobility impairment.

--

Darcy D. Marciniuk, MD, Master FCCP, Professor, Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, University of Saskatoon, Saskatoon, Saskatchewan, Canada.

Darcy D. Marciniuk, MD, Master FCCP, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: Alberta Lung Association; AstraZeneca; Boehringer Ingelheim; Canadian Foundation for Healthcare Improvement; GlaxoSmithKline; Heath Canada; Lung Association of Saskatchewan; Mylan; Novartis; Saskatchewan Ministry of Health; Saskatchewan Health Authority; Yukon Health and Social Services
Received research funding (managed by University of Saskatchewan) from: AstraZeneca; Boehringer Ingelheim; Canada Health Infoway; Canadian Institute of Health Research; GlaxoSmithKline; Grifols; Lung Association of Saskatchewan; Lung Health Institute of Canada; Novartis; Sanofi; Saskatchewan Health Research Foundation; Schering-Plough
Serve(s) as deputy editor of: CHEST Journal.