Changes in recommended treatments for mild and moderate asthma

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Applied Evidence

Changes in recommended treatments for mild and moderate asthma

J Fam Pract. 2004 September;53(9):692-700

By

Gregory J. Redding, MD

Stuart W. Stoloff, MD

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References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Practice recommendations

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

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

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

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

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

Search function

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

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

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

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

2002 Stepwise approach to asthma management

New criteria for classifying asthma severity

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

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

TABLE 1
Criteria for children with intermittent wheeze

Infants and young children meeting these criteria should receive controller therapy for asthma:

Significant exacerbations that occur <6 weeks apart
≥4 episodes of wheeze in the past year lasting >1 day and affecting sleep,

AND presence of risk factors for development of persistent asthma:

Atopic dermatitis or parental asthma,
OR 2 of the following:

– Diagnosis of allergic rhinitis
– >4% peripheral blood eosinophilia
– Wheezing apart from colds

Choosing pharmacologic treatment according to asthma classification

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

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