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

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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.-

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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.

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

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

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

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

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

Safety of long-term ICS use in pregnant women

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

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

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

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

Effects of early treatment on asthma progression

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

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

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

Drug brand names

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

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