Inhaled corticosteroids do not prevent the development of asthma

Abstract

Question In children with early wheezing, does the use of inhaled corticosteroids (ICS) prevent loss of lung function or reduce the incidence of asthma later in childhood? Design Randomized, double-blind, controlled study. Setting South Manchester, United Kingdom. Participants 1073 children were followed prospectively, of whom 333 were eligible, and 200 began treatment. One hundred and seventy-three completed follow-up at 5 years of age. Intervention Fluticasone propionate 100 μg twice daily in young children who were randomized after either one prolonged (>1 month) or two medically confirmed wheezy episodes. The dose of study drug was reduced every 3 months to the minimum needed. If the symptoms were not under control by 3 months, open-label fluticasone propionate 100 μg twice daily was added to the treatment. Outcomes Children’s lung function (specific airways resistance [sRaw], forced expiratory volume in 1 second [FEV1]) and airway reactivity (eucapnic voluntary hyperventilation [EVH] challenge). Main Results The groups did not differ significantly in the proportion of children with current wheeze, physician-diagnosed asthma or use of asthma medication, lung function, or airway reactivity (percentage change in FEV1, adjusted mean for placebo 5.5% [95% CI −2.5-13.4]) vs for treatment 5.0% [−2.2-12.2], P = .87). There were no differences in the results after adjustment for open-label fluticasone propionate, nor between the two groups in the time before the open-label drug was added (estimated hazard ratio 1.12 [95% CI 0.73–1.73], P = .60) or the proportion needing the open-label drug. Conclusions The early use of inhaled fluticasone propionate for wheezing in preschool children had no effect on the natural history of asthma or wheeze later in childhood, and it did not prevent lung function decline or reduce airway reactivity. Commentary Asthma is characterized by chronic airway inflammation and obstructive lung physiology that frequently cause symptoms in early childhood. Studies in school-aged children with mild to moderate asthma demonstrated that inhaled corticosteroid (ICS) therapy improves asthma symptoms and airway hyperreactivity, but it does not improve lung function.1The Childhood Asthma Management Program Research GroupLong-term effects of budesonide or nedocromil in children with asthma.N Engl J Med. 2000; 343: 1054-1063Crossref PubMed Scopus (1297) Google Scholar Therefore, it has been hypothesized that an earlier intervention with anti-inflammatory therapy may be able to alter the natural course of asthma and prevent the decline in lung function over time. The IFWIN study instituted ICS therapy in preschool children after their second wheezing episode and failed to show any difference in lung function or asthma diagnosis at 5 years of age compared with placebo. This agrees with two recent studies (PEAK2Guilbert T.W. Morgan W.J. Zeiger R.S. Mauger D.T. Boehmer S.J. Szefler S.J. et al.Long-term inhaled corticosteroids in preschool children at high risk for asthma.N Engl J Med. 2006; 354: 1985-1997Crossref PubMed Scopus (884) Google Scholar and PAC3Bisgaard H. Hermansen M.N. Loland L. Halkjaer L.B. Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing.N Engl J Med. 2006; 354: 1998-2005Crossref PubMed Scopus (477) Google Scholar) that also did not demonstrate improvement in pulmonary function with chronic or intermittent ICS therapy in children with early wheezing. These studies suggest that the predisposition to asthma may be set very early in life and/or that development of asthma is insensitive to the effects of corticosteroids. These early treatment approaches are complicated by the high incidence of wheezing in preschool children, and the fact that these “early wheezers” are a heterogeneous population from which only a subgroup will progress to chronic asthma. Despite these findings, it is important to point out that the evidence remains strong that ICS therapy improves control of asthma symptoms in preschool children. Therefore, judicious use of ICS in early childhood is still warranted in those with chronic wheezing in accordance with established guidelines for the treatment of childhood asthma.