Objectives

To evaluate whether administering inhaled corticosteroids to 24–36-month-old children at risk of developing asthma prevented the development of persistent asthma.

Background

The prevalence of asthma has increased in all age groups, but most particularly in children under the age of 18 years. Despite major advances in understanding the etiology and pathophysiology of asthma and the development of new therapeutic modalities to control symptoms and prevent exacerbations, effective therapies are not widely used in the pediatric health care community. Furthermore, the long-term effects and side effects of asthma medications in children, especially children under the age of 12 years, are not well understood. Treatment of school-age children using inhaled corticosteroids has been associated with improvements in asthma control, however these improvements were not sustained after medication discontinuation. The PEAK investigators hypothesized that a sustained effect may be observed in patients treated with inhaled corticosteroids early in life, prior to the development of persistent disease and chronic loss of lung function.

Participants

Enrolled children had no clinically significant medical disorders apart from wheezing or allergy and were at high risk for the persistence of asthma-like symptoms during their school years, according to a positive modified asthma predictive index.

Children who had received more than four months of treatment with inhaled corticosteroids before enrollment and/or whose asthma symptoms required inhaled corticosteroids during the run-in month were excluded from the trial.

A total of 285 children were randomly assigned to receive either the inhaled corticosteroid (fluticasone propionate [Flovent] at a dose of two 44-μg puffs) twice daily by metered-dose inhaler) or placebo for two years.

Design

PEAK was a multicenter, double-blind, randomized, placebo-controlled, parallel-group trial of inhaled fluticasone as compared with placebo in children two to three years of age who were at high risk for asthma.

During the enrollment period, total eosinophil, IgE measurements, and skin testing were performed. At randomization, evaluation of pulmonary function and Quality-of-Life (QOL) Questionnaires were completed. Lung function was measured by spirometry and oscillometry technique at 4-month intervals throughout the study. Bronchodilator reversibility and exhaled nitric oxide (ENO) studies were performed at the end of the treatment and observation periods.

The treatment period lasted for 2 years. Once the treatment period was completed, subjects entered an observation period of 1 year. The primary outcome was the difference between the study groups in the proportion of episode-free days during the year-long observation period. Episode-free days were defined as those during which there were no asthma-like symptoms, no unscheduled medical visits for respiratory symptoms, and no use of any supplementary asthma medications, including albuterol before exercise. Episode-free days were reported by the parents during interviews and were based on two-week recall.

Conclusions

The CARE-PEAK study did not show a statistically significant response in children at high risk for asthma. Although the use of inhaled corticosteroid reduced symptoms and exacerbations during the treatment period, it was not successful in decreasing the proportion of episode-free days, the number of exacerbations, or lung function during the observation year.

Guilbert TW, Morgan WJ, Zeiger RS, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354(19):1985-1997. doi:10.1056/NEJMoa051378

Request Data

Please note that researchers must be registered on this site to submit a request, and you will be prompted to log in. If you are not registered on this site, you can do so via the Request button. Registration is quick, easy and free.