Bacharier LB, Phillips BR, Zeiger RS, et al. J Allergy Clin Immunol. 2008;122(6):1127–1135
PURPOSE OF THE STUDY. To examine the effectiveness of episodic use of an inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA) in preschool-aged children with moderate-to-severe intermittent wheezing associated with respiratory tract illness (RTI).
STUDY POPULATION. Children 12 to 59 months of age with ≥2 episodes of wheezing with RTI in the previous year and either 2 urgent care visits for wheezing, 2 wheezing episodes requiring oral steroid treatment (<6 courses), or 1 episode requiring urgent care and oral steroid treatment.
METHODS. The study design was a randomized, double-blind, placebo-controlled trial, with children assigned randomly to 1 of 3 treatment groups with instructions to treat for 7 days at the onset of each RTI-associated symptom set during a 12-month period: (1) budesonide suspension (1 mg twice daily) plus LTRA placebo, (2) montelukast (4 mg daily) plus ICS placebo, or (3) ICS placebo plus LTRA placebo. All groups received albuterol 4 times per day for the first 48 hours of illness plus as-needed dosing. Orally administered steroids were available if needed, but other asthma medications were prohibited. Symptom/treatment diaries were maintained, and clinic/telephone follow-up evaluations were conducted. The primary outcome was the proportion of episode-free days (EFDs). Secondary outcomes included severity of lower respiratory tract symptoms in the 14-day period after initiation of treatment, time to initiation and number of orally administered steroids, number of wheezing episodes, days missed from day care and work, caregiver quality of life, unscheduled visits because of acute wheezing, and linear growth.
RESULTS. Two hundred thirty-eight children were randomly assigned and were well matched with respect to baseline characteristics. Adherence to therapy was similar between the groups. EFDs did not differ among the 3 treatment groups (adjusted EFD mean: budesonide: 76%; montelukast: 73%; placebo: 74%). Relative to placebo, there were significant reductions in trouble breathing (budesonide: 37.5%; montelukast: 36.8%; P = .003) and interference with activity (budesonide: 31.9%; P = .01; montelukast: 39.6%; P = .001). Wheezing scores were reduced with montelukast (33.5%; P = .02) but not with budesonide (24.6%; P = .09). Overall, total symptom scores were reduced with montelukast (29.6%; P = .006) and budesonide (24.6%; P = .02). Among participants with positive asthma predictive index status, both budesonide and montelukast significantly reduced scores for trouble breathing (budesonide: 48.0%; P = .001; montelukast: 40.3%; P = .007) and activity interference (budesonide: 43.6%; montelukast: 53.7%; P < .001); only montelukast reduced wheezing (P = .049). Similar findings were seen for children with previous oral steroid therapy use.
CONCLUSIONS. For preschool-aged children with moderate-to-severe intermittent wheezing, episodic use of either budesonide or montelukast early in RTIs did not increase the proportion of EFDs. However episodic use of an ICS or LTRA decreased symptom burden, particularly for those with risk factors for asthma or greater illness severity (use of oral corticosteroid therapy).
REVIEWERS COMMENTS. This study was conducted to address an important clinical question: is the episodic use of an ICS or LTRA effective in decreasing the morbidity associated with severe intermittent wheezing in preschool-aged children? Using a unique study design, the authors demonstrated benefit for children with symptoms and treatment predictive of asthma, indicating consideration for the early use of antiinflammatory medications. Additional study is needed to address this important question fully.
- Copyright © 2009 by the American Academy of Pediatrics