Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing

Abstract

Background: Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity.

Objectives: We sought to examine the effectiveness of episodic use of an inhaled corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing.

Methods: In a randomized, double-blind, placebo-controlled 12-month trial, 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension (1 mg twice daily), montelukast (4 mg daily), or placebo in addition to albuterol with each identified respiratory tract illness (RTI). Proportion of episode-free days (EFDs) during the 12-month trial was the primary outcome.

Results: The 3 treatment groups did not differ in proportions of EFDs, with adjusted mean EFDs of 76% (95% CI, 70% to 81%) for budesonide, 73% (95% CI, 66% to 79%) for montelukast, and 74% (95% CI, 65% to 81%) for conventional therapy (P = .66). The 3 groups did not differ in oral corticosteroid use, health care use, quality of life, or linear growth. However, during RTIs, budesonide and montelukast therapy led to modest reductions in trouble breathing (38% [P = .003] and 37% [P = .003], respectively) and interference with activity scores (32% [P = .01] and 40% [P = .001], respectively) that were most evident in those with positive asthma predictive indices.

Conclusions: In preschool children with moderate-to-severe intermittent wheezing, episodic use of either budesonide or montelukast early in RTIs, when added to albuterol, did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period. However, indicators of severity of acute illnesses were reduced, particularly in children with positive asthma predictive indices.

Trial registration: ClinicalTrials.gov NCT00000622.

Figure 1. Enrollment and outcome

Treatment failure rates were comparable across treatment groups (p=0.5). Dropouts were more frequent in the montelukast group (12.6%) compared to budesonide (5.2%) and the conventional therapy group (2.1%) (p=0.04 across groups) and were predominantly due to loss to follow-up.

Figure 2. Area Under the Curve (AUC) during respiratory tract illnesses

Area under the curve was calculated for the 14 days following initiation of study medication (shaded in dark grey) for symptoms scores of trouble breathing score (Panel A), interference with activity score (Panel B), wheezing (Panel C), daytime cough (Panel D), and mean total symptom score (Panel E). This value was analyzed as a difference from ‘baseline’ symptom levels, defining baseline as twice the AUC from Days −13 to −7, which preceded onset of symptoms (shaded in light grey). The tables present the AUCs (95% CIs) and p-values comparing each active therapy to conventional therapy. There were no significant differences between montelukast and budesonide for any of these symptom measures (p>0.4). * Mean of Daytime Cough + Wheezing + Trouble Breathing + Interference with Activity

Figure 2. Area Under the Curve (AUC) during respiratory tract illnesses

Area under the curve was calculated for the 14 days following initiation of study medication (shaded in dark grey) for symptoms scores of trouble breathing score (Panel A), interference with activity score (Panel B), wheezing (Panel C), daytime cough (Panel D), and mean total symptom score (Panel E). This value was analyzed as a difference from ‘baseline’ symptom levels, defining baseline as twice the AUC from Days −13 to −7, which preceded onset of symptoms (shaded in light grey). The tables present the AUCs (95% CIs) and p-values comparing each active therapy to conventional therapy. There were no significant differences between montelukast and budesonide for any of these symptom measures (p>0.4). * Mean of Daytime Cough + Wheezing + Trouble Breathing + Interference with Activity

Figure 2. Area Under the Curve (AUC) during respiratory tract illnesses

Area under the curve was calculated for the 14 days following initiation of study medication (shaded in dark grey) for symptoms scores of trouble breathing score (Panel A), interference with activity score (Panel B), wheezing (Panel C), daytime cough (Panel D), and mean total symptom score (Panel E). This value was analyzed as a difference from ‘baseline’ symptom levels, defining baseline as twice the AUC from Days −13 to −7, which preceded onset of symptoms (shaded in light grey). The tables present the AUCs (95% CIs) and p-values comparing each active therapy to conventional therapy. There were no significant differences between montelukast and budesonide for any of these symptom measures (p>0.4). * Mean of Daytime Cough + Wheezing + Trouble Breathing + Interference with Activity