Effects of montelukast treatment and withdrawal on fractional exhaled nitric oxide and lung function in children with asthma

Background: Leukotriene receptor antagonists (LTRAs) reduce fractional exhaled nitric oxide (FENO) concentrations in children with asthma, but the effect of LTRA withdrawal on FENO and lung function is unknown. We aimed to study the effect of treatment and withdrawal of montelukast, a LTRA, on airway inflammation as reflected by FENO and lung function in children with asthma. Methods: A double-blind, randomized, placebo controlled, parallel group study was undertaken in 14 atopic children with mild persistent asthma who were treated with oral montelukast (5 mg/d for 4 weeks) and 12 atopic children with mild persistent asthma who received matching placebo. A follow-up visit was performed 2 weeks after montelukast or placebo withdrawal. Results: Montelukast reduced FENO concentrations by 17% (p = 0.067), an effect that was more pronounced (35%) [p = 0.0029] when children with seasonal atopy who were exposed to relevant allergens during the treatment phase were excluded from analysis (n = 3). Compared to those at the end of treatment, FENO concentrations were increased 2 weeks after montelukast withdrawal (p = 0.023) concomitant with a reduction in absolute FEV₁ values (p = 0.011), FEV₁ percentage of predicted values (p = 0.006), FEV₁/FVC ratio (p = 0.002), and forced expiratory flow at 25% to 75% of FVC values (p = 0.021). These changes were not observed in the placebo group. Conclusions: LTRAs reduce FENO concentrations in children with asthma, and withdrawal can result in increased FENO values and worsening of lung function in children with asthma.