Onset and duration of attenuation of exercise-induced bronchoconstriction in children by single-dose of montelukast

Abstract

Single-dose montelukast attenuates exercise-induced bronchoconstriction (EIB) in adults within 2 hours postdose and lasting through 24 hours. This study evaluated the onset and duration of EIB attenuation in children after a single dose of montelukast. A randomized, double-blind, placebo-controlled, two-period crossover study was performed. Patients (n = 66) aged 4-14 years, with preexercise forced expiratory volume in 1 second of (FEV(1)) ≥70% predicted and maximum percentage fall in FEV(1) of ≥20% at two screening exercise challenges were eligible. Patients were to receive single-dose montelukast (4 or 5 mg) or placebo before performing standardized exercise challenges at 2 and 24 hours postdose. A 3- to-7-day washout separated the two crossover periods. The primary end point was maximum percentage fall in FEV(1) after exercise challenge 2 hours postdose. Secondary end points included maximum percentage fall in FEV(1) after the 24-hour postdose challenge; each of the following at 2 and 24 hours postdose-maximum percentage fall in FEV(1) categorized as <10%, 10-20%, or >20%; area under the curve (AUC) during 60 minutes postchallenge; time to recovery of FEV(1) to within 5% of preexercise baseline; and need for rescue medication. The mean maximum percentage fall in FEV(1) after the 2-hour postdose exercise challenge was significantly attenuated after single-dose montelukast compared with placebo (15.35% versus 20.00%; p = 0.020). Montelukast was also significantly more effective than placebo for maximum percentage fall after the 24-hour challenge (12.92% versus 17.25%; p = 0.005), the categorized maximum percent fall in FEV(1) at 2 hours (p = 0.034), and AUC at 2 hours (p = 0.022) and 24 hours (p = 0.013). Single-dose montelukast provided rapid and sustained EIB attenuation in children. Clinicaltrials.gov identifier: NCT00534976.

Clinical effectiveness and safety of montelukast in asthma. What are the conclusions from clinical trials and meta-analyses?

“…The efficacy of montelukast for preventing a maximum decrease in forced expiratory volume in 1 second (FEV1) after exercise is significantly higher than that of FP, and the high leukotriene E4/fractional exhaled nitric oxide ratio is associated with a greater response to montelukast than to FP for EIB therapy 70. Another randomized, double-blind, placebo-controlled, two-period crossover study evaluated the onset and duration of EIB attenuation in children after a single dose of montelukast and found single-dose montelukast provided rapid and sustained EIB attenuation in children 71. Effect of montelukast was also shown to be better than salmeterol added to inhaled fluticasone on EIB in children in a randomized, double-blind, double-dummy, multicenter, two-period, 4-week, crossover study 72.…”

The role of leukotriene receptor antagonists in exercise induced bronchoconstriction in children

“…Effective treatment showed an increased AUC over a given time period when compared to a control. One study [3] measured the AUC for the first 60 min postexercise and found montelukast to be significantly more effective at attenuating EIB than placebo [3]. The results for AUC obtained by Stelmachet al demonstrate that coadministration of budesonide with montelukast, and montelukast monotherapy were significantly more efficacious than treatment with budesonide alone or budesonide with formoterol.…”

“…The therapeutic benefits were sustained for up to 8 h post-treatment. Wasfi et al evaluated the onset and duration of therapeutic effect, following a single dose of montelukast in a crossover study [3]. This study measured maximum percentage fall in FEV1 after EC, 2 and 24 h post-treatment.…”

“…outline the risk of bias in the articles we identified through computer based-searching as described above. [3].…”

“…Short acting beta agonists (SABAs) such as salbutamol can be used effectively prior to exercise, however their relatively short duration of action limits their benefit. Children often engage in unplanned physical activity, which can make EIB prophylaxis difficult [3]. There is a role for a medication which is long acting and effective in preventing bronchoconstriction.…”