Characterization of Within-Subject Responses to Fluticasone and Montelukast in Childhood Asthma
Authors: Banks James R. , Andrews Timothy 
Published: September 2006

Purpose of the Study.
Asthmatic individuals vary in their responses to inhaled corticosteroids (ICSs) and leukotriene antagonists (LTRAs). The authors of this study sought to determine if responses are concordant for both types of drugs and sought markers for responses.

Study Population.
Children (aged 6–17 years) with mild-to-moderate asthma. They had asthma symptoms or bronchodilator use on average at least 3 days/week over the preceding 4 weeks and improvement in forced expiratory volume in 1 second (FEV1) of ≥12% after maximal bronchodilation or methacholine PC20 (provocative concentration causing a 20% decrease in FEV1) of ≤12.5 mg/mL. Children with severe asthma were excluded, as were those with recent use of corticosteroid or LTRA.

Methods.
After a 5- to 10-day characterization phase, participants were randomly assigned to 1 of 2 crossover treatment sequences with 8-week periods of either active ICS (fluticasone 100 μg twice daily) or an age-appropriate dose of montelukast. During the active-treatment period for one drug, the participant received a placebo for the alternative drug. Baseline-only characterization included various asthma biomarkers. The primary outcome measure was percentage change in prebronchodilator FEV1 from baseline to the end of the treatment period. “Response” was defined as improvement in FEV1 of at least 7.5%.

Results.
Fifty-five percent of the 126 participants showed no response to either drug, whereas 23% responded to fluticasone alone, 17% responded to both, and 5% responded to montelukast alone. Compared with those who responded to neither drug, those who responded to fluticasone alone had higher exhaled nitric oxide, serum immunoglobulin E, serum eosinophilic cationic protein, and total eosinophil count, along with lower methacholine PC20 and lower pulmonary function. Favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use and response, along with higher exhaled nitric oxide and serum eosinophilic cationic protein levels and lower methacholine PC20 and pulmonary function.

Conclusions.
Responses to fluticasone and montelukast vary. Children with low pulmonary function or high levels of biomarkers should start with ICSs. In children with less severe disease, it would be reasonable to start with either ICSs or LTRAs. Asthma therapy might soon move from the current approach, which is based on mean responses in populations, to one predicated on a given person’s asthma phenotype and genotype.

Reviewer Comments.
The vast majority of asthmatic patients in a primary care practice can maintain excellent control with one or the other of the above-mentioned drugs as simple monotherapy. History is paramount in assessing asthma severity, especially because the above-described biomarkers are largely unavailable to the pediatrician. It is tantalizing to consider a time when we will be able to more accurately target successful treatment in advance.