Montelukast as Add-on Therapy to β-Agonists and Late Airway Response
Authors: Rangsithienchai Pitud A. , Phipatanakul Wanda 
Published: October 2008

Rosewich M, Rose MA, Eickmeier O, Travaci M, Kitz R, Zielen S. Eur Respir J. 2007;30(1):56–61

PURPOSE OF THE STUDY. To evaluate montelukast's ability to inhibit the late-phase airway response after allergen exposure in adults with house dust mite–induced asthma.

STUDY POPULATION. Thirty-five adults (19 men, 16 women) aged 18 to 31 with mild, stable asthma and sensitivity to house dust mites were included.

METHODS. This study was designed as a randomized, double-blind, single-dose, placebo-controlled, crossover trial. Subjects underwent serum testing for antigen-specific immunoglobulin E (IgE) to house dust mite. Sensitized subjects were then examined for airway infections and underwent spirometry and determination of their fraction of nitric oxide in exhaled air (FeNO). They were then challenged with increasing concentrations of inhaled Dermatophagoides farinae via a nebulizer system. Testing was stopped when the patient's forced expiratory volume in 1 second (FEV1) decreased at least 20% (early airway response [EAR]), they experienced significant clinical symptoms, or they received a cumulative dose of 1270 mg. Patients were then given 1 puff of salbutamol (0.1 mg) and either montelukast (10 mg) or a placebo. FEV1 was measured for the following 8 hours with a decrease of at least 20% demonstrating a late airway response (LAR). Formoterol (12 μg) was then given to treat those patients. Subjects returned at least 2 weeks later and were crossed-over into the other group.

RESULTS. Of the 35 subjects in the study, 12 showed no significant EAR on 1 or both study days, 11 showed only an EAR, and 12 demonstrated both an EAR and LAR. This last group was analyzed further. The difference in FEV1 from baseline values 3 to 8 hours after challenge was expressed as the area under the FEV1 time-response curve (FEV1-AUC). The FEV1-AUC of patients on placebo was −2.47 ± 1.32 vs −0.768 ± 1.68 for the patients on montelukast (P &lt; .005). Subjects with a dual response had a significantly higher baseline FeNO than those with no response (56.4 vs 21.0 ppb; P &lt; .05).

CONCLUSIONS. Montelukast was able to block the late-phase airway response in subjects who responded dually to the allergen challenge. In addition, patients with a higher baseline FeNO seemed more likely to develop an LAR than those with lower ones.

REVIEWER COMMENTS. The results of this study implicate a role for montelukast as an “add-on,” therapeutic option for symptomatic relief after allergen exposure in subjects with mild asthma. It also suggests a rapid onset of action that allows for its usage in such a setting. This study supports existing ones that have demonstrated the effect of montelukast within 2 to 3 hours for up to 24 hours. There was also a “trend toward significance” showing subjects on montelukast with higher FEV1 values than those on placebo. However, this study was limited in its sample size and should be expanded to fully elicit montelukast's role in acute exacerbations. It would also be worthwhile to investigate its effects on subjects with moderate-to-severe asthma in the same setting. Last, this study also alluded to the fact that a patient's baseline FeNO may be a predictor of whether he or she develops an LAR. This should also be explored further in expanded studies and in children.