Chest
Volume 130, Issue 6, December 2006, Pages 1726-1732
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Original Research: Asthma
Improvements in Distal Lung Function Correlate With Asthma Symptoms After Treatment With Oral Montelukast

https://doi.org/10.1378/chest.130.6.1726Get rights and content

Study objectives

The distal airways are likely to contribute to asthma pathobiology and symptoms but have rarely been specifically evaluated in relation to systemic oral therapy. We hypothesized that treatment with montelukast, an oral cysteinyl-leukotriene receptor antagonist, would improve both proximal and distal lung physiology in patients with mild asthma.

Design

Randomized, double-blind, crossover design.

Setting

Academic referral center.

Patients

Subjects with mild asthma limited to using short-acting inhaled β2-agonists.

Interventions

Nineteen subjects with mild asthma underwent a baseline assessment of lung function, lung mechanics, and symptoms, followed by randomization to therapy with montelukast, 10 mg taken in the evening, or placebo in a crossover, double-blind fashion. Each treatment phase lasted 4 weeks, with a 2-week washout period. A repeat evaluation was performed during the last week of each treatment phase.

Measurements and results

Montelukast resulted in improvement in (mean ± SD) proximal and distal lung function parameters (change in FEV1: montelukast, 0.16 ± 0.06 L; placebo, −0.05 ± 0.05 L; p = 0.008); change in specific conductance: montelukast, 7.2 ± 2.9% predicted; placebo, −17 ± 8% predicted; p = 0.007; change in % predicted residual volume [RV]: montelukast, 18.4 ± 8.3% predicted; placebo, 3.0 ± 2.9% predicted; p = 0.05). Improvement in symptoms (ie, wheeze and chest tightness) correlated with improvements in RV while receiving montelukast, but not while receiving placebo (Pearson coefficients: 0.55 and 0.66, respectively; p < 0.008 and 0.04, respectively).

Conclusions

The systemically acting oral agent montelukast improves proximal and distal lung physiology. Improvements in distal lung function correlate with improvements in asthma symptoms.

Section snippets

Subjects

Nineteen subjects 18 to 60 years of age with asthma, as defined by the American Thoracic Society,11 were recruited for the study. Subjects were required to have had a diagnosis of asthma for at least 6 months, to demonstrate an increase in FEV1 or FVC of ≥ 200 mL and 12% after receiving therapy with an inhaled bronchodilator, or to have a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) of < 8 mg/mL. In addition, they were required to demonstrate a residual volume

Subjects

Nineteen subjects met inclusion criteria, and their baseline characteristics are presented in Table 1. The subjects were considered to have mild asthma when FEV1 was 83% predicted, TLC was 107% predicted, and the geometric mean of the PC20 was 0.79 mg/mL.

Lung Physiology

See Table 2 for a summary of lung function studies prior to each treatment period and the change with montelukast and placebo, respectively. The p values represent a comparison between the change in the variable while the patient was receiving

Discussion

This study demonstrates that therapy with montelukast significantly improves asthma symptoms as well as physiology in both the proximal and distal lung compartments. The improvement in more proximal lung physiology is reflected by improvements in sGaw, while the distal lung compartment improvements are perhaps best reflected by a reduction in RV. The FEV1, a global measure of airway function, reflects the physiology of both the proximal and distal lung compartments, the conditions of which were

Conclusion

In summary, we determined that the systemic delivery of montelukast, at doses used clinically for the treatment of asthma, improved proximal and distal lung function in patients with mild asthma, particularly in those patients with evidence of air trapping, as demonstrated by an increase in RV. These improvements in distal lung function correlated significantly with improvements in asthma symptoms. This finding may explain why, in the face of modest FEV1 improvements with montelukast therapy,

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  • Cited by (0)

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    Drs. Kraft, Irvin, and Wenzel have served as speakers and consultants for Merck, Inc. Dr. Cairns received salary support and has been a speaker for Merck, Inc. Dr. Ellison and Mr. Pak have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    This research was supported by Merck, Inc.

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