Background: Inhaled corticosteroid therapy suppresses nitric oxide levels (NO) of airway origin but not necessarily NO of alveolar or small airway origin. Systemic therapy with an oral anti-leukotriene agent may suppress NO production in distal airways and alveoli not reached by inhaled therapy.
Methods: Adult patients with mild asthma were treated for 3 weeks with inhaled fluticasone 250 microg twice daily then with inhaled fluticasone plus oral montelukast 10 mg daily for 3 additional weeks. We monitored exhaled NO (eNO), spirometry, lung volumes, and asthma symptoms scores at baseline and at the end of each treatment period. In a subset of patients, we continued with montelukast monotherapy and repeated these measurements.
Results: In the 18 patients studied, pulmonary function parameters and asthma symptom scores were not altered significantly from baseline by any therapy. The total eNO at baseline was 55+/-35.3 ppb, dropping to 28.1+/-15.3 ppb (p=0.005) after 3 weeks of fluticasone and to 23.5+/-14 ppb (p=0.001 vs. baseline) after the addition of montelukast. The trend towards reduced total eNO with the combination therapy vs. monotherapy was not statistically significant. Alveolar eNO dropped from 4.2+/-2.4 at baseline to 3.0+/-1.5 (p=0.1) after fluticasone and then to 2.2+/-0.9 (p=0.08 vs. baseline) after fluticasone plus montelukast, increasing then to 3.8+/-1.8 after montelukast alone (p=0.6 vs. baseline).
Conclusions: Leukotriene receptor antagonists administered systemically might decrease small airway/alveolar sites of inflammation when combined to inhaled corticosteroid therapy.