PURPOSE: Bronchial and alveolar nitric oxide (NO) levels are increased in individuals with asthma. Oral medications may be more effective than inhaled medications in suppressing NO synthase in alveoli. The objectives of this study are to determine whether the addition of montelukast to inhaled fluticasone (FP) could result in further suppression of alveolar and bronchial eNO levels.
METHODS: Mild non-smoking asthmatics were enrolled if they had a baseline FEV1 greater than 80% of predicted and a baseline exhaled NO at 50 ml/second of greater than 20 ppb. For 3 weeks they inhaled FP 250 mcg bid; in the subsequent 3 weeks montelukast 10mg daily was added to this regimen. Exhaled NO was measured at five separate constant expiratory flow rates: 50, 100, 150, 200 and 250 ml/seconds. The technique of Soukias and George was used to calculate bronchial NO maximal flux and alveolar NO concentration.
RESULTS: 15 subjects were enrolled, with a mean (+ SD) age of 39 + 14 years and FEV1 87 + 14.2% of predicted. The baseline exhaled NO at 50ml/second was 60.75 + 37.43 ppb, dropping to 28.073 + 15.8 ppb (p=0.005) after FP. A further decrement was observed after the addiction of montelukast, to 21.22 + 10.75 ppb, although this trend was not statistically significant (p=0.18). Alveolar NO concentration was 2.16 + 1.81 ppb after FP, dropping to 1.67 + 1.49 ppb after montelukast (p=0.42). Bronchial NO maximal flux was 1.29 + 0.75 nl/second, dropping to 0.97 + 0.52 after with montelukast (p=0.26).
CONCLUSION: These pilot data show a trend towards reduction in both alveolar and bronchial sites of nitric oxide with the addition of montelukast to inhaled corticosteroid therapy.
CLINICAL IMPLICATIONS: The benefits of montelukast might be further explained by its action in both bronchial and alveolar sites of inflammation.
DISCLOSURE: Leandro Fritscher, No Product/Research Disclosure Information; Grant monies (from industry related sources) The study was supported by a research grant from Merck Canada.