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Effect of Montelukast on Exhaled Nitric Oxide and Nonvolatile Markers of Inflammation in Mild Asthma^*

^* From the Asthma & Airway Centre of the Toronto Western Hospital (Drs. Sandrini, Ferreira, Gutierrez, Zamel, and Chapmen), Division of Respiratory Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; and the Respirology Division (Dr. Jardim), Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil.

Correspondence to: Kenneth R. Chapman, MD, MSc, FCCP, Asthma and Airway Centre of The University Health Network, Suite 4–011 ECW, 399 Bathurst St, Toronto, ON, Canada M5T 2S8; e-mail: kchapman{at}ca.inter.net

Study objectives: Leukotriene receptor antagonists appear to exert anti-inflammatory activity in asthma. We undertook the present study to evaluate the effect of montelukast on levels of exhaled nitric oxide (ENO) and two inflammatory markers, hydrogen peroxide (H₂O₂), and cysteinyl leukotrienes (cys-LTs), in the exhaled breath condensate of subjects with mild asthma.

Patients: Twenty stable subjects with mild asthma (15 women and 5 men; mean [± SD] age, 34.8 ± 12.6 years) were included in the study.

Intervention: A 1-week run-in period was followed by 2 weeks of treatment (with montelukast or placebo) that was administered in randomized, double-blind, crossover fashion. One week of washout followed each treatment arm.

Results: Montelukast significantly reduced the levels of ENO from baseline (median, 52.5 parts per billion [ppb]; 25th to 75th percentile, 37.8 to 101.8 ppb) during the entire treatment period (ie, day 1 to day 14), with the effect measurable as early as day 1 (median, 45.9 ppb; 25th to 75th percentile, 29.3 to 92.5 ppb) and with the maximal effect being observed on day 7 (median, 35.7 ppb; 25th to 75th percentile, 27.6 to 66.6 ppb). The levels of ENO did not change significantly with placebo therapy. Montelukast improved symptom score and reduced peak expiratory flow (PEF) variability. Changes in PEF variability correlated positively with changes in ENO (r = 0.46; p = 0.04). No significant changes in FEV₁ or concentration of H₂O₂ in the exhaled breath condensate were observed. Levels of cys-LTs were undetectable in the exhaled breath condensate.

Conclusions: We concluded that montelukast reduces the levels of ENO in patients with mild asthma, a finding that is compatible with an anti-inflammatory effect of montelukast, and that ENO appears to be more sensitive in detecting this effect than FEV₁ and H₂O₂ levels in the exhaled breath condensate.

Key Words: asthma • breath tests • hydrogen peroxide • leukotriene antagonists • leukotrienes • nitric oxide

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