Effect of montelukast on exhaled nitric oxide and nonvolatile markers of inflammation in mild asthma.
OBJECTIVE
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 (H(2)O(2)), and cysteinyl leukotrienes (cys-LTs), in the exhaled breath condensate of subjects with mild asthma.


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


METHODS
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 FEV(1) or concentration of H(2)O(2) 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 FEV(1) and H(2)O(2) levels in the exhaled breath condensate.
Sandrini
Alessandra
A
Asthma & Airway Centre of the Toronto Western Hospital, Division of Respiratory Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
Ferreira
Ivone M
IM
Gutierrez
Carlos
C
Jardim
Jose R
JR
Zamel
Noe
N
Chapman
Kenneth R
KR
D000085:Acetates / Q000494:pharmacology*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D018592:Cross-Over Studies; D003521:Cyclopropanes; D003545:Cysteine / Q000032:analysis*; D004311:Double-Blind Method; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis*; D018836:Inflammation Mediators / Q000032:analysis*; D015289:Leukotrienes / Q000032:analysis*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D012720:Severity of Illness Index; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D003521:Cyclopropanes; D018836:Inflammation Mediators; D015289:Leukotrienes; D011804:Quinolines; D013440:Sulfides; C112381:cysteinyl-leukotriene; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D003545:Cysteine; C093875:montelukast