Sandrini Alessandra, Ferreira Ivone M, Gutierrez Carlos, Jardim Jose R, Zamel Noe, Chapman Kenneth R
Asthma & Airway Centre of the Toronto Western Hospital, Division of Respiratory Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
Chest. 2003 Oct;124(4):1334-40. doi: 10.1378/chest.124.4.1334.
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.
Twenty stable subjects with mild asthma (15 women and 5 men; mean [+/- SD] age, 34.8 +/- 12.6 years) were included in the study.
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.
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.
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.
白三烯受体拮抗剂似乎在哮喘中发挥抗炎活性。我们进行本研究以评估孟鲁司特对轻度哮喘患者呼出气冷凝物中呼出气一氧化氮（ENO）水平以及两种炎症标志物过氧化氢（H₂O₂）和半胱氨酰白三烯（cys-LTs）的影响。
20名轻度哮喘稳定患者（15名女性和5名男性；平均[±标准差]年龄，34.8±12.6岁）纳入研究。
1周的导入期后是2周的治疗（使用孟鲁司特或安慰剂），采用随机、双盲、交叉方式给药。每个治疗组之后有1周的洗脱期。
在整个治疗期间（即第1天至第14天），孟鲁司特使ENO水平较基线显著降低（中位数，52.5十亿分之一[ppb]；第25至75百分位数，37.8至101.8 ppb），早在第1天就可检测到这种效应（中位数，45.9 ppb；第25至75百分位数，29.3至92.5 ppb），且在第7天观察到最大效应（中位数，35.7 ppb；第25至75百分位数，27.6至66.6 ppb）。安慰剂治疗时ENO水平无显著变化。孟鲁司特改善了症状评分并降低了呼气峰值流速（PEF）变异性。PEF变异性的变化与ENO的变化呈正相关（r = 0.46；p = 0.04）。未观察到呼出气体冷凝物中FEV₁或H₂O₂浓度有显著变化。呼出气冷凝物中未检测到cys-LTs水平。
我们得出结论，孟鲁司特可降低轻度哮喘患者的ENO水平，这一发现与孟鲁司特的抗炎作用相符，并且ENO在检测这种效应方面似乎比呼出气体冷凝物中的FEV₁和H₂O₂水平更敏感。
