Micheletto C, Tognella S, Visconti M, Pomari C, Trevisan F, Dal Negro R W
Lung Department, Orlandi Hospital, Bussolengo, Verona, Italy.
Allergy. 2004 Mar;59(3):289-94. doi: 10.1046/j.1398-9995.2003.00351.x.
Aspirin-induced asthma (AIA) is a clinical syndrome characterized by acute airway reaction to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS). The most recent etiological hypothesises is that an overexpression of the enzyme LTC(4) synthase occurs in AIA, with the consequent production of sulfidopeptide leukotrienes (LTs).
Aim of the present study was to assess the effect of Montelukast, a selective cys-LT receptor antagonist, on nasal function, nasal reactivity to ASA and blood markers of eosinophilic inflammation in mild-to-moderate AIA.
Thirty-six nonsmoker subjects with AIA (17 males, 22-52 years) performed a nasal provocation test (NPT) with lysine-aspirin (L-ASA) in baseline and after a 4-week Montelukast 10 mg or placebo treatment. Nasal function was assessed by the acoustic rhinomanometry, and they also performed a lung function test (forced expiratory volume in 1 s), and a blood sample for the eosinophil count and the eosinophil cationic protein (ECP) plasma measurements. After both treatments, all subjects repeated the NPT, the lung function, and the ECP and the eosinophil blood count.
t-Test was used to compare mean values +/- SD between groups, and P < 0.05 was assumed as the level for statistical significance.
Airway patency was never affected by the NPT with L-ASA. In baseline, NPT with L-ASA precipitated a nasal reaction in all subjects, with a substantial increase in nasal resistance (calculated resistance [REQ]; from 0.89 +/- 0.18 to 2.2 +/- 0.17 cmH(2)O/l/min in group M, P < 0.001; and from 0.91 +/- 0.48 to 2.3 +/- 0.21 cmH(2)O/l/min in group P, P < 0.001); and a significant reduction in total nasal volume in at least one nostril (volume [VOL]; from 11.1 +/- 3.2 to 8.1 +/- 4.1 cm(3) in the group M, P < 0.001, and from 12.3 +/- 4.1 to 7.9 +/- 4.5 cm(3) in the group P, P < 0.001). The nasal reaction to L-ASA remained unchanged following placebo, but it was completely minimized following a 4-week treatment with Montelukast. Also nasal function, the nasal symptom score, and the markers of eosinophilic inflammation proved significantly affected and improved by the active drug only.
Montelukast 10 mg daily for 4 weeks, but not placebo, improves nasal function and nasal response to Aspirin substantially in ASA-sensitive asthmatics.
阿司匹林诱发的哮喘（AIA）是一种临床综合征，其特征为对阿司匹林和其他非甾体抗炎药（NSAIDs）产生急性气道反应。最新的病因假说认为，AIA中白三烯C4（LTC4）合酶过度表达，进而产生硫肽白三烯（LTs）。
本研究旨在评估选择性半胱氨酰白三烯（cys-LT）受体拮抗剂孟鲁司特对轻至中度AIA患者鼻功能、对阿司匹林的鼻反应性及嗜酸性粒细胞炎症血液标志物的影响。
36例AIA非吸烟患者（17例男性，年龄22 - 52岁）在基线期及接受4周10 mg孟鲁司特或安慰剂治疗后，用赖氨酸阿司匹林（L-ASA）进行鼻激发试验（NPT）。通过鼻声反射测量法评估鼻功能，他们还进行了肺功能测试（第1秒用力呼气量），并采集血样检测嗜酸性粒细胞计数及血浆嗜酸性粒细胞阳离子蛋白（ECP）。两种治疗后，所有受试者重复NPT、肺功能测试、ECP及嗜酸性粒细胞血常规检查。
采用t检验比较组间均值±标准差，P < 0.05被视为具有统计学意义的水平。
L-ASA进行的NPT从未影响气道通畅性。在基线期，L-ASA进行的NPT使所有受试者出现鼻反应，鼻阻力显著增加（计算阻力[REQ]；M组从0.89±0.18增至2.2±0.17 cmH₂O/l/min，P < 0.001；P组从0.91±0.48增至2.3±0.21 cmH₂O/l/min，P < 0.001）；至少一个鼻孔的总鼻腔容积显著减小（容积[VOL]；M组从11.1±3.2降至8.1±4.1 cm³，P < 0.001，P组从12.3±4.1降至7.9±4.5 cm³，P < 0.001）。安慰剂治疗后对L-ASA的鼻反应未改变，但孟鲁司特治疗4周后该反应完全减轻。同样，仅活性药物显著影响并改善了鼻功能、鼻症状评分及嗜酸性粒细胞炎症标志物。
每日10 mg孟鲁司特治疗4周，而非安慰剂，可显著改善阿司匹林敏感哮喘患者的鼻功能及对阿司匹林的鼻反应。
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