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[摘要] 目的 探讨孟鲁司特联合酮替酚对咳嗽变异性哮喘（CVA）患者金属蛋白酶（MMP）-2、9水平的影响及疗效观察。 方法 将90例CVA患者随机分为观察组和对照组。两组予以舒喘灵气雾剂治疗，咳嗽消失后停药。观察组加用孟鲁司特咀嚼片（10 mg/次，1次/d，口服）联合酮替酚片（1 mg/次，2次/d，口服）治疗，对照组予以单纯孟鲁司特咀嚼片治疗，剂量与用法同观察组，两组疗程8周。 结果 治疗8周后，两组血清MMP-2和MMP-9均明显下降（P<0.05或P<0.01），且观察组下降较对照组更明显（P<0.05）；观察组总有效率较对照组更明显（χ2=4.41，P<0.05）。对照组发生不良反应3例，观察组6例，症状均较轻微，两组比较差异不明显（χ2=0.49，P>0.05）。随访1年，观察组复发率低于对照组（χ2=6.33，P<0.05）。 结论 孟鲁司特联合酮替酚治疗CVA的效果及安全性均较好，且能降低复发率，作用可能与降低血清MMP-2和MMP-9水平密切相关。
[关键词] 咳嗽变异性哮喘；孟鲁司特；酮替酚；金属蛋白酶-2；金属蛋白酶-9；复发
[中图分类号] R725.6 [文献标识码] B [文章编号] 1673-9701（2015）04-0070-03
[Abstract] Objective To discuss curative effect and influence on plasma of MMP-2 and MMP-9 levels of Montelukast combined with ketotifen on cough variant asthma （CVA）. Methods A total of 90 cases of patients with CVA were divided into observation group and control group by numeration table at random. The patients in two groups were given Salbutamol Aerosol treatment until the disappearing of cough. The patients in observation group were additionally given Montelukast Dulcets（10 mg per time， once a day， through the mouth） combined with ketotifen tablets （1 mg per time， twice a day， through the mouth）， while the patients in control group were given the pure Montelukast Dulcets with the same dose and method as those in observation group， for 8 weeks as the course of treatment. Results After 8 weeks’treatment， the plasma MMP-2 and MMP-9 levels descended significantly（P<0.05 or P<0.01），and the rangeabilities of budesonide group were more significantly obviously than those in control group（P<0.05）， and the total efficiency of patients in observation group was much higher than that in control group （χ2=4.41，P<0.05）， 3 and 6 cases of untoward effect appeared in control group and observation group respectively， with light symptom and the untoward effect occurrence rates of patients in two groups appeared no obvious differences after comparison（χ2=0.49，P>0.05）. According to the one-year following-up after the withdrawal of drugs， reoccurrence rate of patients in observation group was much lower than that in control group（χ2=6.33，P<0.05）. Conclusion Montelukast combined with Ketotifen has favorable clinical curative effect on CVA with high security，and can reduce the reoccurrence rate. May its mechanism relates to down-regulating MMP-2 and MMP-9.
[Key words] Cough variant asthma；Montelukast；Ketotifen；MMP-2；MMP-9；Reoccurrence
咳嗽变异性哮喘（cough variant asthma， CVA）是一种隐匿型哮喘，以慢性顽固性干嗽为主要表现，易误诊，部分患者可发展为典型哮喘[1]。研究证实CVA病理机制与典型哮喘基本相似，近年来研究已证实，慢性气道炎症与气道重构在其中起极其重要的作用，基质金属蛋白酶（MMPs）是引起哮喘患者气道慢性炎症与气道重构的主要原因[2]。酮替酚是临床较常用的抗变态反应药，具有较好的抗过敏和抗炎作用，治疗CVA的近期疗效较好，但治疗后病情易复发[3]。孟鲁司特是一种常用的非甾体抗炎药，近年来研究发现其治疗及预防CVA复发疗效较好，但其联合酮替酚治疗CVA目前报道不多[4，5]。本研究观察了孟鲁司特联合酮替酚对CVA的血清MMP-2、9水平的影响及疗效，现报道如下。 1 资料与方法
1.1 一般资料
选取我院内科门诊2011年1月～2013年5月就诊的CVA患者90例。纳入标准：均符合《咳嗽的诊断与治疗指南（2009版）》中的诊断标准[6]。排除标准：慢性扁桃体炎、腺样体肥大、鼻窦炎、结核、鼻后滴漏综合征或气道异物等引起的慢性咳嗽。采用随机数字表法将其分为观察组（n=45）和对照组（n=45）；两组患者的性别构成、年龄分布和发病时间等比较差异无统计学意义（P>0.05），具有可比性。
1.2 治疗方法
两组均予以舒喘灵气雾剂200 μg/次，隔6～8 h 1次，咳嗽消失后停药。观察组加用孟鲁司特咀嚼片（10 mg/次，1次/d，口服）联合酮替酚片（1 mg/次，2次/d，口服）治疗，对照组予以单纯的孟鲁司特咀嚼片治疗，剂量与用法与观察组相同，两组疗程均为8周。观察两组治疗前后MMP-2、9水平、治疗后效果及不良反应，停药后1年观察其复发率。
1.3 观察指标及疗效评价
1.3.1 血清MMP-2和MMP-9水平检测 取静脉血3～5 mL，离心后取上清，采用酶联免疫吸附法测定血清MMP-2和MMP-9水平。试剂盒购自美国 R
[关键词] 咳嗽变异性哮喘；孟鲁司特；酮替酚；金属蛋白酶-2；金属蛋白酶-9；复发
[中图分类号] R725.6 [文献标识码] B [文章编号] 1673-9701（2015）04-0070-03
[Abstract] Objective To discuss curative effect and influence on plasma of MMP-2 and MMP-9 levels of Montelukast combined with ketotifen on cough variant asthma （CVA）. Methods A total of 90 cases of patients with CVA were divided into observation group and control group by numeration table at random. The patients in two groups were given Salbutamol Aerosol treatment until the disappearing of cough. The patients in observation group were additionally given Montelukast Dulcets（10 mg per time， once a day， through the mouth） combined with ketotifen tablets （1 mg per time， twice a day， through the mouth）， while the patients in control group were given the pure Montelukast Dulcets with the same dose and method as those in observation group， for 8 weeks as the course of treatment. Results After 8 weeks’treatment， the plasma MMP-2 and MMP-9 levels descended significantly（P<0.05 or P<0.01），and the rangeabilities of budesonide group were more significantly obviously than those in control group（P<0.05）， and the total efficiency of patients in observation group was much higher than that in control group （χ2=4.41，P<0.05）， 3 and 6 cases of untoward effect appeared in control group and observation group respectively， with light symptom and the untoward effect occurrence rates of patients in two groups appeared no obvious differences after comparison（χ2=0.49，P>0.05）. According to the one-year following-up after the withdrawal of drugs， reoccurrence rate of patients in observation group was much lower than that in control group（χ2=6.33，P<0.05）. Conclusion Montelukast combined with Ketotifen has favorable clinical curative effect on CVA with high security，and can reduce the reoccurrence rate. May its mechanism relates to down-regulating MMP-2 and MMP-9.
[Key words] Cough variant asthma；Montelukast；Ketotifen；MMP-2；MMP-9；Reoccurrence
咳嗽变异性哮喘（cough variant asthma， CVA）是一种隐匿型哮喘，以慢性顽固性干嗽为主要表现，易误诊，部分患者可发展为典型哮喘[1]。研究证实CVA病理机制与典型哮喘基本相似，近年来研究已证实，慢性气道炎症与气道重构在其中起极其重要的作用，基质金属蛋白酶（MMPs）是引起哮喘患者气道慢性炎症与气道重构的主要原因[2]。酮替酚是临床较常用的抗变态反应药，具有较好的抗过敏和抗炎作用，治疗CVA的近期疗效较好，但治疗后病情易复发[3]。孟鲁司特是一种常用的非甾体抗炎药，近年来研究发现其治疗及预防CVA复发疗效较好，但其联合酮替酚治疗CVA目前报道不多[4，5]。本研究观察了孟鲁司特联合酮替酚对CVA的血清MMP-2、9水平的影响及疗效，现报道如下。 1 资料与方法
1.1 一般资料
选取我院内科门诊2011年1月～2013年5月就诊的CVA患者90例。纳入标准：均符合《咳嗽的诊断与治疗指南（2009版）》中的诊断标准[6]。排除标准：慢性扁桃体炎、腺样体肥大、鼻窦炎、结核、鼻后滴漏综合征或气道异物等引起的慢性咳嗽。采用随机数字表法将其分为观察组（n=45）和对照组（n=45）；两组患者的性别构成、年龄分布和发病时间等比较差异无统计学意义（P>0.05），具有可比性。
1.2 治疗方法
两组均予以舒喘灵气雾剂200 μg/次，隔6～8 h 1次，咳嗽消失后停药。观察组加用孟鲁司特咀嚼片（10 mg/次，1次/d，口服）联合酮替酚片（1 mg/次，2次/d，口服）治疗，对照组予以单纯的孟鲁司特咀嚼片治疗，剂量与用法与观察组相同，两组疗程均为8周。观察两组治疗前后MMP-2、9水平、治疗后效果及不良反应，停药后1年观察其复发率。
1.3 观察指标及疗效评价
1.3.1 血清MMP-2和MMP-9水平检测 取静脉血3～5 mL，离心后取上清，采用酶联免疫吸附法测定血清MMP-2和MMP-9水平。试剂盒购自美国 R