Aggressive control of gastroesophageal reflux does not appear to improve asthma symptoms, according to a study in the April 8 New England Journal of Medicine.

The findings challenge the theory that people with poorly controlled asthma frequently have reflux, and that treatment would lead to better asthma control.

The multicenter, double-blind, randomized controlled trial involved 412 adults whose symptoms of asthma were inadequately controlled despite the use of moderate-to-high doses of inhaled corticosteroids. Participants were assigned to receive either a placebo or 40 mg of esomeprazole, a prescription proton pump inhibitor, twice daily for 24 weeks. This dose was higher than that typically used to treat symptomatic gastroesophageal reflux (N. Engl. J. Med. 2009;360:1487-99).

The study was conducted by the research group of the American Lung Association Asthma Clinical Research Centers, and the article was prepared by a writing committee led by Dr. John G. Mastronarde of Ohio State University Medical College, Columbus.

Although only 15% of the participants reported a history of gastroesophageal reflux, ambulatory pH monitoring revealed that 41% of patients in the placebo group and 40% in the esomeprazole group had evidence of reflux. This is a common finding among patients with asthma – for many, their reflux is asymptomatic.

Patients kept daily diaries of their asthma symptoms, and they were assessed by spirometry every 4 weeks. Depending on the definition of poor asthma control, between 42% and 61% of all participants experienced at least one episode, and 18% required an urgent-care visit or a course of prednisone. There were no significant differences in any of those measures between patients taking placebo and those taking esomeprazole.

About half of the participants reported night awakening caused by asthma symptoms, and that rate also did not differ significantly between the two groups.

The study was powered to detect a difference of 33% in the proportion of participants having one or more episodes of poor asthma control.

There were no significant differences between the groups in any of the secondary outcomes, including several measures of pulmonary function, asthma symptoms, asthma control, and quality of life.

Nor were there significant differences when the investigators attempted to identify any subgroup of patients who had some benefit from esomeprazole therapy. For example, when the analysis was restricted to patients who had documented gastroesophageal reflux, there was still no difference between the groups. Other negative subgroup analyses included those based on body mass index; the presence or absence of night awakening; age; ethnic group; sex; obesity; smoking status; asthma control or severity scores; use of long-acting beta-agonists; and self-reported sinusitis, rhinitis, or gastroesophageal reflux.

The study was supported by grants from the U.S. National Heart, Lung, and Blood Institute and the American Lung Association. Esomeprazole and placebo were supplied by AstraZeneca, which manufactures esomeprazole. Several members of the writing committee disclosed receiving consulting or lecture fees from AstraZeneca, and they also reported relationships with several other pharmaceutical companies including GlaxoSmithKline, Genentech, Boehringer Ingelheim, Cornerstone Therapeutics, Novartis, Sepracor, MedImmune, Schering-Plough, and Forest.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

4月8号出版的《新英格兰医学杂志》上一项研究显示：积极地治疗胃食管反流并不能有效改善哮喘症状。

原有理论认为难治性哮喘常伴有胃食管反流，积极地治疗胃食管反流能较好地控制哮喘。这项研究对该理论无疑是一个挑战。

该多中心、双盲、随机对照试验涉及412例成人患者，尽管他们吸入中到高剂量的糖皮质激素，但是哮喘症状并没有得到良好的控制。受试者被分为两组，对照组服用安慰剂，治疗组服用奥美拉唑（质子泵抑制剂），40mg，每日两次，持续服用24周。该剂量高于通常治疗胃食管反流症的剂量 (N. Engl. J. Med. 2009;360:1487-99) 。

此项研究由美国肺脏协会哮喘临床研究中心的研究小组主持，文章由俄亥俄州立大学医学院的John G. Mastronarde博士领导的写作委员会撰写。

虽然只有15%的受试者报告既往有胃食管反流病史，但是动态pH监测证实41%的对照组患者和40%的奥美拉唑治疗组患者有反流。这是哮喘患者中一种常见的现象，只不过多数情况下反流是没有症状的。

受试者每天记录哮喘症状变化，每隔4周通过肺量测定法评估状况。基于哮喘控制不良的定义，在所有受试者中，42%到61%的人经历至少一次控制不良，另外18%的受试者需要急诊治疗或短期接受泼尼松治疗。分析结果表明：奥美拉唑治疗组和安慰剂对照组的疗效无显著性差异。

大约有一半的受试者报告因哮喘发作夜间醒来，且两组的发生率也没有明显差异。

两组辅助评估结果（几次肺功能测定、哮喘症状、哮喘控制和生活质量）都无明显差异。

当研究者试图找出一些受益于奥美拉唑治疗的患者时，发现也都无显著差异。例如，当受试者仅限于既往有胃食管反流史的病人时，两组之间的结果仍无明显差异。其他一些对体重指数、有无夜间觉醒、年龄、种族、性别、肥胖、吸烟情况、哮喘控制或严重评分、使用长效β激动剂、自我报告的鼻窦炎、鼻炎或胃食管返流等因素的分析结果也为阴性。

此项研究得到了美国国家心、肺、血液研究所和美国肺脏协会的资助，奥美拉唑和安慰剂由生产奥美拉唑的阿斯利康制药公司提供。写作委员会的几名委员从阿斯利康制药公司接受了咨询或讲演费。他们也报告了与其他几家制药公司有关系，包括葛兰素史克公司、基因泰克公司、勃林格殷格翰制药公司、Cornerstone Therapeutics 公司、诺华制药公司、斯巴可公司、MedImmune公司、先灵葆雅公司、Forest公司。

爱思唯尔  版权所有