美国密歇根大学MeiLan K. Han团队研究了有症状和肺功能保留的烟草暴露者接受支气管扩张剂的疗效与安全性。2022年9月4日出版的《新英格兰医学杂志》发表了这项成果。

许多有吸烟史的人有临床上显著的呼吸症状，尽管通过肺活量测定评估没有气流阻塞。他们经常使用药物治疗慢性阻塞性肺病（COPD），但缺乏支持这种治疗的证据。

研究组随机分配至少有10包-年吸烟史、COPD评估测试得分至少为10（评分范围为0-40，分数越高表示症状越严重）的呼吸症状，以及肺活量测定（1秒用力呼气量[FEV1]与用力肺活量[FVC]之比≥0.70，使用支气管扩张药后FVC≥预测值的70%）为肺功能保留的参与者，分别接受茚达特罗（27.5μg）加格隆溴铵（15.6μg）或安慰剂治疗，每日两次，持续12周。

主要结局是无治疗失败（定义为使用长效吸入性支气管扩张剂、糖皮质激素或抗生素治疗后下呼吸道症状增加）12周后，圣乔治呼吸问卷（SGRQ）评分（评分范围从1到100，评分越高表示健康状况越差）至少下降4分（即改善）。

共有535名参与者接受了随机分组。在改良意向治疗人群（471名参与者）中，治疗组227名参与者中有128名（56.4%）的SGRQ评分下降了4点，安慰剂组244名中有144名（59.0%），差异为−2.6个百分点，校正后的优势比为0.91。

治疗组预测FEV1百分比平均增加2.48个百分点，安慰剂组平均降低0.09个百分点；治疗组的吸气量平均增加0.12升，安慰剂组平均增加0.02升。治疗组共发生4起严重不良事件，安慰剂组发生11起；没有一项被认为与治疗或安慰剂潜在相关。

研究结果表明，通过肺活量测定评估，吸入双支气管扩张剂治疗并没有减少有症状的、肺功能保留的烟草接触者的呼吸症状。

附：英文原文

Title: Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function | NEJM

Author: MeiLan K. Han, M.D.,, Wen Ye, Ph.D.,, Di Wang, M.S.,, Emily White, M.S.,, Mehrdad Arjomandi, M.D.,, Igor Z. Barjaktarevic, M.D.,, Stacey-Ann Brown, M.D.,, Russell G. Buhr, M.D.,, Alejandro P. Comellas, M.D.,, Christopher B. Cooper, M.D.,, Gerard J. Criner, M.D.,, Mark T. Dransfield, M.D.,, Frank Drescher, M.D.,, Rodney J. Folz, M.D.,, Nadia N. Hansel, M.D.,, Robert J. Kaner, M.D.,, Richard E. Kanner, M.D.,, Jerry A. Krishnan, M.D.,, Stephen C. Lazarus, M.D.,, Veeranna Maddipati, M.D.,, Fernando J. Martinez, M.D.,, Anne Mathews, M.D.,, Catherine Meldrum, Ph.D.,, Charlene McEvoy, M.D.,, Toru Nyunoya, M.D.,, Linda Rogers, M.D.,, William W. Stringer, M.D.,, Christine H. Wendt, M.D.,, Robert A. Wise, M.D.,, Stephen R. Wisniewski, M.D.,, Frank C. Sciurba, M.D.,, and Prescott G. Woodruff, M.D.

Issue&Volume: 2022-09-04

Abstract:

Background

Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking.

Methods

We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 μg) plus glycopyrrolate (15.6 μg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George’s Respiratory Questionnaire (SGRQ) score (scores range from 1 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent).

Results

A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had a 4-point decrease in the SGRQ score (difference, 2.6 percentage points; 95% confidence interval [CI], 11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P=0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and 0.09 percentage points (95% CI, 1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, 0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo.

Conclusions

Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry.

DOI: 10.1056/NEJMoa2204752

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2204752