The impact of smoking status on the efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review

Objectives: Inhaled corticosteroids (ICS) reduce exacerbation rates and the decline in lung function in people with chronic obstructive pulmonary disease (COPD). There is evidence that smoking causes 'steroid resistance' and thus reduces the effect of ICS. This systematic review aimed to investigate the effect of smoking on efficacy of ICS in COPD in terms of lung function and exacerbation rates. Design: Systematic review Data Sources: An electronic database search of PubMed, Ovid Medline, Ovid Embase and Cochrane Library (Jan 2000-Jan 2020). Eligibility criteria: Fully published RCTs, in the English language, evaluating the use of ICS in COPD adults that stratified the participants by smoking status. Trials that included participants with asthma, lung cancer and pneumonia were excluded. The primary outcome measures were changes in lung function and yearly exacerbation rates. Data extraction and synthesis: Two independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration's tool. Results: Seven studies were identified. Four trials (17,892 participants) recorded change in forced expiratory volume (FEV1) from baseline to up to 30 months after starting treatment. Heavier smokers (>36 pack years) using ICS had a greater decline in FEV1 that ranged from -22ml to -75ml in comparison to lighter smokers. Smokers using ICS had mixed results in FEV1 change: -8ml to +77ml in comparison to ex-smokers. Four trials (21,270 participants) recorded difference in COPD exacerbation rates at 52 weeks. The rate ratios favoured more exacerbations in ICS users who were current or heavier smokers than those who were ex- or lighter smokers (0.81 to 0.99 versus 0.92 to 1.29). Conclusions: In COPD, heavier or current smokers do not gain the same benefit from ICS use on lung function and exacerbation rates as lighter or ex-smokers do, however effects may not be clinically important. Trial registration: Prospero, registration CRD42019121833.研究目的：吸入性糖皮质激素（Inhaled corticosteroids, ICS）可降低慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）患者的急性加重发生率，并延缓其肺功能下降。现有证据表明，吸烟会引发“糖皮质激素抵抗”，从而削弱ICS的治疗效果。本系统评价旨在从肺功能与急性加重发生率两个维度，探究吸烟对COPD患者使用ICS的疗效影响。 研究设计：系统评价 数据来源：检索PubMed、Ovid Medline、Ovid Embase及考克兰图书馆（Cochrane Library）2000年1月至2020年1月的电子数据库文献。 纳入排除标准：纳入所有已正式发表的英文随机对照试验（randomized controlled trial, RCT），研究对象为成年COPD患者，且按吸烟状态进行分层分析；排除纳入哮喘、肺癌及肺炎患者的试验。主要结局指标为肺功能变化与年急性加重发生率。 数据提取与合成：由两名独立评价员采用考克兰协作网（Cochrane Collaboration）偏倚风险评估工具进行数据提取与偏倚风险评价。 研究结果：共检索到7项相关研究。其中4项试验（纳入17892名受试者）报告了从基线至治疗后最长30个月的一秒用力呼气容积（forced expiratory volume in one second, FEV1）变化情况。与轻度吸烟者相比，重度吸烟者（吸烟量＞36包-年）使用ICS后FEV1下降幅度更大，为-22ml至-75ml。当前吸烟者使用ICS的FEV1变化结果不一，相较于既往吸烟者，其FEV1变化范围为-8ml至+77ml。另有4项试验（纳入21270名受试者）报告了52周时COPD急性加重发生率的差异。率比结果显示，当前吸烟或重度吸烟者使用ICS时，急性加重发生率高于既往吸烟或轻度吸烟者（率比分别为0.81~0.99与0.92~1.29）。 研究结论：对于COPD患者，重度或当前吸烟者从ICS治疗中获得的肺功能改善与急性加重发生率降低的获益，不及轻度或既往吸烟者；不过上述差异可能不具有临床重要性。 试验注册：本研究已在普洛斯佩罗（Prospero）平台注册，注册号为CRD42019121833。