National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Department of Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom.
Am J Respir Crit Care Med. 2023 Sep 1;208(5):549-558. doi: 10.1164/rccm.202212-2287OC.
Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes. To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD. People with moderate to very severe COPD and an exacerbation history were recruited from three UK centers and randomized to 12 months of doxycycline 100 mg once daily or placebo. The primary study outcome was the exacerbation rate per person-year. A total of 222 people were randomized. Baseline mean FEV was 1.35 L (SD, 0.35 L), 52.5% predicted (SD, 15.9% predicted). The median number of treated exacerbations in the year before the study was 2 (SD, 1-4). A total of 71% of patients reported two or more exacerbations, and 81% were already prescribed inhaled corticosteroids at baseline. The COPD exacerbation rate did not differ between the groups (doxycycline/placebo rate ratio [RR], 0.86; 95% confidence interval [CI], 0.67-1.10; = 0.23). No difference was seen if only treated exacerbations or hospitalizations were considered. In preplanned subgroup analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR, 0.36; 95% CI, 0.15-0.85; = 0.019) and in those with an eosinophil count <300 cells/μl (RR, 0.50; 95% CI, 0.29-0.84; = 0.01). Health status measured by St. George's Respiratory Questionnaire was 5.2 points worse in the doxycycline group at 12 months ( < 0.007). Doxycycline did not significantly reduce the exacerbation rate, over 12 months, in participants with COPD who exacerbated regularly, but it may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/μl. Clinical trial registered with www.clinicaltrials.gov (NCT02305940).
慢性阻塞性肺疾病（COPD）加重是发病率和死亡率的主要原因，预防加重是治疗的关键目标。长期使用大环内酯类药物治疗可有效减少加重，但其他抗生素类别的证据有限。评估 12 个月使用多西环素是否可降低 COPD 患者的加重率。在英国的三个中心招募了中重度至极重度 COPD 和有加重史的患者，并随机分为多西环素 100mg 每日一次或安慰剂治疗 12 个月。主要研究结果为每人每年的加重率。共有 222 人随机分组。基线时平均 FEV1 为 1.35L（标准差，0.35L），预计值的 52.5%（标准差，预计值的 15.9%）。在研究前一年中，治疗性加重的中位数为 2 次（标准差，1-4 次）。共有 71%的患者报告了两次或两次以上加重，81%的患者在基线时已使用吸入性皮质类固醇。两组的 COPD 加重率无差异（多西环素/安慰剂比值[RR]，0.86；95%置信区间[CI]，0.67-1.10； = 0.23）。如果仅考虑治疗性加重或住院治疗，差异也不明显。在预先设定的亚组分析中，多西环素似乎可更好地降低重度 COPD（RR，0.36；95%CI，0.15-0.85； = 0.019）和嗜酸性粒细胞计数<300 细胞/μl（RR，0.50；95%CI，0.29-0.84； = 0.01）患者的加重率。12 个月时，多西环素组圣乔治呼吸问卷健康状况评分差 5.2 分（ < 0.007）。多西环素在定期加重的 COPD 患者中并未显著降低 12 个月的加重率，但可能使中重度 COPD 或嗜酸性粒细胞计数<300 细胞/μl 的患者获益。临床试验在 clinicaltrials.gov 注册（NCT02305940）。
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