Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
Faculty of Medicine, University of Belgrade; Clinic for Pulmonary Diseases, Belgrade, Serbia.
Respirology. 2016 Jul;21(5):883-90. doi: 10.1111/resp.12758. Epub 2016 Mar 11.
BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GERD) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesize that treatment with proton pump inhibitors reduces the risk of exacerbation in patients with stable COPD. METHODS: A total of 638 patients with stable COPD for ≥6 weeks, ≥10 pack-years of smoking and Global Initiative for Chronic Obstructive Lung Disease II-IV seeking care in tertiary hospitals in eight European countries in the Predicting Outcome using Systemic Markers in Severe Exacerbations-COPD cohort was prospectively evaluated by us. Comorbidities including associated medical treatment were assessed at baseline, at exacerbation and at biannual visits. Median observation time was 24 months. The primary study outcomes were exacerbation and/or death. RESULTS: A total of 85 (13.3%) of COPD patients were on anti-GERD therapy. These patients had higher annual and higher severe exacerbation rates (P = 0.009 and P = 0.002), decreased quality of life (SF-36: activity score P = 0.004, St. George's Respiratory Questionnaire: physical functioning P = 0.013 and social functioning P = 0.007), higher body mass airflow obstruction, dyspnea and exercise capacity index (P = 0.033) and Modified Medical Research Council scores (P = 0.002), shorter 6-min walking distance (P = 0.0004) and a higher adjusted Charlson score (P < 0.0001). Anti-GERD therapy was associated with a shorter time to severe exacerbation (HR 2.05 95% CI 1.37-3.08). Using three multivariable Cox-regression models, this association was independent of the following: (i) adjusted Charlson score and FEV1% predicted (HR 1.91 95% CI 1.26-2.90); (ii) adjusted Charlson score, body mass, airflow obstruction, dyspnea and exercise capacity index and Modified Medical Research Council (HR 1.62 95% CI 1.04-2.54); and (iii) adjusted Charlson score, FEV1% predicted and nine classes of medication for comorbidities (HR 1.63 95% CI 1.04-2.53). CONCLUSION: These findings suggest that patients with stable COPD receiving acid-suppressive therapy with proton pump inhibitors remain at high risk of frequent and severe exacerbations.
背景与目的：胃食管反流病（GERD）症状与慢性阻塞性肺疾病（COPD）恶化的风险增加有关。我们假设质子泵抑制剂（PPI）治疗可降低稳定型 COPD 患者恶化的风险。
方法：我们前瞻性评估了来自欧洲 8 个国家 8 家三级医院的预测严重 COPD 加重中系统标志物预后（Predicting Outcome using Systemic Markers in Severe Exacerbations-COPD）队列中 638 例稳定 COPD 患者（≥6 周，≥10 包年吸烟史，GOLD II-IV 期）。在基线、加重时和每半年就诊时评估合并症（包括相关治疗）。中位观察时间为 24 个月。主要研究结局为加重和/或死亡。
结果：85 例（13.3%）COPD 患者接受了抗 GERD 治疗。这些患者的年加重率和重度加重率较高（P=0.009 和 P=0.002），生活质量下降（SF-36：活动评分 P=0.004，圣乔治呼吸问卷：身体机能 P=0.013 和社会功能 P=0.007），身体质量指数（BMI）、气流受限、呼吸困难和运动能力指数（P=0.033）和改良医学研究委员会评分（P=0.002）升高，6 分钟步行距离较短（P=0.0004），Charlson 调整评分较高（P＜0.0001）。抗 GERD 治疗与严重加重的时间较短相关（HR 2.05，95%CI 1.37-3.08）。使用三个多变量 Cox 回归模型，这种关联独立于以下因素：（i）调整 Charlson 评分和 FEV1%预计值（HR 1.91，95%CI 1.26-2.90）；（ii）调整 Charlson 评分、BMI、气流受限、呼吸困难和运动能力指数和改良医学研究委员会评分（HR 1.62，95%CI 1.04-2.54）；和（iii）调整 Charlson 评分、FEV1%预计值和九类合并症药物（HR 1.63，95%CI 1.04-2.53）。
结论：这些发现表明，接受质子泵抑制剂酸抑制治疗的稳定型 COPD 患者仍有频繁和严重加重的高风险。
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