| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 105 === Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease, characterized by airflow limitation and persistent respiratory symptoms of dyspnea, cough and sputum production. Acute exacerbations of COPD (AECOPD), an acute deterioration of respiratory symptoms resulting in additional therapy, seriously impair lung function and quality of life, is associated with increased mortality. Since exacerbations are important events in COPD, a key target for intervention is to prevent them from occurring. Gastroesophageal reflux disease (GERD) is not only a common disorder worldwide but also highly prevalent in patients with COPD. Recently, GERD has received enhanced attention as a potential risk factor for AECOPD. The aims of this study were to explore the impact of GERD on exacerbations and mortality in COPD and evaluate the effects of medications in patients with coexisting COPD and GERD.
Method: We conducted a retrospective nationwide cohort study using the National Health Insurance Research Database in Taiwan from January 1, 2000, through December 31, 2011. Newly diagnosed COPD patients between 2000 and 2009 who were over 40 years of age with prescribed COPD medications were extracted. COPD subjects with newly diagnosed GERD who subsequently received proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) and underwent endoscopy or 24-hour ambulatory esophageal pH monitoring prior to diagnosis were identified as an exposure cohort. Each subject in the exposure cohort was matched to 4 subjects randomly selected from the comparison group comprising COPD patients without GERD by matching age, sex, and index year. Rate ratios of exacerbations between the two groups were calculated; treatment during AECOPD was also analyzed. Cox proportional hazard models were applied to evaluate the risk of AECOPD and mortality for GERD. Furthermore, time-dependent Cox proportional hazard models were performed to investigate the effect of acid suppression medications and respiratory medications on the risk of AECOPD among the exposure group.
Results: Among the COPD cohort, 3,485 COPD patients with GERD and 13,938 COPD patients without GERD were enrolled within the study period. Rates of AECOPD and severe exacerbations were higher in the exposure cohort when comparing to the comparison group with rate ratios of 1.78 (95% confidence interval [CI] 1.69-1.87) and 2.48 (95% CI 2.28-2.69). During the exacerbations, patients with GERD used higher average doses of steroids (P < 0.0001) and longer duration of pneumonia-related antibiotics (P < 0.0001) than those without GERD. Multivariable Cox regression models revealed that GERD was associated with significantly increased risks of moderate-to-severe exacerbation (hazard ratio [HR] 1.35, 95% CI 1.23-1.48), severe exacerbation (HR 1.47, 95% CI 1.29-1.67) and mortality (HR 1.42, 95% CI 1.25-1.61) in patients with COPD. Among the exposure group, the adjusted HRs for AECOPD in patients taking PPIs and H2RAs over 1 defined daily dose (DDD) per day were 0.32 (95% CI 0.20-0.50) and 0.69 (95% CI 0.49-0.99), respectively. Besides, the adjusted HRs for AECOPD in patients taking PPIs over 1 DDD per day comparing to patients taking H2RAs over 1 DDD per day was 0.31 (95% CI 0.16-0.58). However, the adjusted HRs for AECOPD in COPD patients with GERD taking xanthines, short-acting beta2-agonists (SABAs), and long-acting antimuscarinic antagonists (LAMAs) were 1.47 (95% CI 1.20-1.79), 1.96 (95% CI 1.58-2.43), and 1.82 (95% CI 1.15-2.89), respectively.
Conclusion: Patients with coexisting COPD and GERD were associated with more frequent and more severe exacerbations, and GERD was also associated with an increased risk of mortality. COPD patients with GERD taking acid suppression medications were associated with a reduced risk of AECOPD, and PPIs was associated with a decreased risk of AECOPD when comparing to H2RAs. Further prospective research is warranted to clarify the effect of acid suppression medications and respiratory medications on AECOPD in this condition.
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