研究目的：調查失智症患者使用氫離子幫浦抑制劑(PPI)和隨後發生肺炎風險之間的關聯。
研究方法及資料：利用台灣健保資料庫資料作一個世代型研究。我們從2009年至2013年篩選出786位使用PPI的失智症患者，及786位沒有使用PPI的失智症患者進行世代研究分析。研究終點定義為肺炎的發生。Cox比例風險模型用於估計肺炎的風險。此外，以世界衛生組織藥物日劑量方法(DDD)來評估PPI的累積和劑量反應與發生肺炎的關係。
研究結果：使用PPI的失智症患者，其肺炎發病率較高 [校正風險比（HR）= 1.89; 95％信賴區間 = 1.51-2.37]。 此外，Cox模型顯示年齡（校正的HR = 1.05; 95％信賴區間 = 1.03-1.06），男性性別（校正的HR = 1.57; 95％信賴區間 = 1.25-1.98），腦血管疾病（校正的HR = 1.30; 95％信賴區間 = 1.04-1.62），慢性肺疾病（校正的HR = 1.39; 95％信賴區間 = 1.09-1.76），充血性心衰竭（校正的HR = 1.54; 95％信賴區間 = 1.11-2.13），糖尿病（校正的HR = 1.54; 95％信賴區間 = 1.22-1.95），抗精神病藥物的使用（校正的HR = 1.29; 95％信賴區間 = 1.03-1.61）皆是肺炎的獨立危險因素。然而，使用膽鹼酯?抑製劑（校正的HR = 0.4; 95％信賴區間 = 0.25-0.65）和組胺受體-2拮抗劑（校正的HR = 0.62; 95％信賴區間 = 0.5-0.78）顯示可減少肺炎的發生風險。
結論與建議：失智症患者使用PPI會增加89％肺炎發生的風險。因此，醫師在臨床上予失智症患者開立PPI時應該注意肺炎併發症。
Objective：The objective of this study is to determine the association between proton pump inhibitors (PPIs) usage and subsequent risk of pneumonia in dementia patients.
Methods and Materials：A retrospective cohort study was performed by using Taiwan National Health Insurance Research Database. The study cohort consisted of 786 dementia patients with new PPI usage and 786 matched dementia patients without PPI usage between year 2009 and 2013. The study endpoint was defined as the occurrence of pneumonia. Cox proportional hazards models were used to estimate the risk of pneumonia. Defined daily dose methodology was applied to evaluate cumulative and dose-response relationship of PPI. Statistical analysis was performed using SPSS 18.0 (SPSS Inc.) and SAS 9.4 (SAS Institute).
Results：The incidence of pneumonia was higher among patients with PPI usage [adjusted hazard ratio (HR) = 1.89; 95% CI = 1.51–2.37]. Cox models also showed that age (adjusted HR = 1.05; 95%CI = 1.03-1.06), male gender (adjusted HR = 1.57; 95% CI = 1.25–1.98), underlying cerebrovascular disease (adjusted HR = 1.30; 95% CI = 1.04–1.62), chronic pulmonary disease (adjusted HR = 1.39; 95% CI = 1.09–1.76), congestive heart failure (adjusted HR = 1.54; 95% CI = 1.11–2.13), diabetes mellitus (adjusted HR = 1.54; 95% CI = 1.22–1.95), and usage of antipsychotics medications (adjusted HR = 1.29; 95% CI = 1.03–1.61) were independent risk factors for pneumonia. However, usage of cholinesterase inhibitors (adjusted HR = 0.4; 95%CI = 0.25-0.65) and histamine receptor-2 antagonists (adjusted HR = 0.62; 95%CI = 0.5-0.78) were shown to reduce pneumonia risk.
Conclusion and Suggestion：PPI usage in dementia patients is associated with an 89% increased risk of pneumonia. Therefore, physicians should pay attention to pneumonia complication when prescribing PPIs to dementia patients.
