使用胃酸抑制藥物與肺炎之風險

Use of acid-suppressive drugs and risk of pneumonia

梁心怡(Shin-Yi Liang)

指導教授 ： 楊奕馨

高雄醫學大學/藥學院/藥學研究所/碩士(2013年)

摘要

背景：胃酸抑制藥物，如質子幫浦抑制劑(proton pump inhibitor, PPIs) 以及第二型組織胺受體拮抗劑(histamine 2 receptor antagonist, H2RAs)為最普遍使用的藥物之一。許多研究證實使用胃酸抑制藥物，可能藉由抑制胃酸分泌而使得胃內pH值增加，造成胃中細菌移生，而容易引發肺炎感染。回顧已發表的文獻，不乏有使用國家研究資料庫為材料研究，但亞洲人族群為題材之研究仍有限。2011年台灣十大死因統計，肺炎排名為第五順位。在台灣，由於胃酸抑制藥物廣泛的使用，因此了解胃酸抑制藥物是否會造成肺炎的風險，是一個需要被正視的公共衛生議題。
目的：以病例對照研究設計，探討使用胃酸抑制藥物與肺炎風險之相關性。
方法：以病例對照研究，利用台灣全民健康保險研究資料庫進行分析。病例組包含1998年至2010年首次肺炎住院的病人，每位病例利用隨機取樣以1：4比例配對同年齡及同性別沒有肺炎者為對照組，並以首次肺炎住院日期為指標日期(index date)，由指標日期回推胃酸抑制藥物使用時序、每日劑量、累積天數及劑量。統計方法包含卡方檢定、單變數與多變數邏輯斯迴歸分析。
研究結果：本研究收錄之首次診斷為肺炎住院病例共有16,763人，配對對照組有67,052人，平均年齡49歲(標準差為16歲)，肺炎病例組之察爾森共病症指數分數明顯高於對照組。此外，相較於對照組，肺炎病例組於指標日期前一年內罹患的共病症且合併藥物較多。相較於未使用者，目前使用PPIs發生肺炎風險的調整勝算比為2.53( 95% CI: 2.15-2.98)；目前使用H2RAs造成肺炎的風險為1.98倍 (95% CI=1.81-2.17)。PPIs與H2RAs在治療初期(特別是前7天)與肺炎之間的風險具有強烈相關性，隨著使用天數增加，肺炎風險反而降低。針對目前使用PPIs者，每日劑量有觀察到顯著的劑量反應正相關。
結論：目前使用PPIs與H2RAs可能與肺炎風險增加有關。基於此潛在的不良反應，臨床醫師對於本身是肺炎感染高風險族群患者，處方胃酸抑制藥物須更加謹慎。

關鍵字

胃酸抑制藥物 ； 質子幫浦抑制劑 ； 肺炎

並列摘要

Background: Acid-suppressive drugs, such as histamine 2 receptor antagonist (H2RAs) and proton pump inhibitors (PPIs), are one of the most commonly prescribed classes of therapeutic agents. Acid-suppressive drugs could increase susceptibility to pneumonia because these drugs increase gastric pH, thus allowing bacterial colonization. Although there were population-based studies on this issue, there are still limited reports from Asian population, including Taiwan. In 2011, pneumonia ranks number fifth in the top 10 leading causes of death in Taiwan. Because acid-suppressive drugs are widespread used in Taiwan, it needs to be clarified whether acid-suppressive therapy causes risks of pneumonia is very important to public health.
Objective: This is a retrospective population-based study to investigate the association between use of acid-suppressive drugs and risk of pneumonia.
Method: A nested case-control study was conducted using the National Health Insurance Research Database (NHIRD). Cases included all patients with first admission of pneumonia to a hospital between 1998 and 2010. For each case, four randomly selected controls without pneumonia were matched by age and gender. The date of first admission of pneumonia is used as the index date which can be used to trace the time course, daily dose, cumulative days and doses of the acid -suppressive drugs. Statistical methods include the Chi-square test, univariate and multivariablelogistic regressions.
Result: This research includes 16,763 people who have first hospitalized pneumonia diagnosis as cases. Matched controls include 67,052 people. The average age are 49(±16) years old. Pneumonia subjects had higher Charlson comorbidity index score. In addition, case subjects had greater number of comorbidity and concomitant medication at the year before the index date than controls. The adjusted odds ratio of current users of proton pump inhibitors (PPIs) was 2.53(95% CI= 2.15-2.98). Current users of H2-receptor antagonists had a 1.98-fold increased risk of pneumonia (95% CI=1.81-2.17) compared with non-users. Recent initiation of treatment with PPIs and H2-receptor antagonists (0-7days before index date) showed a significant association with pneumonia, while the risk decreased with treatment that was started a long time ago. For current PPIs users, a significant positive dose-response relationship was observed.
Conclusion: Current use of a proton pump inhibitor or H2-receptor antagonist may be associated with an increased risk of pneumonia. Given these potential adverse effects, clinicians should use with caution in prescribing acid-suppressive drugs for patients at risk.

並列關鍵字

Acid suppressive drugs ； proton pump inhibitors ； pneumonia

參考文獻

1. Community-acquired pneumonia and acid-suppressive drugs: position statement. Canadian journal of gastroenterology. 2006;20:119-21, 23-5.

2. Delaney BC, Innes MA, Deeks J, et al. Initial management strategies for dyspepsia. Cochrane database of systematic reviews (Online) 2000:CD001961.

3. Gregor JC. Acid suppression and pneumonia: a clinical indication for rational prescribing. JAMA : the journal of the American Medical Association 2004;292:2012-3.

4. Vanderhoff BT, Tahboub RM. Proton pump inhibitors: an update. American family physician 2002;66:273-80.

5. Laine L, Ahnen D, McClain C, Solcia E, Walsh JH. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. Alimentary pharmacology & therapeutics 2000;14:651-68.