Pharmaco-Epidemiology Group, Massachusetts Veterans Epidemiology Research and Information Center, VA Cooperative Studies Program, VA Boston Healthcare System, Boston, Massachusetts 02130, USA.
Clin Infect Dis. 2012 Jan 1;54(1):33-42. doi: 10.1093/cid/cir767. Epub 2011 Nov 18.
Observational studies linking proton pump inhibitor (PPI) exposure with community-acquired pneumonia (CAP) have reported either modest or no associations. Accordingly, we studied PPI exposure and CAP in veteran patients, using a retrospective, nested case-control design.
From linked pharmacy and administrative databases of the New England Veterans Healthcare System, we identified 71985 outpatients newly prescribed PPIs between 1998 and 2007; 1544 patients met criteria for CAP subsequent to PPI initiation; 15440 controls were matched through risk-set sampling by age and time under observation. Crude and adjusted odds ratios comparing current with past PPI exposures, as well as tests for interactions, were conducted for the entire and stratified samples.
Current PPI use associated with CAP (adjusted odds ratio [OR], 1.29 [95% confidence interval {CI}, 1.15-1.45]). Risks were not substantially altered by age or year of diagnosis. Dementia (n = 85; P = .062 for interaction) and sedative/tranquilizer use (n = 224; P = .049 for interaction) were likely effect modifiers increasing a PPI-CAP association; conversely, for some chronic medical conditions, PPI-associated CAP risks were reversed. PPI exposures between 1 and 15 days increased CAP risks, compared with longer exposures, but PPI initiation also frequently occurred shortly after CAP diagnoses. Prescribed PPI doses >1 dose/day also increased PPI-associated CAP risks.
Among the veterans studied, current compared with past PPI exposures associated modestly with increased risks of CAP. However, our observations that recent treatment initiation and higher PPI doses were associated with greater risks, and the inconsistent PPI-CAP associations between patient subgroups, indicate that further inquiries are needed to separate out coincidental patterns of associations.
将质子泵抑制剂（PPI）暴露与社区获得性肺炎（CAP）联系起来的观察性研究报告的相关性要么适度，要么不存在。因此，我们使用回顾性嵌套病例对照设计，在退伍军人患者中研究 PPI 暴露与 CAP 的关系。
我们从新英格兰退伍军人医疗保健系统的关联药房和行政数据库中确定了 1998 年至 2007 年间新开具 PPI 的 71985 名门诊患者；1544 名患者在 PPI 启动后符合 CAP 标准；通过年龄和观察时间的风险集抽样对 15440 名对照进行匹配。对整个和分层样本进行了比较当前和过去 PPI 暴露的粗比值比和调整比值比，以及交互作用检验。
当前 PPI 使用与 CAP 相关（调整后的比值比[OR]，1.29 [95%置信区间{CI}，1.15-1.45]）。风险在年龄或诊断年份上没有明显改变。痴呆（n = 85；交互作用 P =.062）和镇静/安定剂使用（n = 224；交互作用 P =.049）可能是增加 PPI-CAP 关联的效应修饰剂；相反，对于某些慢性疾病，PPI 相关的 CAP 风险则相反。与较长时间的暴露相比，1 至 15 天的 PPI 暴露增加了 CAP 的风险，但 PPI 启动也经常发生在 CAP 诊断后不久。每天服用 1 次以上剂量的 PPI 也增加了 PPI 相关 CAP 的风险。
在所研究的退伍军人中，与过去相比，当前的 PPI 暴露与 CAP 风险增加相关，但我们观察到最近的治疗开始和更高的 PPI 剂量与更高的风险相关，并且患者亚组之间的 PPI-CAP 相关性不一致，这表明需要进一步调查以区分偶然的关联模式。
