Abstract
Background
Several studies suggest that proton pump inhibitors (PPIs) and histamine 2-receptor
antagonists (H2s) increase risk of community-acquired pneumonia. To test this hypothesis,
we examined a prospective population-based cohort predisposed to pneumonia: elderly
patients (≥65 years) who had survived hospitalization for pneumonia.
Methods
This study featured a nested case-control design where cases were patients hospitalized
for recurrent pneumonia (≥30 days after initial episode) and controls were age, sex,
and incidence-density sampling matched but never had recurrent pneumonia. PPI/H2 exposure
was classified as never, past, or current use before recurrent pneumonia. The association
between PPI/H2s and pneumonia was assessed using multivariable conditional logistic
regression.
Results
During 5.4 years of follow-up, 248 recurrent pneumonia cases were matched with 2476
controls. Overall, 71 of 608 (12%) current PPI/H2 users had recurrent pneumonia, compared
with 130 of 1487 (8%) nonusers (adjusted odds ratio [aOR] 1.5; 95% confidence interval
[CI], 1.1-2.1). Stratifying the 608 current users according to timing of PPI/H2 initiation
revealed incident current-users (initiated PPI/H2 after initial pneumonia hospitalization,
n=303) bore the entire increased risk of recurrent community-acquired pneumonia (15%
vs 8% among nonusers, aOR 2.1; 95% CI, 1.4-3.0). The 305 prevalent current-users (PPI/H2
exposure before and after initial community-acquired pneumonia hospitalization) were
equally likely to develop recurrent pneumonia as nonusers (aOR 0.99; 95% CI, 0.63-1.57).
Conclusion
Acid-suppressing drug use substantially increased the likelihood of recurrent pneumonia
in high-risk elderly patients. The association was confined to patients initiating
PPI/H2s after hospital discharge. Our findings should be considered when deciding
to prescribe these drugs in patients with a recent history of pneumonia.
Keywords
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References
- Epidemiology of community-acquired pneumonia in the elderly.Semin Respir Infect. 1990; 5: 260-268
- Trends in hospitalizations for pneumonia among persons aged 65 years or older in the United States, 1988-2002.JAMA. 2005; 294: 2712-2719
- Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland.Am J Epidemiol. 1993; 137: 977-988
- Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.JAMA. 2004; 292: 1955-1960
- Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study.Arch Intern Med. 2007; 167: 950-955
- Proton-pump inhibitor use and the risk for community-acquired pneumonia.Ann Intern Med. 2008; 149: 391-398
- Risk of community-acquired pneumonia and the use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study.Pharmacoepidemiol Drug Saf. 2009; 18: 269-275
- Chronic acid-related disorders are common and underinvestigated.Am J Gastroenterol. 2003; 98: 2409-2414
- Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: a population-based study.Clin Infect Dis. 2006; 43: 1272-1276
- The incidence and effect on outcome of hypoxemia in hospitalized medical patients.Am J Med. 1994; 97: 38-46
- Omeprazole, Helicobacter pylori status, and alterations in the intragastric milieu facilitating bacterial N-nitrosation.Gastroenterology. 2000; 119: 339-347
- Gastric mucosal morphological consequences of acid suppression: a balanced view.Best Pract Res Clin Gastroenterol. 2001; 15: 497-510
- Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: differential findings in gastric juice and gastric mucosa.Aliment Pharmacol Ther. 2001; 15: 379-388
- Relationship between gastric secretion and infection.Gut. 1987; 28: 96-107
- Mortality reduction with influenza vaccine in patients with pneumonia outside “flu” season: pleiotropic benefits or residual confounding?.Am J Respir Crit Care Med. 2008; 178: 527-533
- Patients admitted to hospital with suspected pneumonia and normal chest radiographs: epidemiology, microbiology, and outcomes.Am J Med. 2004; 117: 305-311
- Arterial carbon dioxide tension on admission as a marker of in-hospital mortality in community-acquired pneumonia.Am J Med. 2005; 118: 145-150
- Statins and outcomes in patients admitted to hospital with community acquired pneumonia: population based prospective cohort study.BMJ. 2006; 333: 999
- Factors influencing in-hospital mortality in community-acquired pneumonia: a prospective study of patients not initially admitted to the ICU.Chest. 2005; 127: 1260-1270
- Effect of pneumococcal vaccination in hospitalized adults with community-acquired pneumonia.Arch Intern Med. 2007; 167: 1938-1943
- Long-term morbidity and mortality after hospitalization with community-acquired pneumonia: a population-based cohort study.Medicine (Baltimore). 2008; 87: 329-334
- A prediction rule to identify low-risk patients with community-acquired pneumonia.N Engl J Med. 1997; 336: 243-250
- ICD-10 codes are a valid tool for identification of pneumonia in hospitalized patients aged ≥65 years.Epidemiol Infect. 2008; 136: 232-240
- Accuracy of administrative data for identifying patients with pneumonia.Am J Med Qual. 2005; 20: 319-328
- Validation of a pneumonia prognostic index using the MedisGroups Comparative Hospital Database.Am J Med. 1993; 94: 153-159
- Pneumonia: still the old man's friend?.Arch Intern Med. 2003; 163: 317-323
- Prognosis after community-acquired pneumonia in the elderly: a population-based 12-year follow-up study.Arch Intern Med. 1999; 159: 1550-1555
- Biased selection of controls for case-control analyses of cohort studies.Biometrics. 1984; 40: 63-75
- Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure.BMC Med Res Methodol. 2005; 5: 5
- The central role of the propensity score in observational studies for causal effects.Biometrika. 1983; 70: 41-55
- Early heartburn relief with proton pump inhibitors: a systematic review and meta-analysis of clinical trials.Clin Gastroenterol Hepatol. 2005; 3: 553-563
- Review article: immediate-release proton-pump inhibitor therapy—potential advantages.Aliment Pharmacol Ther. 2005; 22: 25-30
- Acid suppression in healthy subjects following lansoprazole or pantoprazole.Aliment Pharmacol Ther. 2002; 16: 425-433
- Time to maximum effect of lansoprazole on gastric pH in normal male volunteers.Aliment Pharmacol Ther. 1996; 10: 897-904
- Rabeprazole produces rapid, potent, and long-acting inhibition of gastric acid secretion in subjects with Helicobacter pylori infection.Aliment Pharmacol Ther. 2000; 14: 701-708
- Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors.Aliment Pharmacol Ther. 2003; 17: 1507-1514
Article info
Footnotes
Funding: An establishment grant from the Alberta Heritage Foundation for Medical Research; grants-in-aid from Capital Health; and unrestricted grants from Abbott Canada, Pfizer Canada, and Janssen-Ortho Canada (all to TJM). DTE and SRM receive salary support awards from the Alberta Heritage Foundation for Medical Research, and DTE and SHS receive salary support from the Canadian Institutes of Health Research.
Conflict of Interest: All authors have no association that might pose a conflict of interest (eg, pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).
Authorship: As authors we have all participated in the conduct of the analysis and writing of this manuscript, and all authors have met the criteria for authorship.
Identification
Copyright
© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
