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Published ahead of print on June 12, 2008, doi:10.1164/rccm.200802-282OC

Am. J. Respir. Crit. Care Med., Volume 178, Number 5, September 2008, 527-533

A more recent version of this article appeared on September 1, 2008
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Submitted on February 17, 2008
Accepted on June 12, 2008

Mortality Reduction with Influenza Vaccine in Patients with Pneumonia Outside "Flu" Season

Dean T Eurich1*, Thomas J Marrie2, Jennie Johnstone2, and Sumit R Majumdar3

1 Department of Public Health Science, School of Public Health, University of Alberta, Edmonton, Alberta, Canada, 2 Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, 3 Department of Public Health Science, School of Public Health, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada

* To whom correspondence should be addressed. E-mail: deurich{at}ualberta.ca.

Rationale: Observational studies suggest a 50% mortality reduction for older patients receiving influenza vaccination; some deem this magnitude of benefit implausible and invoke confounding by the "healthy-user effect" as an alternate explanation. Objective: To evaluate unrecognized confounding by hypothesizing the presence of a 50% mortality reduction with vaccination for patients with pneumonia outside influenza season. Methods: Clinical, laboratory, and functional data were prospectively collected on 1813 adults with community-acquired pneumonia admitted to 6 hospitals outside of influenza season in Capital Health (Alberta, Canada). Vaccination status was ascertained by interview and chart review. Outcome was in-hospital mortality. Influenza-vaccinated patients were matched to a non-vaccinated control using propensity scores, and then multivariable regression was used to determine the independent association between vaccination and mortality. Main Results: The cohort consisted of 354 vaccine-recipients and 354 matched-controls. Most (85%) patients were ≥65 years, 29% had severe pneumonia, and 12% died. Influenza vaccination was associated with a 51% mortality reduction (28 of 354 [8%] died vs 53 of 354 [15%] controls, unadjusted OR 0.49, 95%CI [0.30-0.79]; p=0.004) outside influenza season. Adjustment for age, sex, and comorbidities did not alter these findings (adjusted OR 0.45 [0.27-0.76]). More complete adjustment for confounding (e.g., functional and socioeconomic status) markedly attenuated these benefits and their statistical significance: adjusted OR 0.81 [0.35-1.85], p=0.61. Conclusion: The 51% reduction in mortality with vaccination initially observed in patients with pneumonia who did not have influenza was most likely a result of confounding. Previous observational studies may have over-estimated mortality benefits of influenza vaccination.
Key words: Influenza, Bias, Prospective Study, Pneumonia




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