Influenza vaccine in chronic obstructive pulmonary disease among elderly male veterans

Yinong Young-Xu; Jeremy Smith; Joshua Nealon; Salaheddin M Mahmud; Robertus Van Aalst; Edward W Thommes; Nabin Neupane; Jason K H Lee; Ayman Chit

doi:10.1371/journal.pone.0262072

Influenza vaccine in chronic obstructive pulmonary disease among elderly male veterans

PLoS One. 2022 Jan 4;17(1):e0262072. doi: 10.1371/journal.pone.0262072. eCollection 2022.

Authors

Yinong Young-Xu^{1

2}, Jeremy Smith¹, Joshua Nealon³, Salaheddin M Mahmud⁴, Robertus Van Aalst^{5

6}, Edward W Thommes^{6

7}, Nabin Neupane¹, Jason K H Lee^{8

9}, Ayman Chit^{6

8}

Affiliations

¹ Clinical Epidemiology Program, Veterans Affairs Medical Center, White River Junction, Vermont, United States of America.
² Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
³ Sanofi Pasteur, Medical Evidence Generation, Lyon, France.
⁴ Department of Community Health Sciences, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Faculty of Medical Sciences, University of Groningen, Groningen, The Netherlands.
⁶ Sanofi Pasteur, Swiftwater, Pennslyvania, United States of America.
⁷ Department of Mathematics & Statistics, University of Guelph, Guelph, Ontario, Canada.
⁸ Leslie Dan School of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
⁹ Sanofi Pasteur, Toronto, Ontario, Canada.

Abstract

Background: Prior studies have established those elderly patients with chronic obstructive pulmonary disease (COPD) are at elevated risk for developing influenza-associated complications such as hospitalization, intensive-care admission, and death. This study sought to determine whether influenza vaccination could improve survival among elderly patients with COPD.

Materials/methods: This study included Veterans (age ≥ 65 years) diagnosed with COPD that received care at the United States Veterans Health Administration (VHA) during four influenza seasons, from 2012-2013 to 2015-2016. We linked VHA electronic medical records and Medicare administrative files to Centers for Disease Control and Prevention National Death Index cause of death records as well as influenza surveillance data. A multivariable time-dependent Cox proportional hazards model was used to compare rates of mortality of recipients of influenza vaccination to those who did not have records of influenza vaccination. We estimated hazard ratios (HRs) adjusted for age, gender, race, socioeconomic status, comorbidities, and healthcare utilization.

Results: Over a span of four influenza seasons, we included 1,856,970 person-seasons of observation where 1,199,275 (65%) had a record of influenza vaccination and 657,695 (35%) did not have a record of influenza vaccination. After adjusting for comorbidities, demographic and socioeconomic characteristics, influenza vaccination was associated with reduced risk of death during the most severe periods of influenza seasons: 75% all-cause (HR = 0.25; 95% CI: 0.24-0.26), 76% respiratory causes (HR = 0.24; 95% CI: 0.21-0.26), and 82% pneumonia/influenza cause (HR = 0.18; 95% CI: 0.13-0.26). A significant part of the effect could be attributed to "healthy vaccinee" bias as reduced risk of mortality was also found during the periods when there was no influenza activity and before patients received vaccination: 30% all-cause (HR = 0.70; 95% CI: 0.65-0.75), 32% respiratory causes (HR = 0.68; 95% CI: 0.60-0.78), and 51% pneumonia/influenza cause (HR = 0.49; 95% CI: 0.31-0.78). However, as a falsification study, we found that influenza vaccination had no impact on hospitalization due to urinary tract infection (HR = 0.97; 95% CI: 0.80-1.18).

Conclusions: Among elderly patients with COPD, influenza vaccination was associated with reduced risk for all-cause and cause-specific mortality.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Influenza Vaccines*

Substances

Influenza Vaccines

Grants and funding

Funding Statement: YYX, JS, and NN report having received grant funds from Sanofi Pasteur that were awarded to the Veterans Education and Research Association of Northern New England Inc. The funder provided support in the form of salaries for authors JN, RVA, EWT, JKL, and AC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.