Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD

doi:10.1016/j.chest.2018.10.044

Chest

Volume 155, Issue 1, January 2019, Pages 69-78

https://doi.org/10.1016/j.chest.2018.10.044 Get rights and content

Background

The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal.

Methods

Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations.

Results

Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]).

Conclusions

Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population.

Trial Registry

ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov

Section snippets

Patients and Methods

A post hoc analysis of data collected in a national multicenter prospective cohort study was conducted to evaluate the effectiveness of influenza vaccination in adult patients hospitalized with acute respiratory illness.17, 18 Data from the Canadian Immunization Research Network Serious Outcomes Surveillance (SOS) database were analyzed. The SOS database contains information from adult patients (≥ 16 years of age) hospitalized for acute respiratory infection (including pneumonia, acute COPDE or

Results

A total of 4,755 adult patients with COPD were identified who were hospitalized with acute respiratory infection or exacerbation during the study. PCR-confirmed influenza was diagnosed in 38.5% (1,833 of 4,755) of patients.

Discussion

In this multicenter prospective cohort study, influenza vaccination was associated with a significant reduction in influenza-related hospitalizations (38%). Our estimates of seasonal vaccine effectiveness against hospitalization in this study mirror those reported by the Centers for Disease Control and Prevention in the general outpatient population. The available vaccine was not an accurate match for the predominant circulating strain for H3N2 during the 2014 to 2015 season, which accounted

Conclusions

The present study reported a significant reduction in influenza-related hospitalizations associated with seasonal influenza vaccination and identified a high burden of influenza infection among hospitalized patients with COPD. Important clinical care gaps were also identified, including low influenza vaccination rates and delayed initiation of antiviral therapy in this high-risk population of patients with COPD.

Future research should focus on knowledge translation interventions to increase and

Acknowledgments

Author contributions: S. M. takes full responsibility for the content of the manuscript, including the data analysis. S. A. M., S. M., L. Y., T. H., M. K. A., and A. A. were involved in the conception and design of the study. S. A. M., M. K. A., and A. A. were responsible for acquisition of data. T. H. and M. E. conducted/supervised the Canadian Immunization Research Network SOS Network central laboratory. S. M., L. Y., L. L., T. H., M. K. A., and S. A. M. analyzed and interpreted the data.

References (42)

W.A. Zwaans et al.
The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease—a systematic review
J Clin Virol
(2014)
T.W. Clark et al.
Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample
J Infect
(2014)
J.D. Beckham et al.
Respiratory viral infections in patients with chronic, obstructive pulmonary disease
J Infect
(2005)
F.W. Ko et al.
Viral etiology of acute exacerbations of COPD in Hong Kong
Chest
(2007)
F.W. Ko et al.
A 1-year prospective study of the infectious etiology in patients hospitalized with acute exacerbations of COPD
Chest
(2007)
P. Wongsurakiat et al.
Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study
Chest
(2004)
C.H. Howells et al.
Prophylactic use of influenza vaccine in patients with chronic bronchitis. A pilot trial
Lancet
(1961)
R. Garrastazu et al.
Prevalence of influenza vaccination in chronic obstructive pulmonary disease patients and impact on the risk of severe exacerbations
Arch Bronconeumol
(2016)
M.L. Jackson et al.
The test-negative design for estimating influenza vaccine effectiveness
Vaccine
(2013)
K.E. Ainslie et al.
On the bias of estimates of influenza vaccine effectiveness from test-negative studies
Vaccine
(2017)

P. Peduzzi et al.

A simulation study of the number of events per variable in logistic regression analysis

J Clin Epidemiol

(1996)

C.S. Wang et al.

Impact of influenza vaccination on major cause-specific mortality

Vaccine

(2007)

L. Simonsen et al.

Mortality benefits of influenza vaccination in elderly people: an ongoing controversy

Lancet Infect Dis

(2007)

P. Loubet et al.

Factors associated with poor outcomes among adults hospitalized for influenza in France: a three-year prospective multicenter study

J Clin Virol

(2016)

W. Fukushima et al.

Basic principles of test-negative design in evaluating influenza vaccine effectiveness

Vaccine

(2017)

G. De Serres et al.

Importance of viral and bacterial infections in chronic obstructive pulmonary disease exacerbations

J Clin Virol

(2009)

The Human and Economic Burden of COPD. 2010. https://lungontario.ca/wp-content/uploads/2017/09/COPDReport_E_0.pdf...

A. Mohan et al.

Prevalence of viral infection detected by PCR and RT-PCR in patients with acute exacerbation of COPD: a systematic review

Respirology

(2010)

P.A. Koul et al.

Contribution of influenza to acute exacerbations of chronic obstructive pulmonary disease in Kashmir, India, 2010-2012

Influenza Other Respi Viruses

(2015)

D.E. O’Donnell et al.

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease—2007 update

Can Respir J

(2007)

Global Initiative for COPD: Guidelines. http://goldcopd.org/. Accessed November 30,...

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: Dr Dos Santos is currently at GlaxoSmithKline (Wavre, Belgium); Ms Ibarguchi is currently at Bayer Inc. (Mississauga, ON, Canada); and Dr Shinde is currently at Novavax Vaccines (Washington, DC).

: FUNDING/SUPPORT: Multiple funding sources facilitated and sustained the SOS Network, including the Canadian Institutes for Health Research [FRN#96974], the Public Health Agency of Canada, and a collaborative Research Grant from GlaxoSmithKline Biological SA.

^∗: Collaborators from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) are listed in the Acknowledgements.

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Chest

Original Research: COPDEffectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD

Background

Methods

Results

Conclusions

Trial Registry

Section snippets

Patients and Methods

Results

Discussion

Conclusions

Acknowledgments

J Clin Virol

J Infect

J Infect

Chest

Chest

Chest

Lancet

Arch Bronconeumol

Vaccine

Vaccine

J Clin Epidemiol

Vaccine

Lancet Infect Dis

J Clin Virol

Vaccine

J Clin Virol

Prevalence of viral infection detected by PCR and RT-PCR in patients with acute exacerbation of COPD: a systematic review

Respirology

Contribution of influenza to acute exacerbations of chronic obstructive pulmonary disease in Kashmir, India, 2010-2012

Influenza Other Respi Viruses

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease—2007 update

Can Respir J

Original Research: COPD
Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD