TOPLINE

Influenza vaccination was associated with a 39% lower risk for hospitalization for influenza among patients with chronic obstructive pulmonary disease (COPD) during epidemic periods across six influenza seasons in England. However, vaccination was also linked to a 17% lower risk for urinary tract infection, which served as a negative control outcome with no plausible causal connection to the vaccine, suggesting that residual confounding may have biased the findings. 

METHODOLOGY

• Using data from England's Clinical Practice Research Datalink linked to Hospital Episode Statistics, researchers conducted a cohort study evaluating the effectiveness of influenza vaccination in patients with COPD from September 2014 to March 2020.
• They included 56,652 matched pairs of vaccinated and unvaccinated patients with COPD aged 40 years or older who had initiated inhaled treatment. Patients were matched within the same 7-day period based on their time-conditional propensity scores. The mean age at follow-up commencement was 65.4 years, and 50% of the patients were women.
• Researchers divided each study year into four windows: a preepidemic period (September 1 until the start of flu activity), an epidemic window (from the start to the end of the influenza epidemic, extended by a week to account for delayed diagnoses), a postepidemic phase (through April), and an off-season period (from May 1 to August 31).
• The primary outcome was hospitalization for influenza during epidemic periods; a five-component secondary outcome included moderate and severe acute COPD exacerbations, moderate and severe community-acquired influenza-related pneumonia, and severe influenza.
• Negative control outcomes (urinary tract infections and trauma during epidemic periods) and off-season estimates (May-August) were used to detect residual confounding.

TAKEAWAY

• During epidemic periods, hospitalization for influenza was less frequent in vaccinated patients with COPD than in their unvaccinated counterparts (incidence rate, 0.7 per 1000 person-months vs 1.1 per 1000 person-months; weighted HR, 0.61; 95% CI, 0.48-0.77).
• For the five-point composite secondary outcome (moderate or severe COPD exacerbations, moderate or severe pneumonia, and severe influenza), risk was lower in vaccinated patients during epidemic periods (weighted HR, 0.89; 95% CI, 0.86-0.91) but not during the off-season (weighted HR, 0.99; 95% CI, 0.94-1.04). 
• For the combined severe outcomes (hospitalized exacerbations, pneumonia, and influenza), risk was similarly lower in vaccinated patients during epidemic periods (weighted HR, 0.78; 95% CI, 0.73-0.82).
• Vaccinated patients had a 17% lower risk for urinary tract infection, which was a negative control outcome with no plausible link to influenza vaccination, during epidemic periods (weighted HR, 0.83; 95% CI, 0.77-0.90).

IN PRACTICE

"Until further methodological improvements are made, this study supports the need to include negative control outcomes during influenza epidemics alongside off-season estimates to better detect residual confounding in cohort studies on influenza vaccine effectiveness," the study authors wrote.

SOURCE

The study was led by Simon Galmiche, Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital in Montreal, Canada. It was published online on September 12, 2026, in Clinical Microbiology and Infection.

LIMITATIONS

The broad definition of the composite secondary outcome may have included events unrelated to influenza, potentially underestimating effectiveness. Residual confounding likely affected the results. Misclassification of vaccinated patients as unvaccinated may have occurred if vaccination was not documented in primary care records.

DISCLOSURES

No specific funding was reported for this study. One author is the recipient of the Distinguished James McGill Professorship award, and Simon Galmiche received a postdoctoral award from the Fonds de Recherche du Québec – Santé. In the past three years, the same author attended scientific advisory meetings for Novartis and Panalgo and received speaking fees from Covis Pharma and CSL Behring. Another author declared being an employee of Sanofi Pasteur between January 2016 and June 2024. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.