Influenza vaccine effectiveness in patients with chronic obstructive pulmonary disease: a cohort study emulating a randomized trial

Why clinicians should know about it

• Picked for Family Practice (paper of the day, 14 September 2026): Influenza vaccine effectiveness in COPD patients
• Picked for Epidemiology (paper of the day, 14 September 2026): Cohort emulating RCT of influenza vaccine effectiveness in COPD

Abstract

OBJECTIVES: Many observational studies of influenza vaccine effectiveness have faced issues of residual confounding and immortal time bias. We aimed to assess the effectiveness in people with COPD, using a novel study design to address these methodological challenges. METHODS: We conducted a cohort study emulating a randomized trial within the primary care practices contributing data to England's Clinical Practice Research Datalink. We identified the base cohort of patients diagnosed with COPD, aged 40 years and above, initiating an inhaled treatment. Those vaccinated between September 2014 and March 2020 were matched 1:1 with unvaccinated people on the week of vaccination and the time-conditional propensity score. The primary outcome was hospitalized influenza during epidemic periods. Secondary outcomes included a composite of acute exacerbations of COPD, pneumonia, and hospitalized influenza. Urinary tract infections during epidemic periods and the composite outcome outside of influenza seasons (May - August) were used to detect residual confounding. RESULTS: The emulated trial included 56,652 matched pairs of vaccinated and unvaccinated patients with COPD. The hazard ratio for hospitalized influenza was 0.61 (95% confidence interval 0.48-0.77) during epidemic periods. The HR for the composite secondary outcome was 0.89 (95% CI 0.87-0.92) during epidemic periods and 0.99 (95% CI 0.94-1.04) outside influenza seasons. The HR for urinary tract infection was 0.83 (95% CI 0.77-0.90). Results were consistent in several sensitivity analyses, such as when excluding patients consulting for reasons likely precluding vaccination. CONCLUSION: Influenza vaccine was associated with a reduced risk of hospitalized influenza in patients with COPD, but a reduced risk of urinary tract infection suggests important residual confounding. While this study design addresses immortal time bias, methodological improvements are needed to better address residual confounding in cohort studies of the influenza vaccine. In the meantime, negative control outcomes should be assessed during influenza epidemics to better detect residual confounding.

Abstract as published, via PubMed.