Research Summary

Influenza Vaccination Linked to Lower Hospitalization Risk in COPD Patients

Edited by:
Brian McCurdy

Key Highlights

  • The study included 56,652 matched pairs of vaccinated and unvaccinated patients with COPD.
  • Vaccination was associated with a lower risk of hospitalized influenza during epidemic periods (HR, 0.61; 95% CI, 0.48–0.77).
  • A lower risk of urinary tract infection, assessed as a negative control outcome, suggested important residual confounding.

Influenza vaccination was associated with reduced risk of hospitalized influenza among patients with chronic obstructive pulmonary disease (COPD), according to a cohort study published in Clinical Microbiology and Infection. However, an accompanying association with fewer urinary tract infections (UTIs) raised concerns about residual confounding, despite a design intended to address methodological weaknesses in observational vaccine research.

Researchers used data from primary care practices contributing to England’s Clinical Practice Research Datalink. The base cohort comprised patients aged ≥40 years with diagnosed COPD who were initiating an inhaled treatment. Patients vaccinated between September 2014 and March 2020 were matched 1:1 with unvaccinated patients during the vaccination week and by time-conditional propensity score.

The primary outcome was hospitalized influenza during epidemic periods. A secondary composite included acute COPD exacerbations, pneumonia, and hospitalized influenza. To detect residual confounding, investigators also assessed UTIs during epidemic periods and the composite outcome outside influenza seasons, defined as May through August.

Study Findings

The emulated trial included 56,652 matched pairs. During epidemic periods, influenza vaccination was associated with a lower hazard of hospitalized influenza (HR, 0.61; 95% CI, 0.48–0.77). The hazard of the secondary composite outcome was also lower among vaccinated patients during epidemics (HR, 0.89; 95% CI, 0.87–0.92). Outside influenza seasons, the composite outcome showed no clear difference between groups (HR, 0.99; 95% CI, 0.94–1.04).

Vaccinated patients also had a lower hazard of UTIs during epidemic periods (HR, 0.83; 95% CI, 0.77–0.90). The authors interpreted this negative control finding as evidence of important residual confounding. Results were consistent across several sensitivity analyses, including an analysis excluding patients consulting for reasons likely to preclude vaccination.

Clinical Implications

According to the authors, the study design addresses immortal time bias, but further methodological improvements are needed to address residual confounding in observational influenza vaccine studies. They emphasized assessing negative control outcomes during influenza epidemics to identify this problem better.

Expert Commentary

“Although this study design addresses immortal time bias, methodological improvements are needed to better address residual confounding in cohort studies of the influenza vaccine,” the researchers concluded.

Reference

Galmiche S, Dell'Aniello S, Lévesque L, Suissa S. Influenza vaccine effectiveness in patients with chronic obstructive pulmonary disease: a cohort study emulating a randomised trial. Clin Microbiol Infect. Published online September 12, 2026. doi:10.1016/j.cmi.2026.09.006