Live Zoster Vaccination and the Reduced Risk of Chronic Respiratory Diseases: An Emulated Target Trial

Background: Recent previous study suggests that live zoster vaccination may reduce the risk of diseases like dementia and cardiovascular diseases, through prevention of herpes zoster. Thus, this study aims to evaluate whether live zoster vaccination can reduce the risk of chronic respiratory disease including chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD). Methods: This target trial emulation study utilized a nationwide, population-based cohort of 2,519,582 individuals aged ≥ 50 years in South Korea. The cohort was constructed by integrating health insurance data from the Korea Health Insurance Review and Assessment Service, national health examination data from the Korean National Health Insurance Service, and vaccination records from the Korea Disease Control and Prevention Agency. The exposure was receipt of at least one dose of live zoster vaccination between January 1, 2012, and December 31, 2021. Outcomes included the incidence of newly diagnosed COPD, asthma, and ILD, as well as hospitalizations associated with these conditions. Following stabilized inverse probability of treatment weighting, we employed the Cox proportional hazards model to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) and calculated restricted mean survival time (RMST) for the risk of outcomes associated with live zoster vaccination. The observation period extends from the index date to January 31, 2024. Measurements and main results: After stabilized inverse probability of treatment weighting, 745,644 individuals were assigned to the vaccinated group and 1,069,230 to the unvaccinated group, with a mean age of 62.12 years (SD, 3.45) and 49.18% were male. Live zoster vaccination significantly reduced the risk of COPD (aHR, 0.70 [95% CI, 0.69-0.71]; RMST difference, 23.22 days [95% CI, 21.72-24.71]), asthma (0.68 [0.67-0.69]; 25.96 days [24.52-27.40]) and ILD (0.78 [0.73-0.82]; 2.39 days [2.05-2.74]). Additionally, the vaccination significantly reduced the risk of hospital admissions due to these conditions: COPD (0.59 [0.53-0.65]), asthma (0.54 [0.49-0.59]), and ILD (0.68 [0.58-0.79]). The observed protective benefit was more pronounced in non-smokers compared to current smokers. The time-attenuated effect was strongest during 1 to 2 years following live zoster vaccination and remained evident for up to 6 years. Conclusions: Live zoster vaccination significantly reduced the incidence of chronic respiratory disease and related hospitalizations. These findings suggest that live zoster vaccination may provide public health benefits beyond preventing herpes zoster in adults aged ≥ 50 years.