Chronic obstructive pulmonary disease and risk of digestive diseases: observational and mendelian randomization analyses in the China Kadoorie Biobank

BACKGROUND: Several digestive diseases have been reported as comorbidities of COPD. However, consistent evidence supporting their associations is limited. Our study aims to investigate the associations between prevalent COPD and incident digestive diseases in the Chinese population. METHODS: We used data from the China Kadoorie Biobank (CKB), enrolling 512,724 participants aged 30-79 years at baseline from 10 areas in China. COPD was defined by spirometry (without bronchodilator) and self-reported emphysema/chronic bronchitis at baseline. We employed stratified Cox proportional regression models to assess the prospective associations of prevalent COPD and airflow obstruction severity with the risks of incident digestive diseases. A total of 31 digestive diseases were included, including the overall digestive diseases, 15 major disease categories, and 15 specific subtypes nested within the major categories. We further conducted one-sample Mendelian randomization analyses to assess the associations of genetically predicted COPD with digestive diseases. RESULTS: During a median follow-up of 15.3 years, a total of 131,993 participants experienced at least one hospitalization or death due to the included digestive diseases. For the composite outcome and major categories, prevalent COPD at baseline was significantly associated with a higher risk of overall digestive diseases (hazard ratio and 95% confidence interval: 1.05 [1.03-1.08]), gastrointestinal inflammation (1.11 [1.07-1.15]) and abdominal pain (1.20 [1.12-1.28]). Dose-response associations of airflow obstruction severity with the overall digestive diseases (P value for trend: < 0.001) and six other disease types were identified. In MR analyses, a genetically predicted higher probability of COPD was significantly associated with overall digestive diseases (OR per doubling of genetically-predicted COPD prevalence: 3.21 [1.71-6.03]) and three other disease types. CONCLUSIONS: Prevalent COPD is associated with various digestive diseases in the Chinese population, with MR analyses further supporting a potential causal link. These findings underscore the importance of considering disease severity when managing COPD-related digestive diseases. While COPD was defined based on baseline spirometry in this study, future research incorporating post-bronchodilator assessment could further refine these associations and help distinguish COPD from other reversible airflow limitations.