Penicillin Allergy Labels, Broad-Spectrum Antibiotic Use, and Chronic Obstructive Pulmonary Disease Exacerbations: A Population-Based Cohort Study from China

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and acute exacerbations drive most of its burden. Around half of exacerbations are infection related, and penicillin-class antibiotics are widely used. However, penicillin allergy labels, often inaccurate, may divert prescribing towards broader-spectrum agents and worsen outcomes. We therefore examined whether such labels are associated with antibiotic prescribing patterns and subsequent risk of COPD exacerbations in a large cohort. Methods: We conducted a retrospective cohort study in the Kunshan Aging Research with E-health (KARE) database (2016– 2024). We included 14,900 patients with COPD aged ≥ 40 years. Exposure was a documented penicillin allergy label in the electronic medical record. Outcomes were the risk and rate of subsequent COPD exacerbations. Cox proportional hazards models estimated the association with time to first exacerbation, and negative binomial regression assessed exacerbation rates. Results: Of 14,900 patients, 722 (4.8%) had a penicillin allergy label. Overall, 2018 (13.5%) experienced at least one exacerbation during a median follow-up of 4.1 years. Compared with unlabeled patients, those with a penicillin allergy label received more broad-spectrum antibiotics and had a higher risk of exacerbations (adjusted hazard ratio 1.39, 95% confidence interval 1.17– 1.65) and higher exacerbation rates (adjusted incidence rate ratio 1.56, 95% confidence interval 1.25– 1.93). Conclusion: In this Chinese COPD cohort, penicillin allergy labels were associated with broader-spectrum antibiotic use and an increased burden of exacerbations. Systematic verification and de-labelling of penicillin allergy may help optimise antibiotic use and improve COPD outcomes.