Risk of Pneumonia Associated with Inhaled Corticosteroid in Patients with Chronic Obstructive Pulmonary Disease: A Korean Population-Based Study

Introduction: Inhaled corticosteroids (ICSs) are recommended for patients with frequent exacerbation of chronic obstructive pulmonary disease (COPD). However, accumulating evidence has indicated the risk of pneumonia from the use of ICS. This study aimed to investigate the association between ICS and pneumonia in the real-world clinical setting. Methods: A retrospective cohort study was performed using nationwide population data from the Korea National Health Insurance Service. Subjects who had a new diagnosis of COPD and who received inhaled bronchodilators without a diagnosis of pneumonia before the initiation of bronchodilators were identified. Subjects were followed up until their first diagnosis of pneumonia. The risk of pneumonia in ICS users was compared to that in non-ICS users. Results: A total of 87,594 subjects were identified and 1:1 matched to 22,161 ICS users and non-ICS users. More ICS users were diagnosed with pneumonia compared to non-ICS users (33.73% versus 24.51%, P<0.0001). The incidence rate per 100,000 person-years was 8904.98 for ICS users and 6206.79 for non-ICS users. The hazard ratio (HR) of pneumonia for ICS users was 1.62 (95% CI 1.54-1.70). The HR of subjects prescribed with the lowest ICS cumulative dose was 1.35 (1.27-1.43). The HR increased to 1.51 (1.42-1.60), 1.96 (1.85-2.09), and 2.03 (1.89-2.18) as the cumulative dose increased. Pneumonia was strongly associated with fluticasone propionate (1.79 (1.70-1.89)) and fluticasone furoate (1.80 (1.61-2.01)) use, compared to the use of other types of ICS. Conclusion: ICS increases the risk of pneumonia in patients with COPD. Hence, ICS should be carefully prescribed in patients with risk factors for pneumonia while considering the cumulative doses and subtypes of ICS.