Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Infection in Chronic Airway Disease: A Nationwide Population-Based Study

Abstract

Background: Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroid (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases.

Methods: We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability of treatment weighting (IPTW) to ensure a balanced analysis of covariates.

Results: Of the 57,553 patients (mean age 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including nine among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI], 1.48 to 15.58). Higher risks were significant for patients ≥65 years (adjusted HR, 6.40; 95% CI, 1.28 to 31.94), females (adjusted HR, 10.91; 95% CI, 2.24 to 53.20), never-smokers (adjusted HR, 6.31; 95% CI, 1.49 to 26.64), systemic steroid users (adjusted HR, 50.19; 95% CI, 8.07 to 312.19), and those with higher comorbidity scores (adjusted HR, 6.64; 95% CI, 1.19 to 37.03).

Conclusion: ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.

Keywords: Asthma; Chronic Airway Diseases; Chronic Obstructive Pulmonary Disease; Epidemiology; Infection.

Fig. 1.

Patient enrolment. NHIS: National Health Insurance Service; COPD: chronic obstructive pulmonary disease; ICS: inhaled corticosteroid; NTM: nontuberculous mycobacteria.

Fig. 2.

Covariate balance before and after inverse probability of treatment weighting treatment. Dot plot displaying the covariate balance before and after adjustment. The Y-axis lists the covariates, and the X-axis shows the standardized mean differences. Red dots represent unadjusted values, and blue dots represent adjusted values post-propensity score matching, with dots closer to the vertical zero line indicating a better balance between groups. BMI: body mass index; COPD: chronic obstructive pulmonary disease; CCI: Charlson comorbidity index; LABA: long-acting beta-agonist; LAMA: long-acting muscarinic antagonist; SABA: short-acting beta-agonist; LTRA: leukotriene receptor antagonist.