Inhaled and oral corticosteroid use and the risk of pulmonary aspergillosis: a Danish population-based case–control study

Background Pulmonary aspergillosis is a rare, high mortality lung infection caused by the Aspergillus sp. Chronic lung diseases and immunosuppression are known risk factors, but data on the impact of corticosteroids and their route of administration are limited. Methods To evaluate the association between corticosteroid use and pulmonary aspergillosis, we conducted a retrospective case–control study in all Danish citizens who redeemed at least one prescription for inhaled medicine between 1994 and 2025. We identified 1351 patients with aspergillosis other than allergic bronchopulmonary aspergillosis (ABPA) and matched them to controls (1:5) by age, sex and calendar year using risk set sampling. Conditional logistic regression was used to estimate adjusted incidence rate ratios (aIRRs) for chronic pulmonary aspergillosis (CPA) and invasive pulmonary aspergillosis (IPA) across dose categories and 90-day exposure windows. The use of risk-set sampling allowed for estimating IRRs. Results Inhaled corticosteroids were associated with non-ABPA aspergillosis in a dose-dependent manner (aIRR 1.7 (95% CI 1.3 to 2.2) for use ≤640 µg/day, aIRR 2.8 (2.2 to 3.6) for use >640 µg/day, compared with no use) but only associated with IPA for higher doses. Oral corticosteroids (OCS) were similarly associated with non-ABPA aspergillosis (aIRR 3.0 (95% CI 2.2 to 4.1) for OCS use ≤5.6 mg/day, aIRR 4.0 (2.9 to 5.4) for OCS use >5.6 mg/day, both compared with no use), affecting both CPA and IPA. The risk decreased with increasing time since exposure. Conclusion Our results demonstrate a strong and seemingly dose-dependent association between both systemic and inhaled corticosteroid use and aspergillosis.