Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus aureus (S. aureus) infections in patients with BE, but this is unexplored. We examined the association between ICS use prior to BE diagnosis at different doses and the risk of S. aureus isolation in patients with BE. Methods: We conducted a national register-based cohort study including Danish patients with a BE diagnosis code between 2001 and 2018 with a 1-year follow-up time from the date of diagnosis. ICS exposure was categorized based on accumulated prescriptions redeemed 365 days before BE diagnosis and divided into none, low, moderate, or high use based on clinically relevant doses. A cause-specific Cox proportional hazards regression model was used to estimate the risk of S. aureus isolation. A sensitivity analysis, an inverse probability of treatment weighted model (IPTW), was performed. Results: A total of 5093 patients were included in this study. S. aureus was isolated in 156 patients (3.1%). High-dose ICS was associated with an increased risk of S. aureus isolation, HR 3.81 (95% CI 2.51; 5.79). No association for low or moderate use was found, low-dose HR 1.22 (95% CI 0.77; 1.93), and moderate-dose HR 1.24 (95% CI 0.72; 2.16). IPTW analysis yielded similar results. Conclusions: High-dose ICS use in patients with BE was associated with an increased risk of S. aureus isolation. ICS should be used cautiously in patients with BE.

Rationale: Cardiovascular disease is a major comorbidity in chronic obstructive pulmonary disease (COPD). Previous studies evaluating the association between inhaled corticosteroids (ICS) and cardiovascular events (CVEs) in COPD have yielded conflicting results and a potential dose–response relationship remains unclear. Objectives: To determine the association between ICS exposure and risk of CVE in COPD patients. Methods: In this nationwide, retrospective register-based cohort study, we included patients with a specialist-verified COPD diagnosis between January 2008 and January 2022. ICS exposure was quantified as mean daily budesonide-equivalent dose redeemed in the year prior to index and categorised as none, low (>0 µg/day and 800 µg/day). We assessed CVE risk using adjusted cause-specific Cox proportional hazards models, with additional sensitivity analyses including a complete-case analysis, time-varying Cox regression, Fine-Gray competing risk model, and a negative control outcome analysis. Results: Among 82 327 patients, 8948 (10.9 %) experienced a CVE during a 1-year follow-up. In the primary analysis, low- and moderate-dose ICS was associated with a significantly reduced CVE rate compared with no ICS use. A modest decrease in CVE rate was observed for moderate-dose ICS largely across all sensitivity analyses. Conclusion: ICS use in COPD was not associated with an increased risk of CVE at any dose level. A modest association with reduction in CVE risk was confined to moderate-dose ICS. These findings support the cardiovascular safety of ICS and reinforce that ICS prescribing should be guided by exacerbation risk and symptom burden rather than cardiovascular concern.