Background
The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown.
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Objective
To examine the association between ICS exposure and corticosteroid (CS)-related AEs.

Methods
We conducted an observational cohort study using nationwide Swedish registry data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration. We included patients with asthma aged ≥18 years between 2009 and 2019 and calculated their current ICS exposure and average daily ICS dose (budesonide equivalent) in follow-up. The association between ICS exposure and CS-related AEs was analyzed using Cox proportional hazards models adjusting for age, sex, and OCS dose.
Results
We included 529,203 patients with asthma. Overall, we observed increased hazard ratios (HRs) in those exposed to high-dose (≥800-1599 μg) and very high dose (≥1600 μg) ICS for several AEs, including cardiovascular disease, type 2 diabetes mellitus (T2DM), osteoporosis, and pneumonia compared with those not exposed to ICS. HRs for the current use of high-dose ICS ranged from 1.11 (95% confidence interval [CI]: 1.06-1.16) for T2DM to 1.65 (95% CI: 1.58-1.72) for pneumonia. Likewise, HRs linked to average daily high-dose ICS ranged from 1.16 (95% CI: 1.02-1.33) for pneumonia to 1.70 (95% CI: 1.38-2.08) for osteoporosis. Sensitivity analysis excluding patients using OCS showed that high-dose ICS was still associated with an increased risk of CS-related AEs. Overall, ICS <800 μg per day had no increased risk, except for cataract.

Conclusion
High-dose ICS is associated with an increased risk of several CS-related AEs. This highlights the importance of clinicians considering this risk in patients treated with high-dose and very high dose ICS.