Inhaled Corticosteroids Use and Risk of Invasive Pneumococcal Disease in a Population-based Study

Rationale: The use of inhaled corticosteroids (ICS) is associated with increased pneumonia risk, but the risk of invasive pneumococcal disease (IPD) associated with ICS is not characterized. Objectives: The aim was to test the hypothesis that the use of ICS increases the risk of IPD. Methods: Cases were persons 20–65 years of age included in a Swedish national registry of invasive infection caused by Streptococcus pneumoniae classified as any IPD as well as the subset of IPD with pneumonia. The case index date was the day the infection was diagnosed. Six control subjects for each case (matched for sex, age, and region) were selected from the Swedish National Population Registry and were assigned the index date of their corresponding case. Current and past users of ICS were defined by the last prescriptions dispensed within 60 or 61–365 days of the index date. Nonusers were defined as those with no dispensed prescription the last 365 days. Current users were characterized by use of fluticasone or budesonide. We used conditional logistic analysis, including matching and covariates, to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of IPD, IPD with pneumonia, and IPD without pneumonia associated with current or past use of ICS. Results: Current use of ICS increased the risk for IPD and IPD with pneumonia (OR, 1.71; 95% CI, 1.39–2.10 and OR, 1.94; 95% CI, 1.53–2.47, respectively), but there was no statistical association between current use of ICS and IPD without pneumonia (OR, 1.18; 95% CI 0.78–1.80). Past use of ICS increased the risk for IPD and IPD with pneumonia but not for IPD without pneumonia. Among current ICS users, the odds for IPD were similar for budesonide (OR, 1.34; 95% CI, 1.14–1.57) and fluticasone (OR, 1.41; 95% CI, 1.04–1.90). Among current ICS users, the odds for IPD with pneumonia were slightly higher but of similar magnitude for both budesonide and for fluticasone. Conclusions: ICS use is associated with an increased risk of IPD and IPD with pneumonia. The risk is driven by IPD with pneumonia. We found similar risks for budesonide and fluticasone.