Inhaled Corticosteroid Use in Chronic Obstructive Pulmonary Disease and Risk of Pneumonia: A Nested Case-Control Population-based Study in Lazio (Italy)—The OUTPUL Study

Inhaled corticosteroid (ICS) use in chronic obstructive pulmonary disease (COPD) patients is associated with a reduction of exacerbations and a potential risk of pneumonia. The objective was to determine if ICS use, with or without long-acting β₂-agonist, increases pneumonia risk in COPD patients. A cohort study was performed using linked hospital and drug prescription databases in the Lazio region. Patients (45+) discharged with COPD in 2006–2009 were enrolled and followed from cohort entry until first admission for pneumonia, death or study end, 31 December, 2012. A nested case-control approach was used to estimate the rate ratio (RR) associated with current or past use of ICS adjusted for age, gender, number of exacerbations in the previous year and co-morbidities. Current users were defined as patients with their last ICS prescribed in the 60 days prior to the event. Past users were those with the last prescription between 61 and 365 days before the event. Current use was classified into three levels (high, medium, low) according to the medication possession ratio. Among the cohort of 19288 patients, 3141 had an event of pneumonia (incidence rate for current use 87/1000py, past use 32/1000py). After adjustment, patients with current use were 2.29 (95% confidence interval [CI]: 1.99–2.63) times more likely to be hospitalised for pneumonia with respect to no use; for past use RR was 1.23 (95% CI: 1.07–1.42). For older patients (80+), the rate was higher than that for younger patients. ICS use was associated with an excess risk of pneumonia. The effect was greatest for higher doses and in the very elderly.