Background Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia among patients with chronic obstructive pulmonary disease (COPD). In recent years, ICS formulated as extra-fine particles have been introduced to improve the distribution of medicine in the airways. It remains unclear if extra-fine particle ICS administration alters the risk of pneumonia compared to standard particle size ICS.

Methods An observational cohort study including all Danish COPD outpatients receiving ICS from 2010 to 2017. The primary outcome was pneumonia hospitalization in the different ICS particle dosing regimens. The primary analysis was an adjusted Cox model. For sensitivity analysis, a subgroup analysis of patients receiving spray devices was done. Further, we created a propensity score matched cohort, in which we matched for the same covariates as adjusted for in the main analysis.

Results A total of 35,691 patients were included of whom 1,471 received extra-fine particles. Among these patients, 4,657 were hospitalized due to pneumonia. COPD patients receiving extra-fine particle ICS had a lower risk of hospitalization due to pneumonia compared to patients receiving standard particle size ICS in our primary analysis (HR 0.75; 95% CI 0.63-0.89; p=0.002), subgroup analysis (HR 0.54; CI 0.45-0.65; p <0.0001), and the Propensity-matched population (HR 0.72; CI 0.60-0.87; p=0.0006).

Interpretation The use of extra-fine particle ICS administration was associated with a lower risk of pneumonia hospitalization in COPD patients compared to those who received standard size treatment.