Extra-fine-particle inhaled corticosteroid (ICS) use in patients with chronic obstructive pulmonary disease (COPD) is strongly associated with a decreased risk for hospitalization from pneumonia compared with use of standard-particle-size ICS, investigators reported in BMJ Open Respiratory Research.
The observational cohort study evaluated the effect of ICS particle size on the risk for hospitalization due to pneumonia among patients with COPD in several Danish databases who were followed after visiting outpatient clinics. The participants were followed for 1 year or until an initial hospitalization resulting from pneumonia or until death between 2010 and 2017.
The researchers identified ICS prescriptions, given as monotherapy or in combination with bronchodilators, that were redeemed within 365 days of patients’ start date for the study. All prescription dosages were converted to budesonide-equivalent doses for analysis. ICS particle size was categorized as standard particle size (median mass aerodynamic diameter [MMAD] >2) or extra-fine particle size (MMAD ≤2).
A total of 35,691 patients with COPD were followed in outpatient clinics; of those, 1471 received an extra-fine particle ICS. The cohort using standard-particle-size ICS had a median age of 70.7 years (45.0% male) and the cohort using extra-fine-particle-size ICS had a median age of 69.1 years (43.9% male). The median daily budesonide-equivalent doses of ICS for patients using extra-fine-particle ICS were 671 µg vs 657 µg in those using standard-particle ICS.
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This study is the first ever to explore the association between ICS particle size and risk of hospitalisation due to pneumonia in a large, well-characterised cohort of COPD outpatients with complete follow-up.
In the overall adjusted Cox model, patients who received extra-fine-particle ICS had a reduced risk of hospitalization due to pneumonia (hazard ratio [HR], 0.75; 95% CI, 0.63-0.89; P =.002). The risk was lower in a subgroup analysis of patients who received spray inhalation (HR, 0.54; 95% CI, 0.45-0.65; P <.0001).
Similar findings were observed in a propensity-matched cohort that matched as many as 5 control individuals who received standard-particle-size ICS with those who had extra-fine-particle ICS (HR, 0.72; 95% CI, 0.60-0.87; P =.0006). Increased use of ICS, male sex, older age, low body mass index, low forced expiratory volume in the first second percentage, and current smoking were associated with a higher risk for hospitalization due to pneumonia.
A time-adjusted HR for use of extra-fine particle ICS was similar to the main analysis (HR, 0.78; 95% CI, 0.66-0.94; P =.009). In the 1-year follow-up, 4657 patients had a hospitalization event due to pneumonia.
Cumulative incidence curves revealed an increased incidence of hospitalization due to pneumonia in patients who received standard-particle-size ICS vs those who had extra-fine-particle ICS.
Among several limitations, a pneumonia diagnosis was based on hospitalization records; the study used data on redeemed prescriptions instead of actual medication intake; the comparison between the 2 groups was not based only on ICS particle size but also on ICS type used; and residual confounding is possible.
“This study is the first ever to explore the association between ICS particle size and risk of hospitalisation due to pneumonia in a large, well-characterised cohort of COPD outpatients with complete follow-up,” said the study authors. “Until randomized controlled trials can inform us further, ICS formulations with extra-fine particles, using the lowest possible dose, seem like a safe choice, in patients with COPD at high risk of this serious adverse effect to corticosteroids,” said the investigators.
Disclosure: The study was financed by grants from Novo Nordisk Fonden. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
