Risk of pneumonia with inhaled corticosteroid versus long-acting bronchodilator regimens in chronic obstructive pulmonary disease: a new-user cohort study

• Published in: PloS one Vol. 9; no. 5; p. e97149
• Main Authors: DiSantostefano, Rachael L, Sampson, Tim, Le, Hoa Van, Hinds, David, Davis, Kourtney J, Bakerly, Nawar Diar
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.05.2014; Public Library of Science (PLoS)
• Subjects: Acetylcholine receptors (muscarinic); Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - therapeutic use; Aged; Aged, 80 and over; Antagonists; Biomarkers - metabolism; Bronchodilator Agents - therapeutic use; Bronchodilators; Censorship; Channeling; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cohort analysis; Cohort Studies; Corticosteroid drugs; Corticosteroids; Disease control; Dose-Response Relationship, Drug; Electronic Health Records; Electronic medical records; Female; Glucocorticoids; Hazards; Health risk assessment; Humans; Lung diseases; Male; Medical records; Medical research; Medicine and Health Sciences; Middle Aged; Mortality; Observational studies; Obstructive lung disease; Patients; Pneumonia; Pneumonia - complications; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - metabolism; Research and Analysis Methods; Risk; Risk factors; Statistical models; Studies; North Carolina; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0097149

Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs. To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy. Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding. United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. severe pneumonia (primary) and any pneumonia (secondary). Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted. The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.