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

PLoS One. 2014 May 30;9(5):e97149. doi: 10.1371/journal.pone.0097149. eCollection 2014.


Introduction: 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.

Objective: To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.

Methods: 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.

Setting: 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.

Outcomes: severe pneumonia (primary) and any pneumonia (secondary).

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Bronchodilator Agents / therapeutic use*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Electronic Health Records
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pneumonia / complications*
  • Pulmonary Disease, Chronic Obstructive / complications*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Risk


  • Adrenal Cortex Hormones
  • Biomarkers
  • Bronchodilator Agents

Grant support

This study was funded by GlaxoSmithKline. The funder provided support in the form of salaries for authors RLD, TS, HVL, DH and KJD, but did not have any additional role in the study design, data collection and analysis or preparation of the manuscript. The decision to submit for publication is required by GSK policy as part of being transparent regarding research activities. The specific roles of these authors are articulated in the ‘author contributions’ section. Editorial support in the form of development of the manuscript first draft in consultation with the authors, editorial suggestions to draft versions of this paper, assembling tables and figures, collating author comments, copyediting, fact checking, referencing and graphic services was provided by David Cutler, PhD and Laura Maguire, MChem at Gardiner-Caldwell Communications (Macclesfield, UK), and was funded by GlaxoSmithKline. The open-access charge was paid for by GlaxoSmithKline.