Budesonide and the risk of pneumonia: a meta-analysis of individual patient data

Lancet. 2009 Aug 29;374(9691):712-9. doi: 10.1016/S0140-6736(09)61250-2.


Background: Concern is continuing about increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD) who use inhaled corticosteroids. We aimed to establish the effects of inhaled budesonide on the risk of pneumonia in such patients.

Methods: We pooled patient data from seven large clinical trials of inhaled budesonide (320-1280 mug/day), with or without formoterol, versus control regimen (placebo or formoterol alone) in patients with stable COPD and at least 6 months of follow-up. The primary analysis compared treatment groups for the risk of pneumonia as an adverse event or serious adverse event during the trial or within 15 days of the trial end. Cox proportional hazards regression was used to analyse the data on an intention-to-treat basis. Data were adjusted for patients' age, sex, smoking status, body-mass index, and postbronchodilator percent of predicted forced expiratory volume in 1 s (FEV(1)).

Findings: We analysed data from 7042 patients, of whom 3801 were on inhaled budesonide and 3241 were on control treatment, with 5212 patient-years of exposure to treatment. We recorded no significant difference between treatment groups for the occurrence of pneumonia as an adverse event (3% [n=122 patients] vs 3% [n=103]; adjusted hazard ratio 1.05, 95% CI 0.81-1.37) or a serious adverse event (1% [n=53] vs 2% [n=50]; 0.92, 0.62-1.35), or for time to pneumonia as an adverse event (log-rank test 0.94) or a serious adverse event (0.61). Increasing age and decreasing percent of predicted FEV(1) were the only two variables that were significantly associated with occurrence of pneumonia as an adverse event or a serious adverse event.

Interpretation: Budesonide treatment for 12 months does not increase the risk of pneumonia in patients with COPD during that time and therefore is safe for clinical use in such patients.

Funding: Michael Smith Foundation for Health Research.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Anti-Inflammatory Agents / adverse effects*
  • Bronchodilator Agents / adverse effects*
  • Budesonide / adverse effects*
  • Ethanolamines / adverse effects
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Formoterol Fumarate
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pneumonia / chemically induced*
  • Pneumonia / epidemiology
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Safety
  • Smoking / epidemiology
  • Time Factors


  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Ethanolamines
  • Budesonide
  • Formoterol Fumarate