Concomitant inhaled corticosteroid use and the risk of pneumonia in COPD: a matched-subgroup post hoc analysis of the UPLIFT® trial

Respir Res. 2018 Oct 5;19(1):196. doi: 10.1186/s12931-018-0874-0.


Background: Use of inhaled corticosteroids (ICS) increases the risk of pneumonia in chronic obstructive pulmonary disease (COPD), but the magnitude of risk with different ICS remains unclear.

Methods: A post hoc analysis of the 4-year UPLIFT® trial to assess whether pneumonia risk differed by type of ICS (fluticasone propionate [FP], other ICS, or no ICS) in permanent users (defined by use until end of study) or in users at baseline (sensitivity analysis).

Results: For the permanent-users analysis, 825 patients receiving FP throughout the trial, 825 patients receiving other ICS and 825 patients not receiving ICS were matched on relevant baseline features 1:1:1. A significantly greater risk of pneumonia was observed for FP versus no ICS: the hazard ratio (HR) for risk of pneumonia was 1.33 (95% confidence interval [CI] 1.00, 1.75; p = 0.046) and the rate ratio (RR) was 1.58 (95% CI 1.05, 2.37; p = 0.028). A greater risk was also found for FP versus other ICS: HR 1.28 (95% CI 0.97, 1.68; p = 0.078) and RR 1.48 (95% CI 1.00, 2.19; p = 0.049). A higher proportion of patients on FP were hospitalized with pneumonia (7.9%) versus other ICS (6.7%) or no ICS (5.9%). Whilst other ICS use was associated with the highest number of fatal pneumonia events, the total number of fatal pneumonia incidents was low. A similar pattern was observed in the sensitivity analyses, which included 4002 patients on different treatments at baseline (FP, other ICS, and no ICS) and considered potential switches during the study.

Conclusion: The results support existing evidence of an increased pneumonia risk with FP use compared with other ICS and no ICS use in patients with COPD. Healthcare professionals should evaluate the risk-benefit ratio of using ICS when making treatment decisions with their patients.

Trial registration: Post hoc analysis of UPLIFT®. number: NCT00144339 . Retrospectively registered September 2, 2005.

Keywords: COPD; Fluticasone propionate; Inhaled corticosteroids; Pneumonia; UPLIFT®.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Aged
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Double-Blind Method
  • Female
  • Fluticasone / administration & dosage*
  • Fluticasone / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Pneumonia / chemically induced*
  • Pneumonia / diagnosis
  • Pneumonia / epidemiology
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Research Design
  • Risk Factors
  • Tiotropium Bromide / administration & dosage*
  • Tiotropium Bromide / adverse effects


  • Adrenal Cortex Hormones
  • Bronchodilator Agents
  • Fluticasone
  • Tiotropium Bromide

Associated data