Inhaled corticosteroids in chronic obstructive pulmonary disease and risk of death and hospitalization: time-dependent analysis

Am J Respir Crit Care Med. 2003 Dec 15;168(12):1488-94. doi: 10.1164/rccm.200301-019OC. Epub 2003 Oct 2.


Observational studies of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD) have shown improved survival whereas randomized trials have not. It has been suggested that this difference may be due to immortal time bias. To investigate this further, we performed a prospective cohort study of patients with COPD, using time-dependent methods to determine whether use of inhaled corticosteroids more than 80% of the time reduced the risk of all-cause mortality and COPD exacerbations. Of 8,033 patients, 2,686 (33%) received inhaled corticosteroids. We did not find a significant reduction in mortality for average inhaled steroid use at either low (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.69-1.33) or medium/high dose (HR, 0.86; 95% CI, 0.67-1.10). Similarly, recent inhaled corticosteroid use was not associated with a reduction in mortality at low (HR, 0.80; 95% CI, 0.60-1.07) or medium/high doses (HR, 0.88; 95% CI, 0.71-1.09). There was no association between inhaled corticosteroid use and hospitalizations or exacerbations due to COPD. Patients using medium/high-dose inhaled corticosteroids did not have a significantly lower risk of COPD hospitalizations (HR, 0.85; 95% CI, 0.64-1.13) or COPD exacerbations (HR, 1.13; 95% CI, 0.94-1.36). In a time-dependent study of outpatients with COPD, adherence to inhaled corticosteroid use was not associated with a decreased risk of mortality or exacerbations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Aged
  • Anti-Inflammatory Agents / administration & dosage*
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Outpatients
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality*
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents