Inhaled corticosteroids associated with increased risk of severe pneumonia in COPD patients

Evidence Updates from the BMJ Evidence Centre


Reference: Suissa S, Patenaude V, Lapi F, et al. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013 Nov;68(11):1029-36.

BACKGROUND: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.

METHODS: We formed a new-user cohort of patients with COPD treated during 1990-2005. Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalization for or death from pneumonia. A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.

RESULTS: The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year). Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75). The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17). The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).

CONCLUSIONS: ICS use by patients with COPD increases the risk of serious pneumonia. The risk is particularly elevated and dose related with fluticasone. While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials.


  • General Internal Medicine-Primary Care(US)  This information is very important for clinicians who provide primary care. I believe that many providers are not aware of this relationship and, even if they are aware, this well-done study confirms prior research. The increased risk of pneumonia requiring hospitalization or resulting in death is very significant and the higher rate for fluticasone compared to budesonide is clinically important.
  • General Practice/Family Practice  Important, new information that changes my clinical practice.
  • General Practice/Family Practice  An important finding, adding weight to the concerns about ICS use in COPD. As always in a retrospective study, many methodological problems exist, especially around the diagnosis of COPD and pneumonia, but given the significantly absolute rate of pneumonia in the COPD population, primary care clinicians must pay heed of this harm especially when using higher doses especially of fluticasone.
  • Internal Medicine  This study used subjective measures to define outcomes (didn´t had spirometry to diagnose COPD or chest x-ray to diagnose pneumonia). They didn´t take into account variables that affect mortality of these patients (FEV1 and cigarette smoking), didn´t classify the level of severity of the disease (GOLD stage and Bode Index). Regardless, the results are similar to other clinical studies where the presence of pneumonia is associated with higher doses of inhaled steroid. It would have been more appropriate to conduct a proper analysis of confounding variables.
  • Respirology/Pulmonology Very good study which confirms clinical findings of a number of clinical trials.

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