Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD

Int J Chron Obstruct Pulmon Dis. 2017 Oct 19:12:3055-3064. doi: 10.2147/COPD.S143656. eCollection 2017.


Inhaled corticosteroids (ICSs) treatment combined with long-acting β2-adrenoceptor agonists (LABAs) reduces the risk of exacerbations in COPD, but the use of ICSs is associated with increased incidence of pneumonia. There are indications that this association is stronger for fluticasone propionate than for budesonide. We have examined systematic reviews assessing the risk of pneumonia associated with fluticasone propionate and budesonide COPD therapy. Compared with placebo or LABAs, we found that fluticasone propionate was associated with 43%-78% increased risk of pneumonia, while only slightly increased risk or no risk was found for budesonide. We have evaluated conceivable mechanisms which may explain this difference and suggest that the higher pneumonia risk with fluticasone propionate treatment is caused by greater and more protracted immunosuppressive effects locally in the airways/lungs. These effects are due to the much slower dissolution of fluticasone propionate particles in airway luminal fluid, resulting in a slower uptake into the airway tissue and a much longer presence of fluticasone propionate in airway epithelial lining fluid.

Keywords: COPD; budesonide; fluticasone; inhaled corticosteroids; pneumonia.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / classification
  • Adrenal Cortex Hormones / pharmacokinetics
  • Animals
  • Budesonide / administration & dosage
  • Budesonide / adverse effects*
  • Budesonide / classification
  • Budesonide / pharmacokinetics
  • Fluticasone / administration & dosage
  • Fluticasone / adverse effects*
  • Fluticasone / classification
  • Fluticasone / pharmacokinetics
  • Humans
  • Immunocompromised Host
  • Lung / drug effects*
  • Lung / immunology
  • Lung / physiopathology
  • Pneumonia / chemically induced*
  • Pneumonia / diagnosis
  • Pneumonia / immunology
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Budesonide
  • Fluticasone