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

Inhaled corticosteroids (ICSs) treatment combined with long-acting β ₂ -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.
Competing Interests: Disclosure CJ has served in an advisory board and/or served as a speaker and/or participated in education arranged from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Chiesi, and TEVA. KL has served in an advisory board and/or served as a speaker and/or participated in education arranged by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Meda, Takeda, Novartis, and Pfizer. TWH has served in an advisory board and/or served as a speaker and/or participated in education arranged from AstraZeneca, Boehringer Ingelheim, NaPP, Vectura, TEVA, and Roche. GS is a fulltime employee of AstraZeneca Nordic. AML is a fulltime employee of AstraZeneca Gothenburg and holds AstraZeneca shares. The authors report no other conflicts of interest in this work.