Beclomethasone has lesser suppressive effects on inflammation and antibacterial immunity than fluticasone or budesonide in experimental infection models

Inhaled corticosteroids (ICS) are mainstay therapies in COPD but are consistently linked with increased pneumonia susceptibility. There is speculation regarding possible intraclass differences in pneumonia risk between ICS agents, with some studies suggesting that budesonide and beclomethasone dipropionate (BDP) confer lower pneumonia risk than fluticasone propionate (FP). This has not been consistently shown and remains controversial. In the absence of head-to-head comparator trials, it is impossible to conclusively ascertain intraclass differences in pneumonia propensity. No previous studies have compared the relative potential of these three ICS agents to impair host defense in experimental infection models, and mechanisms underlying any potential differential effects on pneumonia susceptibility are unknown. The agents differ in terms of glucocorticoid receptor affinity, solubility, and antiinflammatory potency, and thus they may have differing abilities to impair critical components of antimicrobial host defense. We have recently reported that FP can impair epithelial control of the pneumonia-causing pathogen Streptococcus pneumoniae, mechanistically through inhibition of the antimicrobial peptide (AMP) cathelicidin. Using experiments in human cells and mouse infection models, we performed a head-to-head comparison of the effects of the major ICS agents used in COPD on innate immunity.