Respiratory virus infections precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations, with most exacerbations due to rhinovirus infection. Both asthma and COPD exacerbations are not well controlled by steroid therapies, and there is a much research interest in finding improved therapies or combinations of therapies for controlling exacerbations. CHF6001 is a new, inhaled highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor. Using in vitro human bronchial epithelial cells (BEASâ2B), we investigated the potential antiâinflammatory effects of CHF6001 on rhinovirus (RV1B)âinduced cytokines. Cytokine mRNA was measured by realâtime PCR, while protein release was measured by ELISA. CHF6001 was used in a 7âpoint doseâresponse curve (1000â0.001 nmol/L) as a 1.5âh pretreatment prior to infection in comparison with roflumilast. Both roflumilast and CHF6001 reduced RV1Bâinduced ILâ8, ILâ29, IPâ10, and RANTES mRNA and protein in a concentrationâdependent manner. Generally, CHF6001 was 13â to 16âfold more potent (subnanomolar EC
50 values) than roflumilast at reducing ILâ8, ILâ29, IPâ10, and RANTES mRNA and protein release, but had similar efficacies. In combination with the steroid fluticasone propionate (1Â nmol/L), CHF6001 had additive effects, significantly reducing RVâinduced cytokines when compared with steroid or CHF6001 alone. Combined lowâdose steroid and lowâdose CHF6001 had a similar efficacy as highâdose steroid or CHF6001 alone, indicating the combination had steroid and PDE4 inhibitor sparing effects. Overall results indicate that PDE4 inhibitors have antiâinflammatory activity against virusâinduced inflammatory mediators and that CHF6001 is more potent than roflumilast.