Effects of Roflumilast on Airway Hyperresponsiveness (AHR)
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Robert G. Townley, MD FAAAAI, Swati Agrawal, MBBS, Mina R Hanna, MS, Bryston Y Chang, BS, Peter J Oldenburg, PhD

Roflumilast has been shown to treat asthma and chronic obstructive pulmonary disease (COPD) in patients via inhibiting phosphodiesterase 4 (PDE-4). Since its method of action remains poorly elucidated, we used a mouse model to explore its mechanism, hypothesizing that it would have a similar effect to its role in human patients.


Whole body plethysmography (Penh) data on wild C57B1/6 mice (WT) were collected. Each experiment was set up so a sample of mice was either pre-exposed to room air, roflumilast, albuterol, IL-13, or a combination of them before they were exposed to increasing concentrations of methacholine (MCh). This allowed us to develop a dose response curve (DRC) quantifying the extent of airway hyperresponsiveness (AHR) under each condition.


Provocative dose percent increase (PDPI) was used to indicate a valid DRC for each treatment and to analyze the differences between treatments. The albuterol treated mice (202.53%) had lower PDPI than controls (256.57%). Interestingly, roflumilast-treated group had higher PDPI (451.53%) than controls and was partially reversed via albuterol (339.44%). Asthma and COPD conditions induced in mice by IL-13 did not show any signs of bronchodilation or bronchoprotection when treated with roflumilast or albuterol: 894.57% or 631.36% respectively—compared to IL-13 treated mice (319.24% at 48 hours and 387.02% at 72 hours). Although the time factor varied, it was clear that treatment with roflumilast or albuterol did not restore AHR back to normal conditions.


In conclusion, roflumilast does not cause bronchodilation or bronchoprotection in naïve mice or airway inflamed mice—induced by IL-13.