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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
Rationale:

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.

Methods:

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.

Results:

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.

Conclusions:

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