An evaluation of roflumilast and PDE4 inhibitors with a focus on the treatment of asthma
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INTRODUCTION: Asthma is a common chronic airway inflammatory disease characterized by diverse inflammatory events leading to airway hyperresponsiveness and reversible airflow obstruction. Corticosteroids have been the mainstay for asthma treatment due to their broad anti-inflammatory actions; however, other medications such as phosphodiesterase 4 inhibitors also demonstrate anti-inflammatory activity in the airways. Areas covered: This review describes tissue expression of phosphodiesterase 4 in the airways, the different phosphodiesterase 4 isoenzymes identified, and the anti-inflammatory activities of phosphodiesterase 4 inhibition in asthma and related findings in chronic obstructive pulmonary disease (COPD). The authors further review clinical trials demonstrating that drugs such as roflumilast have an excellent safety profile and efficacy in patients with asthma and COPD. Expert opinion: Phosphodiesterase 4 inhibitors suppress the activity of immune cells, an effect similar to corticosteroids although by acting through different anti-inflammatory pathways and uniquely blocking neutrophilic inflammation. Roflumilast and other phosphodiesterase 4 inhibitors have been shown to provide additive protection in asthma when added to corticosteroid and anti-leukotriene treatment. Developmental drugs with dual phosphodiesterase 3 and 4 inhibition are thought to be able to provide bronchodilation and anti-inflammatory activities and will consequently be pushed forward in their clinical development for the treatment of asthma and COPD.
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