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Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease

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Abstract

Phosphodiesterase (PDE) 4 inhibitors prevent the metabolism of cyclic adenosine monophosphate, thereby reducing inflammation. Inhaled PDE4 inhibitors aim to restrict systemic drug exposure to enhance the potential for clinical benefits (in the lungs) versus adverse events (systemically). The orally administered PDE4 inhibitor roflumilast reduces exacerbation rates in the subgroup of chronic obstructive pulmonary disease patients with a history of exacerbations and the presence of chronic bronchitis, but can cause PDE4 related adverse effects due to systemic exposure. CHF6001 is an inhaled PDE4 inhibitor, while inhaled ensifentrine is an inhibitor of both PDE3 and PDE4; antagonism of PDE3 facilitates smooth muscle relaxation and hence bronchodilation. These inhaled PDE inhibitors have both reported positive findings from early phase clinical trials, and have been well tolerated. Longer term trials are needed to firmly establish the clinical benefits of these drugs.

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Acknowledgments

Dave Singh, Simon Lea and Alexander Mathioudakis are supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC).

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  1. Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK

    Dave Singh, Simon Lea & Alexander G. Mathioudakis

  2. Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Hospital Trust, The Langley Building, Southmoor Road, Manchester, M23 9QZ, UK

    Dave Singh

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DS has received sponsorship to attend and speak at international meetings, honoraria for lecturing or attending advisory boards from the following companies: Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Teva, Theravance and Verona. AGM reports a competitive research grant from Boehringer Ingelheim, outside the submitted work. SL has no conflict of interests.

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D.S., S.L. and A.G.M. conducted the literature reviews and contributed to the writing and critical review of the manuscript. The final version was approved by all authors.

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Singh, D., Lea, S. & Mathioudakis, A.G. Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease. Drugs 81, 1821–1830 (2021). https://doi.org/10.1007/s40265-021-01616-9

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