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    Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough

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    Author
    Mazzone, SB; McGarvey, L
    Date
    2020-08-28
    Source Title
    Clinical Pharmacology and Therapeutics
    Publisher
    WILEY
    University of Melbourne Author/s
    Mazzone, Stuart
    Affiliation
    Anatomy and Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Mazzone, S. B. & McGarvey, L. (2020). Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough. CLINICAL PHARMACOLOGY & THERAPEUTICS, 109 (3), https://doi.org/10.1002/cpt.2003.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/252514
    DOI
    10.1002/cpt.2003
    Abstract
    Chronic cough, defined as a cough lasting > 8 weeks, is a common medical condition that exerts a substantial physical, mental, and social burden on patients. A subset of patients with chronic cough are troubled with a cough that persists despite optimal treatment of presumed associated common and uncommon conditions (refractory chronic cough; RCC) or in which no diagnosable cause for cough can be identified despite extensive assessment (unexplained chronic cough; UCC). Many of these patients exhibit clinical features of cough hypersensitivity, including laryngeal paresthesia, hypertussia, and allotussia. Over-the-counter cough remedies are ineffective and can lead to intolerable side effects when used for RCC/UCC, and the lack of approved treatments indicated for these conditions reflects a major unmet need. An increased understanding of the anatomy and neurophysiology of protective and pathologic cough has fostered a robust clinical development pipeline of several targeted therapies for RCC/UCC. This manuscript reviews the mechanisms presumed to underly RCC/UCC together with the rationale and clinical evidence for several targeted therapies currently under clinical investigation, including transient receptor potential channel antagonists, P2X3-receptor antagonists, voltage-gated sodium channel blockers, neuromodulators, and neurokinin-1-receptor antagonists. Finally, we provide an overview of targets that have been investigated in preclinical models of cough and other airway diseases that may hold future promise for clinical studies in RCC/UCC. Development of targeted therapies with different sites of action may foster a precision medicine approach to treat this heterogeneous, underserved patient population.

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