{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:39:27Z","timestamp":1792003167298,"version":"4.4.0"},"reference-count":112,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic cough is a burdensome condition characterized by persistent cough lasting longer than 8\u00a0weeks. Chronic cough can significantly affect quality of life, physical function and productivity, with many people troubled with a cough that lasts for months or even years. People with chronic cough commonly report a persistent urge to cough with frequent bouts of coughing triggered by innocuous stimuli, which has led to the concept of cough hypersensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>Both central and peripheral neural pathways regulate cough, and although mechanisms driving development of cough hypersensitivity are not fully known, sensitization of these neural pathways contributes to excessive cough triggering in cough hypersensitivity. Effective therapies that control chronic cough are currently lacking. Recent therapeutic development has focused on several ion channels and receptors involved in peripheral activation of cough (e.g., transient receptor potential channels, P2\u00a0\u00d7\u00a03 receptors and voltage\u2010gated sodium channels) or central cough processing (e.g., neurokinin\u20101 [NK\u20101] receptors and nicotinic acetylcholine receptors).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These targeted therapies provide novel insights into mechanisms underlying cough hypersensitivity and may offer new treatment options for people with chronic cough. In this review, we explore preclinical and clinical studies that have improved our understanding of the mechanisms responsible for chronic cough and discuss the most promising targeted approaches to date, including trials of P2\u00a0\u00d7\u00a03\u2010receptor antagonists and NK\u20101\u2013receptor antagonists.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1343","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:14:47Z","timestamp":1690503287000},"source":"Crossref","is-referenced-by-count":29,"title":["From bench to bedside: The role of cough hypersensitivity in chronic cough"],"prefix":"10.1002","volume":"13","author":[{"given":"Matthew G.","family":"Drake","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine Oregon Health and Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorcan P.","family":"McGarvey","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson Institute for Experimental Medicine, School of Medicine Dentistry &amp; Biomedical Science, Queen's University Belfast Belfast United Kingdom of Great Britain and Northern Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-9610","authenticated-orcid":false,"given":"Alyn H.","family":"Morice","sequence":"additional","affiliation":[{"name":"Respiratory Research Group Hull York Medical School University of Hull Cottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"issue":"11","key":"e_1_2_6_2_1","first-page":"832","article-title":"What are the most common conditions in primary care? Systematic review","volume":"64","author":"Finley CR","year":"2018","journal-title":"Can Fam Physician"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-015-9701-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1745-9974-3-5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.05.038"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.07.022"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60967-1"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-1485"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(13)70043-2"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-010-9272-1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01136-2019"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-009-9185-z"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00218613"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2015.10.004"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.10.016"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2017.9.5.394"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00793-2020"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00758-2020"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2015-207425"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002130"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/427125"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00191"},{"issue":"55","key":"e_1_2_6_23_1","first-page":"3513","article-title":"Utility of the Hull airways reflux questionnaire in the assessment of patients in the acute admissions unit [abstract]","volume":"38","author":"Morice A","year":"2011","journal-title":"Eur Respir J"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/17534666231162246"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02203-2018"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.04.042"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2023.107142"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2018.11.003"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.11.019"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2010.01859.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2022.106929"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201912-2347OC"},{"issue":"7","key":"e_1_2_6_33_1","first-page":"S699","article-title":"Approach to chronic cough: the neuropathic basis for cough hypersensitivity syndrome","volume":"6","author":"Chung KF","year":"2014","journal-title":"J Thorac Dis"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-1481"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/2049-6958-7-5"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.720538"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-007-9045-7"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00889-2019"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2006.10.012"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19041222"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01387-2020"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201709-1813OC"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00235.2016"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00411"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/140.1.137"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.230383"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1006\/pupt.2002.0338"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01889-4"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00267"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.07.034"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.93.05030296"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2019.09.011"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2008.02996.x"},{"issue":"6","key":"e_1_2_6_54_1","first-page":"719","article-title":"Role of gender and pubertal stage on cough sensitivity in childhood and adolescence","volume":"59","author":"Varechova S","year":"2008","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00217813"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00439-2019"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02348-5"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202010-3783ED"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2019.101810"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.934395"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-013-9533-x"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2011-201443"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2019.103267"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00075.2014"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.121.000641"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201704-0769OC"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.01.038"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00269-2021"},{"key":"e_1_2_6_69_1","first-page":"712","article-title":"Effects of a novel sodium channel blocker, GSK2339345, in patients with refractory chronic cough","volume":"55","author":"Smith JA","year":"2017","journal-title":"Int J Clin Pharmacol Ther"},{"key":"e_1_2_6_70_1","first-page":"4564","article-title":"The efficacy of bradanicline in refractory chronic cough","volume":"56","author":"Kanemitsu Y","year":"2020","journal-title":"Eur Respir J"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00039.2015"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.088435"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.10.030"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-2285"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.4.1905"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1617"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200910-1506OC"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01452-2016"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005389"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2019.08.001"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/146.1.159"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00050.2018"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701822"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/148.6_Pt_1.1628"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(03)01784-6"},{"key":"e_1_2_6_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2011.07.010"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200304-597OC"},{"key":"e_1_2_6_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91547-9"},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200607-892OC"},{"key":"e_1_2_6_90_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e3280115145"},{"key":"e_1_2_6_91_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.65.3.1125"},{"key":"e_1_2_6_92_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.064337"},{"key":"e_1_2_6_93_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-208843"},{"key":"e_1_2_6_94_1","doi-asserted-by":"publisher","DOI":"10.1177\/1479972318755722"},{"key":"e_1_2_6_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2003"},{"key":"e_1_2_6_96_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.15-1271"},{"key":"e_1_2_6_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.04.027"},{"key":"e_1_2_6_98_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-023-00606-w"},{"key":"e_1_2_6_99_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01700-8"},{"key":"e_1_2_6_100_1","article-title":"Improvements in cough frequency over 24 hours with BLU\u20105937, a selective P2\u00d73 antagonist, in patient subgroups defined by baseline awake cough frequencies [abstract]","volume":"203","author":"Smith J","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"e_1_2_6_101_1","volume-title":"Improvements in awake cough frequency in participants treated with BLU\u20105937 in a phase 2b trial of BLU\u20105937 in refractory chronic cough","author":"Smith J","year":"2022"},{"key":"e_1_2_6_102_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-022-00592-5"},{"key":"e_1_2_6_103_1","unstructured":"InserroA Companies provide trial updates on P2\u00d73 blockers for chronic cough.https:\/\/www.ajmc.com\/view\/companies\u2010provide\u2010trial\u2010updates\u2010on\u2010p2x3\u2010blockers\u2010for\u2010chronic\u2010cough"},{"key":"e_1_2_6_104_1","unstructured":"TaylorP Bayer's pipeline takes a hit as it drops eliapixant.https:\/\/pharmaphorum.com\/news\/bayers\u2010pipeline\u2010takes\u2010a\u2010hit\u2010as\u2010it\u2010drops\u2010eliapixant"},{"key":"e_1_2_6_105_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-023-02384-8"},{"key":"e_1_2_6_106_1","unstructured":"Bayer Global.Bayer's eliapixant significantly decreased cough frequency in phase IIb trial in patients with refractory chronic cough.https:\/\/www.bayer.com\/media\/bayers\u2010eliapixant\u2010significantly\u2010decreased\u2010cough\u2010frequency\u2010in\u2010phase\u2010iib\u2010trial\u2010in\u2010patients\u2010with\u2010refractory\u2010chronic\u2010cough"},{"key":"e_1_2_6_107_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.04240-2020"},{"key":"e_1_2_6_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30471-0"},{"key":"e_1_2_6_109_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00007-2023"},{"key":"e_1_2_6_110_1","unstructured":"AdamsB Shionogi licenses out 3rd\u2010gen HIV asset to ViiV notches a flop in chronic cough.https:\/\/www.fiercebiotech.com\/biotech\/shionogi\u2010licences\u2010third\u2010gen\u2010hiv\u2010asset\u2010ultra\u2010long\u2010dosing\u2010prospect\u2010from\u2010its\u2010partly\u2010owned"},{"issue":"63","key":"e_1_2_6_111_1","article-title":"The neurokinin\u20101 receptor antagonist orvepitant improves chronic cough symptoms: results from a phase 2b trial","volume":"54","author":"Smith J","year":"2019","journal-title":"Eur Respir J"},{"key":"e_1_2_6_112_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202006-2359OC"},{"key":"e_1_2_6_113_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201508-1602OC"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.1343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:36:31Z","timestamp":1695342991000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.1343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":112,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/ctm2.1343"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.1343","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]},"article-number":"e1343"}}