{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:40:56Z","timestamp":1790894456864,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Effective cough treatments are a significant unmet need in patients with lung cancer. Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of NK-1 (neurokinin 1) receptors, a mechanism also implicated in cough.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess aprepitant in patients with lung cancer with cough and evaluate mechanisms in vagal nerve tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Randomized double-blind crossover trial of patients with lung cancer and bothersome cough. They received 3 days of aprepitant or matched placebo; after a 3-day washout, patients crossed to the alternative treatment. The primary endpoint was awake cough frequency measured at screening and Day 3 of each treatment; secondary endpoints included patient-reported outcomes. In vitro, the depolarization of isolated guinea pig and human vagus nerve sections in grease-gap recording chambers, indicative of sensory nerve activation, was measured to evaluate the mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Twenty patients with lung cancer enrolled, with a mean age 66 years (\u00b17.7); 60% were female and 80% had non\u2013small cell cancer, 50% had advanced stage, and 55% had World Health Organization performance status 1. Cough frequency improved with aprepitant, reducing by 22.2% (95% confidence interval [CI], 2.8\u201337.7%) over placebo while awake (P\u2009=\u20090.03), 30.3% (95% CI, 12.7\u201344.3) over 24 hours (P\u2009=\u20090.002), and 59.8% (95% CI, 15.1\u201386.0) during sleep (P\u2009=\u20090.081). Patient-reported outcomes all significantly improved. Substance P depolarized both guinea pig and human vagus nerve. Aprepitant significantly inhibited substance P\u2013induced depolarization by 78% in guinea pig (P\u2009=\u20090.0145) and 94% in human vagus (P\u2009=\u20090.0145).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Substance P activation of NK-1 receptors appears to be an important mechanism driving cough in lung cancer, and NK-1 antagonists show promise as antitussive therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202006-2359oc","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T18:01:38Z","timestamp":1600884098000},"page":"737-745","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":50,"title":["Aprepitant for Cough in Lung Cancer. 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