{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:20:53Z","timestamp":1789640453641,"version":"4.0.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lung"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a genetic neurodegenerative condition associated with chronic cough and cough hypersensitivity. The neuropathic mechanisms underlying cough in CANVAS are unknown. In a father and son with CANVAS-associated cough, we investigated clinical and neuropathophysiological features including bronchial and skin biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients completed assessments for cough severity (visual analogue scale, VAS), impact (Leicester Cough Questionnaire, LCQ), triggers (Cough Hypersensitivity Questionnaire), objective frequency with Leicester Cough Monitor, and reflex sensitivity with capsaicin cough challenge. Bronchoscopic airway biopsies were analysed for nerve morphology and compared to a healthy control. Neurological assessments included skin biopsies, nerve conduction studies, and microneurography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The father (age 62) and son (age 37) had advanced and early CANVAS, with a refractory chronic cough of 37 and 9\u00a0years duration, respectively. The cough in the father and son was of moderate severity (VAS 58 and 54\u00a0mm) and impact (LCQ score 15.9 and 13.1), with raised objective cough frequencies of 6 and 16\u00a0coughs\u00a0hr\n                      <jats:sup>\u22121<\/jats:sup>\n                      , and heightened cough reflex sensitivity to capsaicin with concentrations to evoke five coughs (C5) of 14.9 and 3.3\u00a0\u03bcmol\u00a0L\n                      <jats:sup>\u22121<\/jats:sup>\n                      , respectively. Bronchoscopic airway biopsies demonstrated severely depleted sensory small nerve fibres in the father and son compared to a healthy control: median (IQR) total nerve length 0 (0\u20130) and 0 (0\u2013125)\u00a0\u03bcm vs 944 (461\u20131323)\u00a0\u03bcm, respectively. Skin biopsies showed absent intraepidermal nerve fibres, with densities of 0.0 fibres.mm\n                      <jats:sup>\u22121<\/jats:sup>\n                      in both patients. Functional microneurography revealed nociceptor fibre paucity and dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In CANVAS, despite the loss of bronchial and cutaneous nerve fibres, there was heightened cough reflex sensitivity. Further studies are needed to elucidate underlying neural mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00408-025-00838-y","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T04:12:32Z","timestamp":1754626352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Unnerving Cough in CANVAS: Cough Hypersensitivity Despite Airway Nerve Depletion"],"prefix":"10.1007","volume":"203","author":[{"given":"Barnaby","family":"Hirons","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Rhatigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"McNulty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"Hull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J.","family":"Jolley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Hadden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cortese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S. 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