Depleted airway nerves in patients with chronic cough due to RFC1-disorder

<bold>Introduction:</bold> RFC1 neurodegenerative disorders, associated with biallelic AAGGG repeats in the RFC1 gene, often present with chronic cough (RFC1-CC). Neurological features include cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). We investigated cough reflex sensitivity (CRS) and airway nerve morphology in related patients with RFC1-CC. <bold>Methods:</bold> A father and son with RFC1-CC completed cough severity VAS, LCQ for QoL, capsaicin challenge for CRS, objective cough frequency (CF) with LCMonitor, and endobronchial biopsy. Airway epithelial nerve density was quantified by immunostaining (PGP9.5/neurofilament) and 3D confocal microscopy imaging. <bold>Results:</bold> Father and son with CANVAS/RFC1-disorder; aged 62/32 years, neurological symptom duration 20/1 years, and CC for 37/8 years, respectively. Cutaneous sensory nerve action potentials were absent (father) and reduced (son). Spirometry and chest radiography were normal. VAS scores 58/54 mm; LCQ scores 15.9/13.1; CF 6/16 coughs.hr⁻¹; CRS heightened: C5 5.7/3.3 μmol.L⁻¹, in father and son respectively. Airway epithelial nerves were absent (father) and reduced (son) compared to historic healthy controls (Figure). <bold>Conclusion:</bold> Airway epithelial innervation was reduced or absent in both patients with RFC1-CC; despite this, CRS was heightened. Further study should determine the peripheral and central neural mechanisms of cough in RFC1-disorders. ERS NeuroCOUGH CRC site-King’s <fig><object-id>erj;64/suppl_68/PA2145/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>