LAUSR

Introduction Refractory chronic cough (RCC), persisting despite addressing contributory diagnoses, is likely underpinned by neurally mediated cough hypersensitivity. RFC1 disorders are genetic neurodegenerative conditions caused by biallelic RFC1 repeat expansion sequences, commonly presenting with cough, followed by neurological features including cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). The prevalence and identifying clinical characteristics of RFC1 repeat-expansion disorders in patients with RCC are unknown. Methods Consecutive patients with RCC underwent RFC1 genotyping, cough severity visual analogue scale (VAS) and cough-specific health status assessment (Leicester Cough Questionnaire (LCQ)). Participants with biallelic RFC1 repeat expansions (RFC1++) also underwent nerve conduction studies, brain imaging (MRI) and cough reflex sensitivity testing. Results 51 participants with RCC were recruited; 36 (71%) female, median (IQR) age 65 (56–70) years, duration of cough 12.8 (6.9–20.0) years. Four (8%) were RFC1++, five (10%) monoallelic carriers (RFC1+−) and 42 (82%) of wild-type genotype (RFC1−−). No difference was observed in age, sex, cough duration, spirometry, VAS or LCQ scores between RFC1++ and RFC1−− subjects (p>0.05). The symptom of pins and needles was more frequent in RFC1++ (n=4, 100%) compared to RFC1−− (n=12, 33%) (p=0.01). RFC1++ participants had impaired sensory action potentials, and one had cerebellar atrophy. RFC1++ participants had heightened cough reflex sensitivity to capsaicin, similar to previous CANVAS and RCC studies. Conclusion Biallelic RFC1 repeat expansions (RFC1++) were present in 8% of RCC patients. RFC1++ participants demonstrated features of cough reflex hypersensitivity. RFC1++ chronic cough had few identifying features, although symptoms of pins and needles were more common. Shareable abstract CANVAS/RFC1 disorders are an important cause of chronic cough. Here, a prevalence of 8% in patients is reported with refractory chronic cough. In RFC1 disorders, there is cough reflex hypersensitivity, impaired nerve conduction and neurological symptoms. https://bit.ly/3ynoJsk