Refractory chronic cough (RCC) has a detrimental impact on quality of life. However, despite an optimal management, RCC patients still have no formal diagnosis. Recently, it has been found a high prevalence of chronic cough in patients suffering from CANVAS, a neurological disease associated with a repeated expansion of the RFC1 gene (RE-RFC1).

The aim of this study was to describe the prevalence of patients with RE-RFC1 among a cohort of patients with RCC.

A prospective study was conducted from December, 1st 2021 to June, 30th 2022. RCC was defined as chronic cough with either no cause of cough despite extensive investigation including chest CT scan or a persistent cough despite optimal treatment of cough causes with a systematic trial of inhaled corticosteroids. To identify RE-RFC1, long-PCR flanking the AAGGG, AAAAG, AAAGG and AAGAG repeats of the RFC1 gene was performed.

Among 68 RCC patients, 17 (25.0%) patients had at least one RE-RFC1. Eleven (16.2%) patients had biallelic RE-RFC1 and 6 (8.8%) monoallelic RE-RFC1 (Mono-RE-RFC1). There was no difference in terms of sex between patients with and with no RE-RFC1. However, all patients with mono-RE-RFC1 were female. Patients with RE-RFC1 were statistically younger than patients with no RE-RFC1 (44.6 ± 12.4 vs. 51.2 ± 10.8, respectively, p=0.04). The proportion of patients with dust/smoke or food as triggering factors was statistically higher in patients with RE-RFC1 than those with RE-RFC1 (25 (43.9%) vs. 14 (82.4%), p=0.02 and 12 (21.1%) vs. 12 (70.6%), p=0.0009, respectively).

For the first time, we show that RE-RFC1 is observed in 25.0% of patients with RCC. RCC patients with RE-RFC1 were statistically younger compared to RCC patients with no RE-RFC1.