Table 1.
Demographics and cough characteristics in CANVAS-associated chronic cough
| Father | Son | |
|---|---|---|
| Demographics | ||
| Age (years) | 62 | 37 |
| BMI (kg.m−2) | 21 | 22 |
| Medication | Pregabalin, minimal self-reported benefit to cough | Nortriptyline, minimal self-reported benefit to cough |
| Cough characteristics | ||
| Duration of cough | 37 years | 9 years |
| Cough severity VAS (0–100) | 58 mm | 54 mm |
| LCQ total score (3–21) | 15.9 | 13.1 |
| CHQ score (0–22) | 12 | 18 |
| Chest radiography | Normal | Normal |
| 24 h Objective cough frequency | 6 coughs hr−1 | 16 coughs hr−1 |
| Capsaicin cough challenge | ||
| C5 | 14.9 μmol L−1 | 3.3 μmol L−1 |
| CS5 | 36.2 μmol L−1 | 6.3 μmol L−1 |
| Bronchoscopy | ||
| Culture | No growth | No growth |
| Differential cell count | Alveolar macrophages 95% | Alveolar macrophages 90% |
| Neutrophils < 1% | Neutrophils 8% | |
| Lymphocytes 4–5% | Lymphocytes 2% | |
| Eosinophils 0% | Eosinophils 0% | |
| Histopathology | Bronchial tissue with no inflammation, including eosinophils | Very mild and non-specific inflammation in the stroma; predominantly lymphocytes and occasional eosinophil |
| Neurological features | ||
| Duration of neurological symptoms | 20 years | 1 year |
| Diagnosis | Advanced CANVAS | Early CANVAS |
| CANVAS features | All features of CANVAS; autonomic disturbance (orthostatic); cramping pains | Mild peripheral sensation loss (feet) only |
| Subtypes of pain by NPSI | ||
| Superficial spontaneous burning | 0/10 | 0/10 |
| Deep spontaneous pressing | 3/10 | 0/10 |
| Paroxysmal | 10/10 | 0/10 |
| Evoked | 0/10 | 3/10 |
| Paraesthesia/dysesthesia | 0/10 | 0/10 |
| Walking aids | Stick (1 or 2) | Nil |
| Arnold’s reflex | Present | Absent |
| Airway biopsy | Absent pan-neuronal and Aδ epithelial nerve fibres | Severe depletion of pan-neuronal and Aδ epithelial nerve fibres |
| Unmyelinated total nerve length* | 0 (0–0) μm | 0 (0–125) μm |
| Aδ nerve length* | 0 (0–0) μm | 0 (0–206) μm |
| Skin biopsy IENFD (distal leg) | 0.0 fibre.mm−1 | 0.0 fibre.mm−1 |
| Nerve conduction study | Severe sensory axonal polyneuropathy affecting both upper and lower extremities | Severe sensory axonal polyneuropathy affecting the lower more than upper extremities; may suggest a length-dependent involvement |
| Motor responses are normal | Motor responses are normal | |
| Microneurography | Low number of fibres recorded (axon loss). Dysfunction of small nerve fibres, both somatosensory and sympathetic | Lack of C-nociceptors and sympathetic fibres. Suggestive of a loss of somatosensory and sympathetic fibres |
*median (IQR). CANVAS; Cerebellar ataxia with peripheral neuropathy and vestibular areflexia syndrome; BMI body mass index, VAS Visual analogue scale, LCQ Leicester Cough Questionnaire health status (lower scores indicate worse cough-specific health status), CHQ Cough Hypersensitivity Questionnaire (higher scores indicate more cough triggers), C5 concentration of capsaicin required to evoke five coughs without attempted cough suppression, CS5 C5 with attempted cough suppression, IENFD intraepidermal nerve fibre density (normal range mean ± SD 12.4 ± 4.6 fibre.mm−1) [20]; NPSI, Neuropathic pain symptom inventory