Functional brain imaging in individuals with chronic cough demonstrates reduced activation in cortical regions associated with voluntary cough suppression. Little is known about the ability of patients with chronic cough to suppress cough. This study aimed to compare the ability to voluntarily suppress cough during inhaled capsaicin challenge in participants with chronic refractory cough with that in healthy controls. In addition, this study aimed to assess the repeatability of capsaicin challenge test with voluntary cough suppression.Participants with chronic refractory cough and healthy controls underwent inhaled capsaicin challenge tests while attempting to suppress their cough responses. After 5 days, either a conventional capsaicin challenge test with no cough suppression attempt, or a repeat test with an attempt at cough suppression was performed. Threshold capsaicin concentrations required to elicit one, two and five coughs were calculated by interpolation. Objective 24-h cough frequency was measured in individuals with chronic refractory cough.Healthy controls were able to suppress capsaicin-evoked cough while participants with chronic refractory cough were not. Geometric mean±sdcapsaicin dose thresholds for five coughs with (CS5) and without (C5) suppression attempts were 254.40±3.78versus45.89±3.95 µmol·L⁻¹, respectively, in healthy controls (p=0.033) and 3.34±5.04versus3.86±5.13 µmol·L⁻¹, respectively, in participants with chronic refractory cough (p=0.922). Capsaicin dose thresholds for triggering five coughs with self-attempted cough suppression were significantly lower in participants with chronic refractory cough than in healthy controls; geometric mean±sd4.94±4.43versus261.10±4.34 µmol·L⁻¹, respectively; mean difference (95% CI) 5.72 (4.54–6.91) doubling doses (p<0.001). Repeatability of cough suppression test in both patients and healthy controls was high; intraclass correlation coefficients of log(CS5) values 0.81 and 0.87, respectively. CS5 was associated with objective cough frequency (ρ=−0.514, p=0.029).Participants with chronic refractory cough were less able to voluntarily suppress capsaicin-evoked cough compared to healthy controls. This may have important implications for the pathophysiology and treatment of chronic cough.

Chronic cough (CC; ≥8 weeks in duration) is a common and burdensome feature of respiratory diseases. The understanding of cough has progressed significantly in recent years, albeit largely in refractory (unexplained) chronic cough (RCC) in the absence of other respiratory conditions. The prevalence of CC in respiratory diseases is poorly described, but estimates have been reported: asthma (8–58%), chronic obstructive pulmonary disease (COPD; 10–74%), bronchiectasis (82–98%), interstitial lung disease (ILD; 50–89%) and sarcoidosis (3–64%). CC in respiratory conditions generally predicts impaired health status and more severe disease. It is associated with increased symptom burden and disease severity in asthma, COPD, bronchiectasis and ILD, higher exacerbation frequency in asthma and bronchiectasis, and increased mortality and lung transplantation in idiopathic pulmonary fibrosis (IPF). Physiologically, heightened cough reflex sensitivity (CRS) has been reported and postulated to be mechanistic in isolated RCC. Cough reflex hypersensitivity (CRH) has also been reported in asthma, COPD, bronchiectasis, ILD and sarcoidosis. Unlike recent advances in isolated RCC, there are limited studies and understanding of central cough neuropathways in other respiratory conditions. Of note, dysfunctional central voluntary cough suppression neuropathways and physiology were observed in isolation in RCC; cough suppression is preserved in COPD. Understanding in the mechanism of RCC cannot be simply extrapolated to other respiratory conditions. The restricted understanding of cough mechanisms in these conditions has limited cough-specific therapeutic options in this context. There is currently an unmet need to expand our understanding of cough in chronic respiratory conditions, both in order to improve the quality of life of patients, and to improve knowledge of cough in general. This review aims to describe the prevalence, impact, pathophysiology and management of CC in asthma, COPD, bronchiectasis, ILD and sarcoidosis.

There are few effective pharmacological therapies available to treat refractory chronic cough. Functional MRI studies of the brain have recently shown that patients with chronic cough have dysfunctional inhibitory control of cough. Self-management therapies delivered by physiotherapists or speech therapists are effective at suppressing cough. They enable patients to consciously suppress the urge to cough. The intervention consists of education, laryngeal hygiene, cough suppression and distraction measures and behaviour modification. The efficacy of Physiotherapy and Speech And Language Intervention (PSALTI) has been confirmed in two randomised control trials. In one trial, there was a 41% reduction in cough frequency with PSALTI, assessed objectively with the Leicester Cough Monitor, and a clinically significant improvement in quality of life. Importantly, the improvement in cough was sustained when therapy was discontinued. The addition of the Speech Pathology Treatment to neuromodulator drug therapy, Pregabalin has also been evaluated in a clinical trial. There was a clinically significant improvement in quality of life, and this was sustained when therapy was discontinued. The mechanism of action of PSALTI is not known and this should be investigated in future. Further studies are needed to identify the components of PSALTI that deliver the most benefit, and determine whether PSALTI is effective in cough associated with other chronic lung disorders.

The Patient Global Impression of Severity (PGI-S) scale is a self-reported, single-item categorical scale which is increasingly used when assessing chronic cough (CC). This study aimed to establish validity, repeatability and responsiveness of the PGI-S scale in CC, and use the scale to define discrete categories of severity when measured with other commonly used patient-reported outcome (PRO) tools. Consecutive patients with CC completed the PGI-S scale, cough severity and urge-to-cough visual analogue scales (VAS), and cough-specific health status Leicester Cough Questionnaire (LCQ) at a clinic visit. Validity, repeatability and responsiveness were assessed, and threshold scores for PRO severity categories determined. Participants (n=482; median (IQR) age 57 (46-67) years, 71% female and duration of cough 48 (24-120) months) reported median (IQR) PGI-S score 3 (3-4; moderate severity), severity VAS 57 (31-75) mm, urge VAS 62 (40-81) mm, and LCQ 11.5 (8.7-14.4). There were strong associations between PGI-S scores and severity VAS (ρ=0.81), urge VAS (ρ=0.73), and LCQ (ρ=-0.73) (all p<0.001). Repeatability of the PGI-S scale was high (n=77); intraclass correlation coefficients (95%CI) 0.85 (0.77-0.91) (p<0.001). The PGI-S scale was responsive in participants with a treatment response (p<0.001). The suggested PRO thresholds to define severe cough are ≥61 mm (cough severity VAS), ≥71 mm (urge-to-cough VAS) and ≤10 (LCQ). The PGI-S scale is a simple and valid tool that characterises cough severity, and is repeatable and responsive in CC. The proposed categorical severity thresholds for VAS and LCQ can provide intuitive meaning for patients and clinicians.

Chronic cough is a common reason for medical consultations and is associated with considerable physical and psychological morbidity. This study investigated healthcare use and cost in chronic cough...