Cough desensitization treatment: A randomized, sham-controlled pilot trial for patients with refractory chronic cough

Chronic cough is a common condition which has a significant impact on quality of life. Assessment and management are hampered by the absence of well validated outcome measures. The development and validation of the Leicester Cough Questionnaire (LCQ), a self-completed health related quality of life measure of chronic cough, is presented. Patients with chronic cough were recruited from outpatient clinics. The development of the LCQ consisted of three phases: phase 1 (item generation); phase 2 (item reduction, allocation of items to domains and validation of questionnaire); phase 3 (repeatability and responsiveness testing of final version of questionnaire). Phase 1: Literature review, multidisciplinary team meeting and 15 structured interviews with chronic cough patients generated 44 items (LCQ1) with a 7 point Likert response scale. Phase 2: 104 chronic cough outpatients completed the LCQ1 along with an importance rating for each item. The clinical impact factor method was used for item reduction to 19 items (LCQ2: final version). These items were divided into three domains (physical, psychological and social) following expert opinion. Internal reliability, as assessed using Cronbach's alpha coefficients, varied between 0.79 and 0.89. Concurrent validity was high when the LCQ2 (n=56) was compared with a cough visual analogue score (r=-0.72). There was a moderate relationship with response to the St George's Respiratory Questionnaire (r=-0.54) and SF36 total score (r=0.46). Phase 3: Two week repeatability (n=24) was high with intraclass correlation coefficients for domains varying between 0.88 and 0.96. Responsiveness in nine patients whose cough was successfully treated varied within domains from an effect size of 0.84 to 1.75. The LCQ is a valid, repeatable 19 item self-completed quality of life measure of chronic cough which is responsive to change. It should be a useful tool in clinical trials and longitudinal studies.

Transient receptor potential vanniloid-1 (TRPV-1) mediates the cough response induced by the pepper extract capsaicin and is expressed in sensory nerves that innervate the airway wall. We determined the expression of TRPV-1 in the airways of patients with chronic persistent cough of diverse causes and with an enhanced capsaicin cough response. We obtained airway mucosal biopsies by fiberoptic bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without a cough. Immunostaining for nerve profiles with anti-protein gene product (PGP)-9.5 antibody showed no increase in nerve profiles in the airway epithelium of patients with chronic cough; however, with an anti-TRPV-1 antibody, there was a fivefold increase of TRPV-1 staining nerve profiles (p < 0.001). There was a significant correlation between capsaicin tussive response and the number of TRPV-1-positive nerves within the patients with cough. Our findings indicate that TRPV-1 receptors may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes.