Cough desensitization treatment for patients with refractory chronic cough: results of a second pilot randomized control trial.

OBJECTIVE: The purpose of this study was to collect pilot efficacy data on a novel treatment for refractory chronic cough (RCC), which we call cough desensitization treatment (CDT). DESIGN AND METHODS: In this parallel cohort, sham-controlled, randomized controlled trial, 21 adults with RCC were randomly assigned to 12 sessions of either CDT (progressive doses of aerosolized capsaicin while behaviorally suppressing cough; n = 11) or a sham treatment (repeated exposure to aerosolized saline; n = 9). The Leicester Cough Questionnaire (LCQ) was the primary outcome measure. Perceived cough severity with a visual analogue scale and cough challenge testing (for measuring cough-reflex sensitivity) were secondary outcome measures. Data were analyzed with mixed effects linear regression and follow-up contrasts. RESULTS: Results on all measures favored CDT. Excluding one sham participant, whose baseline LCQ scores were deemed unreliable, mean change in LCQ at 3-weeks post treatment was 6.35 and 2.17 in the CDT and sham groups, respectively. There was moderate to strong evidence of a greater improvement in the CDT group in total LCQ score (p = .058) and LCQ Psychological domain (p = .026) and Physical domain (p = .045) scores. Strong evidence was found for a greater reduction in urge-to-cough during CCT in the CDT group (p = .037) and marginal for a reduction in the capsaicin cough-reflex sensitivity (p = .094). There was weak evidence of a greater reduction in cough severity in the CDT group (p = .103). DISCUSSION: Although the study is limited due to the small sample size, the data provide additional evidence supporting further research on CDT. CDT resulted in a greater change in the primary efficacy measure (LCQ) than both pharmaceutical and behavioral treatments currently found in the literature. TRIAL REGISTRATION: This trial (NCT05226299) was registered on Clinicaltrials.gov on 07/02/2022.

Normative Values for the Leicester Cough Questionnaire in Healthy Individuals.

INTRODUCTION: The primary self-assessment questionnaire used for patients with chronic cough is the Leicester Cough Questionnaire (LCQ). The LCQ is a validated questionnaire that ranges in total score from 3 to 21. While it is known that a higher score on the LCQ reflects a better quality of life, normative data have not been reported for this questionnaire. OBJECTIVE: The purpose of this study was to determine normative LCQ scores on a healthy population without cough. METHODS: The LCQ was distributed via electronic survey to the authors' universities, professional affiliation email lists, and personal contacts. Participants were included if they were at least 18, nonsmokers, and without abnormal cough, without pulmonary disease, and without neurological disease. Participants answered questions regarding age, gender, and race/ethnicity, and completed the 19 LCQ questions. RESULTS: One hundred forty-three (118 women) LCQ responses were analyzed. Average participant age was 47 years (SD = 13) and 133 (93%) were Caucasian. The mean LCQ Total score was 20.23 (SD = 0.85) with scores ranging from 17.05 to 21. CONCLUSIONS: This study determined the following LCQ scores should be considered normal threshold scores: Total score - 17.68, Physical domain - 5.36, Psychological domain - 5.81, and Social domain - 6.06. The findings of this study will assist clinicians in determining severity of cough impact on quality of life using the LCQ. Further research is needed to ensure more complete participant demographic representation.

Evaluation and Management Outcomes and Burdens in Patients with Refractory Chronic Cough Referred for Behavioral Cough Suppression Therapy.

PURPOSE: The purpose of this study was to investigate the typical symptoms and medical management characteristics of adult patients with refractory chronic cough (RCC) who are referred to speech-language pathology (SLP) for behavioral cough suppression therapy (BCST) in order to estimate cost-effectiveness and efficiency of current practice patterns for this population. METHODS: One hundred sixty-four (164) patients with RCC referred for BCST were surveyed. Patients completed an initial survey at BCST onset related to symptom pattern and prior treatment, including the Leicester Cough Questionnaire (LCQ). Every four to six weeks patients completed follow-up surveys to assess their response to BCST. RESULTS: Mean age was 58 years (83.5% women). The majority of patients reported their cough began two or more years prior to BCST. Approximately half (49%) reported seeing four or more physicians (including primary care physicians) and being prescribed four or more medications (57%) prior to BCST. Medications targeting post-nasal drip (72%), reflux (70%), asthma (56%), and allergies (56%) were most commonly prescribed. BCST resulted in a clinically significant improvement in 70.1% of participants. The mean change in LCQ for those who improved with BCST was 6.61. Over half (58%) reported they were quite satisfied to completely satisfied with their treatment response. The average time from enrollment to study completion was 64 days. CONCLUSION: The results of this study suggest early intervention with BCST may be a cost-effective and efficient option for patients with RCC.

Altering cough reflex sensitivity with aerosolized capsaicin paired with behavioral cough suppression: a proof-of-concept study.

BACKGROUND: The purpose of this prospective, quasi-experimental, single cohort proof-of-concept study was to determine feasibility and proof-of-concept of programmatically decreasing cough sensitivity through use of cough suppression strategies following inhalation of aerosolized capsaicin, in gradually increasing doses, across repeated treatment sessions. METHODS: Five healthy adults, ages 20-32 years of age, enrolled and completed the study. The study commenced in three phases. Phase I consisted of baseline cough sensitivity testing using pharmaceutical-grade aerosolized capsaicin, delivered via a Koko DigiDoser with nebulizer. The single-inhale, dose-response method was used. Doses that elicited two coughs (C2) and five coughs (C5) were recorded. Testing ceased when participants met the C5 threshold or when they had been given the maximum dose of 1,000 µmol/L. Phase II consisted of 5-6 treatment sessions, during which participants were exposed to increasing doses of aerosolized capsaicin while implementing behavioral cough suppression strategies. In phase III, cough sensitivity was re-tested at 1 and 3 weeks post-treatment. Participants were given explicit instructions to not try to suppress their cough. Participants who did not reach the C2 or C5 threshold at 1,000 µmol/L were assigned a score of 1,250 µmol/L. RESULTS: Each participant demonstrated a gradual increase in maximum capsaicin dose suppressed during each treatment session, with each successfully suppressing at 1,000 µmol/L by the final treatment session. C2 was greater than baseline in 4 of the 5 participants at 1 week post-treatment, and in 3 of the 5, at 3 weeks post-treatment. C5 was greater in all 5 participants at both post-treatment time points. In fact, 4 of the 5 participants did not reach the C5 threshold during either post-treatment testing sessions. Wilcoxon's Signed Rank Test, using the logC2 and logC5 values, revealed a significant difference relative to baseline in logC5 at 1 week (z=-2.02, P=0.04) and 3 weeks (z=-2.03, P=0.04) post-treatment. The difference in logC2 neared significance at 1 week post-treatment (z=-1.77, P=0.077), but was insignificant at 3 weeks post-treatment (z=-1.46, P=0.144). CONCLUSIONS: This study demonstrates the potential of treating patients with refractory chronic cough (RCC), due to cough hypersensitivity, with a progressive desensitization approach paired with behavioral cough suppression. Additional research is needed using a randomized, placebo-controlled trial with patients with RCC.