Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 134, Issue 1, Pages 56-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2014.01.038
Keywords
Cough; transient receptor potential vanilloid 1; capsaicin; cough sounds; sensory nerves
Categories
Funding
- GlaxoSmithKline
- MRC [G0701918]
- MRC [G0701918] Funding Source: UKRI
- Medical Research Council [G0701918] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10040, NF-SI-0510-10249] Funding Source: researchfish
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Background: Inhalation of capsaicin, the extract of hot chili peppers, induces coughing in both animals and human subjects through activation of transient receptor potential vanilloid 1 (TRPV1) on airway sensory nerves. Therefore the TRPV1 receptor is an attractive target for the development of antitussive agents. Objective: We sought to assess the antitussive effect of TRPV1 antagonism in patients with refractory chronic cough. Methods: Twenty-one subjects with refractory chronic cough (> 8 weeks) attending a specialist clinic were recruited to a randomized, double-blind, placebo-controlled crossover trial assessing a TRPV1 antagonist (SB-705498). Cough reflex sensitivity to capsaicin (concentration of capsaicin inducing at least 5 coughs) and 24-hour cough frequency were coprimary end points assessed after a single dose of SB-705498 (600 mg) and matched placebo. Cough severity and urge to cough were reported on visual analog scales, and cough-specific quality of life data were also collected. Results: Treatment with SB-705498 produced a significant improvement in cough reflex sensitivity to capsaicin at 2 hours and a borderline significant improvement at 24 hours compared with placebo (adjusted mean difference of +1.3 doubling doses at 2 hours [95% CI, +0.3 to +2.2; P=.0049] and +0.7doubling doses at 24 hours [95% CI, +0.0 to +1.5; P =.0259]). However, 24-hour objective cough frequency was not improved compared with placebo. Patient-reported cough severity, urge to cough, and cough-specific quality of life similarly suggested no effect of SB-705498. Conclusion: This study raises important questions about both the role of TRVP1-mediated mechanisms in patients with refractory chronic cough and also the predictive value of capsaicin challenge testing in the assessment of novel antitussive agents.
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