Asthma and lower airway diseaseTransient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: A double-blind randomized controlled trial
Section snippets
Methods
Detailed methods are provided in the Methods section in this article's Online Repository at www.jacionline.org.
Subjects
Patients' characteristics are summarized in Table I. The majority of subjects were female and middle aged, as is typical of patients presenting with refractory cough. At screening, subjects were highly sensitive to capsaicin; the median capsaicin C5 value was 7.81 μmol/L (range, 0.49-125 μmol/L). Of 21 patients screened and randomized, 2 withdrew after the first treatment period because of symptoms consistent with a viral upper respiratory tract infection. Both patients had received placebo
Discussion
To the best of our knowledge, this is the first study to assess a TRPV1 receptor antagonist as an antitussive agent in patients. Despite clear evidence of TRPV1 antagonism in the airways, with a significant reduction in experimentally induced cough responses to capsaicin with SB-705498 treatment, this did not translate into any significant improvement in spontaneous cough frequency. Patient reports of cough severity, urge to cough, and cough-specific quality of life similarly suggested no
References (54)
- et al.
Inhalation method determines outcome of capsaicin inhalation in patients with chronic cough due to sensory hyperreactivity
Pulm Pharmacol Ther
(2006) - et al.
Cough and glottic-stop reflex sensitivity in health and disease
Chest
(2005) - et al.
The distribution and regulation of vanilloid receptor VR1 and VR1 5' splice variant RNA expression in rat
Neuroscience
(2001) - et al.
The cloned capsaicin receptor integrates multiple pain-producing stimuli
Neuron
(1998) - et al.
Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans
Pain
(2008) - et al.
Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development
Bioorg Med Chem Lett
(2006) - et al.
The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans
Pain
(2007) - et al.
Evaluation of a cough-specific quality-of-life questionnaire
Chest
(2002) - et al.
Acoustic cough-reflux associations in chronic cough: potential triggers and mechanisms
Gastroenterology
(2010) - et al.
Are there clinical features of a sensitized cough reflex?
Pulm Pharmacol Ther
(2009)
Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain
Pain
Capsaicin cough sensitivity increases during upper respiratory infection
Respir Med
Capsaicin cough sensitivity in smokers with and without airflow obstruction
Respir Med
Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial
Lancet
A novel approach to studying the relationship between subjective and objective measures of cough
Chest
Assessing efficacy of therapy for cough
Otolaryngol Clin North Am
Cough induced by stimulation of capsaicin-sensitive sensory neurons in conscious guinea-pigs
Acta Physiol Scand
Effects of aerosol-applied capsaicin, histamine and prostaglandin E2 on airway sensory receptors of anaesthetized cats
J Physiol
Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans
J Appl Physiol
Sensitivity of the cough reflex in patients with chronic cough
Eur Respir J
The utility of the mannitol challenge in the assessment of chronic cough: a pilot study
Cough
Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non-acid gastro-oesophageal reflux
Respirology
Capsaicin cough sensitivity decreases with successful treatment of chronic cough
Am J Respir Crit Care Med
ERS guidelines on the assessment of cough
Eur Respir J
The capsaicin receptor: a heat-activated ion channel in the pain pathway
Nature
Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human
Proc Natl Acad Sci U S A
Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin
Thorax
Cited by (155)
Tiotropium for refractory cough in asthma via cough reflex sensitivity: A randomized, parallel, open-label trial
2023, Annals of Allergy, Asthma and Immunology
Supported by GlaxoSmithKline. J.A.S. was funded by an MRC Clinician Scientist award (G0701918).
Disclosure of potential conflict of interest: R. Murdoch and A. Newlands are employed by and have stock holdings in GlaxoSmithKline. A. Woodcock has received research support from GlaxoSmithKline, Afferent, and Verona; has received consultancy fees from Merck; and has a patent on ambulatory cough monitor owned by University Hospital of South Manchester. J. A. Smith has received research support from GlaxoSmithKline, AstraZeneca, and Afferent; has received consulting fees from Almirall, GlaxoSmithKline, Xention, Glenmark, Theravance, Novartis, and Reckitt and Benckiser; and has a patent owned by the University Hospital South Manchester for describing methods for detecting cough from sound. The rest of the authors declare they have no relevant conflicts of interest.