Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial.Citation formats

  • External authors:
  • Saifudin Khalid
  • Robert Murdoch
  • Amy Newlands
  • Kevin Smart
  • Angela Kelsall
  • Kimberley Holt
  • Ashley Woodcock
  • Jaclyn A Smith

Standard

Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial. / Khalid, Saifudin; Murdoch, Robert; Newlands, Amy; Smart, Kevin; Kelsall, Angela; Holt, Kimberley; Dockry, Rachel; Woodcock, Ashley; Smith, Jaclyn A.

In: Journal of Allergy and Clinical Immunology, Vol. 134, No. 1, 07.2014, p. 56-62.

Research output: Contribution to journalArticle

Harvard

Khalid, S, Murdoch, R, Newlands, A, Smart, K, Kelsall, A, Holt, K, Dockry, R, Woodcock, A & Smith, JA 2014, 'Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial.' Journal of Allergy and Clinical Immunology, vol. 134, no. 1, pp. 56-62. https://doi.org/10.1016/j.jaci.2014.01.038

APA

Khalid, S., Murdoch, R., Newlands, A., Smart, K., Kelsall, A., Holt, K., ... Smith, J. A. (2014). Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial. Journal of Allergy and Clinical Immunology, 134(1), 56-62. https://doi.org/10.1016/j.jaci.2014.01.038

Vancouver

Khalid S, Murdoch R, Newlands A, Smart K, Kelsall A, Holt K et al. Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial. Journal of Allergy and Clinical Immunology. 2014 Jul;134(1):56-62. https://doi.org/10.1016/j.jaci.2014.01.038

Author

Khalid, Saifudin ; Murdoch, Robert ; Newlands, Amy ; Smart, Kevin ; Kelsall, Angela ; Holt, Kimberley ; Dockry, Rachel ; Woodcock, Ashley ; Smith, Jaclyn A. / Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 134, No. 1. pp. 56-62.

Bibtex

@article{dda43f9c77fc4147a316a74fb750b8eb,
title = "Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial.",
abstract = "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 +0.7 doubling 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.",
keywords = "Cough, capsaicin, cough sounds, sensory nerves, transient receptor potential vanilloid 1",
author = "Saifudin Khalid and Robert Murdoch and Amy Newlands and Kevin Smart and Angela Kelsall and Kimberley Holt and Rachel Dockry and Ashley Woodcock and Smith, {Jaclyn A}",
note = "G0701918, Department of Health, United KingdomG0701918, Medical Research Council, United Kingdom",
year = "2014",
month = "7",
doi = "10.1016/j.jaci.2014.01.038",
language = "English",
volume = "134",
pages = "56--62",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby, Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial.

AU - Khalid, Saifudin

AU - Murdoch, Robert

AU - Newlands, Amy

AU - Smart, Kevin

AU - Kelsall, Angela

AU - Holt, Kimberley

AU - Dockry, Rachel

AU - Woodcock, Ashley

AU - Smith, Jaclyn A

N1 - G0701918, Department of Health, United KingdomG0701918, Medical Research Council, United Kingdom

PY - 2014/7

Y1 - 2014/7

N2 - 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 +0.7 doubling 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.

AB - 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 +0.7 doubling 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.

KW - Cough

KW - capsaicin

KW - cough sounds

KW - sensory nerves

KW - transient receptor potential vanilloid 1

U2 - 10.1016/j.jaci.2014.01.038

DO - 10.1016/j.jaci.2014.01.038

M3 - Article

VL - 134

SP - 56

EP - 62

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 1

ER -