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Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

ABSTRACT: BACKGROUND: Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non-productive chronic cough have not been reported. METHODS: Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and neurokinin-2 receptors (NK-1R and NK-2R, respectively). Informative non-synonymous SNPs were scored using the single base extension method for 312 patients with chronic cough and for 100 age matched healthy controls. The cough response to capsaicin was recorded for 312 patients with chronic cough, and the potential genetic association between cough sensitivity to capsaicin and the NK-1R and NK-2R genotypes was evaluated. RESULTS: Two informative SNPs were identified in NK-2R (Gly231Glu and Arg375His), whereas no informative SNP was found in NK-1R. After adjusting for atopy, sex, age, and smoking, the prevalence of enhanced cough sensitivity to capsaicin was higher in the chronic cough patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)). Moreover, the lowest capsaicin concentration to cause five consecutive coughs (C5) was significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) v 60.9 (55.8) microM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) v 69.6 (52.0) microM/l, p = 0.03). CONCLUSIONS: The results of this study suggest that NK-2R gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of patients with chronic cough.

SUBMITTER: Park HK

PROVIDER: S-EPMC2117043 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

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Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

Park H-K HK Oh S-Y SY Kim T-B TB Bahn J-W JW Shin E-S ES Lee J-E JE Oh H-B HB Kim Y-K YK Park T T Cho S-H SH Min K-U KU Kim Y-Y YY

Thorax 20060807 12

<h4>Background</h4>Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non-productive chronic cough have not been reported.<h4>Methods</h4>Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and neurokinin-2 receptor ...[more]

PMID: 16893949

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Project description:RationaleSpeech language pathology is an effective management intervention for chronic cough that persists despite medical treatment. The mechanism behind the improvement has not been determined but may include active cough suppression, reduced cough sensitivity or increased cough threshold from reduced laryngeal irritation. Objective measures such as cough reflex sensitivity and cough frequency could be used to determine whether the treatment response was due to reduced underlying cough sensitivity or to more deliberate control exerted by individual patients. The number of treatments required to effect a response was also assessed.ObjectiveThe aim of this study was to investigate subjective and objective measures of cough before, during and after speech language pathology treatment for refractory chronic cough and the mechanism underlying the improvement.MethodsAdults with chronic cough (n = 17) were assessed before, during and after speech language pathology intervention for refractory chronic cough. The primary outcome measures were capsaicin cough reflex sensitivity, automated cough frequency detection and cough-related quality of life.ResultsFollowing treatment there was a significant improvement in cough related quality of life (Median (IQR) at baseline: 13.5 (6.3) vs. post treatment: 16.9 (4.9), p = 0.002), objective cough frequency (Mean +/- SD at baseline: 72.5 +/- 55.8 vs. post treatment: 25 +/- 27.9 coughs/hr, p = 0.009), and cough reflex sensitivity (Mean +/- SD log C5 at baseline: 0.88 +/- 0.48 vs. post treatment: 1.65 +/- 0.88, p < 0.0001).ConclusionsThis is the first study to show that speech language pathology management is an effective intervention for refractory chronic cough and that the mechanism behind the improvement is due to reduced laryngeal irritation which results in decreased cough sensitivity, decreased urge to cough and an increased cough threshold. Speech language pathology may be a useful and sustained treatment for refractory chronic cough.Trial registrationAustralian New Zealand Clinical Trials Register, ACTRN12608000284369.

Dataset Information

Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

Publications

Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

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