A Study on the Mechanism of Cough Hypersensitivity

The aim of this study is described as follows,

1. To establish a validated method to test cough reflex sensitivity conducted by transient receptor potential vanilloid 1(TRPV1).
2. To observe the variance of cough reflex sensitivity conducted by transient receptor potential ankyrin 1(TRPA1) of chronic patients and the relationship between cough reflex sensitivity conducted by TRPA1 and conducted by TRPV1.
3. To study the distribution of TRPA1 and TRPV1 channels and their relationship to cough reflex sensitivity.

Study Overview

• Status: Unknown
• Conditions: Cough

Detailed Description

This study is divided into two major part, Firstly,to observe the variance of cough reflex sensitivity of chronic cough patients and the relationship between it and airway inflammation.

1. Recruit chronic cough patients and healthy volunteers as subjects.
2. Help subjects to complete detailed history,physical examination,Hull airway reflux questionnaire,chest x-rays,induced sputum,blood routine test,pulmonary ventilation function test and histamine provocation test before they enter this study.
3. Complete allyl isothiocynate(AITC) cough provocation test the day subjects enter the study,then complete capsaicin（CAP）cough provocation test after 3 days.
4. To detect the substance P(SP),calcitonin gene-related peptide(CGRP),prostaglandin E2(PGE2),et al level in sputum supernatants.

Secondly,to observe the distribution of TRPA1,TRPV1 channels and the relationship between it and cough reflex sensitivity.

1）Recruit chronic cough patients and healthy volunteers and complete related examinations as mentioned before.

2)Collect mucosa specimens from upper trachea via endobronchial biopsy,and airway epithelial cells from 2nd or 3rd order bronchi via brushing.

3)Evaluate the expression level of TRPA1,TRPV1 of mucosa specimens of subjects by immunofluorescent assay and Image analysis software.

4)Cultivate airway epithelial cells from subjects and evaluate the expression of TRPV1,TRPA1 and functional changes of it.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 520120
      • Recruiting
      • Guangzhou Institute of Respiratory Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Chronic cough group:nonsmokers with chronic cough lasting ≥ 8 weeks characterized by irritating dry cough or small amount of sputum, sensitive to fumes，dust, cold air ,and normal chest x-ray were enrolled.

Healthy control:healthy volunteers presented our hospital for healthy examination were enrolled.

Description

Inclusion Criteria:

chronic cough group:

1. cough lasting ≥ 8 weeks,characterized by irritating dry cough.
2. sensitive to fumes，dust,the odorous and cold air.
3. with normal chest x-rays. 4.17-70 years old.

5.without smoking history. healty controls group: 1.17-70 years old. 2.without smoking hitory or stop smoking for more than 2 years. 3.without chronic cough. 4.without chronic respiratory diseases. 5.without chronic heart, liver, kidney,and autoimmune disease. 6.with normal chest x-rays. 7.with normal pulmonary ventilation function,and histamine challenge test showed negative result.

Exclusion Criteria:

chronic cough group and healty controls group:

1. with respiratory tract infection within 8 weeks.
2. with chronic respiratory diseases or severe heart, liver, kidney,and autoimmune disease.
3. using Angiotensin-Converting Enzyme Inhibitors(ACEI),bronchodilators,glucocorticosteroid,antihistaminics within one week.
4. women during pregnancy or lactation.
5. patients with malignant tumours.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
patients with normal cough sensitivity
patients with high cough sensitivity
healty controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TRPA1,TRPV1 channels expression level of chronic cough patients and its relationship with cough reflex sensitivity	Complete AITC cough provocation test the day subjects enter the study,then complete CAP cough provocation test after 3 days,record the threshold of cap and aitc concentration(mmol/L) when it cause subjects cough equal to or more than 5 times.Measure the expression level of TRPA1 and TRPV1 of biopsy sample from chronic cough patients and healthy controls by immunofluoresent assay 7 days post bronchoscopy.Analyze the statistic by spss18.0.	7 days post-bronchoscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relationship between CAP cough reflex sensitivity test conducted by TRPV1 and AITC cough reflex sensitivity test conducted by TRPA1	Complete AITC cough provocation test the day subjects enter the study,then complete CAP cough provocation test after 3 days,record the threshold of cap and aitc concentration(mmol/L) when it cause subjects cough equal to or more than 5 times.Analyze the statistic by spss18.0.	7 days post-bronchoscopy

Collaborators and Investigators

• Sponsor: Kefang Lai

Publications and helpful links

General Publications

• Lai K, Long L, Yi F, Tang J, Chen Z, Chen F, Zhou J, Peng W, Zhang L, Li H, Zhan W, Chen R, Luo W, Chen Q, Chung KF, Zhong N. Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity. Allergy Asthma Immunol Res. 2019 Nov;11(6):871-884. doi: 10.4168/aair.2019.11.6.871.
• Long L, Yao H, Tian J, Luo W, Yu X, Yi F, Chen Q, Xie J, Zhong N, Chung KF, Lai K. Heterogeneity of cough hypersensitivity mediated by TRPV1 and TRPA1 in patients with chronic refractory cough. Respir Res. 2019 Jun 6;20(1):112. doi: 10.1186/s12931-019-1077-z.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: October 21, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Estimate): October 29, 2015
• Last Update Submitted That Met QC Criteria: October 28, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: chronic cough; cough reflex sensitivity; transient receptor potential vanilloid 1; transient receptor potential ankyrin 1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: coughlongli