Cough Responses to Tussive Agents in Health and Disease

NCT ID: NCT01297790

Last Updated: 2011-09-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 102 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2011-05-31

Brief Summary

The sensitivity of a persons cough reflex can be measured by getting them to breath in (inhale) irritant chemicals. The purpose of this clinical research study is to test the sensitivity of the cough reflex to a variety of chemicals that can be inhaled to see if coughing responses are different between healthy people and people with respiratory problems that make them cough.

Detailed Description

Coughing is a distressing symptom which has a major impact on quality of life. It has been estimated that cough costs the UK economy £1 billion each year. Currently there are no effective anti-tussive agents to treat subjects with cough. Although drugs such as morphine may have some anti-tussive effect, side effects unacceptable.

Currently our understanding of the mechanisms which lead to coughing in different diseases is poor. Many mechanistic studies rely on testing the sensitivity of the cough reflex by inhalation of capsaicin (chilli-pepper extract) or citric acid. These challenges do not differentiate well between health and disease or between different disease states. Other agents such as prostaglandins and bradykinin are known to stimulate a coughing but responses to these agents have rarely been used as a measure of cough reflex sensitivity and not been compared to standard challenges.

It is clear that patients with common airway diseases such as COPD and asthma cough significantly more than healthy subjects. Moreover subjects presenting with chronic cough have cough rates an order of magnitude higher than most patients with airway disease. These differences are poorly represented by the differences in current cough challenge tests.

The investigators hypothesize that patterns of cough responses to different tussive agent may better differentiate between health and different disease states. These patterns may also suggest the different mechanisms leading to cough in different diseases.

Conditions

Chronic Obstructive Airway Disease; Asthma; Chronic Cough

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Asthma

Subjects with asthma more than 18 years old with minimal or no smoking history and evidence of bronchial hyperreactivity

Cough Challenge Tests

Intervention Type: OTHER

Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2

ambulatory cough recording

Intervention Type: OTHER

Cough recording with a portable device to capture cough sounds

Cough questionnaires

Intervention Type: OTHER

Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Chronic obstructive pulmonary disease

Subjects with diagnosis of COPD who must be ex smokers and have evidence of airflow obstruction on breathing tests.

Cough Challenge Tests

Intervention Type: OTHER

Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2

ambulatory cough recording

Intervention Type: OTHER

Cough recording with a portable device to capture cough sounds

Cough questionnaires

Intervention Type: OTHER

Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Healthy Volunteers

Healthy non smoking adults.

Cough Challenge Tests

Intervention Type: OTHER

Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2

ambulatory cough recording

Intervention Type: OTHER

Cough recording with a portable device to capture cough sounds

Cough questionnaires

Intervention Type: OTHER

Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Healthy smokers

Current smokers with normal breath tests (spirometry)

Cough Challenge Tests

Intervention Type: OTHER

Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2

ambulatory cough recording

Intervention Type: OTHER

Cough recording with a portable device to capture cough sounds

Cough questionnaires

Intervention Type: OTHER

Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Chronic cough

Subjects with idiopathic chronic cough.

Cough Challenge Tests

Intervention Type: OTHER

Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2

ambulatory cough recording

Intervention Type: OTHER

Cough recording with a portable device to capture cough sounds

Cough questionnaires

Intervention Type: OTHER

Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Interventions

Cough Challenge Tests

Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2

Intervention Type: OTHER

ambulatory cough recording

Cough recording with a portable device to capture cough sounds

Intervention Type: OTHER

Cough questionnaires

Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• General

• Adult subjects aged 18 years and over
• Meet criteria for subject groups as outlined below

(1) Healthy volunteers

• Non-smokers
• No history of respiratory disease

(2) Healthy smokers

• Current smokers with smoking history of ≥10 pack years
• Spirometry within normal limits i.e. FEV1>80% predicted and FEV1/FVC ratio >75% predicted

(3) Asthma

• Physician diagnosis of asthma
• Airways hyperresponsiveness to methacholine; PC20<16mg/ml (within last 2 years)
• Non-smokers or ex-smoker with smoking history of ≤10 pack years

(4) COPD

• Physician diagnosis of COPD
• Ex-smokers with smoking history of ≥20 pack years
• Spirometry demonstrating airflow obstruction i.e. FEV1/FVC ratio <70%

(5) Chronic Cough

• History of a dry cough for >8 weeks
• Normal CXR
• Non-smokers or ex-smoker with smoking history of ≤10 pack years

Exclusion Criteria

• 1) Symptoms of upper respiratory tract infection within the last 6 weeks 2) Participation in another clinical trial of an investigational drug within the last 4 weeks 3) Use of medication likely to alter cough reflex sensitivity i.e. ACE inhibitors, codeine phosphate, morphine sulphate, 4) Patients with severe respiratory disease i.e. FEV1 < 1 litre, 5) Significant medical co-morbidities likely to affect ability to participate in the trial or affect cough reflex sensitivity e.g. diabetes, stroke, Parkinson's disease, multiple sclerosis etc.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ashley A Woodcock, FRCP, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of South Manchester

Locations

University Hospital of South Manchester

Manchester, Lancashire, United Kingdom

Countries

United Kingdom

References

Belvisi MG, Birrell MA, Khalid S, Wortley MA, Dockry R, Coote J, Holt K, Dubuis E, Kelsall A, Maher SA, Bonvini S, Woodcock A, Smith JA. Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies. Am J Respir Crit Care Med. 2016 Jun 15;193(12):1364-72. doi: 10.1164/rccm.201508-1602OC.

Reference Type: DERIVED

PMID: 26741046 (View on PubMed)

Other Identifiers

JAS Protocol 2

Identifier Type: -

Identifier Source: org_study_id