Cough Responses to Tussive Agents in Health and Disease

Study Description

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment
Chronic Obstructive Airway Disease; Asthma; Chronic Cough	Other: Cough Challenge Tests; Other: ambulatory cough recording; Other: Cough questionnaires

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.

Study Design

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Actual Enrollment :	102 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Cough Responses to Tussive Agents in Health and Disease
Study Start Date :	November 2009
Actual Primary Completion Date :	May 2011
Actual Study Completion Date :	May 2011

Groups and Cohorts

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort	Intervention/treatment
Asthma; Subjects with asthma more than 18 years old with minimal or no smoking history and evidence of bronchial hyperreactivity	Other: Cough Challenge Tests; Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2 Other: ambulatory cough recording; Cough recording with a portable device to capture cough sounds Other: Cough questionnaires; 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.	Other: Cough Challenge Tests; Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2 Other: ambulatory cough recording; Cough recording with a portable device to capture cough sounds Other: Cough questionnaires; 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.	Other: Cough Challenge Tests; Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2 Other: ambulatory cough recording; Cough recording with a portable device to capture cough sounds Other: Cough questionnaires; 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)	Other: Cough Challenge Tests; Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2 Other: ambulatory cough recording; Cough recording with a portable device to capture cough sounds Other: Cough questionnaires; 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.	Other: Cough Challenge Tests; Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2 Other: ambulatory cough recording; Cough recording with a portable device to capture cough sounds Other: Cough questionnaires; Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Outcome Measures

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Cough response to tussive agents [ Time Frame: 45 minutes ]

   To measure cough responses to capsaicin, citric acid, prostaglandin E2 (PGE2) and Bradykinin (BK) in healthy volunteers, airway diseases (asthma and COPD) and chronic cough.

   To compare the ability of individual challenges and patterns of challenge response to discriminate between diagnostic groups.

2. Objective cough recording [ Time Frame: 24 Hours ]
   To perform ambulatory cough recording over 24 hours to assess if there are any differences

Secondary Outcome Measures :

1. C2 to inhaled tussive agents [ Time Frame: 45 minutes ]
   C2 concentration difference between different diagnostic groups after inhalation of tussive agents

Biospecimen Retention:   Samples Without DNA

Sputum.

Eligibility Criteria

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Adults aged 18 and over who are healthy non smokers, or are current smokers with no respiratory conditions and normal spirometry, or have a diagnosis of asthma, chronic cough or COPD.

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.

Contacts and Locations

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United Kingdom
University Hospital of South Manchester
Manchester, Lancashire, United Kingdom, M23 9LT

Sponsors and Collaborators

Manchester University NHS Foundation Trust

Investigators

Principal Investigator:	Ashley A Woodcock, FRCP, MD	University Hospital of South Manchester

More Information

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Manchester University NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT01297790 History of Changes
Other Study ID Numbers:	JAS Protocol 2
First Posted:	February 17, 2011
Last Update Posted:	September 16, 2011
Last Verified:	September 2011

Keywords provided by Manchester University NHS Foundation Trust:

Cough; Inhalational cough challenges; Cough reflex sensitivity; Chronic cough.

Additional relevant MeSH terms:

Cough; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiration Disorders	Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Lung Diseases