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Cough Responses to Tussive Agents in Health and Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital of South Manchester NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01297790
First received: February 15, 2011
Last updated: September 15, 2011
Last verified: September 2011
History of Changes
  Purpose

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 Intervention
Chronic Obstructive Airway Disease
Asthma
Chronic Cough
 Other: Cough Challenge Tests
Other: ambulatory cough recording
Other: Cough questionnaires

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cough Responses to Tussive Agents in Health and Disease

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital of South Manchester NHS Foundation Trust:

Primary Outcome Measures:
  • Cough response to tussive agents [ Time Frame: 45 minutes ] [ Designated as safety issue: No ]

    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.


  • Objective cough recording [ Time Frame: 24 Hours ] [ Designated as safety issue: No ]
    To perform ambulatory cough recording over 24 hours to assess if there are any differences


Secondary Outcome Measures:
  • C2 to inhaled tussive agents [ Time Frame: 45 minutes ] [ Designated as safety issue: No ]
    C2 concentration difference between different diagnostic groups after inhalation of tussive agents


Biospecimen Retention:   Samples Without DNA

Sputum.


Enrollment: 102
Study Start Date: November 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01297790

Locations
United Kingdom
University Hospital of South Manchester
Manchester, Lancashire, United Kingdom, M23 9LT
Sponsors and Collaborators
University Hospital of South Manchester NHS Foundation Trust
Investigators
Principal Investigator: Ashley A Woodcock, FRCP, MD University Hospital of South Manchester
  More Information

No publications provided

Responsible Party: University Hospital of South Manchester NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01297790     History of Changes
Other Study ID Numbers: JAS Protocol 2
Study First Received: February 15, 2011
Last Updated: September 15, 2011
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University Hospital of South Manchester NHS Foundation Trust:
Cough
Inhalational cough challenges
Cough reflex sensitivity
Chronic cough.

Additional relevant MeSH terms:
Asthma
Cough
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases
 Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms

ClinicalTrials.gov processed this record on May 16, 2013