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

February 15, 2011
September 15, 2011
November 2009
May 2011   (final data collection date for primary outcome measure)
  • 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
Same as current
Complete list of historical versions of study NCT01297790 on ClinicalTrials.gov Archive Site
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
Same as current
Not Provided
Not Provided
 
Cough Responses to Tussive Agents in Health and Disease
Cough Responses to Tussive Agents in Health and Disease

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

Sputum.

Non-Probability Sample

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.

  • Chronic Obstructive Airway Disease
  • Asthma
  • 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.
  • Asthma
    Subjects with asthma more than 18 years old with minimal or no smoking history and evidence of bronchial hyperreactivity
    Interventions:
    • Other: Cough Challenge Tests
    • Other: ambulatory cough recording
    • Other: Cough questionnaires
  • Chronic obstructive pulmonary disease
    Subjects with diagnosis of COPD who must be ex smokers and have evidence of airflow obstruction on breathing tests.
    Interventions:
    • Other: Cough Challenge Tests
    • Other: ambulatory cough recording
    • Other: Cough questionnaires
  • Healthy Volunteers
    Healthy non smoking adults.
    Interventions:
    • Other: Cough Challenge Tests
    • Other: ambulatory cough recording
    • Other: Cough questionnaires
  • Healthy smokers
    Current smokers with normal breath tests (spirometry)
    Interventions:
    • Other: Cough Challenge Tests
    • Other: ambulatory cough recording
    • Other: Cough questionnaires
  • Chronic cough
    Subjects with idiopathic chronic cough.
    Interventions:
    • Other: Cough Challenge Tests
    • Other: ambulatory cough recording
    • Other: Cough questionnaires
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
102
May 2011
May 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01297790
JAS Protocol 2
No
University Hospital of South Manchester NHS Foundation Trust
University Hospital of South Manchester NHS Foundation Trust
Not Provided
Principal Investigator: Ashley A Woodcock, FRCP, MD University Hospital of South Manchester
University Hospital of South Manchester NHS Foundation Trust
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP