Cough Responses to Tussive Agents in Health and Disease

NHS Foundation Trust

Status: Completed

Conditions: Chronic Obstructive Airway Disease; Asthma; Chronic Cough

Treatments: Other: Cough Challenge Tests; Other: ambulatory cough recording; Other: Cough questionnaires

Study type: Observational

Funder types: Other

Identifiers

NCT01297790

JAS Protocol 2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 102 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

102 participants in 5 patient groups

Asthma

Description:

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

Treatment:

Other: Cough questionnaires

Other: ambulatory cough recording

Other: Cough Challenge Tests

Chronic obstructive pulmonary disease

Description:

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

Treatment:

Other: Cough questionnaires

Other: ambulatory cough recording

Other: Cough Challenge Tests

Healthy Volunteers

Description:

Healthy non smoking adults.

Treatment:

Other: Cough questionnaires

Other: ambulatory cough recording

Other: Cough Challenge Tests

Healthy smokers

Description:

Current smokers with normal breath tests (spirometry)

Treatment:

Other: Cough questionnaires

Other: ambulatory cough recording

Other: Cough Challenge Tests

Chronic cough

Description:

Subjects with idiopathic chronic cough.

Treatment:

Other: Cough questionnaires

Other: ambulatory cough recording

Other: Cough Challenge Tests