Cough Responses to Tussive Agents in Health and Disease

Manchester University NHS Foundation Trust102 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

102

Conditions

Chronic Obstructive Airway Disease Asthma Chronic Cough

Interventions

Cough Challenge TestsOTHER

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

ambulatory cough recordingOTHER

Cough recording with a portable device to capture cough sounds

Cough questionnairesOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

University Hospital of South Manchester

Manchester, Lancashire, United Kingdom

Outcomes

Primary Outcomes

Cough response to tussive agents

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.

Time frame: 45 minutes

Objective cough recording

To perform ambulatory cough recording over 24 hours to assess if there are any differences

Time frame: 24 Hours

Secondary Outcomes

C2 to inhaled tussive agents

C2 concentration difference between different diagnostic groups after inhalation of tussive agents

Time frame: 45 minutes

Data from ClinicalTrials.gov

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