Cough Responses to Tussive Agents in Health and Disease

Asthma Clinical Trial

Official title:

Cough Responses to Tussive Agents in Health and Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297790
• Other study ID #: JAS Protocol 2
• Status: Completed
• Phase: N/A
• First received: February 15, 2011
• Last updated: September 15, 2011
• Start date: November 2009
• Est. completion date: May 2011

Study information

• Verified date: September 2011
• Source: University Hospital of South Manchester NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Asthma
• Chronic Cough
• Chronic Obstructive Airway Disease
• Cough
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Other:
• Cough Challenge Tests
Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2
• ambulatory cough recording
Cough recording with a portable device to capture cough sounds
• Cough questionnaires
Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.

Locations

Country	Name	City	State
United Kingdom	University Hospital of South Manchester	Manchester	Lancashire

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of South Manchester NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	45 minutes	No
Primary	Objective cough recording	To perform ambulatory cough recording over 24 hours to assess if there are any differences	24 Hours	No
Secondary	C2 to inhaled tussive agents	C2 concentration difference between different diagnostic groups after inhalation of tussive agents	45 minutes	No