Clinical trial NCT01297790: Cough Responses to Tussive Agents in Health and Disease
Official title: Cough Responses to Tussive Agents in Health and Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Obstructive Airway Disease
Asthma
Chronic Cough
Keywords: Cough
Inhalational cough challenges
Cough reflex sensitivity
Chronic cough.
Lead sponsor: Manchester University NHS Foundation Trust
Sponsor class: OTHER_GOV
First posted: 2011-02-17
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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 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.

Primary outcomes:
measure: Cough response to tussive agents
timeFrame: 45 minutes
measure: Objective cough recording
timeFrame: 24 Hours
Secondary outcomes:
measure: C2 to inhaled tussive agents
timeFrame: 45 minutes
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester
state: Lancashire
Study officials:
affiliation: University Hospital of South Manchester
name: Ashley A Woodcock, FRCP, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Belvisi MG, Birrell MA, Khalid S, Wortley MA, Dockry R, Coote J, Holt K, Dubuis E, Kelsall A, Maher SA, Bonvini S, Woodcock A, Smith JA. Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies. Am J Respir Crit Care Med. 2016 Jun 15;193(12):1364-72. doi: 10.1164/rccm.201508-1602OC.