Plain English Summary
Background and study aims
Asthma is a common disorder of the small tubes that carry air in and out of the lungs (airways). Patients with asthma intermittently complain of symptoms such as wheezing, coughing, shortness of breath and chest tightness during asthma attacks. However, some asthmatics do not describe all of the classical symptoms detailed above, whilst others only have one main symptom, such as cough. Some patients have symptoms triggered by different things like pollen, cold air, exercise or taking medication like aspirin or ibuprofen.
We also now understand that some asthmatics respond to treatment in different ways or develop asthma at different ages. This has led doctors to realise that asthma is not one disease but a group of different diseases and we need to better understand the actual mechanism of how asthma patients experience symptoms within these groups.
This study aims to understand cough in asthmatics. We hope to show differences in cough responses within asthmatics, particularly allergic and non-allergic asthmatics. This study could therefore help us develop new medications to specifically target cough in asthmatics.
Who can participate?
In this study we aim to recruit 100 volunteers (aged over 18 years) with stable mild to moderate asthma from the Manchester area to attend either the University Hospital of South Manchester NHS Foundation Trust or The Wellcome Trust Clinical Research Facility, depending on their location.
What does the study involve?
The study involves attending a participating centre for three visits, described below:
Visit 1: This visit will last about 1 hour. A researcher will ask the participants questions about their medical history, including asthma, smoking history, allergies and details of any medications being taken. A physical examination will be performed which includes measuring height and weight, listening to the chest and recording blood pressure. Basic observations will be performed which include recording heart rate, oxygen saturation and respiratory rate.
During this visit participants will be asked to perform an exhaled nitric oxide test by exhaling into a mouthpiece, breathing out at different speeds. We will analyse the gas in the airways by asking participants to breathe into a bag (called a Breath Test). A simple lung function test called spirometry will also be performed to measure the amount of air in the lungs. We will ask participants to complete two questionnaires designed to understand how well their asthma is controlled and how coughing affects their daily life.
Lastly, participants will be fitted with a cough monitor which will record the number of times they cough over a period of 24 hours.
Visit 2: This visit will last about 1 hour and 30 minutes. During this visit participants will be asked to provide a blood sample (about 3 teaspoons) to check for any evidence of allergy or proteins which may alter the way the nerves work. We will perform a skin allergy test. A methacholine challenge test will be performed, which involves inhaling a mist containing different concentrations of methacholine. Participants will be asked to perform sputum induction, which requires the inhalation of a salty mist through a nebuliser which will provoke the production of sputum (phlegm). We will ask participants to record their best (of three) peak flow measurements in the morning and evening for 1 week after visit 2. We will provide them with a peak flow meter and diary.
Visit 3: This visit will last about 45 minutes. A researcher will perform some breathing tests before the start of the test to ensure it is safe for participants to undergo a cough challenge. A cough challenge is a test designed to make you to cough. Participants will be asked to take a breath of a weak solution called capsaicin (chilli pepper extract) through a nebulizer machine. A cough monitor will be re-attached for the duration of the test using a clothing clip only to capture coughing.
All participants will receive the same interventions.
What are the possible benefits and risks of participating?
There will be no direct benefit for participants in this study. However, we hope that the results of this study will help us to understand the mechanisms of chronic cough and improve treatments in the future.
We do not foresee any significant risks associated with taking part in this study. Capsaicin (chilli pepper extract) inhalation is a well-established safe technique and no associated serious adverse events have been reported. The main side effects are an irritation or burning sensation at the back of the throat.
Where is the study run from?
This is a multicentre study and is taking place at the University Hospital of South Manchester NHS Foundation Trust (lead centre) and The Wellcome Trust Clinical Research Facility, UK.
When is the study starting and how long is it expected to run for?
Recruitment started in September 2013 and the study will finish in September 2014.
Who is funding the study?
The study is being funded internally by the University of Manchester (UK) as part of a PhD qualification. Salary costs are being funded by the Respiratory and Allergy Clinical Research Facility, UK.
Who is the main contact?
Dr Imran Satia, Clinical Research Fellow
imran.satia@manchester.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Imran Satia
ORCID ID
Contact details
University Hospital of South Manchester NHS Foundation Trust
North West Lung Research Centre
Southmoor Road
Manchester
M23 9LT
United Kingdom
+44 161 291 5846
imran.satia@manchester.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
13/COA/002
Study information
Scientific title
Studying Cough in Asthma phenotypes
Acronym
CoAst
Study hypothesis
Atopic asthmatics will have heightened cough response to inhaled capsaicin, which may be attributable to a change in nerve function mediated by neurotrophins.
Ethics approval
NRES Committee North West - Preston, 08/07/ 2013, ref: 13/NW/0403
Study design
Observational multi-centre study
Primary study design
Observational
Secondary study design
Longitudinal study
Trial setting
Other
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet.
Condition
Mild to moderate asthmatics
Intervention
This study involves a number of tests which are designed to understand the mechanisms of cough in asthma and include: exhaled nitric oxide, breath test, spirometry, 24 hr cough monitoring, skin allergy test, methacholine challenge test, a blood test, sputum induction, peak flow monitoring, a cough challenge test and completion of questionnaires.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
The influence of allergic inflammation on capsaicin dose response curves (ED50/Emax)* in mild to moderate asthmatics.
* Emax is the maximum number of coughs provoked and ED50 is the capsaicin dose provoking half the Emax. Primary and secondary outcomes will be measured at baseline only.
Secondary outcome measures
The influence of airway hyper-responsiveness (PD20 Methacholine), and serum/plasma neurotrophin levels on ED50 and Emax will also be explored and their relationships with 24 hr cough frequency and Leicester cough questionnaire (LCQ) and asthma control (ACQ).
Overall trial start date
16/09/2013
Overall trial end date
15/09/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged 18 years or over
2. Person with a primary or secondary care doctor diagnosis of asthma
3. The subject is treated with:
3.1. Short-acting beta 2 agonist
3.2. AND/OR inhaled corticosteroid (≤500 mcg fluticasone propionate daily or equivalent)
3.3. AND/OR a long-acting beta 2 agonist
3.4. AND/OR a leukotriene receptor antagonist
4. Controlled or has partial asthma control according to the GINA classification
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant exclusion criteria
1. Symptoms of upper respiratory tract infection (URTI) in the last 1 month which have not resolved.
2. Lower respiratory tract infection or pneumonia in the last 6 weeks.
3. Current smoker or ex-smoker with ≥10 pack-year smoking history, abstinence of 6 months or lesser
4. Asthma exacerbation in the previous month requiring an increase or starting of an ICS or OCS
5. Asthma medication which includes theophylline or anti-cholinergic drugs.
6. Subject has changed asthma medication within the past 4 weeks prior to screening
7. A previous asthma exacerbation requiring Intensive Care Unit (ICU) admission.
8. Significant other primary pulmonary disorders, in particular; pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis.
9. Pregnancy or breast-feeding
10. Use of ACE inhibitors
11. Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex
12. History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.
Recruitment start date
16/09/2013
Recruitment end date
15/09/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University Hospital of South Manchester NHS Foundation Trust
Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom
Funders
Funder type
University/education
Funder name
University of Manchester (UK) - funded internally
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Respiratory and Allergy Clinical Research Facility (UK) - funded salary costs
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27444176