Neuroinflammatory Interactions of ATP and P2X3 Receptor in the Airways of Chronic Cough Patients: an Exploratory Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Imperial College London
- Enrollment
- 20
- Primary Endpoint
- Does ATP inhalation compared to that of saline inhalation change capsaicin cough sensitivity and laryngeal sensitivity?
Study Overview
Brief Summary
This is a laboratory-based study that will be performed at the Clinical Research Centre at the Royal Brompton Hospital,London. The objectives are:
- Determine whether adenosine triphosphate (ATP) is present or released in airways of idiopathic chronic cough patients
- Determine whether there is an increase in cough sensitivity and laryngeal sensitivity to exogenous ATP
- Examine the effects of exogenous ATP on the inflammatory response in the upper and lower airways.
The participants will be: (i) Healthy subjects: non-smoker (8 subjects) and (ii) Chronic cough subjects attending Chronic Cough clinic (12 subjects). Each will be involved in:
Study 1. Following recruitment, subjects will attend for a fiberoptic bronchoscopy.
Study 2: Subjects will take part in a study of the effect of inhaling nebulized ATP. Subjects will be studied on 2 days separated by at least 5 days. On each day, after measurements of lung function, FeNO and cough questionnaires, the subject will inhale either saline or ATP solution from a nebulizer, following which laryngeal hypersensitivity, capsaicin cough challenge and sputum induction will be performed.
Results will be expressed as mean ± standard error of the mean (SEM). Study data will be analysed by the Investigators at the completion of the study. Planned analyses will be done by comparing chronic cough patients to the healthy controls. The Spearman rank-correlation test will be used to determine correlations.
Detailed Description
These are the objectives of this study:
- Determine whether ATP is present or released in airways of idiopathic chronic cough patients
- Determine whether there is an increase in cough sensitivity and laryngeal sensitivity to exogenous ATP
- Examine the effects of exogenous ATP on the inflammatory response in the upper and lower airways.
Outcome measures
These are all primary outcome measures of this study:
- Presence of ATP in airways of idiopathic chronic cough patients and the localisation of P2X2/3 receptors in the airways
- Cough sensitivity and laryngeal sensitivity to exogenous ATP
- Inflammatory response in the upper and lower airways to exogenous ATP.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- Double (Participant, Investigator)
Masking Description
Participant and Investigator will be blinded as to whether saline or ATP is being given.
Eligibility Criteria
- Ages
- 30 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •For Normal non-smoking subject:
- •Healthy individuals, free of significant disease No history of asthma/rhinitis, No therapies, Baseline FEV1 ≥80% predicted with FEV1/FVC ratio >70% Non-smoker for at least the past 12 months with a pack history of ≤5 pack-years
- •For chronic cough participants:
- •History of chronic cough of at least 8 weeks' duration and should have been followed in the Cough Clinic for at least 6 months.
- •Undergone a protocol with a diagnostic pathway as recommended by the ERS guidelines for management of cough.
- •Would have either an identifiable cause for their cough that have failed therapies targeted towards the identified cause or classed as having chronic idiopathic cough where no identifiable cause has been found.
- •General Inclusion Criteria:
- •Give written informed consent prior to participation in the study including all of its procedures.
- •Comply with the requirements and restrictions listed in the consent form. Male or female subject aged between 30 and 70 years old at screening. Able to complete the study and all measurements. Able to read, comprehend, and write at a sufficient level to complete study related materials.
Exclusion Criteria
- •General exclusion criteria:
- •Subjects will not be eligible if any of the following apply: -
- •As a result of medical interview, physical examination or screening investigation the investigators consider the subject unfit either because of risk to the subject due to the study or the influence this may have on the study results.
- •A history of recreational drug use or allergy which in the opinion of the investigators contra-indicates their participation.
- •Female who is pregnant or lactating or up to 6 weeks post-partum or 6 weeks cessation of breast feeding at any point in the study.
- •Any participants who are involved in current research or have recently been involved in any research prior to recruitment.
- •Those, in the opinion of the investigator, who may prove non-compliant with study procedures.
- •History of an upper or lower respiratory infection (including coryza) within 3 weeks of baseline assessments (assessments and entry could be deferred).
- •Persons who might not adequately understand verbal explanations or written information given in English, or who have special communication needs.
- •Subjects who are currently involved in other research.
- •Specific exclusion criteria for patients with chronic cough:
- •Exclusion of chronic cough patients with a clear history of asthma and Chronic obstructive pulmonary Disease (COPD) on maintenance therapy
- •Subjects who are current smokers or ex-smokers with a greater than 10 pack-year history of smoking
- •Subjects with significant presence of airflow obstruction with an FEV1 of <70% of predicted for age and gender.
- •Significant vocal cord disorder (VCD).
- •Long term antibiotic treatment or receipt of a course within 4 weeks of bronchoscopy.
- •Diagnosis of Allergic bronchopulmonary aspergillosis (ABPA), Churg-Strauss, rheumatoid arthritis, connective tissue disorders; Angiotensin-converting enzyme inhibitor and beta-blockers treatment.
- •Morbid obesity (BMI>35).
- •Non-steroid immunosuppressive treatments including methotrexate.
Outcomes
Primary Outcomes
Does ATP inhalation compared to that of saline inhalation change capsaicin cough sensitivity and laryngeal sensitivity?
Time Frame: 18 months
Capsaicin cough sensitivity will be measured as the concentration of capsaicin causing 2 or 5 coughs, ie C2 or C5 concentrations in micromolar units. Laryngeal sensitivity will be measured as the change in the area of the glottic aperture between expiration and inspiration maneouvre.
Compare the levels of ATP in bronchoalveolar lavage fluid and in exhaled breath condensate from chronic cough patients to those of non-coughing healthy subjects
Time Frame: 18 months
This will be done by measurement of ATP concentration in nanomolar units using an off-line luminometer in broncholaveolar lavage fluid and exhaled breath condensate by a paired analysis.
Secondary Outcomes
- Determine the number of coughs and cough frequency after ATP and saline inhalation in chronic cough and in non-coughing participants.(18 months)
- Does ATP inflammation induce granulocytic inflammation after inhalation of ATP?(18 months.)