None listed
Conditions
Brief summary
Fixed airway narrowing is a common complication of long standing asthma. It occurs despite good treatment with puffers that are effective in controlling inflammation. It causes symptoms such as wheeze, cough, shortness of breath and there is no known treatment for asthma related fixed airway narrowing because the mechanisms and causes are poorly understood. It is more common in older patients who have had asthma for many years, in whom there are also greater symptoms. The underlying mechanism of airway and lung tissue remodelling are unknown but preliminary data support a crucial role for inflammatory cells, and in particular, neutrophils and macrophages. Neutrophils, as well as other inflammatory cells such as macrophages release proteolytic enzymes that mediate tissue remodelling and tissue destruction. This is supported by both CT and histological evidence of lung tissue remodelling that explains the loss of lung elastic recoil in longstanding asthma. Inflammation driven remodelling of peripheral airways and surrounding lung is therefore a likely mechanism causing FAO in older people with longstanding asthma. The aim of this research is to determine how neutrophils and macrophages affect the function of the smaller airways, and how they can cause airway and lung damage in older people with asthma. We will recruit people with asthma who are >40 years of age, are non-smokers and have no other significant lung or heart problems. Participants will undergo breathing tests, CT scanning and a bronchoscopy, using a small camera on the end of a flexible tube, to obtain samples from their lungs. The significance of this study will be the discovery of the mechanisms that underlies this major complication of asthma. It will assist in overcoming the major barrier halting progress to an effective treatment strategy for which the mechanisms are unknown.
Interventions
Participants with asthma will complete a clinical questionnaire and will undergo lung function tests, allergy tests, a CT-scan procedure and a bronchoscopy.
1). The lung function tests will include: spirometry, lung volumes, DLCO, methacholine challenge, exhaled nitric oxide, multiple breath nitrogen wash out, forced oscillation technique and lung elastic recoil measurements. The lung function tests will involve the study participants breathing into a mouth piece attached to different machines.
Participants with asthma will complete a clinical questionnaire and will undergo lung function tests, allergy tests, a CT-scan procedure and a bronchoscopy. 1). The lung function tests will include: spirometry, lung volumes, DLCO, methacholine challenge, exhaled nitric oxide, multiple breath nitrogen wash out, forced oscillation technique and lung elastic recoil measurements. The lung function tests will involve the study participants breathing into a mouth piece attached to different machines. During the methacholine challenge, an aerosol of methacholine will be inhaled to look at how sensitive the airways are. During the lung elastic recoil test a fine flexible tube with a latex balloon attached at the end, will be passed through the nose down to the oesophagus (with local anaesthetic, 1.5ml Xylocaine viscous, applied to the nostrils prior) to test the elasticity of the lungs. 2) A skin prick test will be used to test for allergies. A small droplet of allergen will be placed on the subject's forearm and the skin will be pricked lightly through the droplet. If subject is allergic to any of the allergens you will develop a small itchy lump. 3) A low-dose inspiratory and expiratory CT-scan will be performed by department technicians, from which the lung tissue density will be analysed (CT scans will be made without intravenous contrast injection). 4) The bronchoscopy involves placing a bronchoscope (thin flexible tube-like instrument with a mini camera at its tip) through the nose or mouth into the lungs to allow us to look into the airways. Local anaesthetic and sedating medications will be used prior to the bronchoscopy. The local anaesthetic (10% Xylocaine) will be applied topically to each nostril (1 spray each) and to the back of the throat (1 spray) 5-10 minutes before the procedure. Sedation will be administered intravenously (0.5-5mg diazepam +/- 12.5-100mcg fentanyl) before the procedure. Further local anaesthetic (1% Xylocaine) will be applied to the vocal cords and to the airways in 2.5 ml aliquots via the bronchoscope channel (maximum dose 4-5 mg/kg). During the bronchoscopy small samples from the lining of lung will be taken and fluid (sterile saline) will be flushed down the bronchoscope. This fluid will be sucked back up the bronchoscope and cells in the fluid will be analysed. A blood test will be taken at the time of the bronchoscopy and this will also be analysed. The study will involve 3 visits: Visit 1 will involve the clinical questionnaire, lung function tests and allergy test and will take up to 3 hours. Visit 2 will involve the CT scan procedure and lung elastic recoil test and will take up to 3 hours. In visit 3 the bronchoscopy will be performed and this visit will take up to 6 hours. All visits will take place at the Royal North Shore Hospital, Sydney and the three visits will be separated by at least 48 hours.
Sponsors
Woolcock Institute of Medical Research
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1) Age 40-80 years 2) Physician-diagnosis of asthma 3) History of asthma medication use in the previous year 4) Willing and able to give written informed consent 5) Non smoker (no smoking for > 6 months and < 10 pack/year smoking history)
Exclusion criteria
1) Significant cardiac disease (ischemic heart disease or arrhythmia) 2) Documented hypersensitivity to, or intolerance of, anti-cholinergic therapies 3) Significant respiratory infection or exacerbation of Asthma within the previous 6 weeks 4) Intensive Care Unit admissions in the last 12 months. 5) Other active or chronic respiratory pathologies 6) History of lung surgery 7) Unable to perform lung function testing 8) Unable to provide informed consent 9) Current enrolment in other trials 10) Women who are pregnant or attempting to get pregnant due to radiation exposure
Outcome results
None listed