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. Airway inflammation due to neutrophils is more common in older people with asthma who have fixed airway narrowing. Neutrophils are a type of cell that are part of the body's immune system which causes inflammation. Neutrophilic airway inflammation can cause damage to the airways and lung tissue. The aim of this research is to determine how neutrophils affect the function of the smaller airways in older people with asthma. We will also determine how neutrophils cause airway and lung damage, which can lead to fixed airway narrowing. 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 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
Subjects with asthma will undergo breathing tests, allergy tests and a bronchoscopy. The breathing tests will include spirometry, lung volumes, DLCO, methacholine challenge, exhaled nitric oxide, multiple breath nitrogen wash out, forced oscillation technique and lung elastic recoil. The breathing tests will involve the subject 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 ai
Subjects with asthma will undergo breathing tests, allergy tests and a bronchoscopy. The breathing tests will include spirometry, lung volumes, DLCO, methacholine challenge, exhaled nitric oxide, multiple breath nitrogen wash out, forced oscillation technique and lung elastic recoil. The breathing tests will involve the subject 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. A skin prick test will be used to test for allergies. 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 4 visits (3 visits for breathing tests and 1 visit for the bronchoscopy). The breathing tests will take place at the start of the study, 1 month and 2 months after recruitment. The first and last visit for breathing tests will take up to 4 hours. The second visit for breathing tests will take up to an hour. The bronchoscopy will be performed 2 months after recruitment and will take up to 6 hours.
Sponsors
Woolcock Institute of Medical Research
Eligibility
Sex/Gender
All
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Doctor diagnosis of asthma. Age > 40 years. Non smoker (no smoking for > 6 months and < 10 pack/year smoking history).
Exclusion criteria
Other significant cardiac or pulmonary diseases. Using regular oral corticosteroid medication.
Outcome results
None listed