Regulation of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease

This study involves a comparison of the inflammatory responses of leukocytes derived from 3 separate subject groups. The aim of the study is to compare the responses of leukocytes from patients with COPD with subjects that smoke and healthy non-smokers. One part of the study will involve isolation of different leukocyte populations from blood from each of the subject groups. In a second part of the study, we will examine the expression of inflammatory mediators in leukocytes derived from bronchoalveolar lavage samples from patients with COPD, smokers without COPD and healthy non-smokers. In subjects that are willing to participate, we will compare blood derived leukocytes and cells derived from those undergoing BAL, although not every subject will provide both blood and BAL samples. The isolated leukocytes (both from blood and BAL) will be used for in vitro experiments to determine the differences in gene expression in inflammatory cells from patients with COPD. Details of interventions to subjects 1. Medical History and Physical Examination A full medical history and physical examination (including height and weight) will be performed on the initial screening visit, in addition to that recorded in the clinical case notes. 2. Respiratory Assessments Forced Expiratory Volume per second (FEVI) will be measured using a dry wedge spirometer (Vitalograph, Buckingham, UK) and expressed as a percent of predicted value. Subjects will be trained in the use of the apparatus before beginning the study. The baseline value at each visit will be measured after at least fifteen minutes of quiet rest, and will be taken as the highest of three readings made at one-minute intervals. Single readings only will be taken at other times. 3. Endoscopic Bronchoscopy An operator approved by the Royal Brompton Ethics Committee will perform all bronchoscopies. The bronchoscopist that will perform these procedures is Dr Borja Cosio. Subjects will attend the bronchoscopy suite at 8.30 am after having fasted from midnight. Subjects will have pre-treatment with atropine (0.6 mg iv) and midazolam (5-10 mg iv). Oxygen (3 l/min) will be administered via nasal prongs throughout the procedure and oxygen saturation monitored with a digital oximeter. Using local anaesthesia with lidocaine (4%) to the upper airways and larynx, a fibreoptic bronchoscope (Olympus BF10 Key-Med) will be passed through the nasal passages into the trachea. Bronchoalveolar lavage (BAL) will be performed from the right middle lobe using warmed 0.9% NaCl with 4 successive aliquots of 60 ml. This is well-tolerated in subjects with COPD. Patients may experience pharyngeal irritation following the procedure; there is a 5% chance of fever following the procedure. Subjects undergoing bronchoscopy for clinical reasons will also be included in this study. 4. Venous Blood Sampling 60 ml of blood will be taken by venopuncture.