Assessment Of Disease Pathology And Key Therapeutic Targets In Severe Asthma

Inclusion criteria: * History of asthma with exclusion of other significant pulmonary disease. * Body Mass Index between 19-31 kg.m-2. * Subjects will be assigned to group 1(mild to moderate) or Group 2 (severe asthmatics) depending on their Lung Function test results. Exclusion criteria: * As a result of medical interview, physical examination or screening investigation the physician responsible considers the subject unfit for the study. * History of drug or other allergy, which, in the opinion of the responsible physician, contra-indicates their participation. * Subject is female who is pregnant or lactating. * Currently or planning to take during the study regular medication (including over-the-counter) except for medication allowed in inclusion criteria. * Having participated within 30 days or 5 half-lives, whichever is longer of the first dose in a study using new molecular entity, or the first dose in any other study investigating drugs or having participated within one month of the first dose in a study with invasive procedures. * History or current evidence of an upper or lower respiratory infection or symptoms (including common cold) within 2 weeks of baseline assessments. * History of abnormal bruising or bleeding. * History of alcohol or drug abuse. * Doing night-shift work within at least 5 days prior to dosing until completion of the study. * Anticoagulants except low dose of Aspirin (80 mg per day) (for bronchoscopy). * Beta blockers except for low dose Atenolol (25 mg/day) or Metoprolol (50 mg/day) (for bronchoscopy). * Use of Cytochrome P450 inhibitors. * History of hypersensitivity to any of the following medications: Lidocaine, Fentanyl, Versed, Demerol, Midazolam, Epinephrine, Flumazenil and Naloxone. * History of hypersensitivity to bronchodilator (such as Albuterol). In addition, the following additional exclusion criteria must apply to mild to moderate persistent asthmatics on regular inhaled steroids: * Changed asthma medication within the 4 weeks prior to screening. * Has had an asthma exacerbation in the previous month. * Known sensitivity or allergy to prednisolone. * Current use or use within the previous 3 months of oral corticosteroids. * Current use of Methotrexate, cyclosporine and PDE inhibitors * History of tuberculosis, diabetes mellitus, osteoporosis, severe hypertension, glaucoma , severe affective disorder and peptic ulceration. In addition, the following additional exclusion criteria must apply to severe persistent asthmatics with clinical controlled asthma symptoms: * Changed asthma medication within the 4 weeks prior to screening. * Has had an asthma exacerbation in the previous month. * sensitivity or allergy to prednisolone. * History of tuberculosis, diabetes mellitus, osteoporosis, hypertension, glaucoma, severe affective disorder and peptic ulceration. * Current use or use within the previous 4 weeks of oral prednisolone or equivalent of greater than 20mg daily. * Current use of Methotrexate, cyclosporin.