Factors Involved in Asthma and Airway Inflammation

ASTHMATICS: Must be between 18 and 65 years of age, male or female, and must be at least 5 feet in height. The diagnosis of asthma requires a history of intermittent, reversible expiratory flow limitation. Patients will have mild-to-moderately severe asthma as defined by a baseline forced expiratory flow in one second (FEV(1)) greater than 70% of predicted (at least 6 hours after bronchodilator use) and therapy limited to inhaled beta-agonists. Positive skin prick-puncture test to one or more common aeroallergens. A positive inhaled methacholine challenge as defined by a decrease in FEV(1) of at least 20% (PC(20)) in response to inhalation of less than 25 mg/ml of methacholine. A decrease in FEV(1) of at least 20% in response to inhalation of up to 10,000 bioequivalency allergy units (BAU) or allergy units (AU) per ml of a selected common aeroallergen (house dust mite, cat hair or grasses) or up to 150 Antigen E units per ml of short ragweed. Asthmatic patients must also demonstrate a late asthmatic response (defined as a 20% fall from the baseline established following completion of the early asthmatic response). Normal complete blood count, PT, PTT, and serum electrolytes, mineral and hepatic panels (less than 30 ml of blood will be drawn), normal EKG and chest radiograph without acute pulmonary infiltrates. Women of childbearing potential must have a negative pregnancy test within 2 weeks prior to study and willingness to adhere to reliable birth control methods during the study. Must not have a diagnosis of a pulmonary disorder other than asthma (e.g., chronic bronchitis, cystic fibrosis, bronchiectasis, HIV-related lymphocytic airway inflammation). Must not have a baseline FEV(1) of less than 70% predicted. Must not have respiratory tract infection or asthma exacerbation within 4 weeks of screening. Must not use theophylline, oral or inhaled corticosteroids, nedocromil sodium, cromolyn sodium, zilueton, leukotriene receptor antagonists (e.g., zafirlukast or montelukast), or anti-cholinergic agents within the prior 3 months. In addition, patients requiring ongoing therapy with anti-histamines, hydroxyzine, and tricyclic anti-depressants will be excluded. Research subjects can continue therapy with inhaled beta-agonists during the study. No history of anaphylaxis or severe allergic response. No history of adverse reactions to lidocaine or other local anesthetics. No history of active inhaled or intravenous drug abuse or alcohol abuse. Must not have an abnormal EKG or evidence of coronary artery disease. Must not require chronic anti-coagulant therapy. Must not use aspirin within 2 weeks of the bronchoscopic study or non-steroidal anti-inflammatory agents within 2 days of the bronchoscopic study. No history of cigarette smoking within the past 3 years. No history of allergy immunotherapy within the past year. Not allergic to methacholine. PT or PTT must not be prolonged 2 seconds greater than normal range. Platelet count must be greater than or equal to 150,000/mm(3). Must not test positive for human immunodeficiency virus. RESEARCH VOLUNTEERS: Must be between 18 and 65 years of age, male or female, and must be at least 5 feet in height. A negative inhaled methacholine challenge as defined by the absence of a decrease in FEV(1) by 20% (PC(20)) in response to inhalation of 25 mg/ml of methacholine. A negative skin test to a panel of common aeroallergens. Normal complete blood count, PT, PTT, and serum electrolytes, mineral and hepatic panels (less than 30 ml of blood will be drawn). Negative hepatitis serology. Normal EKG and chest radiograph without acute pulmonary infiltrates. Women of childbearing potential must have a negative pregnancy test within 2 weeks prior to study and willingness to adhere to reliable birth control methods during the study. No history of asthma, allergic rhinitis, or atopic dermatitis. Must not have a diagnosis of a pulmonary disorder other than asthma (e.g., chronic bronchitis, cystic fibrosis, bronchiectasis, HIV-related lymphocytic airway inflammation). Must not have a baseline FEV(1) of less than 70% predicted. Must not have respiratory tract infection or asthma exacerbation within 4 weeks of screening. Must not use theophylline, oral or inhaled corticosteroids, nedocromil sodium, cromolyn sodium, zilueton, leukotriene receptor antagonists (e.g., zafirlukast or montelukast), or anti-cholinergic agents within the prior 3 months. In addition, patients requiring ongoing therapy with anti-histamines, hydroxyzine, and tricyclic anti-depressants will be excluded. Research subjects can continue therapy with inhaled beta-agonists during the study. No history of anaphylaxis or severe allergic response. No history of adverse reactions to lidocaine or other local anesthetics. No history of active inhaled or intravenous drug abuse or alcohol abuse. Must not have an abnormal EKG or evidence of coronary artery disease. Must not require chronic anti-coagulant therapy. Must not use aspirin within 2 weeks of the bronchoscopic study or non-steroidal anti-inflammatory agents within 2 days of the bronchoscopic study. No history of cigarette smoking within the past 3 years. No history of allergy immunotherapy within the past year. Not allergic to methacholine. PT or PTT must not be prolonged 2 seconds greater than normal range. Platelet count must be greater than or equal to 150,000/mm(3). Must not test positive for human immunodeficiency virus.