Immunologic Mechanism of Allergen Immunotherapy

Fecha de inicio: 1 de julio de 1999

INCLUSION CRITERIA: Age 18-50 years. History of asthma for one year or greater. Asthma symptoms (wheezing, chest tightness, shortness of breath) on exposure to allergen (by history or challenge). 10-20 mm erythema and/or 5 mm wheal response to one or more panel allergens via prick testing. Screening forced expiratory volume (FEV(1)) or the ratio of FEV(1) to forced vial capacity (FEV(1)/FVC) must be equal to or greater than 70% of the predicted value for age and sex. Frequency of IL-4 producing allergen specific CD4 T cells must be greater than or equal to 0.01% at time of screening. Baseline values within the following laboratory ranges: White blood cell count greater than or equal to 3,300 and less than 10,500 cells/L; Absolute neutrophil count greater than or equal to 1,500 cells/microliter; Hemoglobin greater than or equal to 12 g/dL; Platelet count greater than or equal to 100,000/microliter; Serum creatinine less than 1.7 mg/dL; Total bilirubin less than 1.5 mg/dL; AST, ALT less than 50 U/L; Urinalysis within normal limits. Written informed consent Women of childbearing potential must agree to use adequate contraception (diaphragm with spermicide, condom with spermicide, intrauterine device (IUD), birth control pills or Norplant) for the duration of the study. EXCLUSION CRITERIA: Asthma that requires more than twice weekly administration of short acting inhaled Beta-agonist bronchodilator. Long acting Beta-agonists such as Salmeterol may be used twice daily. Systemic Corticosteroids (other than physiologic replacement doses) within 3 months of study Beta-blockers (systemic or ophthalmic), doxepin, phenothiazines, tricyclic antidepressant, or immunosuppressive (e.g., methotrexate) therapy within one month of study drug administration System H1 antihistamine use within 1 week of baseline allergen skin testing Use of any investigational drug within 1 month of study History of angina or cardiac arrhythmias requiring drug or devices intervention Clinically significant electrocardiographic (ECG) abnormalities Pregnancy or nursing (at screening or during course of study) Anaphylaxis with hypotension after allergen exposure in the past 10 years Systemic allergic desensitization therapy within two (2) years prior to study entry Rheumatologic or autoimmune disease requiring greater than 1 month of drug therapy in the last 5 years Diabetes HIV seropositivity Screening BP greater than 90 mm Hg diastolic or 160 mm Hg systolic Any other major illness or condition that, in the opinion of the principal investigator, may interfere with the patient's ability to comply with the conditions or substantially increase the risk associated with the patient's participation in this study. Upper respiratory infection affecting the subject's asthma in the 2 weeks prior to study drug. Increase in asthma symptoms of more than 2 additional episodes per week in the 2 weeks prior to study drug. Consistent alcohol use of more than 2 drinks a day in the past 6 months. 1 drink = 8 oz. Wine, 16 oz. beer, 2 oz. liquor.