A Model of Human Asthma Exacerbation Identifies Mechanisms That Drive Allergic Asthma

In this study, we will enroll allergic adults to undergo bronchoscopic segmental allergen challenge, in order to identify differences in the airway immune response to allergen in those with asthma compared to those without asthma. After a discussion about the study and potential risks, subjects giving written informed consent will undergo two bronchoscopies. During the first procedure, samples will be collected from the left lung and allergen will be administered to a small segment of the right lung. The second procedure will be performed 24 hours later, with collection of samples from the allergen-challenged lung segment.]]>
Allergic Asthmatics (AA) A: Inclusion Criteria: Baseline forced expiratory volume in 1 second (FEV1) determined at the initial visit no less than 75% of the predicted value after bronchodilator administration. Clinical history of allergic symptoms to cat or dust mite allergen and demonstrated skin reactivity (a positive allergen skin prick test). Positive methacholine challenge, defined as a provocative concentration inducing a 20% reduction in FEV1 (PC20) <16 mg/ml. Life-long absence of cigarette smoking (defined as a lifetime total of less than 5 pack-year or none within 5 years). Willing and able to give informed consent. Expressed the desire to participate in an interview with the principal investigator. Age between 18 and 50 years.B: Exclusion Criteria:Women of childbearing potential who are documented to be pregnant (based on urine beta-HCG testing), sexually active and not using contraception, seeking to become pregnant, or breast feeding. Spontaneous asthmatic episode or clinical evidence of upper respiratory tract infection within the previous 6 weeks. Participation in a research study involving a drug or biologic during the 30 days prior to the study. Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam. Antihistamines within 7 days of the screening visit. Presence of diabetes mellitus, congestive heart failure, ventricular arrhythmias, history of a cerebrovascular accident, renal failure, history of anaphylaxis, or cirrhosis. Use of systemic steroids, increased use of inhaled steroids, beta blockers or monoamine oxidase inhibitors within 6 weeks of the initial visit. Antibiotic use for respiratory disease within 1 month of the initial visit or a respiratory tract infection within 6 weeks of the bronchoscopy visits. A history of asthma-related respiratory failure requiring intubation. Quantitative skin-prick test positive reaction down to an allergen concentration of 0.056 BAU or AU/ml. Participants with a high possibility of poor compliance with the study. Cigarette smoking within the past 5 years or >= 5 pack-year in total. Having second-hand cigarette smoke exposure or indoor furry pets except in the case of dog, if the subject is not allergic to the dog and the subject has a negative skin test to dog. Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection. Use of targeted biological therapy for asthma or allergic disorders including but not limited to benralizumab, dupilumab, mepolizumab, omalizumab, or reslizumab currently or within the last year. Immunotherapy with cat or dust mite extract now or in the past. Non-English speakers. History of coagulopathy, thrombocytopenia, pulmonary hypertension, and/or use of anti-coagulants/anti-platelet drugs. Allergic Non-asthmatic Controls (AC) C: Inclusion Criteria: History of either (a) allergic rhinitis (with one or more of the following symptoms: nasal congestion, sneezing, runny nose, postnasal drainage), (b) allergic conjunctivitis (ocular itching, tearing and/or swelling) or (c) contact allergy associated with cat dander or dust mite and a positive allergy test to the same allergen. Baseline FEV1 and forced vital capacity (FVC) determined at the initial visit no less than 80% of the predicted value. Positive allergy skin prick test to cat dander or dust mite allergen. Life-long absence of cigarette smoking (defined as a lifetime total of less than 5 pack-year or none within 5 years). Willing and able to give informed consent. Expressed the desire to participate in an interview with the principal investigator. Age between 18 and 50 years. D. Exclusion Criteria: A history of asthma. Exclusion criteria #1, 3-8, and 10-18 from B. Exclusion Criteria (see above). Positive methacholine challenge (PC20 <16 mg/ml). Healthy Controls (HC) E. Inclusion Criteria: No history of allergy and negative allergen skin prick testing. Inclusion criteria #2, and 4-7 from C: Inclusion Criteria (see above). F. Exclusion Criteria: Exclusion criteria #1-3 from D. Exclusion Criteria (see above). ]]>