Lung-Resident Memory Th2 Cells in Asthma

Prior treatment

• The presence of spontaneous asthmatic exacerbation or clinical evidence of upper respiratory tract infection within the previous 6 weeks and not requiring a change in daily inhaled corticosteroids (ICS) in the past 4 weeks.
• Participation in a research study involving a drug or biologic agent during the 30 days prior to the study.
• Use of systemic steroids, increased use of inhaled steroids, beta blockers and MAO inhibitors or a visit for an asthma exacerbation within 1 month of the screening visit.
• Taking beta-adrenergic blocking agents or monoamine oxidase inhibitors.
• Use of Xolair (omalizumab - anti-IgE monoclonal antibody) within 6 months.
• Immunotherapy with cat, dog, or dust mite extract now or in the past 10 years

Other illness

• Presence of diabetes mellitus, congestive heart failure, ventricular arrhythmias, history of a cerebrovascular accident, renal failure, history of anaphylaxis or cirrhosis.
• Antibiotic use for respiratory disease within 1 month of the characterization visit or a respiratory tract infection within 6 weeks of the bronchoscopy visits.
• A history of asthma-related respiratory failure requiring intubation.
• No history of cigarette smoking within the past 5 years or \> 5 pack years total.
• No indoor animal or second-hand cigarette smoke exposure. (It is also preferred but not required that dust mite allergic subjects have dust mite-proof encasings on their mattress and pillows.)
• Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection.
• A history of allergy, asthma, nasal or sinus disease.
• Exclusion criteria #1, 3-8 and 10-17 as indicated above for mild to moderate allergic asthma.

Age

• Use of other biologics for treatment of asthma or other medical condition, such as Nucala (mepolizumab, anti-IL-5 monoclonal antibody), Cinqair (reslizumab, anti-IL-5 monoclonal antibody), Fasenra (benralizumab, anti-IL-5 receptor monoclonal antibody), Dupixent (dupilumab, anti-IL-4 receptor-alpha monoclonal antibody), or other immunomodulatory biologics within 6 months.
  • Healthy Control (HC) Subjects HC subjects will be individuals who are in good overall health, age and sex matched to the asthmatic group, age 18 - 55 and nonallergic, i.e. entirely negative on a panel of prick skin tests that includes trees, grasses, weeds, cat, dog, dust mites, cockroach and molds, with no history of allergic rhinitis or asthma, no history of allergic symptoms caused by cats, dogs, or dust mite allergen exposure, life-long nonsmokers of cigarettes (defined as a lifetime total of \< 5 packyears and none in 5 years), normal spirometry (i.e. FEV1 and FVC of at least 90% of predicted) and with a negative methacholine challenge test (PC20 of \> 25 mg/ml).

Other

• Women of childbearing potential who are pregnant (based on urine beta-HCG testing), are sexually active and not using contraception, are seeking to become pregnant or who are nursing.
• Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.
• Antihistamines within 7 days of the screening visit.
• Subjects with a high possibility of poor compliance with the study.

• All subjects will have a baseline FEV1 no less than 75% of the predicted value.
• All subjects will have a clinical history of allergic symptoms to an indoor allergen present in their home environment, either cat, dog or dust mite allergen, and confirmed skin reactivity (a positive allergen prick test) to the same allergen. The investigators will recruit both:
  • subjects with mild intermittent or mild persistent asthma (consistent with NAEP Step 1 or Step 2 treatment options) who are not taking regular daily inhaled corticosteroids (ICS), and
  • subjects with moderate persistent asthma (consistent with NAEP Step 3 treatment options) who are taking regular daily inhaled corticosteroids (ICS). In this subgroup, the maximum allowable daily ICS dose will be 220 MCG twice daily of fluticasone or equivalent ICS at screening.
• Life-long absence of cigarette smoking (lifetime total of \< 5 pack-years and none in 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 55 years.
• All subjects will have a positive methacholine challenge with a PC20 \< 16 mg/ml.

Criteria the registry did not label

• Mild to moderate allergic asthma (AA) subjects