Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma is a heterogeneous disorder in which multiple potential inflammatory pathways
 contribute to airway obstruction. The biological basis for airway inflammation is the subject
 of intensive investigation. This work is designed to identify airway factors that are
 responsible for recruiting cells and associate their airway presence with atopy and asthma.
The production of chemotactic cytokines or chemokines by the airways is one of the mechanisms
 thought to be responsible for the recruitment of inflammatory cells to the airways (Makay
 2001). While the chemokine receptor-ligand systems responsible for immune cell homing to the
 mucosal surface of the gastrointestinal tract have been clarified, those responsible for
 allergic airway inflammation remain unknown. This work is designed to identify airway factors
 that are responsible for recruiting cells and associate their airway presence with atopy and
 asthma.
A. Subjects with Allergic Asthma (AA subjects)

 Inclusion Criteria:

 1. All subjects will have a baseline FEV1 determined at the characterization visit that
 is no less than 75 % of the predicted value.

 2. All subjects will have a clinical history of allergic symptoms to cat or dust mite
 allergen and demonstrated skin reactivity (a positive allergen prick test).

 3. Life-long absence of cigarette smoking (defined as a lifetime total of less than 5
 pack-years); none in 5 years).

 4. Willing and able to give informed consent.

 5. Expressed the desire to participate in an interview with the principal investigator.

 6. Age between 18 and 50 years.

 Exclusion Criteria:

 1. Women of childbearing potential who are documented to be pregnant (based on Urine
 beta-HCG testing), are sexually active and not using contraception, are seeking to
 become pregnant, or who are nursing.

 2. The presence of spontaneous asthmatic episode or clinical evidence of upper
 respiratory tract infection within the previous 6 weeks.

 3. Participation in research study involving a drug or biologic during the 30 days prior
 to the study.

 4. Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.

 5. Antihistamines within 7 days of the screening visit.

 6. Presence of diabetes mellitus, congestive heart failure, ventricular arrhythmias,
 history of a cerebrovascular accident, renal failure, history of anaphylaxis, or
 cirrhosis.

 7. 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.

 8. Antibiotic use for respiratory disease within 1 month of the characterization visit or
 a respiratory tract infection within 6 weeks of the bronchoscopy visits.

 9. A history of asthma-related respiratory failure requiring intubation.

 10. Quantitative skin-prick test positive reaction down to an allergen concentration of
 0.056 BAU or AU/ml .

 11. Taking beta-adrenergic blocking agents or monoamine oxidase inhibitors.

 12. Subjects with a high possibility of poor compliance with the study.

 13. No history of cigarette smoking within the past 5 years or > 10 pack years total.

 14. 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 (It is also preferred but not required that dust mite allergic subjects
 have dust mite-proof encasings on their mattress and pillows.)

 15. Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection.

 16. Use of Xolair (omalizumab - anti-IgE monoclonal antibody) for 6 months.

 17. Immunotherapy with cat or dust mite extract now or in the past.

 18. Non-English speakers.

 19. History of coagulopathy, thrombocytopenia, pulmonary hypertension, and/or use of
 anti-coagulants/anti-platelet drugs.

 B. Healthy Normal Control Subjects (NC subjects)

 Normal control subjects will be individuals who are in good overall health, age and sex
 matched to the asthmatic group, age 18 - 50 and nonallergic, i.e. entirely negative on the
 panel of prick skin tests listed in section V (Study Procedures), with no history of
 allergic rhinitis or asthma, no history of allergic symptoms caused by cats or dust mite
 allergen exposure, life-long nonsmokers of cigarettes (defined as a lifetime total of less
 than 5 pack-years and none in 5 years), normal spirometry (i.e. FEV1 and FVC of at least
 90% of predicted) and with a methacholine PC20 of > 16 mg/ml.

 Exclusion Criteria:

 1. A history of allergy, asthma, nasal or sinus disease.

 2. Exclusion criteria #1, 3-8 and 10-19 from (A.) above.

 C. Allergic Nonasthmatic Subjects (ANA subjects)

 Inclusion Criteria:

 1. ANA subjects will have a 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.

 2. All subjects will have a baseline FEV1 and FVC determined at the characterization
 visit that is no less than 90 % of the predicted value.

 3. All subjects will have a positive allergy skin prick test to cat dander or dust mite
 allergen.

 4. All subjects will be in good general health.

 5. Life-long absence of cigarette smoking (defined as a lifetime total of less than 5
 pack-years and none in 5 years).

 6. Willing and able to give informed consent.

 7. Expressed the desire to participate in an interview with the principal investigator.

 8. Age between 18 and 50 years.

 Exclusion Criteria:

 1. A history of asthma.

 2. Exclusion criteria #1, 3-8 and 10-19 from (A.) above.

 3. A methacholine PC20 < 16 mg/ml.