Brief Summary
Asthma is a heterogeneous disorder in which multiple potential inflammatory pathways<br /> contribute to airway obstruction. The biological basis for airway inflammation is the subject<br /> of intensive investigation. This work is designed to identify airway factors that are<br /> responsible for recruiting cells and associate their airway presence with atopy and asthma.
Detailed Description
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.
Study Criteria
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.
