Clinical trial NCT00595491: Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Official title: Inflammatory Cellular Trafficking in Asthma in Response to Segmental Allergen Challenge
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Asthma
Keywords: Asthma
Inflammation
Allergic
Airway
Challenge
Chemokines
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: U.S. Army Medical Research and Development Command
First posted: 2008-01-16
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: airway inflammation
timeFrame: 1,6, or 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Benjamin D Medoff, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in asthmatics. Am Rev Respir Dis. 1985 Jul;132(1):180-2. doi: 10.1164/arrd.1985.132.1.180.
citation: Busse WW, Lemanske RF Jr. Asthma. N Engl J Med. 2001 Feb 1;344(5):350-62. doi: 10.1056/NEJM200102013440507. No abstract available.
citation: Djukanovic R, Wilson JW, Lai CK, Holgate ST, Howarth PH. The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma. Am Rev Respir Dis. 1991 Apr;143(4 Pt 1):772-7. doi: 10.1164/ajrccm/143.4_Pt_1.772.
citation: Jarjour NN, Peters SP, Djukanovic R, Calhoun WJ. Investigative use of bronchoscopy in asthma. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):692-7. doi: 10.1164/ajrccm.157.3.9705020.
citation: Kay AB. Allergy and allergic diseases. Second of two parts. N Engl J Med. 2001 Jan 11;344(2):109-13. doi: 10.1056/NEJM200101113440206. No abstract available.
citation: Mackay CR. Chemokines: immunology's high impact factors. Nat Immunol. 2001 Feb;2(2):95-101. doi: 10.1038/84298.