The Genetics of Environmental Asthma

NCT00018096 | Completed

• 2 other identifiers: NCRR-M01RR00030-01832357
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

In this project, we hypothesize that polymorphisms of genes expressed by the airway epithelia in asthmatics following specific airway challenges predispose individuals to the development of asthma. To test this hypothesis, we identify the genes that are differentially expressed by airway epithelial cells following challenge with stimuli that induce acquired (house dust mite) or innate (LPS) immune responses, and then determine whether polymorphisms in these genes are associated with the development of asthma in a separate, well characterized, familial cohort of asthmatics. This is a powerful approach that is designed to identify novel genes that are associated with both asthma pathogenesis (differentially expressed in the exposure-response study) and asthma susceptibility (genetically associated with asthma in a linkage/association study).

Conditions

Asthma

Keywords

Genetics; Lipopolysaccharide

Outcome Measures

Primary Outcomes (1)

• BAL and endobronchial brush biopsy are measured and cell samples are analyzed to identify the genes in airway epithelia and inflammatory cells that are differentially expressed in response to LPS and dust mite antigen.RNA is isolated for gene expression.

  4 hours post first instillation bronchoscopy

Secondary Outcomes (1)

• post bronchoscopy symptom followup

  48 hours

Study Arms (1)

bronchoscopy

EXPERIMENTAL

2 bronchoscopies 4 hours apart; The first to instill the 3 experimental biologic agents in separate airways (HDM, LPS and saline-placebo), the second to perform BAL and brush biopsies 4 hours later in the same airways.

Biological: LPS endotoxin, saline, HDM

Interventions

LPS endotoxin, saline, HDM BIOLOGICAL

instillation of interventional products during bronchoscopy each down a different airway, each subject acts as their own control.

Also known as: CCRE lipopolysaccharide endotoxin E.Coli O:113,Lot# 67801, House dust mite allergen (D.farinae) Greer Lab Lot #22574

bronchoscopy

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Atopic/asthmatic, atopic/non-asthmatic, non-atopic/asthmatic, or non-atopic/non-asthmatic
• Asthma subjects will be required to have either mild or moderate persistent asthma; positive methacholine challenge
• Atopic subjects should have seasonal allergy symptoms requiring medication and have positive skin test to house dust mite and at least 3 additional allergens. Serum IgE level \>100.
• Willing/able to give informed consent \& adhere to visit/protocol schedules.
• Screening visit laboratory, C-Xray, EKG, results within normal limits
• Women of childbearing potential must have a negative serum pregnancy test
• Screening Pulmonary Function testing above study criteria parameters

You may not qualify if:

• Systemic corticosteroid administration for asthma within the previous 90days
• Antibiotic administration within the previous 30 days.
• Viral respiratory infection within the previous 14 days.
• History of severe asthma requiring intubation.
• Occupational exposure to hay or grain dust.
• Significant exposure history to cigarette smoke
• Past or present history of allergen immunotherapy
• Underlying illnesses that may result in altered lung function
• Students or employees under direct supervision by protocol investigators are ineligible
• Subjects allergic to medications used (or potentially used) in the study will be excluded.
• Subjects using aspirin will be excluded
• Subjects who abuse alcohol or illicit substances will be excluded
• Medication use other than for asthma, allergies or contraception
• Other medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
• Nursing mothers

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

Sodium Chloride; Antigens, Dermatophagoides

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Antigens; Biological Factors

Study Officials

• Sundy S. Sundy, MD. PhD.

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 2, 2001
• First Posted: July 4, 2001
• Study Start: June 1, 2001
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: May 6, 2008

Record last verified: 2008-05

Locations

US (1)