Immune Dysregulation in Children and Adults With Asthma
Information source: National Heart, Lung, and Blood Institute (NHLBI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma; Lung Diseases
Intervention: nedocromil budesonide (Drug)
Phase: N/A
Status: Completed
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI) Official(s) and/or principal investigator(s):
Mark Schuyler (Subproject PI), Affiliation: University of New Mexico
Summary
To immunize both normal and asthmatic subjects with a neoantigen, keyhole limpet hemocyanin
(KLH) and observe the type of antibody and T cell response that develops.
Clinical Details
Study design: Treatment, Placebo Control
Detailed description:
BACKGROUND:
Asthma is a result of a dysregulated immune response to inhaled antigens. The development of
an immune response dominated by T cells (Th2) that secrete interleukin 4 (IL-4) and IL-5
results in the constellation of findings associated with asthma, including elevated IgE and
increased blood eosinophilia. Epidemiological studies indicate that there are several
predisposing factors that may dictate whether asthma may develop in certain individuals
including genetic, environmental, and age-related factors. Any one factor alone may not
determine whether an inappropriate immune response develops with subsequent development of
asthma; rather, asthma likely results from a combination of factors. However, once a Th2
response in the lung has occurred, the hypothesis is that it dominates and results in the
development of Th2 response to inhaled neoantigens. Further, the acquired predisposition to a
Th2 response may override other preexisting predisposing factors and therefore becomes the
prime target for asthma therapy.
DESIGN NARRATIVE:
The study was a subproject in a Specialized Center of Research (SCOR) in Fibrotic Lung
Disease from 1997 through 2001. Both normal and asthmatic subjects were immunized with a
neoantigen, keyhole limpet hemocyanin (KLH), via intrapulmonary and subcutaneous routes and
observed for the type of antibody and T cell response that developed. Furthermore, the effect
of inhaled anti-inflammatory medications on primary immune responses to KLH was assessed.
Additional studies examined the effect of regional pulmonary Th2 responses on peripheral
blood asthma-associated effector cells, basophils and eosinophils. Finally, the investigators
determined whether chronic therapy of asthmatic children with either nedocromil or budesonide
modulated their immune response to a systemically administered neoantigen, hepatitis B
vaccine. These studies were designed to provide important information on the regulation of
immune responses in humans with asthma. Furthermore, they helped to determine whether
anti-inflammatory medications could inhibit development of a Th2 responses or only prevent
inflammatory events downstream from Th2 development.
The subproject had three specific aims. The first was to test the hypothesis that the lower
respiratory tracts of asthmatics would respond differently to a neo-antigen. In part A of
specific aim 1, the lower respiratory tracts of asthmatics were challenged with KLH.
Bronchoalveolar lavage (BAL) was repeated after 12 days and blood samples collected after a
number of time points. Immunoglobulins were measured in blood and BAL, and lymphocytes were
collected from the BAL and assayed for response to antigen in an in vitro test. In part B,
individuals were treated with six weeks of anti-inflammatory therapy after which responses to
intrapulmonary antigen were assessed.
Specific aim 2 assessed the role of acute challenge of the lung with antigen on eosinophil
and basophil responsiveness. The lung was challenged by intrapulmonary installation of
antigen through the bronchoscope and samples were collected from the peripheral blood at
various time points. An allergen challenge was performed after six weeks of therapy with
nedocromil budesonide or placebo.
In specific aim 3, asthmatic children were tested in two stages. In stage one, a preliminary
study was performed in children with relatively mild asthma who were immunized with hepatitis
vaccine. Samples were collected at various time points and assayed for antigen-specific
antibody. The hypothesis that asthmatic children would have a Th2 type response rather than
the Th1 type response in normal children was evaluated by determining times at which samples
could be collected from the larger Childhood Asthma Management Program (CAMP) study.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
No eligibility criteria
Locations and Contacts
Additional Information
Starting date: December 1996
Ending date: November 2001
Last updated: August 23, 2005
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