Asthma Clinical Trial
To investigate whether isocyanate-induced asthma is dependent on isocyanate antigen-driven T-cell mediated, airway inflammation.
BACKGROUND:
Isocyanates are a group of highly reactive widely used low-molecular weight chemicals, and
are the most commonly reported cause of occupation asthma in developed countries. Yet, the
mechanisms by which isocyanates cause asthma are not well defined.
DESIGN NARRATIVE:
The study investigates isocyanate antigen-driven T-cell responses in vitro-, following in
vivo exposure using patient samples acquired through collaboration with ongoing field
epidemiological and clinical studies. The study compares isocyanate antigen-reactive T-cells
from primary exposure sites (skin/lung) with those from blood, to evaluate potential routes
of sensitization and identify diagnostic indicators of isocyanate
sensitivity/susceptibility. Specifically, the study : generates and characterizes
hexamethylene diisocyanate (HDI) antigens including isocyanate metabolites, and isocyanate
conjugated t normal human and foreign proteins; evaluates the T-cell antigenicity of the HDI
antigens, based on blood and lung lymphocyte proliferation, cytokine production, and
phenotype in order to identify the molecular form of HDI that initiates airway cytokine
production in asthma patients; establishes T-cell lines from the skin, lung and peripheral
blood of HDI asthma patients and characterizes the phenotype, antigen specificity, cytokine
production and TCR expression of isocyanate responsive T-cells in these different
compartments; compares isocyanate responsive of T-cells found in the skin, lung and blood
and correlates with clinical sensitivity to determine characteristics associated with
exposure and sensitization leading to clinical asthma.
The study was renewed in FY 2002 to extend follow-up and analysis through March 2007.
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