Grantee Research Project Results

Final Report: Inhalation of Particulate Matter Alters the Allergic Airway Response to Inhaled Allergen

EPA Grant Number: R825702C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R825702
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children
Center Director: Schwartz, David A.
Title: Inhalation of Particulate Matter Alters the Allergic Airway Response to Inhaled Allergen
Investigators: Gelfand, Erwin
Institution: National Jewish Medical and Research Center
EPA Project Officer: Chung, Serena
Project Period: February 16, 1998 through February 28, 2003 (Extended to February 28, 2004)
RFA: Environmental Lung Disease Center (National Jewish Medical and Research Center) (1998) RFA Text |  Recipients Lists
Research Category: Targeted Research

Objective:

The objectives of this research project were to: (1) demonstrate the adjuvant effects of diesel exposure in ovalbumin-sensitized mice in the development of airway hyperresponsiveness (AHR); and (2) characterize the dose-response relationship of diesel exhaust particles (DEP) to pulmonary antigen presenting cell function.

Summary/Accomplishments (Outputs/Outcomes):

There has been a general assumption that allergic diseases and asthma in particular have increased in parallel to urbanization. Of increasing concern was that particulate matter exposure was a culprit in this association. Diesel exhaust, a complex mixture of gases, vapors, and soot, was said to elicit a pulmonary inflammatory response. The toxicity of DEP has been attributed to the particulate fraction with little toxicity exhibited by the gaseous fraction; toxicity of DEP could be attributed to the core carbonaceous particles. Carbon black (CB) can serve as a surrogate for the elemental carbon matrix of diesel exhaust soot.

The influence of DEP on asthma in humans or in experimental animals has been studied extensively but the results are inconsistent. Careful scrutiny of the published literature showed at best minor enhancement of airway inflammation and airway eosinophilia and limited changes in airway responsiveness to inhaled methacholine. Only increases in allergen-specific IgE appeared to be consistent.

In our studies, we utilized a standard preparation of diesel exhaust soot obtained from the National Institutes of Standards and Technology or CB. Despite repeated attempts to induce increases in airway inflammation and AHR and enhanced responses to allergen exposure, we were unable to reliably and consistently alter responses in a significant way despite many protocol manipulations and even obtaining material from others that reported small changes. This was clearly not a problem in delivering or accessing the lungs, as histochemical analysis revealed that airway macrophages were laden with black particles. Our only conclusion (which is currently being written up for publication) is that DEP and CB are poor inducers of lung airway inflammation, AHR, or enhancers of the response to allergen sensitization and challenge.

For these reasons, we modified our approach to study the effects of ozone.

Supplemental Keywords:

air toxics, acute lung injury, air pollutants, airway disease, animal studies, environmental toxicant, exposure, genetic susceptibility, health effects, human exposure, human health risk, lung disease, lung epithelial cells, occupational disease, occupational exposure,, Health, RFA, Air, Scientific Discipline, Health Risk Assessment, Risk Assessments, particulate matter, mobile sources, Environmental Chemistry, Epidemiology, Allergens/Asthma, Biochemistry, diesel exhaust, inhalability, inhaled, vehicle emissions, vehicular exhaust, cytokines, emissions, pulmonary disease, airway inflammation, carbon, diesel, human exposure, immune response, lung inflammation, respiratory, motor vehicle emissions, lung, pulmonary, particulate exposure, environmental health effects, engines, exposure, particulates, PM, allergens, motor vehicles, airborne pollutants, allergic response, air pollution, human health effects, human health risk, air toxics, automobiles, automotive exhaust, carbon black, inhalation

Relevant Websites:

http://www.nationaljewish.org/patient-info/progs/med/environmental/index.aspx Exit

Progress and Final Reports:

Original Abstract

1998

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2002

2003

Main Center Abstract and Reports:

R825702    Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R825702C001 SP-A and SP-D in Environmental Lung Disease
R825702C003 Adaptation to Nitrogen Dioxide: Role of Altered Glycolytic Pathway Enzyme Expression and NF-κB-Dependent Cellular Defenses Against Apoptosis
R825702C005 Inhalation of Particulate Matter Alters the Allergic Airway Response to Inhaled Allergen
R825702C006 Particle-Induced Lung Inflammation and Extracellular EC-SOD
R825702C007 Indoor-Outdoor Relationships of Airborne Particle Count and Endotoxin Concentrations
R825702C008 The Role of Mitochondrial DNA Mutations in Oxidant-Mediated Lung Injury
R825702C009 Immunopathogenesis of Hypersensitivity Pneumonitis in the Mouse
R825702C010 Activation of Natural T Lymphocytes by Diesel Exhaust Particulates Leads to Their Production of Interleukin-4 and TH2 Lymphocyte Differentiation to Allergen
R825702C011 Latex Antigen Levels During Powdered and Powderless Glove Use
R825702C012 Adjuvant Effects of Ozone in a Model of Allergen-Induced Airway Inflammation and Hyperresponsiveness
R825702C013 Acute Exposure to Particulate Air Pollution in Childhood Asthma
R825702C014 Mechanisms of Ozone Toxicity to the Lung