Atopic asthmatic subjects but not atopic subjects without asthma have enhanced inflammatory response to ozone

Center for Environmental Medicine Asthma and Lung Biology, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, NC 27599-7310, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 09/2010; 126(3):537-44.e1. DOI: 10.1016/j.jaci.2010.06.043
Source: PubMed


Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined.
We sought to determine whether atopic status modulates ozone response phenotypes in human subjects.
Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations.
All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significantly change in any group with ozone. All groups had similar levels of hyaluronic acid at baseline, with increased levels after ozone exposure in atopic and atopic asthmatic subjects.
Atopic asthmatic subjects have increased airway inflammatory responses to ozone. Increased Toll-like receptor 4 expression suggests a potential pathway through which ozone generates the inflammatory response in allergic asthmatic subjects but not in atopic subjects without asthma.

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Available from: David Diaz-Sanchez, Feb 18, 2014
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    • "Endogenous and xenobiotic metabolites (mostly of drugs) were studied. Clinical (Brown et al. 2008; Hernandez et al. 2010) and epidemiological (Jia et al. 2011; Wood et al. 2010) studies of acute and chronic effects of ambient air exposures have long had important roles in quantifying human variability in the risks of exposures to widespread toxicants such as ozone and airborne particulates. The addition of GWAS to these established tools has the potential to widen the capability for quantification of effects on susceptibility of many individual genotypic variants that individually have rela­ tively modest effects (Holloway et al. 2012). "
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