You are here:
Aptopic asthmatic subjects but not aptopic subjects without asthma have enhanced inflammatory response to ozone**
Citation:
Hernandez, M., J. Lay, B. Harris, C. Esther, W. Brickey, P. Bromberg, R. Devlin, D. Diaz-Sanchez, N. Alexis, AND D. Peden. Aptopic asthmatic subjects but not aptopic subjects without asthma have enhanced inflammatory response to ozone**. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. Journal of Allergy Clinical Immunology, 126(3):537-44, (2010).
Impact/Purpose:
This manuscript was orginally approved via paper file EPHD-12-054 and entered into the Science Inventory
Description:
Background Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone (03) causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of 03-induced inflammation has not been determined. Objective To determine if atopic status modulates 03 response phenotypes in humans. Methods Fifty volunteers (25 normal volunteers, 14 atopic non-asthmatics, 11 atopic asthmatics not requiring maintenance therapy) underwent a 0.4 ppm 03 exposure protocol. Ozone response was determined by changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell surface markers, cytokine and hyaluronic acid concentration. Results All cohorts experienced similar decreases in lung function post 03. Atopics and atopic asthmatics had increased sputum neutrophils and IL-B after 03 exposure; levels did not significantly change in normal volunteers. Following 03 exposure, atopic asthmatics had significantly increased sputum IL-6 and IL-1 ~, and airway macrophage TLR4, FceRI, and CD23 expression; levels in normal volunteers and atopic non-asthmatics showed no significant change. Atopic asthmatics had significantly decreased IL-10 at baseline compared to normal volunteers: IL-10 did not significantly change in any group with 03. All groups had similar levels of hyaluronic acid at baseline, with increased levels after 03 exposure in atopies and atopic asthmatics. Conclusion Atopic asthmatics have increased airway inflammatory responses to 03. Elevated TLR4 expression suggests a potential pathway through which 03 generates the inflammatory response in allergic asthmatics but not in atopies without asthma. Clinical Implications These observations suggest that mild atopic asthma confers increased risk for exacerbation of 03-induced lung disease through promoting an enhanced innate immune inflammatory response to 03.