Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling

Background: Current treatment strategies for asthma in teenagers derive primarily from information on chronic disease in adults. More detailed understanding of risk factors related to teenage asthma might aid in the development of improved preventive and treatment strategies for this age group. Obje...

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Main Authors: Hollams, E., Deverell, M., Serralha, M., Suriyaarachchi, D., Parsons, F., Zhang, Guicheng, de Klerk, N., Holt, B., Ladyman, C., Sadowska, A., Rowe, J., Loh, R., Sly, P., Holt, P.
Format: Journal Article
Published: Mosby, Inc. 2009
Online Access:http://hdl.handle.net/20.500.11937/36477
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author Hollams, E.
Deverell, M.
Serralha, M.
Suriyaarachchi, D.
Parsons, F.
Zhang, Guicheng
de Klerk, N.
Holt, B.
Ladyman, C.
Sadowska, A.
Rowe, J.
Loh, R.
Sly, P.
Holt, P.
author_facet Hollams, E.
Deverell, M.
Serralha, M.
Suriyaarachchi, D.
Parsons, F.
Zhang, Guicheng
de Klerk, N.
Holt, B.
Ladyman, C.
Sadowska, A.
Rowe, J.
Loh, R.
Sly, P.
Holt, P.
author_sort Hollams, E.
building Curtin Institutional Repository
collection Online Access
description Background: Current treatment strategies for asthma in teenagers derive primarily from information on chronic disease in adults. More detailed understanding of risk factors related to teenage asthma might aid in the development of improved preventive and treatment strategies for this age group. Objective: We sought to identify biomarkers associated with asthma phenotypes in teenagers, particularly atopic asthma, and to identify markers that aid in discriminating between atopic subjects at high versus low risk of asthma. Methods: We studied 1380 unselected 14-year-olds and collected data on clinical history, allergic sensitization, and respiratory and immunoinflammatory function. The latter comprised measurements of circulating inflammatory markers and in vitro innate and adaptive immune functions, including house dust mite T-cell responses. We integrated the data into regression models to identify variables most strongly associated with asthma risk and severity among atopic subjects. Results: Eight hundred twenty-seven subjects were atopic, 140 subjects were asthmatic, and 81% of asthmatic subjects were also atopic. We identified asthma risk variables related to atopy intensity, including specific IgE and eosinophil levels, plus an additional series external to the TH2 cascade but that modified risk only in atopic subjects, including IFN-?, IL-10, and IL-12 responses and neutrophil numbers in blood. Moreover, bronchial hyperresponsiveness was associated strongly with atopic but not nonatopic asthma, and the bronchial hyperresponsiveness risk profile was itself dominated by atopy-associated variables. Conclusions: Asthma in teenagers is predominantly driven by atopy acting in concert with a second tier of TH2-independent immunoinflammatory mechanisms, which contribute to pathogenesis only against the background of pre-existing inhalant allergy. © 2009 American Academy of Allergy, Asthma & Immunology.
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spelling curtin-20.500.11937-364772017-09-13T15:28:50Z Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling Hollams, E. Deverell, M. Serralha, M. Suriyaarachchi, D. Parsons, F. Zhang, Guicheng de Klerk, N. Holt, B. Ladyman, C. Sadowska, A. Rowe, J. Loh, R. Sly, P. Holt, P. Background: Current treatment strategies for asthma in teenagers derive primarily from information on chronic disease in adults. More detailed understanding of risk factors related to teenage asthma might aid in the development of improved preventive and treatment strategies for this age group. Objective: We sought to identify biomarkers associated with asthma phenotypes in teenagers, particularly atopic asthma, and to identify markers that aid in discriminating between atopic subjects at high versus low risk of asthma. Methods: We studied 1380 unselected 14-year-olds and collected data on clinical history, allergic sensitization, and respiratory and immunoinflammatory function. The latter comprised measurements of circulating inflammatory markers and in vitro innate and adaptive immune functions, including house dust mite T-cell responses. We integrated the data into regression models to identify variables most strongly associated with asthma risk and severity among atopic subjects. Results: Eight hundred twenty-seven subjects were atopic, 140 subjects were asthmatic, and 81% of asthmatic subjects were also atopic. We identified asthma risk variables related to atopy intensity, including specific IgE and eosinophil levels, plus an additional series external to the TH2 cascade but that modified risk only in atopic subjects, including IFN-?, IL-10, and IL-12 responses and neutrophil numbers in blood. Moreover, bronchial hyperresponsiveness was associated strongly with atopic but not nonatopic asthma, and the bronchial hyperresponsiveness risk profile was itself dominated by atopy-associated variables. Conclusions: Asthma in teenagers is predominantly driven by atopy acting in concert with a second tier of TH2-independent immunoinflammatory mechanisms, which contribute to pathogenesis only against the background of pre-existing inhalant allergy. © 2009 American Academy of Allergy, Asthma & Immunology. 2009 Journal Article http://hdl.handle.net/20.500.11937/36477 10.1016/j.jaci.2009.06.019 Mosby, Inc. restricted
spellingShingle Hollams, E.
Deverell, M.
Serralha, M.
Suriyaarachchi, D.
Parsons, F.
Zhang, Guicheng
de Klerk, N.
Holt, B.
Ladyman, C.
Sadowska, A.
Rowe, J.
Loh, R.
Sly, P.
Holt, P.
Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
title Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
title_full Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
title_fullStr Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
title_full_unstemmed Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
title_short Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
title_sort elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling
url http://hdl.handle.net/20.500.11937/36477