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Subtypes of eosinop...
Subtypes of eosinophilic asthma with discrete gene pathway phenotypes
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Perotin-Collard, Jeanne-Marie (author)
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Schofield, James Pr (author)
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Nicholas, Ben (author)
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Strazzeri, Fabio (author)
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Brandsma, Joost (author)
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Bansal, Aruna T. (author)
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Yang, Xian (author)
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Guo, Yi-Ke (author)
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Rowe, Anthony (author)
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Corfield, Julie (author)
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Wilson, Susan J. (author)
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Ward, Jonathan (author)
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Lutter, Rene (author)
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Shaw, Dominick E. (author)
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Bakke, Per S. (author)
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Caruso, Massimo (author)
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Dahlen, Sven -Erik (author)
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Fowler, Stephen J. (author)
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Horvath, Ildiko (author)
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Howarth, Peter (author)
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Krug, Norbert (author)
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Montuschi, Paolo (author)
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Sanak, Marek (author)
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- Sandström, Thomas, 1957- (author)
- Umeå universitet,Lungmedicin
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Sun, Kai (author)
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Pandis, Ioannis (author)
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Riley, John (author)
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Auffray, Charles (author)
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De Meulder, Bertrand (author)
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Lefaudeux, Diane (author)
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Sousa, Ana R. (author)
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Sterk, Peter J. (author)
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Adcock, Ian M. (author)
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Chung, Kian Fan (author)
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Skipp, Paul J. (author)
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Djukanovic, Ratko (author)
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(creator_code:org_t)
- European Respiratory Society Journals, 2019
- 2019
- English.
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In: European Respiratory Journal. - : European Respiratory Society Journals. - 0903-1936 .- 1399-3003. ; 54
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Background: Blood eosinophil counts ≥0.3x109/L are used to define Type-2, eosinophilic asthma. However, differential responses to T2 biologics of patients with eosinophilic asthma suggests that this may be a heterogeneous phenotype with subsets driven by different molecular mechanisms.Methods: Blood transcriptomic data, acquired from 99 severe asthmatics from the U-BIOPRED study (62% female, mean age 54 yr, 41% on oral steroids), were clustered by topological data analysis and cluster boundaries defined by the MORSE method. Gene pathway signatures were identified by Ingenuity Pathway Analysis.Results: Analysis revealed 3 clusters with different modulated gene pathways, i.e. molecular phenotypes. Subtype 1 had high IFN-γ, low IL5, low IL13 and low IL17 gene expression, with reduced glucocorticoid-induced gene expression. Subtype 2 had low IFNγ, high IL5, high IL13 and low IL17 gene expression. Subtype 3 had low IFNγ, high IL5, high IL13 and high IL17 gene expression. Pathway analysis suggested a strong steroid response in Subtypes 2 and 3. Clinically, the three clusters were not different in respect of age, gender, prevalence of atopy, blood or sputum eosinophil counts. Subtype 3 was characterized by high neutrophil counts in blood and bronchial epithelium, frequent sinus disease and asthma exacerbations, OCS treatment, low allergic sensitisation and low exhaled NO. Subtype 1 was characterized by high exhaled NO and more frequent IgE therapy.Conclusion: This study suggests that eosinophilic severe asthma (≥0.3x109/L) can be stratified further into 3 subtypes with distinct gene expression profiles that could be developed as molecular diagnostic biomarkers to guide treatment and thereby improve patient outcomes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- Asthma
- Adults
- Genomics
Publication and Content Type
- vet (subject category)
- art (subject category)
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- By the author/editor
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Perotin-Collard, ...
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Schofield, James ...
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Nicholas, Ben
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Strazzeri, Fabio
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Brandsma, Joost
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Bansal, Aruna T.
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show more...
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Yang, Xian
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Guo, Yi-Ke
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Rowe, Anthony
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Corfield, Julie
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Wilson, Susan J.
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Ward, Jonathan
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Lutter, Rene
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Shaw, Dominick E ...
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Bakke, Per S.
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Caruso, Massimo
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Dahlen, Sven -Er ...
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Fowler, Stephen ...
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Horvath, Ildiko
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Howarth, Peter
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Krug, Norbert
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Montuschi, Paolo
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Sanak, Marek
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Sandström, Thoma ...
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Sun, Kai
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Pandis, Ioannis
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Riley, John
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Auffray, Charles
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De Meulder, Bert ...
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Lefaudeux, Diane
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Sousa, Ana R.
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Sterk, Peter J.
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Adcock, Ian M.
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Chung, Kian Fan
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Skipp, Paul J.
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Djukanovic, Ratk ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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European Respira ...
- By the university
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Umeå University
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Karolinska Institutet