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- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Rota, M, et al.
(författare)
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Erratum
- 2020
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Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 146:11, s. E6-E6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Perotin-Collard, Jeanne-Marie, et al.
(författare)
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Subtypes of eosinophilic asthma with discrete gene pathway phenotypes
- 2019
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Ingår i: European Respiratory Journal. - : European Respiratory Society Journals. - 0903-1936 .- 1399-3003. ; 54
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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