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Subtypes of eosinophilic asthma with discrete gene pathway phenotypes
Visa övriga samt affilieringar
2019 (Engelska)Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 54Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
European Respiratory Society Journals , 2019. Vol. 54
Nyckelord [en]
Asthma, Adults, Genomics
Nationell ämneskategori
Lungmedicin och allergi
Identifikatorer
URN: urn:nbn:se:umu:diva-168238DOI: 10.1183/13993003.congress-2019.OA467ISI: 000507372400332OAI: oai:DiVA.org:umu-168238DiVA, id: diva2:1394521
Konferens
European-Respiratory-Society (ERS) International Congress, Madrid, Spain, Sep 28-Oct 02, 2019.
Anmärkning

Supplement: 63. Meeting Abstract: OA467.

Tillgänglig från: 2020-02-19 Skapad: 2020-02-19 Senast uppdaterad: 2020-02-19Bibliografiskt granskad

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Sandström, Thomas

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