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SHR Neuro Cancer Cardio Lipid Metab Microb

Brandsma, J; Schofield, JPR; Yang, X; Strazzeri, F; Barber, C; Goss, VM; Koster, G; Bakke, PS; Caruso, M; Chanez, P; Dahlén, SE; Fowler, SJ; Horváth, I; Krug, N; Montuschi, P; Sanak, M; Sandström, T; Shaw, DE; Chung, KF; Singer, F; Fleming, LJ; Adcock, IM; Pandis, I; Bansal, AT; Corfield, J; Sousa, AR; Sterk, PJ; Sánchez-García, RJ; Skipp, PJ; Postle, AD; Djukanović, R, , U-BIOPRED, Study, Group.
Stratification of asthma by lipidomic profiling of induced sputum supernatant.
J Allergy Clin Immunol. 2023; 152(1):117-125 Doi: 10.1016/j.jaci.2023.02.032
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Co-authors Med Uni Graz
Singer Florian
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Abstract:
BACKGROUND: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features. OBJECTIVE: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls. METHODS: Induced sputum supernatant was collected from 211 adults with asthma and 41 healthy individuals enrolled onto the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study. Sputum lipidomes were characterized by semiquantitative shotgun mass spectrometry and clustered using topologic data analysis to identify lipid phenotypes. RESULTS: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of 9 molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthma patients and healthy controls, but also within the asthma patient population. Matching clinical, pathobiologic, proteomic, and transcriptomic data helped inform the underlying disease processes. Sputum lipid phenotypes with higher levels of nonendogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts. CONCLUSION: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthma patients resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator.
Find related publications in this database (using NLM MeSH Indexing)
Humans - administration & dosage
Sputum - metabolism
Lipidomics - administration & dosage
Proteomics - methods
Cross-Sectional Studies - administration & dosage
Prospective Studies - administration & dosage
Asthma - administration & dosage
Lipids - administration & dosage

Find related publications in this database (Keywords)
Asthma
induced sputum
epithelial lining fluid
pulmo-nary surfactant
lipidomics
molecular phenotyping
extracellular vesicles
granulocytic inflammation
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