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@article{Brandsma:2023:10.1016/j.jaci.2023.02.032,
author = {Brandsma, J and Schofield, JPR and Yang, X and Strazzeri, F and Barber, C and Goss, VM and Koster, G and Bakke, PS and Caruso, M and Chanez, P and Dahlén, S-E and Fowler, SJ and Horváth, I and Krug, N and Montuschi, P and Sanak, M and Sandström, T and Shaw, DE and Chung, KF and Singer, F and Fleming, LJ and Adcock, IM and Pandis, I and Bansal, AT and Corfield, J and Sousa, AR and Sterk, PJ and Sánchez-García, RJ and Skipp, PJ and Postle, AD and Djukanovi, R and U-BIOPRED, Study Group},
doi = {10.1016/j.jaci.2023.02.032},
journal = {Journal of Allergy and Clinical Immunology},
pages = {117--125},
title = {Stratification of asthma by lipidomic profiling of induced sputum supernatant},
url = {http://dx.doi.org/10.1016/j.jaci.2023.02.032},
volume = {152},
year = {2023}
}

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TY  - JOUR
AB  - 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: To perform 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 healthy controls. METHODS: Induced sputum supernatant was collected from 211 asthmatic adults and 41 healthy individuals enrolled in the U-BIOPRED study. Sputum lipidomes were characterised by semi-quantitative shotgun mass spectrometry, and clustered using topological data analysis to identify lipid phenotypes. RESULTS: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of nine molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthmatics and healthy controls, but within the asthmatic population as well. Matching clinical, pathobiological, proteomic and transcriptomic data informed on the underlying disease processes. Sputum lipid phenotypes with higher levels of non-endogenous, 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 asthmatics, 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. CLINICAL IMPLICATION: Immunomodulation of extracellular vesicle secretion in the lungs may provide a novel therapeutic target for severe asthma.
AU  - Brandsma,J
AU  - Schofield,JPR
AU  - Yang,X
AU  - Strazzeri,F
AU  - Barber,C
AU  - Goss,VM
AU  - Koster,G
AU  - Bakke,PS
AU  - Caruso,M
AU  - Chanez,P
AU  - Dahlén,S-E
AU  - Fowler,SJ
AU  - Horváth,I
AU  - Krug,N
AU  - Montuschi,P
AU  - Sanak,M
AU  - Sandström,T
AU  - Shaw,DE
AU  - Chung,KF
AU  - Singer,F
AU  - Fleming,LJ
AU  - Adcock,IM
AU  - Pandis,I
AU  - Bansal,AT
AU  - Corfield,J
AU  - Sousa,AR
AU  - Sterk,PJ
AU  - Sánchez-García,RJ
AU  - Skipp,PJ
AU  - Postle,AD
AU  - Djukanovi,R
AU  - U-BIOPRED,Study Group
DO  - 10.1016/j.jaci.2023.02.032
EP  - 125
PY  - 2023///
SN  - 0091-6749
SP  - 117
TI  - Stratification of asthma by lipidomic profiling of induced sputum supernatant
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2023.02.032
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36918039
UR  - https://www.sciencedirect.com/science/article/pii/S0091674923002932
UR  - http://hdl.handle.net/10044/1/102990
VL  - 152
ER  -

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