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Stratification of asthma by lipidomic profiling of induced sputum supernatant

Brandsma, Joost (author)
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom
Schofield, James P.R. (author)
National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom; Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom
Yang, Xian (author)
Data Science Institute, Imperial College, London, United Kingdom
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Strazzeri, Fabio (author)
Mathematical Sciences, University of Southampton, Southampton, United Kingdom
Barber, Clair (author)
National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom
Goss, Victoria M. (author)
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom
Koster, Grielof (author)
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom
Bakke, Per S. (author)
Department of Clinical Science, University of Bergen, Bergen, Norway
Caruso, Massimo (author)
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Chanez, Pascal (author)
Department of Respiratory Diseases, Aix-Marseille University, Marseille, France
Dahlén, Sven-Erik (author)
Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
Fowler, Stephen J. (author)
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, United Kingdom; Manchester Academic Health Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
Horváth, Ildikó (author)
Department of Pulmonology, Semmelweis University, Budapest, Hungary
Krug, Norbert (author)
Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
Montuschi, Paolo (author)
Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy; National Heart and Lung Institute, Imperial College, London, United Kingdom
Sanak, Marek (author)
Department of Medicine, Jagiellonian University, Krakow, Poland
Sandström, Thomas, 1957- (author)
Umeå universitet,Institutionen för folkhälsa och klinisk medicin
Shaw, Dominick E. (author)
National Institute for Health Research Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom
Chung, Kian Fan (author)
National Heart and Lung Institute, Imperial College, London, United Kingdom
Singer, Florian (author)
Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Paediatrics and Adolescent Medicine, Division of Paediatric Pulmonology and Allergology, Medical University of Graz, Graz, Austria
Fleming, Louise J. (author)
National Heart and Lung Institute, Imperial College, London, United Kingdom
Adcock, Ian M. (author)
National Heart and Lung Institute, Imperial College, London, United Kingdom
Pandis, Ioannis (author)
Data Science Institute, Imperial College, London, United Kingdom
Bansal, Aruna T. (author)
Acclarogen Ltd, St John's Innovation Centre, Cambridge, United Kingdom
Corfield, Julie (author)
Areteva Ltd, Nottingham, United Kingdom
Sousa, Ana R. (author)
Respiratory Therapy Unit, GlaxoSmithKline, London, United Kingdom
Sterk, Peter J. (author)
Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
Sánchez-García, Rubén J. (author)
Mathematical Sciences, University of Southampton, Southampton, United Kingdom
Skipp, Paul J. (author)
Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom
Postle, Anthony D. (author)
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
Djukanović, Ratko (author)
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom
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 (creator_code:org_t)
Elsevier, 2023
2023
English.
In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 152:1, s. 117-125
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

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
epithelial lining fluid
extracellular vesicles
granulocytic inflammation
induced sputum
lipidomics
molecular phenotyping
pulmonary surfactant

Publication and Content Type

ref (subject category)
art (subject category)

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