Ibrahim, M.I.A.

English

Asthma is a heterogeneous disease that presents with multiple clinical manifestations (phenotypes) with variable severities and treatment responses. It remains unclear whether high throughput omics could play a role in asthma phenotypic assessment. The objective of this thesis is to explore the value of omics, particularly the sputum microbiome and the exhaled breath metabolome, in asthma phenotyping using advanced statistical approaches. Part 1 is an introduction to the thesis exploring the importance of asthma precision medicine and the associations of different omics with asthma characteristics. Part 2 highlights the microbiota role in understanding and phenotyping asthma. The studies have shown that the sputum microbiome may play a role in refining the therapeutically challenging neutrophilic asthma phenotype. In this part, we have also shown that combining multiple omics provide more insight into the pathophysiology of asthma disease. Part 3 highlights the role of exhaled breath profiling by eNose in phenotyping and monitoring patients with asthma. The studies have shown that the eNose could serve as a non-invasive tool in screening the atopic asthma phenotype and may allow longitudinal monitoring of patients with asthma. Part 2 and Part 3 have shown the promising value of using omics in phenotyping patients with asthma, which may allow targeting diagnostic and therapeutic decisions to the individual patients' needs. Part 4 is a general discussion of the thesis, in which we have addressed the limitations and the general challenges in applying omics, particularly the microbial and the exhaled breath profiles, in the clinical decision-making process

International Migration, Integration and Social Cohesion online publications

UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl)UvA-DARE (Digital Academic Repository)Omics-guided precision medicineMicrobiomics and breathomics in asthma phenotypingIbrahim, M.I.A.Publication date2022Link to publicationCitation for published version (APA):Ibrahim, M. I. A. (2022). Omics-guided precision medicine: Microbiomics and breathomics inasthma phenotyping. [Thesis, fully internal, Universiteit van Amsterdam].General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s)and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an opencontent license (like Creative Commons).Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, pleaselet the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the materialinaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letterto: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. Youwill be contacted as soon as possible.Download date:10 Mar 2023Omics-guided precision medicine: microbiomics and breathomics in asthma phenotypingMahmoud Ismael Abdelaziz IbrahimColophonOmics-guided precision medicine: microbiomics and breathomics in asthma phenotypingPhD thesis, University of Amsterdam, the Netherlands.ISBN 978-94-93270-23-7Cover Yousra MohamedLayout Guus Gijben | Proefschrift-aio.nlPrinting AIO | Proefschrift-aio.nlThe researcher Mahmoud Ismael Abdelaziz Ibrahim is funded by a full scholarship from the Ministry of Higher Education of the Arab Republic of Egypt.©Mahmoud I. Abdel-Aziz, Amsterdam 2021All rights reserved. No part of this publication may be reproduced, stored in a retrieval system of any nature, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing from the copyright owner.Omics-guided precision medicine: microbiomics and breathomics in asthma phenotypingACADEMISCH PROEFSCHRIFTter verkrijging van de graad van doctoraan de Universiteit van Amsterdamop gezag van de Rector Magnificusprof. dr. ir. K.I.J. Maexten overstaan van een door het College voor Promoties ingestelde commissie,in het openbaar te verdedigen in de Agnietenkapelop woensdag 19 januari 2022, te 16.00 uurdoor Mahmoud Ismael Abdelaziz Ibrahimgeboren te AssiutPromotiecommissie:Promotores: prof. dr. A.H. Maitland-van der Zeeprof. dr. A.D. Kraneveld AMC-UvAUniversiteit UtrechtCopromotores: dr. A.H. van Stuyvenberg-Neerincxdr. S.J.H. VijverbergAMC-UvAAMC-UvAOverige leden: prof. dr. W.J. Wiersingadr. E.G. Haarmanprof. dr. H.J. Bogaardprof. dr. L. Koenderman prof. dr. J. Garssendr. E.M. KemperAMC-UvAAMC-UvAVrije Universiteit AmsterdamUniversiteit UtrechtUniversiteit UtrechtAMC-UvAFaculteit der GeneeskundeTo my dearest family; Nariman, Yassin and YounusTo my beloved parents, peace be upon themTable of ContentsPart 1: Introduction 9Chapter 1.1 General introduction 11Chapter 1.2 Omics for the future in asthma 23Part 2: The microbiome in asthma phenotyping 53Chapter 2.1 The crosstalk between microbiome and asthma: Exploring associations and challenges55Chapter 2.2 Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12-18 months93Chapter 2.3 A multi-omics approach to delineate sputum metagenomics and eicosanoids-associated asthma inflammatory phenotypes121Chapter 2.4 Association of endopeptidases, involved in SARS-CoV-2 infection, with microbial aggravation in sputum of severe asthma179Part 3: The breathome in asthma phenotyping 189Chapter 3.1 eNose breath prints as a surrogate biomarker for classifying patients with asthma by atopy191Chapter 3.2 Cross‐sectional biomarker comparisons in asthma monitoring using a longitudinal design: The eNose premise215Part 4: General discussion and summary 225Chapter 4.1 General discussion 227Chapter 4.2 Summary 249Chapter 4.3 Nederlandse samenvatting 257AppendicesPhD portfolio 266List of publications 268Curriculum vitae 272Acknowledgments 274

Omics-guided precision medicine:Microbiomics and breathomics in asthma phenotyping

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Omics-guided precision medicine:Microbiomics and breathomics in asthma phenotyping

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International Migration, Integration and Social Cohesion online publications