A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma

Mahmoud I Abdel-Aziz; Anne H Neerincx; Susanne J H Vijverberg; Simone Hashimoto; Paul Brinkman; Mario Gorenjak; Antoaneta A Toncheva; Susanne Harner; Susanne Brandstetter; Christine Wolff; Javier Perez-Garcia; Anna M Hedman; Catarina Almqvist; Paula Corcuera-Elosegui; Javier Korta-Murua; Olaia Sardón-Prado; Maria Pino-Yanes; Uroš Potočnik; Michael Kabesch; Aletta D Kraneveld; Anke H Maitland-van der Zee; null On Behalf Of The SysPharmPediA Consortium

doi:10.3390/jpm11060484

A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma

Mahmoud I Abdel-Aziz, Anne H Neerincx, Susanne J H Vijverberg, Simone Hashimoto, Paul Brinkman, Mario Gorenjak, Antoaneta A Toncheva, Susanne Harner, Susanne Brandstetter, Christine Wolff, Javier Perez-Garcia, Anna M Hedman, Catarina Almqvist, Paula Corcuera-Elosegui, Javier Korta-Murua, Olaia Sardón-Prado, Maria Pino-Yanes, Uroš Potočnik, Michael Kabesch, Aletta D KraneveldAnke H Maitland-van der Zee, On Behalf Of The SysPharmPediA Consortium

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the "Systems Pharmacology Approach to Uncontrolled Pediatric Asthma" (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case-control study, moderate-to-severe asthmatic children (age; 6-17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.

Original language	English
Article number	484
Number of pages	16
Journal	Journal of Personalized Medicine
Volume	11
Issue number	6
DOIs	https://doi.org/10.3390/jpm11060484
Publication status	Published - Jun 2021

Bibliographical note

Funding Information:
Conflicts of Interest: M.I.A.-A., S.H. (Simone Hashimoto), P.B., A.A.T., S.H. (Susanne Harner), S.B., C.W., A.M.H., C.A., P.C.E., J.K.-M., O.S.-P. and A.D.K. have no conflicts of interest to disclose. A.H.N. and S.J.H.V. were funded by a grant paid to institution from ERANET Systems Medicine and ZonMW [project number: 9003035001]. M.G. was funded by SysPharmPediA grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020 (AC15/00015). J.P.-G. was funded by a fellowship (FPU19/02175) from the Spanish Ministry of Science and Innovation. M.P.-Y. reports grants from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, the State Research Agency, and the European Regional Development Fund from the European Union (MICINN/AEI/FEDER, UE) during the conduct of the study, and a grant from GlaxoSmithKline Spain, outside of the submitted work. U.P. was funded by a SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (contract number C3330-16-500106), and funded by Slovenian Research Agency (research core funding No. P3-0067). M.K. was funded for this project by institutional funds from the German Ministry of Education and Research (BMBF) [project number FKZ 031L0088]. In the last five years, he received payment for consultancy to Sanofi, Novartis, and Bencard and fees for lectures from ERS, EAACI, ATS, Novartis, Chiesi, Glaxo, Nutricia, Hipp, and Allergopharma. He is part of a patent METHOD FOR TESTING A SUBJECT THOUGHT TO HAVE OR TO BE PREDISPOSED TO ASTHMA, European patent application 5 EP07301135.5. A.H.M.-v.d.Z. was funded by a grant paid to institution from ERANET Systems Medicine and ZonMW [project number: 9003035001], received unrestricted research grants from Vertex and Boehringer Ingelheim, received consulting fees (paid to institution) from Astra Zeneca and Boehringer Ingelheim, and received honoraria (paid to institution) for lectures by GSK. A.H.M.-v.d.Z. is the PI of a P4O2 (Precision Medicine for more Oxygen) public–private partnership sponsored by Health Holland involving many private partners who contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Smartfish, SODAQ, Thirona, TopMD, and Novartis), and she is the president of the federation of innovative drug research in the Netherlands (FIGON) (unpaid) and President of the European Association of Systems Medicine (EASYM). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Funding Information:
Funding: The SysPharmPediA consortium is supported by ZonMW [project number: 9003035001], the Ministry of Education, Science, and Sport of the Republic of Slovenia [contract number C330-16-500106]; the German Ministry of Education and Research (BMBF) [project number FKZ 031L0088]; Instituto de Salud Carlos III (ISCIII) through Strategic Action for Health Research (AES) and European Community (EC) within the Active and Assisted Living (AAL) Program framework [award numbers AC15/00015 and AC15/00058] under the frame of the ERACoSysMed JTC-1 Call. M.P.-Y. was funded by the Ramón y Cajal Program (RYC-2015-17205) by the Spanish Ministry of Science and Innovation (MICINN), the State Research Agency, and the European Regional Development Fund from the European Union (MICINN/AEI/FEDER, UE, grant SAF2017-83417R). J.P.-G. was supported by a Ph.D. fellowship (FPU19/02175) granted by MICINN. U.P. and M.G. were funded by Slovenian Research Agency (research core funding No. P3-0067). M.I.A.-A. was funded by the Egyptian Government Ph.D. Scholarships. The STOPPA study was funded by the Swedish Research Council project grant 2018-02640 and the Swedish Asthma and Allergy Research Foundation.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Omics
Pediatric asthma
Systems medicine
Uncontrolled asthma

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jpm-11-00484Final published version, 1.24 MB

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Abdel-Aziz, M. I., Neerincx, A. H., Vijverberg, S. J. H., Hashimoto, S., Brinkman, P., Gorenjak, M., Toncheva, A. A., Harner, S., Brandstetter, S., Wolff, C., Perez-Garcia, J., Hedman, A. M., Almqvist, C., Corcuera-Elosegui, P., Korta-Murua, J., Sardón-Prado, O., Pino-Yanes, M., Potočnik, U., Kabesch, M., ... On Behalf Of The SysPharmPediA Consortium (2021). A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma. Journal of Personalized Medicine, 11(6), Article 484. https://doi.org/10.3390/jpm11060484

@article{df700bdb1c2d458fbd4dab97549a4833,

title = "A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma",

abstract = "There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the {"}Systems Pharmacology Approach to Uncontrolled Pediatric Asthma{"} (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case-control study, moderate-to-severe asthmatic children (age; 6-17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.",

keywords = "Omics, Pediatric asthma, Systems medicine, Uncontrolled asthma",

author = "Abdel-Aziz, {Mahmoud I} and Neerincx, {Anne H} and Vijverberg, {Susanne J H} and Simone Hashimoto and Paul Brinkman and Mario Gorenjak and Toncheva, {Antoaneta A} and Susanne Harner and Susanne Brandstetter and Christine Wolff and Javier Perez-Garcia and Hedman, {Anna M} and Catarina Almqvist and Paula Corcuera-Elosegui and Javier Korta-Murua and Olaia Sard{\'o}n-Prado and Maria Pino-Yanes and Uro{\v s} Poto{\v c}nik and Michael Kabesch and Kraneveld, {Aletta D} and {Maitland-van der Zee}, {Anke H} and {On Behalf Of The SysPharmPediA Consortium}",

note = "Funding Information: Conflicts of Interest: M.I.A.-A., S.H. (Simone Hashimoto), P.B., A.A.T., S.H. (Susanne Harner), S.B., C.W., A.M.H., C.A., P.C.E., J.K.-M., O.S.-P. and A.D.K. have no conflicts of interest to disclose. A.H.N. and S.J.H.V. were funded by a grant paid to institution from ERANET Systems Medicine and ZonMW [project number: 9003035001]. M.G. was funded by SysPharmPediA grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020 (AC15/00015). J.P.-G. was funded by a fellowship (FPU19/02175) from the Spanish Ministry of Science and Innovation. M.P.-Y. reports grants from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, the State Research Agency, and the European Regional Development Fund from the European Union (MICINN/AEI/FEDER, UE) during the conduct of the study, and a grant from GlaxoSmithKline Spain, outside of the submitted work. U.P. was funded by a SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (contract number C3330-16-500106), and funded by Slovenian Research Agency (research core funding No. P3-0067). M.K. was funded for this project by institutional funds from the German Ministry of Education and Research (BMBF) [project number FKZ 031L0088]. In the last five years, he received payment for consultancy to Sanofi, Novartis, and Bencard and fees for lectures from ERS, EAACI, ATS, Novartis, Chiesi, Glaxo, Nutricia, Hipp, and Allergopharma. He is part of a patent METHOD FOR TESTING A SUBJECT THOUGHT TO HAVE OR TO BE PREDISPOSED TO ASTHMA, European patent application 5 EP07301135.5. A.H.M.-v.d.Z. was funded by a grant paid to institution from ERANET Systems Medicine and ZonMW [project number: 9003035001], received unrestricted research grants from Vertex and Boehringer Ingelheim, received consulting fees (paid to institution) from Astra Zeneca and Boehringer Ingelheim, and received honoraria (paid to institution) for lectures by GSK. A.H.M.-v.d.Z. is the PI of a P4O2 (Precision Medicine for more Oxygen) public–private partnership sponsored by Health Holland involving many private partners who contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Smartfish, SODAQ, Thirona, TopMD, and Novartis), and she is the president of the federation of innovative drug research in the Netherlands (FIGON) (unpaid) and President of the European Association of Systems Medicine (EASYM). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Funding Information: Funding: The SysPharmPediA consortium is supported by ZonMW [project number: 9003035001], the Ministry of Education, Science, and Sport of the Republic of Slovenia [contract number C330-16-500106]; the German Ministry of Education and Research (BMBF) [project number FKZ 031L0088]; Instituto de Salud Carlos III (ISCIII) through Strategic Action for Health Research (AES) and European Community (EC) within the Active and Assisted Living (AAL) Program framework [award numbers AC15/00015 and AC15/00058] under the frame of the ERACoSysMed JTC-1 Call. M.P.-Y. was funded by the Ram{\'o}n y Cajal Program (RYC-2015-17205) by the Spanish Ministry of Science and Innovation (MICINN), the State Research Agency, and the European Regional Development Fund from the European Union (MICINN/AEI/FEDER, UE, grant SAF2017-83417R). J.P.-G. was supported by a Ph.D. fellowship (FPU19/02175) granted by MICINN. U.P. and M.G. were funded by Slovenian Research Agency (research core funding No. P3-0067). M.I.A.-A. was funded by the Egyptian Government Ph.D. Scholarships. The STOPPA study was funded by the Swedish Research Council project grant 2018-02640 and the Swedish Asthma and Allergy Research Foundation. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jun,

doi = "10.3390/jpm11060484",

language = "English",

volume = "11",

journal = "Journal of Personalized Medicine",

issn = "2075-4426",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "6",

}

Abdel-Aziz, MI, Neerincx, AH, Vijverberg, SJH, Hashimoto, S, Brinkman, P, Gorenjak, M, Toncheva, AA, Harner, S, Brandstetter, S, Wolff, C, Perez-Garcia, J, Hedman, AM, Almqvist, C, Corcuera-Elosegui, P, Korta-Murua, J, Sardón-Prado, O, Pino-Yanes, M, Potočnik, U, Kabesch, M, Kraneveld, AD, Maitland-van der Zee, AH & On Behalf Of The SysPharmPediA Consortium 2021, 'A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma', Journal of Personalized Medicine, vol. 11, no. 6, 484. https://doi.org/10.3390/jpm11060484

TY - JOUR

T1 - A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma

AU - Abdel-Aziz, Mahmoud I

AU - Neerincx, Anne H

AU - Vijverberg, Susanne J H

AU - Hashimoto, Simone

AU - Brinkman, Paul

AU - Gorenjak, Mario

AU - Toncheva, Antoaneta A

AU - Harner, Susanne

AU - Brandstetter, Susanne

AU - Wolff, Christine

AU - Perez-Garcia, Javier

AU - Hedman, Anna M

AU - Almqvist, Catarina

AU - Corcuera-Elosegui, Paula

AU - Korta-Murua, Javier

AU - Sardón-Prado, Olaia

AU - Pino-Yanes, Maria

AU - Potočnik, Uroš

AU - Kabesch, Michael

AU - Kraneveld, Aletta D

AU - Maitland-van der Zee, Anke H

AU - On Behalf Of The SysPharmPediA Consortium, null

N1 - Funding Information: Conflicts of Interest: M.I.A.-A., S.H. (Simone Hashimoto), P.B., A.A.T., S.H. (Susanne Harner), S.B., C.W., A.M.H., C.A., P.C.E., J.K.-M., O.S.-P. and A.D.K. have no conflicts of interest to disclose. A.H.N. and S.J.H.V. were funded by a grant paid to institution from ERANET Systems Medicine and ZonMW [project number: 9003035001]. M.G. was funded by SysPharmPediA grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020 (AC15/00015). J.P.-G. was funded by a fellowship (FPU19/02175) from the Spanish Ministry of Science and Innovation. M.P.-Y. reports grants from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, the State Research Agency, and the European Regional Development Fund from the European Union (MICINN/AEI/FEDER, UE) during the conduct of the study, and a grant from GlaxoSmithKline Spain, outside of the submitted work. U.P. was funded by a SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (contract number C3330-16-500106), and funded by Slovenian Research Agency (research core funding No. P3-0067). M.K. was funded for this project by institutional funds from the German Ministry of Education and Research (BMBF) [project number FKZ 031L0088]. In the last five years, he received payment for consultancy to Sanofi, Novartis, and Bencard and fees for lectures from ERS, EAACI, ATS, Novartis, Chiesi, Glaxo, Nutricia, Hipp, and Allergopharma. He is part of a patent METHOD FOR TESTING A SUBJECT THOUGHT TO HAVE OR TO BE PREDISPOSED TO ASTHMA, European patent application 5 EP07301135.5. A.H.M.-v.d.Z. was funded by a grant paid to institution from ERANET Systems Medicine and ZonMW [project number: 9003035001], received unrestricted research grants from Vertex and Boehringer Ingelheim, received consulting fees (paid to institution) from Astra Zeneca and Boehringer Ingelheim, and received honoraria (paid to institution) for lectures by GSK. A.H.M.-v.d.Z. is the PI of a P4O2 (Precision Medicine for more Oxygen) public–private partnership sponsored by Health Holland involving many private partners who contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Smartfish, SODAQ, Thirona, TopMD, and Novartis), and she is the president of the federation of innovative drug research in the Netherlands (FIGON) (unpaid) and President of the European Association of Systems Medicine (EASYM). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Funding Information: Funding: The SysPharmPediA consortium is supported by ZonMW [project number: 9003035001], the Ministry of Education, Science, and Sport of the Republic of Slovenia [contract number C330-16-500106]; the German Ministry of Education and Research (BMBF) [project number FKZ 031L0088]; Instituto de Salud Carlos III (ISCIII) through Strategic Action for Health Research (AES) and European Community (EC) within the Active and Assisted Living (AAL) Program framework [award numbers AC15/00015 and AC15/00058] under the frame of the ERACoSysMed JTC-1 Call. M.P.-Y. was funded by the Ramón y Cajal Program (RYC-2015-17205) by the Spanish Ministry of Science and Innovation (MICINN), the State Research Agency, and the European Regional Development Fund from the European Union (MICINN/AEI/FEDER, UE, grant SAF2017-83417R). J.P.-G. was supported by a Ph.D. fellowship (FPU19/02175) granted by MICINN. U.P. and M.G. were funded by Slovenian Research Agency (research core funding No. P3-0067). M.I.A.-A. was funded by the Egyptian Government Ph.D. Scholarships. The STOPPA study was funded by the Swedish Research Council project grant 2018-02640 and the Swedish Asthma and Allergy Research Foundation. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/6

Y1 - 2021/6

N2 - There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the "Systems Pharmacology Approach to Uncontrolled Pediatric Asthma" (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case-control study, moderate-to-severe asthmatic children (age; 6-17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.

AB - There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the "Systems Pharmacology Approach to Uncontrolled Pediatric Asthma" (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case-control study, moderate-to-severe asthmatic children (age; 6-17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.

KW - Omics

KW - Pediatric asthma

KW - Systems medicine

KW - Uncontrolled asthma

UR - http://www.scopus.com/inward/record.url?scp=85107856349&partnerID=8YFLogxK

U2 - 10.3390/jpm11060484

DO - 10.3390/jpm11060484

M3 - Article

C2 - 34071272

SN - 2075-4426

VL - 11

JO - Journal of Personalized Medicine

JF - Journal of Personalized Medicine

IS - 6

M1 - 484

ER -

A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma

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