Abstract
There is a clinical need to identify children with poor asthma control as early as possi-ble, 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 Slove-nia). 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 |
Journal | Journal of Personalized Medicine |
Volume | 11 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Jun 2021 |
Keywords
- Omics
- Pediatric asthma
- Systems medicine
- Uncontrolled asthma
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In: Journal of Personalized Medicine, Vol. 11, No. 6, 484, 01.06.2021.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - A system pharmacology multi-omics approach toward uncontrolled pediatric asthma
AU - SysPharmPediA Consortium
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.
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 - 2021/6/1
Y1 - 2021/6/1
N2 - There is a clinical need to identify children with poor asthma control as early as possi-ble, 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 Slove-nia). 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 possi-ble, 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 Slove-nia). 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 - https://doi.org/10.3390/jpm11060484
DO - https://doi.org/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 -