CASyM winter school of Systems Medicine took place between March 29th and April 1st 2017 in Ljubljana, Slovenia and is entitled »The 3rd SysBioMed hands-on tutorial: Systems Medicine Approaches in Personalized Medicine«
SysPharmPediA: Systems Pharmacology Approach to Difficult-to-Treat Pediatric Asthma
AH Neerincx1, M Gorenjak2, SJH Vijverberg1, P Brinkman1, AD Kraneveld3,4, U Potocnik2, M Pino-Yanes5, O Sardon Prado6, M Kabesch7, AH Maitland-van der Zee1
1Dept. of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, NL, 2Center for human molecular genetics and pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia, 3Div. of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NL, 4Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NL, 5Research Unit, Hospital Universitario NS de Candelaria, Santa Cruz de Tenerife, Spain, 6Division of Pediatric Respiratory Medicine, Donostia University Hospital, San Sebastián, Spain, 7Dept. of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg, Regensburg, Germany
Asthma is the most common chronic disease starting in childhood and affects 1 out of 10 children . Usually, children respond well to standard therapy with inhaled corticosteroids (ICS), however, a substantial proportion of children achieve only partial control of the disease and 10-15% of the patients will suffer from severe symptoms despite the ICS treatment [2,3]. These symptoms considerably impact the quality of children’s life and therefore, it is important to identify biomarkers for the identification of children who are at risk for uncontrolled asthma at an early stage. Although, ICS are generally safe for long-term use, there is a concern about systemic side effects, including growth retardation . In this project we will use a multi-omics systems medicine driven approach to identify multi-dimensional biomarkers in saliva, blood, feces, urine and exhaled breath samples in well-phenotyped well-controlled asthmatic children and asthmatic children that do not respond to standard therapy with ICS. Data from different -omics layers, together with clinical data, will be integrated using computational, statistical and multilayer analyses. Main objectives of the project are to identify non-invasive biomarkers that allow classification of different disease phenotypes of non-response to ICS asthma therapy. Furthermore, we aim to construct computational algorithms that effectively predict phenotypes of ICS response by using a set of system-wide biomarkers and their interaction with clinical and environmental factors. Design of the study is based on observational case-control study involving children from the Netherlands, Germany, Spain and Slovenia. Data is going to be collected during house, hospital or outpatient clinic visits and also during hospital admissions due to exacerbations. The project is going to sample 200 children between 6 and 18 years old with diagnosed asthma (50 well-controlled and 150 children non-responsive to standard therapy with ICS). Additionally, group specific inclusion criteria for 150 cases are defined as asthma treatment step 3 or higher according to Global Initiative of Asthma (GINA) and should meet at least one of the following criteria: Frequent exacerbations requiring OCS use in the past year; severe exacerbation requiring hospitalization or ER visits in the past year; ACQ score indicating uncontrolled asthma. Cases with an acute exacerbation and GINA step 2 or higher will be also included in order to identify whether children with exacerbation-prone asthma differ from children with uncontrolled asthma. Group specific criteria for 50 controls are defined as GINA step 3 or higher without severe exacerbations and with ACQ scores indicating well controlled asthma. All patients will be followed for 1 year. In conclusion, SysPharmPediA will use a unique approach to classify different phenotypes of asthmatic children that do not respond to ICS, which can improve treatment strategies for pediatric asthma patients in the future. 1. Asher, et al. (2006) Lancet 368, pp.733-43. 2. Pijnenburg, et al. (2015) Respir Rev 16, pp.101-107. 3. Szefler, et al. (2005) JACI 115, pp.233-42. 4. Kelly, et al. (2012) N Engl J Med 6, pp.904-12.
2006 - University of Ljubljana, Faculty of Medicine, Center for Functional Genomics and Bio-chips.