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Prof. Dr. med. Urs Frey

Department of Clinical Research
Profiles & Affiliations

Developmental physiology of newborns with asthma. Influence of environmental factors on lung development and lung growth. Development of non-invasive pulmonary function tests in children. System physiology and bioinformatics: mathematical modeling of temporal behavior of chronic asthma

Chair of Paediatrics and Medical Director at the University Children’s Hospital in Basel, Switzerland, Prof Frey is a long-established researcher in paediatric pulmonology, particularly in the field of asthma and developmental physiology. After completing his MD in Paediatrics at the University of Bern, he conducted postgraduate study in the US and the UK, including a PhD in biomedical engineering at the University of Leicester. Prof Frey has a long track record of high-quality, peer-reviewed publications. He leads a birth cohort study investigating genetic and environmental influences on infant lung development and is also interested in the mathematical modelling of complex airway disease. He has expertise in developmental lung physiology, and experience in statistics and epidemiology of birth cohorts. In the last decade he has been largely involved in data-driven medicine, involving multi-omics data analysis, and computational methods allowing prediction modelling, clustering and phenotyping. In particular, he has worked in the field of paediatric asthma and participated in international consortia such as U-BIOPRED, PASTURE and BIOAIR. As chair of paediatrics in Basel, he is regularly involved in graduate and postgraduate teaching and supervision of MD-PhDs. With regards to his contribution to national research organisations, he was member of the SNF research board from 2014 to 2016, and has been a member of the SAMW and chair of the national steering board of the Swiss Personalized Health Network since 2018. Prof Frey is the recipient of several research grants and awards, including the Guido Fanconi Memorial Prize and ERS Romain Pauwels Asthma Research Fund award. He is also an ERS Fellow.

Selected Publications

Decrue, F., Gorlanova, O., Salem, Y., Vienneau, D., de Hoogh, K., Gisler, A., Usemann, J., Korten, I., Nahum, U., Sinues, P., Schulzke, S., Fuchs, O., Latzin, P., Röösli, M., Frey, U., & Bild Study Group. (2022). Increased impact of air pollution on lung function in preterm versus term infants: the BILD study. Am J Respir Crit Care Med, 205(1), 99–107. https://doi.org/10.1164/rccm.202102-0272oc

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Delgado-Eckert, Edgar, James, Anna, Meier-Girard, Delphine, Kupczyk, Maciej, Andersson, Lars I., Bossios, Apostolos, Mikus, Maria, Junya, Ono, Kenji, Izuhara, Middelveld, Roelinde, Dahlén, Barbro, Gaga, Mina, Siafakas, Nikos M., Papi, Alberto, Beghe, Bianca, Joos, Guy, Rabe, Klaus F., Sterk, Peter J., Bel, Elisabeth H., et al. (2021). Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation. The Journal of Allergy & Clinical Immunology, 148(2), 407–419. https://doi.org/10.1016/j.jaci.2020.12.652

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Decrue, Fabienne, Gorlanova, Olga, Usemann, Jakob, & Frey, Urs. (2020). Lung functional development and asthma trajectories. Seminars in Immunopathology, 42(1), 17–27. https://doi.org/10.1007/s00281-020-00784-2

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Sinha, Anirban, Lutter, René, Xu, Binbin, Dekker, Tamara, Dierdorp, Barbara, Sterk, Peter J., Frey, Urs, & Eckert, Edgar Delgado. (2019). Loss of adaptive capacity in asthmatic patients revealed by biomarker fluctuation dynamics after rhinovirus challenge. eLife, 8, e47969. https://doi.org/10.7554/elife.47969

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Usemann, Jakob, Decrue, Fabienne, Korten, Insa, Proietti, Elena, Gorlanova, Olga, Vienneau, Danielle, Fuchs, Oliver, Latzin, Philipp, Röösli, Martin, Frey, Urs, & Bild study group. (2019). Exposure to moderate air pollution and associations with lung function at school-age: A birth cohort study. Environment International, 126, 682–689. https://doi.org/10.1016/j.envint.2018.12.019

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Selected Projects & Collaborations

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Air Pollution and Effects on Lung Functional Development and Respiratory Morbidity in At-Risk Infants

Research Project  | 4 Project Members

BACKGROUND AND RATIONALE: This is a direct continuation of SNF 182871/1, which investigated the impact of early-childhood environmental factors on lung functional growth and consequences for later respiratory morbidity in healthy term infants. We previously demonstrated that even low-level air pollution exposure during pregnancy and early childhood is associated with impaired lung functional growth in infancy and early childhood. Although the mechanisms are still unclear, they could be related to lung functional growth deficits or remodeling of the lung due to changes in the intrauterine environment. Air pollution is known to induce oxidative stress response and related autophagy and cellular senescence mechanisms, potentially playing a role in pollution-related lung pathology and in remodeling. As novel preliminary evidence in SNF 182871/1, we recently found that, in the cord blood of human infants, autophagy-related biomarkers are correlated with remodeling biomarkers. We also found that air pollution exposure during pregnancy is associated with biomarkers of autophagy and remodeling in the cord blood of healthy term infants. Interestingly, these mechanisms also play an important role in fetal development and preterm birth, and may thus theoretically contribute to the susceptibility of infants-and particularly preterm infants-to oxidative stress and air pollution effects. Indeed, as first evidence from SNF 182871/1, we also found an enhanced impact of air pollutants on lung function impairment of preterm infants. Furthermore, our own preliminary human data show that markers of autophagy, and remodeling already have significant differences between the cord blood of preterm infants compared to term infants at birth prior to early postnatal injury. Bringing this together, we hypothesize that the interaction of oxidative stress response, autophagy and remodeling could be a key mechanism involved in the complex host-environment interaction determining lung functional growth and related respiratory morbidity. Moreover, this response could be different in infants at risk for chronic respiratory symptoms, such preterm infants, infants born from asthmatic mothers or infants exposed to high levels of air pollution during pregnancy. OVERALL OBJECTIVES: We aim to expand the ongoing BILD cohort of (i) term infants with two risk subgroups, (ii) infants born preterm, and (iii) infants born to asthmatic mothers, and we will investigate the differences in response to prenatal air pollution in relation to the above key mechanisms. SPECIFIC AIMS: In comparison to healthy term infants, we will investigate in study phase 1, (i) whether the increased susceptibility of infants to prenatal air pollution in these three risk groups is related to differences in markers of oxidative stress response, autophagy, and remodeling in cord blood and in study phase 2, (ii) whether these pollution-related cord blood profiles are correlated to lung functional development and subsequent symptoms in the first year of life (primary outcomes) and at school age (secondary outcomes). We will replicate these findings in other birth cohorts from collaborators (Germany, Australia) with comparable outcome measures. METHODS: In our prospective BILD birth cohort of 1000 unselected healthy term infants, 400 preterm infants, and 200 infants from asthmatic mothers we will (i) estimate indoor and outdoor air pollution exposure during pregnancy and in early infancy, (ii) assess family, obstetric and birth history, cord-molecular biomarkers (metabolomics, gene expression, proteins), and infant lung function shortly after birth (including exhalomics) and at 6 years of age, as well as respiratory symptoms in the first year of life and at school age. EXPECTED RESULTS AND IMPACT: We expect a 26.03.2021 18:35:26 Page - 14 - significant correlation between air pollution exposure and oxidative stress response and lung remodeling in newborns with effects on lung function and clinical outcomes, the latter effects enhanced in the risk groups. Particularly for these risk groups, today's air pollution may already result in lung remodeling and subsequent impaired lung functional growth even at this early stage of life. Since early-life lung functional impairment often persists until school age and even late adulthood, it is a previously described early-life risk factor known to be associated with asthma in children and chronic obstructive respiratory airway diseases in the elderly. Thus, early-life environmental injury has a potentially very relevant impact on future global respiratory health, with unpredictable costs. We are one of the first groups to look into the impact of these air-pollution-induced mechanisms on oxidative stress response and lung remodeling, subsequent impairment of lung functional growth, and resulting human lung disease. Better understanding of these mechanisms might help the development of preventative and therapeutic strategies, particularly for at-risk infants.