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Article Dans Une Revue Clinical and Experimental Allergy Année : 2024

An integrated molecular risk score early in life for subsequent childhood asthma risk

1 Dr von Hauner Children's Hospital [Munich, Germany]
2 German Center for Lung Research - DZL [Munich, Germany]
3 HMGU - Helmholtz Zentrum München = German Research Center for Environmental Health
4 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
5 CAU - Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel
6 Universität Bielefeld = Bielefeld University
7 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
8 KUNO - University Children's Hospital Regensburg (KUNO), Regensburg, Germany
9 UR - Universität Regensburg
10 MHH - Medizinische Hochschule Hannover = Hannover Medical School
11 Schwarzach Hospital Kardinal Schwarzenberg'sches Krankenhaus
12 University of Eastern Finland
13 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
14 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
15 Département de pédiatrie [CHRU Nancy]
16 DevAH - Développement, Adaptation et Handicap
17 LCE - Laboratoire Chrono-environnement (UMR 6249)
18 Department of Health Security, Finnish Institute for Health and Welfare (THL), Kuopio 70210, Finland
19 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
20 CK-CARE - Christine Kühne – Centre for Allergy Research and Education
21 Inselspital - Bern University Hospital [Berne]
22 UNIBE - Universität Bern / University of Bern
23 Children's Hospital of Eastern Switzerland St.Gallen
24 University Children’s Hospital Zurich
25 UZH - Universität Zürich [Zürich] = University of Zurich
Marjut Roponen

Résumé

Abstract Background Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely patient‐tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome‐wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy). Methods Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5–11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism‐corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve‐Bayes approach) combined with high‐dimensional logistic regression models (LASSO). Results Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism‐corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time ( r = .59, p < .001, 4.5–6 years). Conclusion Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers.
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hal-04613813 , version 1 (17-06-2024)

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Andreas Böck, Kathrin Urner, Jana Kristin Eckert, Michael Salvermoser, Kristina Laubhahn, et al.. An integrated molecular risk score early in life for subsequent childhood asthma risk. Clinical and Experimental Allergy, 2024, 54 (5), pp.314-328. ⟨10.1111/cea.14475⟩. ⟨hal-04613813⟩
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