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

Autor: Böck A; Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany., Urner K; Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany., Eckert JK; Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany., Salvermoser M; Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany., Laubhahn K; Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Comprehensive Pneumology Center - Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany., Kunze S; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Kumbrink J; Institute of Pathology, Medical Faculty, LMU Munich, Munich, Germany., Hoeppner MP; Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany., Kalkbrenner K; Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany., Kreimeier S; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany.; Department of Health Economics and Health Care Management, School of Public Health, Bielefeld University, Bielefeld, Germany., Beyer K; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany.; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany., Hamelmann E; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany.; Department for Pediatrics, Children's Center Bethel, University Hospital OWL, Bielefeld University, Bielefeld, Germany., Kabesch M; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany.; University Children's Hospital Regensburg (KUNO), St. Hedwig's Hospital of the Order of St. John and the University of Regensburg, Regensburg, Germany., Depner M; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany.; Institute of Asthma and Allergy Prevention, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany., Hansen G; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany.; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.; Excellence Cluster Resolving Infection Susceptibility RESIST (EXC 2155), Deutsche Forschungsgemeinschaft, Hannover Medical School, Hannover, Germany., Riedler J; Children's Hospital Schwarzach, Schwarzach, Austria., Roponen M; Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland., Schmausser-Hechfellner E; Institute of Asthma and Allergy Prevention, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany., Barnig C; Department of Respiratory Disease, University Hospital, Besanҫon, France.; INSERM, EFS BFC, LabEx LipSTIC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Univ. Bourgogne Franche-Comté, Besançon, France., Divaret-Chauveau A; Pediatric Allergy Department, Children's Hospital, University Hospital of Nancy, Vandoeuvre les Nancy, France.; EA3450 Development, Adaptation and Handicap (devah), Pediatric Allergy Department, University of Lorraine, Nancy, France.; UMR/CNRS 6249 Chrono-environment, University of Franche Comté, Besançon, France., Karvonen AM; Department of Health Security, Finnish Institute for Health and Welfare, Kuopio, Finland., Pekkanen J; Department of Health Security, Finnish Institute for Health and Welfare, Kuopio, Finland.; Department of Public Health, University of Helsinki, Helsinki, Finland., Frei R; Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.; Division of Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, University of Bern, Bern, Switzerland., Roduit C; Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.; Division of Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, University of Bern, Bern, Switzerland.; Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.; Children's Hospital, University of Zürich, Zürich, Switzerland., Lauener R; Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.; Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland., Schaub B; Pediatric Allergology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Member of the CHildhood Allergy and Tolerance Consortium (CHAMP), LMU Munich, Munich, Germany.; Comprehensive Pneumology Center - Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany.
Jazyk: angličtina
Zdroj: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2024 May; Vol. 54 (5), pp. 314-328. Date of Electronic Publication: 2024 Mar 31.
DOI: 10.1111/cea.14475
Abstrakt: 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.
(© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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