Symptom trajectories in infancy for the prediction of subsequent wheeze and asthma in the BILD and PASTURE cohorts: a dynamic network analysis.

Autor:	Nahum U; University Children's Hospital Basel, University of Basel, Basel, Switzerland; Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Gorlanova O; University Children's Hospital Basel, University of Basel, Basel, Switzerland; Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Decrue F; University Children's Hospital Basel, University of Basel, Basel, Switzerland; Centre for Cardiovascular Science, Queens Medical Research Institute, Edinburgh, UK., Oller H; University Children's Hospital Basel, University of Basel, Basel, Switzerland., Delgado-Eckert E; University Children's Hospital Basel, University of Basel, Basel, Switzerland., Böck A; Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich Haunerschen Kinderklinik, Munich, Germany; Member of German Center for Lung Research-DZL, Ludwig-Maximilians-Universität Munich, Germany., Schulzke S; University Children's Hospital Basel, University of Basel, Basel, Switzerland., Latzin P; Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Schaub B; Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich Haunerschen Kinderklinik, Munich, Germany; Member of German Center for Lung Research-DZL, Ludwig-Maximilians-Universität Munich, Germany., Karvonen AM; Department of Health Security, Finnish Institute for Health and Welfare, Kuopio, Finland., Lauener R; Christine Kühne Center for Allergy Research and Education, Davos, Switzerland; Children's Hospital of Eastern Switzerland, St Gallen, Switzerland., Divaret-Chauveau A; Pediatric Allergy Department, University Hospital of Nancy, Nancy, France; UR3450 Développement Adaptation et Handicap, University of Lorraine, Nancy, France; UMR 6249 Chrono-environment, CNRS and University of Franche-Comté, Respiratory Disease Department, University Hospital of Besançon, Besançon, France., Illi S; Member of German Center for Lung Research-DZL, Ludwig-Maximilians-Universität Munich, Germany; Institute for Asthma and Allergy Prevention, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany; Comprehensive Pneumology Center Munich, Munich, Germany., Roduit C; Christine Kühne Center for Allergy Research and Education, Davos, Switzerland; Division of Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, University of Bern, Bern, Switzerland., von Mutius E; Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich Haunerschen Kinderklinik, Munich, Germany; Member of German Center for Lung Research-DZL, Ludwig-Maximilians-Universität Munich, Germany., Frey U; University Children's Hospital Basel, University of Basel, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: urs.frey@ukbb.ch.
Jazyk:	angličtina
Zdroj:	The Lancet. Digital health [Lancet Digit Health] 2024 Oct; Vol. 6 (10), pp. e718-e728.
DOI:	10.1016/S2589-7500(24)00147-X
Abstrakt:	Background: Host and environment early-life risk factors are associated with progression of wheezing symptoms over time; however, their individual contribution is relatively small. We hypothesised that the dynamic interactions of these factors with an infant's developing respiratory system are the dominant factor for subsequent wheeze and asthma. Methods: In this dynamic network analysis we used data from term healthy infants from the Basel-Bern Infant Lung Development (BILD) cohort (435 neonates aged 0-4 weeks recruited in Switzerland between Jan 1, 1999, and Dec 31, 2012) and replicated the findings in the Protection Against Allergy Study in Rural Environments (PASTURE) cohort (498 infants aged 0-12 months recruited in Germany, Switzerland, Austria, France, and Finland between Jan 1, 2002, and Oct 31, 2006). BILD exclusion criteria for the current study were prematurity (<37 weeks), major birth defects, perinatal disease of the neonate, and incomplete follow-up period. PASTURE exclusion criteria were women younger than 18 years, a multiple pregnancy, the sibling of a child was already included in the study, the family intended to move away from the area where the study was conducted, and the family had no telephone connection. Outcome groups were subsequent wheeze, asthma, and healthy. The first outcome was defined as ever wheezed between the age of 2 years and 6 years. Week-by-week correlations of the determining factors with cumulative symptom scores (CSS) were calculated from weeks 2 to 52 (BILD) and weeks 8 to 52 (PASTURE). The complex dynamic interaction between the determining factors and the CSS was assessed via dynamic host-environment correlation network, quantified by a simple descriptor: trajectory function G(t). Wheeze outcomes at age 2-6 years were compared in 335 infants from BILD and 437 infants from PASTURE, and asthma outcomes were analysed at age 6 years in a merged cohort of 783 infants. Findings: CSS was significantly different for wheeze and asthma outcomes and became increasingly important during infancy in direct comparison with all determining factors. Weekly symptoms were tracked for groups of infants, showing a non-linear increase with time. Using logistic regression classification, G(t) distinguished between the healthy group and wheeze or asthma groups (area under the curve>0·97, p<0·0001; sensitivity analysis confirmed significant CSS association with wheeze [BILD p=0·0002 and PASTURE p=0·068]) and G(t) was also able to distinguish between the farming and non-farming exposure groups (p<0·0001). Interpretation: Similarly to other risk factors, CSS had weak sensitivity and specificity to identify risks at the individual level. At group level however, the dynamic host-environment correlation network properties (G(t)) showed excellent discriminative ability for identifying groups of infants with subsequent wheeze and asthma. Results from this study are consistent with the 2018 Lancet Commission on asthma, which emphasised the importance of dynamic interactions between risk factors during development and not the risk factors per se. Funding: The Swiss National Science Foundation, the Kühne Foundation, the EFRAIM study EU research grant, the FORALLVENT study EU research grant, and the Leibniz Prize. Competing Interests: Declaration of interests PL reports board membership, funding grants, and speaking and lecture fees from Vertex and OM Pharma; speaking and lecture fees from Vifor Pharma Switzerland; and board membership with Polyphor, Santhera Pharmaceuticals Schweiz, Allecra Therapeutics, and Sanofi. AD-C reports consulting fees from Sanofi, Stallergens, ALK, and Aimmune Therapeutics; speaking fees and meeting attendance costs from Novartis and ALK; stock or stock options with Essilor Luxottica; a grant from Novartis and ARAIRLOR for asthma and cough research; received a grant from Don du Souffle, Fondation du Souffle, and ARAIRLOR for the PASTURE research; and received a contract with the French public agency ANSES. AMK reports that payments were made to their institution from the Juho Vanio Foundation, the Päiwikki and Sakari Sohlberg Foundation, the Finnish Cultural Foundation, the Academy of Finland, and the Finnish Institute for Health and Welfare. RL reports a research grant from the Kühne Foundation; and advisory board and lecture fees from ALK, Pfizer, Milupia, VIFOR, and Sanofi. BS reports research grants from Deutsche Forschungsgemeinschaft and consulting fees from GSK, Novartis, and Sanofi. EvM reports funding grants from the PASTURE study, the EFRAIM study, the FORALLVENT study, and the Leibniz Prize; research grants from the German Federal Ministry of Education and Research, the Bavarian State Ministry of Health and Care, OM Pharma, and the European Research Council; royalties or licences from Elsevier, Georg Thieme Verlag, Springer-Verlag, and Springer Nature Group; consulting fees from the Chinese University of Hong Kong, the European Commission, AstraZeneca, Imperial College London, and OM Pharma; lecture, speaker, or educational fees from ALK-Abello Arzneimittel, Japanese Society of Pediatric Allergy and Clinical Immunology, Klinikum Rechts der Isar, University of Colorado, Paul-Martini-Stiftung, AstraZeneca, Imperial College London, Children's Hospital Research Institute of Manitoba Kompetenzzentrum für Ernährung (Kern), OM Pharma, Swedish Pediatric Society for Allergy and Lung Medicine, Chinese College of Allergy and Asthma, Abbott Laboratories, Deutscher Apotheker Verlag, Socieded Chilena de Enfermedades Respiratorias, Japanese Society of Allergology,British Society for Asthma and Clinical Immunology, American Academy of Allergy, Asthma & Immunology, and the European Respiratory Society (ERS); meeting attendance support from Deutsches Zentrum für Lungenforschung, Fraunhofer ITEM Hannover, MCCA Institut für Immunologie Uni Wien, Karl-Landsteiner Privatuniversität für Gesundheitswissenschaften, Swiss Institute of Allergy and Asthma Research, Davos (Associated Institute of the University of Zurich), Medizinische Hochschule Hannover, Natasha Allergy Research Foundation, Deutsche Forschungsgemeinschaft, Gordon Research Conferences, Socieded Chilena de Enfermedades Respiratorias, Arla, Universität Leiden,OM Pharma, American Academy of Allergy, Asthma & Clinical Immunology, Deutsche Forschungsgemeinschaft, ERS, Deutsche Gesellschaft für Kinder- und Jugendmedizin, World Allergy Organization, and European Parliament; has a patent pending (PCT/EP2019/085016) for barn dust extract for the prevention and treatment of diseases; has royalties paid to ProtectImmun for a patent (EP2361632 for specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders, granted on March 19, 2014); has patents licensed to ProtectImmun (EP1411977 for composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases, granted on April 18, 2007; EP1637147 for stable dust extract for allergy protection granted on Dec 10, 2008; and EP1964570 for pharmaceutical compound to protect against allergies and inflammatory diseases, granted on Nov 21, 2012); has a patent (EP21189353.2) for proteins identified from barn dust extract for the prevention and treatment of diseases; has a patent (PCT/US2021/016918) for therapeutic fractions and proteins from asthma-protective farm dust; has a patent (EP21189353.2) for proteins identified from barn dust extract for the prevention and treatment of diseases; and is a member of the EXPANSE (funded by European Commission) Scientific Advisory Board, the BEAMS External Scientific Advisory Board, the Editorial Board of The Journal of Allergy and Clinical Immunology: In Practice, the Scientific Advisory Board of the Children's Respiratory and Environmental Workgroup, the International Scientific & Societal Advisory Board of Utrecht Life Sciences University of Utrecht, the External Review Panel of the Faculty of Veterinary Science (University of Utrecht), the Selection Committee for the Gottfried Wilhelm Leibniz Programme, the International Advisory Board of Asthma UK Centre for Applied Research, the International Advisory Board of The Lancet Respiratory Medicine, the Scientific Advisory Board of the Canadian Healthy Infant Longitudinal Development study (McMaster University, Hamilton, Canada), the Asthma UK Centre for Applied Research, the Pediatric Scientific Advisory Board Iceland, and the Abbott Allergy Risk Reduction Advisory Board. All other authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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