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From a clinician\u2019s point of view, asthma symptoms can commence at any age, although most patients with asthma\u2014regardless of their age of onset\u2014seem to have had some form of airway problems during childhood. Asthma inception and related pathophysiologic processes are therefore very likely to occur early in life, further evidenced by recent lung physiologic and mechanistic research. Herein, we present state-of-the-art updates on the role of genetics and epigenetics, early viral and bacterial infections, immune response, and pathophysiology, as well as lifestyle and environmental exposures, in asthma across the life course. We conclude that early environmental insults in genetically vulnerable individuals inducing abnormal, pre-asthmatic airway responses are key events in asthma inception, and we highlight disease heterogeneity across ages and the potential shortsightedness of treating all patients with asthma using the same treatments. Although there are no interventions that, at present, can modify long-term outcomes, a precision-medicine approach should be implemented to optimize treatment and tailor follow-up for all patients with asthma.<\/jats:p>","DOI":"10.1164\/rccm.202312-2249so","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T14:37:13Z","timestamp":1720535833000},"page":"737-754","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":104,"title":["Asthma Inception: Epidemiologic Risk Factors and Natural History Across the Life Course"],"prefix":"10.1093","volume":"210","author":[{"given":"Erik","family":"Mel\u00e9n","sequence":"first","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Zar","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health and South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Siroux","sequence":"additional","affiliation":[{"name":"University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sejal","family":"Saglani","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Centre for Paediatrics and Child Health, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard H.","family":"Koppelman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology and Pediatric Allergology, Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Beatrix Children\u2019s Hospital, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Hartert","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6667-4708","authenticated-orcid":false,"given":"James E.","family":"Gern","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Gaston","sequence":"additional","affiliation":[{"name":"Indiana University, Indianapolis; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bush","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Centre for Paediatrics and Child Health, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Zein","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,15]]},"reference":[{"key":"2026022020480488100_bib1","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/S0140-6736(22)02125-0","article-title":"Asthma","volume":"401","author":"Porsbjerg","year":"2023","journal-title":"Lancet"},{"key":"2026022020480488100_bib2","doi-asserted-by":"crossref","first-page":"2004173","DOI":"10.1183\/13993003.04173-2020","article-title":"European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5\u201316 years","volume":"58","author":"Gaillard","year":"2021","journal-title":"Eur Respir J"},{"key":"2026022020480488100_bib3","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S2213-2600(20)30363-5","article-title":"The genetics of asthma and the promise of genomics-guided drug target discovery","volume":"8","author":"El-Husseini","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2026022020480488100_bib4","doi-asserted-by":"crossref","first-page":"e13780","DOI":"10.1111\/pai.13780","article-title":"Gene-environment interactions in childhood asthma revisited; 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