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Although biologic therapies have transformed outcomes by reducing exacerbations and systemic corticosteroid exposure, their potential to modify structural airway trajectories\u2014and whether a time\u2010sensitive \u201cwindow of opportunity\u201d exists\u2014remains uncertain. Here, we provide a progressive landscape integrating mechanistic remodeling pathways with measurable structural readouts (biopsy\u2010derived indices and quantitative imaging) and emerging digital biomarkers derived from connected respiratory technologies. We propose an operational framework linking mechanism \u2192 biomarker \u2192 remodeling readout \u2192 timing decision, and we outline a 1\u2010, 3\u2010, and 5\u2010year research roadmap in which advanced artificial intelligence (AI) methods (multimodal learning, causal inference, federated learning, and digital\u2010twin architectures) evolve in parallel with wearable and smart\u2010inhaler ecosystems. This landscape aims to standardize endpoints, sharpen trial design, and accelerate a shift from symptom control toward credible disease modification in severe asthma.<\/jats:p>","DOI":"10.1111\/all.70468","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:11:45Z","timestamp":1787836305000},"page":"3157-3170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Airway Remodeling in Severe Asthma: Is There a Window of Opportunity for Biologic Therapy Predicting Effects Using Causal Artificial Intelligence?"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-6532","authenticated-orcid":false,"given":"Sebastiano","family":"Gangemi","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Allergy and Clinical Immunology Unit University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Manti","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adult and Childhood Gaetano Barresi, Pediatric Unit University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4291-1956","authenticated-orcid":false,"given":"Johann Christian","family":"Virchow","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine, Clinic for Pneumology, Allergology, Intensive Care Medicine Universit\u00e4temedizin Rostock  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-2557","authenticated-orcid":false,"given":"Giorgio Walter","family":"Canonica","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Personalized Medicine, Asthma and Allergy, IRCCS 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