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Polverino, F.* ; Benam, K.H.* ; Cloonan, S.M.* ; Curtis, J.L.* ; Gaggar, A.* ; Kheradmand, F.* ; Lehmann, M. ; Neptune, E.* ; Raju, S.V.* ; Rojas-Quintero, J.* ; Sauler, M.* ; Tesfaigzi, Y.* ; Yildirim, A.Ö. ; Zhou, A.X.* ; Sin, D.D.*

Preclinical models of COPD: A state of the art review.

Eur. Respir. J. 68:2600289 (2026)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
COPD is a progressive and heterogeneous condition characterised by varying combinations of emphysema, small airway disease, chronic bronchitis and exacerbations. Although multiple symptomatic therapies exist, no disease-modifying treatments are available. This gap highlights the need for improved preclinical models with greater translational relevance. Large human cohorts and single-cell/multi-omics studies have informed the development of current COPD models. We provide a state of the art review of the major experimental platforms: in vivo (small and large animals, genetic and injury models, environmental exposures), ex vivo (precision-cut lung slices, organoids, co-cultures, lung-on-a-chip systems) and in silico (aerosol dispersion and computational tools). While each approach has yielded important mechanistic insights, none fully captures the complexity of COPD progression, comorbidities, gene-environment interactions or heterogeneous clinical endotypes. Future progress will depend on the development of more integrated, human-relevant modelling systems, alongside advanced exposure platforms and artificial intelligence-driven multi-omics integration to identify biologically meaningful endotypes and speed the creation of phenotype-specific therapies. We propose a phenotype-driven, cross-platform framework in which hypotheses emerging from human clinical and omics data are validated in in vitro and ex vivo systems, evaluated in phenotype-specific in vivo models, and ultimately confirmed through clinical studies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Obstructive Pulmonary-disease; Smoke-induced Emphysema; Severe Alpha-1-antitrypsin Deficiency; Cigarette-smoke; Mouse Model; Animal-models; Epithelial-cells; Murine Model; Wood Smoke; Spiromics
ISSN (print) / ISBN 0903-1936
e-ISSN 1399-3003
Zeitschrift European Respiratory Journal
Quellenangaben Band: 68, Heft: 4, Seiten: , Artikelnummer: 2600289 Supplement: ,
Verlag European Respiratory Society
Verlagsort Sheffield
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)