{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:07:57Z","timestamp":1787965677678,"version":"build-2784847793"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health and Care Research (NIHR) Academic Clinical Fellowship, University of Birmingham","award":["ACF-2023-09-002"],"award-info":[{"award-number":["ACF-2023-09-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diffuse alveolar haemorrhage (DAH) is rare but associated with high morbidity and mortality. It is underpinned by mechanisms of endothelial dysfunction, inflammation, and vascular remodelling, yet its pathogenesis remains incompletely understood. Progress in translational research is currently limited by the absence of robust animal models of this condition. Equine exercise-induced pulmonary haemorrhage (EIPH), a common and progressive disorder in racehorses, may represent a novel and underutilised translational model for studying DAH, which can be a complication of or associated with other cardiopulmonary conditions, such as pulmonary arterial hypertension (PAH). EIPH occurs spontaneously in up to 95% of thoroughbreds after repeated strenuous exercise and is characterised by haemorrhage into the alveoli, capillary stress failure, inflammatory infiltration, and subsequent parenchymal remodelling. These processes closely parallel the vascular injury and immune activation observed in DAH. Horses further offer distinct advantages as models for human respiratory disease, including large lung size, long lifespan, and comparable pulmonary architecture. The regional distribution of haemorrhage in equine lungs additionally enables within-animal control studies. By leveraging the mechanistic overlaps between equine and human pulmonary pathology, EIPH provides a unique opportunity for biomarker discovery, mechanistic insight, and therapeutic testing in pulmonary vascular disease.<\/jats:p>","DOI":"10.3390\/ijms27104157","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:39:47Z","timestamp":1778150387000},"page":"4157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rare Models: Use of a Novel Translational Model for Diffuse Alveolar Haemorrhage"],"prefix":"10.3390","volume":"27","author":[{"given":"Karan R.","family":"Chadda","sequence":"first","affiliation":[{"name":"Homerton College, University of Cambridge, Cambridge CB2 8PH, UK"},{"name":"Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-2116","authenticated-orcid":false,"given":"Savithri","family":"Sathivelu","sequence":"additional","affiliation":[{"name":"Royal Free London NHS Foundation Trust, London NW3 2QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5344-827X","authenticated-orcid":false,"given":"Susan K.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0959-1455","authenticated-orcid":false,"given":"Charlotte","family":"Edling","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-388X","authenticated-orcid":false,"given":"Kamalan","family":"Jeevaratnam","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/cbf.3173","article-title":"Large animal models of cardiovascular disease","volume":"34","author":"Tsang","year":"2016","journal-title":"Cell Biochem. Funct."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.jcin.2009.03.004","article-title":"The pre-clinical animal model in the translational research of interventional cardiology","volume":"2","author":"Suzuki","year":"2009","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1152\/physrev.00007.2016","article-title":"Murine Electrophysiological Models of Cardiac Arrhythmogenesis","volume":"97","author":"Huang","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_5","first-page":"5950813","article-title":"Conceptualization of Heterogeneity of Chronic Diseases and Atherosclerosis as a Pathway to Precision Medicine: Endophenotype, Endotype, and Residual Cardiovascular Risk","volume":"2020","author":"Genkel","year":"2020","journal-title":"Int. J. Chronic Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1164\/rccm.202311-2086SO","article-title":"From ICU Syndromes to ICU Subphenotypes: Consensus Report and Recommendations for Developing Precision Medicine in the ICU","volume":"210","author":"Gordon","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Murray, J., O\u2019Brien, S., and Mitchell, P. (2025). Diffuse Alveolar Hemorrhage (DAH). Proceedings of the Seminars in Respiratory and Critical Care Medicine, Thieme Medical Publishers, Inc.","DOI":"10.1055\/a-2725-7274"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1097\/00000478-199012000-00003","article-title":"A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation","volume":"14","author":"Travis","year":"1990","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_9","first-page":"e2023004","article-title":"Clinical characteristics of patients with diffuse alveolar hemorrhage diagnosed by cytological examination of 1000 bronchoalveolar lavage samples","volume":"40","author":"Prasad","year":"2023","journal-title":"Sarcoidosis Vasc. Diffus. Lung Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4046\/trd.2013.74.4.151","article-title":"Diffuse alveolar hemorrhage","volume":"74","author":"Park","year":"2013","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3949\/ccjm.75.4.258","article-title":"Diffuse alveolar hemorrhage: Diagnosing it and finding the cause","volume":"75","author":"Ioachimescu","year":"2008","journal-title":"Cleve Clin. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"720","DOI":"10.2214\/ajr.184.3.01840720","article-title":"Pattern-based differential diagnosis in pulmonary vasculitis using volumetric CT","volume":"184","author":"Marten","year":"2005","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1183\/09031936.00075309","article-title":"Diffuse alveolar haemorrhage: Factors associated with in-hospital and long-term mortality","volume":"35","author":"Parrot","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s13054-020-02936-0","article-title":"Severe diffuse alveolar hemorrhage related to autoimmune disease: A multicenter study","volume":"24","author":"Mirouse","year":"2020","journal-title":"Crit. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s00108-017-0190-7","article-title":"Haemoptysis: Intensive care management of pulmonary hemorrhage","volume":"58","author":"Ficker","year":"2017","journal-title":"Internist"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Park, J.A. (2021). Treatment of Diffuse Alveolar Hemorrhage: Controlling Inflammation and Obtaining Rapid and Effective Hemostasis. Int. J. Mol. Sci., 22.","DOI":"10.37247\/PAMOL2ED.2.2021.17"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1017\/S147806150891906X","article-title":"Evidence supporting exercise-induced pulmonary haemorrhage in racing greyhounds","volume":"5","author":"Epp","year":"2008","journal-title":"Comp. Exerc. Physiol."},{"key":"ref_18","first-page":"16","article-title":"Lung physiology at play: Hemoptysis due to underwater hockey","volume":"11","author":"Aversa","year":"2014","journal-title":"Respir. Med. Case Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"375","DOI":"10.4046\/trd.2015.78.4.375","article-title":"A 45-Year-Old Man With Recurrent Dyspnea and Hemoptysis during Exercise: Exercise-Induced Pulmonary Hemorrhage\/Edema","volume":"78","author":"Kim","year":"2015","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00163","DOI":"10.1002\/rcr2.163","article-title":"Exercise-induced endobronchial hemorrhage: A rare clinical presentation","volume":"4","author":"Kruavit","year":"2016","journal-title":"Respirol. Case Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1751-0813.1993.tb06072.x","article-title":"Equine bronchoalveolar lavage cytology: Survey of thoroughbred racehorses in training","volume":"70","author":"McKane","year":"1993","journal-title":"Aust. Vet. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"703","DOI":"10.2460\/ajvr.1981.42.05.703","article-title":"Exercise-induced pulmonary hemorrhage in racing thoroughbreds: A preliminary study","volume":"42","author":"Pascoe","year":"1981","journal-title":"Am. J. Vet. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"596","DOI":"10.2460\/ajvr.2005.66.596","article-title":"Tracheobronchoscopic assessment of exercise-induced pulmonary hemorrhage in horses","volume":"66","author":"Hinchcliff","year":"2005","journal-title":"Am. J. Vet. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.2042-3306.2011.00496.x","article-title":"Risk factors for race-associated sudden death in Thoroughbred racehorses in the UK (2000\u20132007)","volume":"44","author":"Lyle","year":"2012","journal-title":"Equine Vet. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2746\/0425164054530597","article-title":"Sudden death in racing Thoroughbreds in Victoria, Australia","volume":"37","author":"Boden","year":"2005","journal-title":"Equine Vet. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1177\/1040638717700690","article-title":"Postmortem findings in Ontario racehorses, 2003\u20132015","volume":"29","author":"DeLay","year":"2017","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hinchcliff, K.W., Kaneps, A.J., Geor, R.J., and van Erck-Westergren, E. (2024). 35\u2014Exercise-Induced Pulmonary Hemorrhage. Equine Sports Medicine and Surgery, W.B. Saunders. [3rd ed.].","DOI":"10.1016\/B978-0-7020-8370-9.00035-7"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/evj.12957","article-title":"Exercise-induced pulmonary haemorrhage in Thoroughbred racehorses: A longitudinal study","volume":"51","author":"Crispe","year":"2019","journal-title":"Equine Vet. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/jvim.12593","article-title":"Exercise induced pulmonary hemorrhage in horses: American College of Veterinary Internal Medicine consensus statement","volume":"29","author":"Hinchcliff","year":"2015","journal-title":"J. Vet. Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/evj.12412","article-title":"Exercise-induced pulmonary haemorrhage: A progressive disease affecting performance?","volume":"47","author":"Robinson","year":"2015","journal-title":"Equine Vet. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1354\/vp.45-3-316","article-title":"Regional pulmonary veno-occlusion: A newly identified lesion of equine exercise-induced pulmonary hemorrhage","volume":"45","author":"Williams","year":"2008","journal-title":"Vet. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1152\/jappl.1996.81.3.1062","article-title":"Minimal redistribution of pulmonary blood flow with exercise in racehorses","volume":"81","author":"Bernard","year":"1996","journal-title":"J. Appl. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1152\/jappl.1998.85.2.537","article-title":"Regional differences in endothelial function in horse lungs: Possible role in blood flow distribution?","volume":"85","author":"Pelletier","year":"1998","journal-title":"J. Appl. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1152\/japplphysiol.00975.2015","article-title":"Regional heterogeneity in the reactivity of equine small pulmonary blood vessels","volume":"120","author":"Stack","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1152\/japplphysiol.00314.2014","article-title":"Lung region and racing affect mechanical properties of equine pulmonary microvasculature","volume":"117","author":"Stack","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Blott, S., Cunningham, H., Malkowski, L., Brown, A., and Rauch, C. (2019). A Mechanogenetic Model of Exercise-Induced Pulmonary Haemorrhage in the Thoroughbred Horse. Genes, 10.","DOI":"10.3390\/genes10110880"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.2042-3306.1999.tb05202.x","article-title":"Sequential changes in bronchoalveolar cytology after autologous blood inoculation","volume":"31","author":"McKane","year":"1999","journal-title":"Equine Vet. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.2042-3306.2010.00295.x","article-title":"Experimental mild pulmonary inflammation promotes the development of exercise-induced pulmonary haemorrhage","volume":"42","author":"McKane","year":"2010","journal-title":"Equine Vet. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/path.4658","article-title":"Studying human respiratory disease in animals--role of induced and naturally occurring models","volume":"238","author":"Williams","year":"2016","journal-title":"J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00441-019-03117-4","article-title":"The equine asthma model of airway remodeling: From a veterinary to a human perspective","volume":"380","author":"Bullone","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/01902148.2018.1455927","article-title":"MicroRNAs in idiopathic pulmonary fibrosis, new research progress and their pathophysiological implication","volume":"44","author":"Miao","year":"2018","journal-title":"Exp. Lung Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1165\/rcmb.2017-0040OC","article-title":"MicroRNA Dysregulation in Pulmonary Arteries from Chronic Obstructive Pulmonary Disease. Relationships with Vascular Remodeling","volume":"59","author":"Musri","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/j.biopha.2018.11.058","article-title":"MicroRNA-150 relieves vascular remodeling and fibrosis in hypoxia-induced pulmonary hypertension","volume":"109","author":"Li","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","first-page":"133","article-title":"Exercise-induced pulmonary hemorrhage: Where are we now?","volume":"7","author":"Poole","year":"2016","journal-title":"Vet. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1056\/NEJMra2000348","article-title":"Pulmonary Arterial Hypertension","volume":"385","author":"Hassoun","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_47","first-page":"Pi","article-title":"The pathology of primary pulmonary hypertension","volume":"101","author":"Wagenvoort","year":"1970","journal-title":"J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1378\/chest.11-0793","article-title":"Inflammation in pulmonary arterial hypertension","volume":"141","author":"Price","year":"2012","journal-title":"Chest"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/af\/vfac035","article-title":"Equine exercise physiology\u2014Challenges to the respiratory system","volume":"12","author":"Mazan","year":"2022","journal-title":"Anim. Front."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jcyt.2019.02.010","article-title":"Insights into animal models for cell-based therapies in translational studies of lung diseases: Is the horse with naturally occurring asthma the right choice?","volume":"21","author":"Stucchi","year":"2019","journal-title":"Cytotherapy"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Boozarjomehri Amnieh, S., and Ropka-Molik, K. (Anim. Model. Exp. Med., 2026). Equine models in translational medicine: A comparative approach to human health, Anim. Model. Exp. Med., online ahead of print.","DOI":"10.1002\/ame2.70180"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4157\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:42:14Z","timestamp":1778150534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104157"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104157","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]}}}