{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:49:35Z","timestamp":1789487375898,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Postoperative pulmonary complications (PPC) remain a leading cause of perioperative morbidity and mortality, yet the underlying mechanisms are poorly understood. While alveolar stretch from mechanical ventilation is a known driver of lung inflammation, the role of extracellular vesicles (EVs) is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterise the biogenesis of alveolar stretch-induced EVs and determine their role in perioperative alveolar inflammation and PPC development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serial, bilateral bronchoalveolar lavage (BAL) samples were obtained from forty-two patients undergoing esophagectomy and requiring one- and two-lung ventilation. EV subtypes were identified using flow cytometry and correlated with inflammatory mediators and clinical data. Western blotting identified neutrophil-specific inflammatory matrix metalloproteinases (MMP-8\/9) within patient-derived BAL neutrophil-EVs (NEV), and their bioactivity was assessed using a primary human alveolar epithelial cell-macrophage coculture. An in vitro alveolar stretch model, comprising epithelial cells and neutrophils, was used to explore mechanisms of NEV biogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Unphysiological one-lung ventilation, but not two-lung ventilation, induced a marked increase in NEVs (4.8-fold), which were associated with alveolar inflammation and a greater incidence of PPCs. BAL NEVs contained abundant MMP-8\/9, generating pro-inflammatory responses in vitro, which were reduced by MMP inhibition. In vitro, NEV production was induced by injurious stretch of an epithelial-neutrophil co-culture through an ATP-dependent mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identify a novel mechanistic pathway whereby mechanical ventilation induces NEV release, propagating alveolar inflammation via their biologically active cargo, which may be associated with PPCs. This suggests NEVs could become a potential biomarker and therapeutic target for reducing ventilator-induced lung inflammation and PPCs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag457","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:10:11Z","timestamp":1789384211000},"source":"Crossref","is-referenced-by-count":0,"title":["Mechanical ventilation-induced neutrophil extracellular vesicles as mediators of postoperative pulmonary complications"],"prefix":"10.1093","author":[{"given":"Jonny R","family":"Stephens","sequence":"first","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Heng","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Cutting","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Walsh","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piers R","family":"Boshier","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Surgery, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Iki","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Sugarman","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzhi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Wilson","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhianna F","family":"Baldi","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Shah","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]},{"name":"Hammersmith Hospital, Imperial College Healthcare NHS Trust Department of Anaesthesia, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Patel","sequence":"additional","affiliation":[{"name":"Hammersmith Hospital, Imperial College Healthcare NHS Trust Department of Critical Care, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C","family":"Gordon","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George B","family":"Hanna","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Surgery, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Takata","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanooj","family":"Soni","sequence":"additional","affiliation":[{"name":"Imperial College London Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, , London,","place":["UK"]},{"name":"Hammersmith Hospital, Imperial College Healthcare NHS Trust Department of Critical Care, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,15]]},"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article-pdf\/doi\/10.1093\/ajrccm\/aamag457\/71089386\/aamag457.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article-pdf\/doi\/10.1093\/ajrccm\/aamag457\/71089386\/aamag457.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:51:22Z","timestamp":1789480282000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article\/doi\/10.1093\/ajrccm\/aamag457\/8796056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/ajrccm\/aamag457","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"aamag457"}}