Plain-language summary
Serial lung-lavage samples were collected from 42 patients undergoing oesophagectomy who required one-lung ventilation during surgery. One-lung ventilation, which stretches the lung unphysiologically, raised neutrophil-derived extracellular vesicles in the lavage fluid roughly five-fold; two-lung ventilation did not. The rise tracked with alveolar inflammation and with a higher incidence of postoperative pulmonary complications. Those vesicles carried the neutrophil proteases MMP-8 and MMP-9, and when applied to human alveolar epithelial cell and macrophage co-cultures they provoked a pro-inflammatory response that MMP inhibition largely removed. In a stretch model, release depended on ATP, pointing to an active, mechanosensitive secretion route rather than simple cell damage.
Key findings
- Alveolar stretch from one-lung ventilation increased neutrophil-derived extracellular vesicles in patient bronchoalveolar lavage fluid 4.8-fold; two-lung ventilation did not.
- Vesicle levels correlated with alveolar inflammation and with a greater incidence of postoperative pulmonary complications.
- Patient-derived neutrophil vesicles carried the inflammatory matrix metalloproteinases MMP-8 and MMP-9.
- In human alveolar epithelial cell and macrophage co-culture, those vesicles drove a pro-inflammatory response that MMP inhibition reduced.
- Vesicle production in a stretch model was ATP-dependent, indicating regulated secretion rather than passive release.
- The authors propose these vesicles as a candidate biomarker and a possible target for reducing ventilator-induced lung inflammation; clinical utility is not yet established.
Why this matters for lung repair
Patients who go on to develop postoperative lung complications are currently identified only after the injury is established. This study points to a measurable vesicle signal that appears in lavage fluid and rises with the mechanical insult, which is a plausible route to earlier detection. It also frames a purely mechanical stressor as something that propagates between cell types through vesicles, reinforcing the view that extracellular vesicles are active participants in lung inflammation rather than debris. The work is observational and mechanistic in a surgical cohort; it does not test any therapy.
Original abstract
Rationale: 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. Objectives: To characterise the biogenesis of alveolar stretch-induced EVs and determine their role in perioperative alveolar inflammation and PPC development. Methods: 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. Measurements And Main Results: 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. Conclusions: 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.
Frequently asked questions
What did this study find?
Serial lung-lavage samples were collected from 42 patients undergoing oesophagectomy who required one-lung ventilation during surgery. One-lung ventilation, which stretches the lung unphysiologically, raised neutrophil-derived extracellular vesicles in the lavage fluid roughly five-fold; two-lung ventilation did not. The rise tracked with alveolar inflammation and with a higher incidence of postoperative pulmonary complications. Those vesicles carried the neutrophil proteases MMP-8 and MMP-9, and when applied to human alveolar epithelial cell and macrophage co-cultures they provoked a pro-inflammatory response that MMP inhibition largely removed. In a stretch model, release depended on ATP, pointing to an active, mechanosensitive secretion route rather than simple cell damage.
Was this tested in humans or in the laboratory?
This is preclinical work — the findings come from laboratory models, not from human participants.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1093/ajrccm/aamag457
Does this study prove that JuvGuard works?
No. This is an independent, peer-reviewed study on extracellular vesicles. JuvGuard references the published literature for education only. A single paper cannot establish that any product works, and nothing here is medical advice.
How to cite this paper
Stephens Jonny R, Heng Shan, Cutting Ana, Walsh Rebecca, Boshier Piers R, Iki Yoichi et al.. Mechanical ventilation-induced neutrophil extracellular vesicles as mediators of postoperative pulmonary complications.. American journal of respiratory and critical care medicine. 2026, 2026-09-15. DOI: 10.1093/ajrccm/aamag457
Source & verification
- Journal: American journal of respiratory and critical care medicine
- Published: 15 September 2026
- DOI: 10.1093/ajrccm/aamag457
- PubMed ID: 42742361
- Indexed via: pubmed
- MeSH terms: —