Extracellular vesicles in ventilator-acquired pneumonia (VAP)
Research type
Research Study
Full title
The role of extracellular vesicles in peri-operative and ventilator-acquired pneumonia
IRAS ID
345988
Contact name
Sanooj Soni
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
2 years, 10 months, 4 days
Research summary
Peri-operative complications are an important source of morbidity and mortality and have been associated with longer hospital stays, increased mortality, increased healthcare costs and overall decreased long-term survival. Pneumoniae occur after major surgeries despite preventative strategies like broad-spectrum antibiotic administration and enhanced recovery programs, so there may be alternative cellular pathways that cause this. Mechanical ventilation has shown to have an injurious effect on the lung micro-environment and in the peri-operative and ICU setting there are a variety of factors that can lead to potentially injurious ventilation. Extracellular vesicles (EVs) are key mediators that have exhibited an important role in the worsening of ventilator-induced lung injury.
This research plans to study how EVs (nano-sized molecules released by cells), released as a result of intra-operative mechanical ventilation, may affect alveolar macrophage (AM) function; thereby rendering them incapable of protecting the host from pathogen infiltration as the first line of defence, leading to post-operative pneumoniae. We will recruit suitable patients undergoing elective major surgeries, as well as ICU patients (capturing a wide range of ventilation practices). We aim to take bronchoalveolar lavage fluid (BALF), plasma and urine samples from peri-operative patients on the day of their operation (at the start, middle and end of surgery) and for ICU patients within 24 hours of their admission, 48 hours later and beyond. We will analyse EVs, inflammatory markers and AMs within these samples and correlate them with clinical outcomes and parameters of pneumonia. We will analyse which ventilatory factors cause EV release, study the cellular mechanisms by which EVs communicate with AMs to impair their key immune functions and assess whether preventing this process may augment AM regulatory function, thus reducing pneumoniae.By improving our understanding of these mechanisms that lead to peri-operative/ventilator-associated pneumoniae, we may aid the development of future preventative and therapeutic strategies.
REC name
London - Camden & Kings Cross Research Ethics Committee
REC reference
24/PR/1606
Date of REC Opinion
28 Apr 2025
REC opinion
Further Information Favourable Opinion