Ventilator induced lung injury: translational and clinical studies

Bakground:

Mechanical ventilation(MV) is used in anaesthesia and intensive care as life-sustaining tool. When not correctly titrated, MV can lead to hyperinflation or cyclic opening-and-closing of lung alveoli. The consequent inflammatory reaction characterizes the Ventilator Induced Lung Injury (VILI).

VILI can appear also during the weaning from MV as Patient Self Induced Lung Injury (P-SILI): the patient and the ventilator synchronously develop high tidal volumes and dangerous alveolar strain. VILI and P-SILI characterize also the Covid-19, being responsible of the transition from the simple pneumonia to respiratory distress.

Objectives:

Our hypothesis is that respiratory therapy for lung failure, including Covid-19 pneumonia, is still not optimal and can cause lung damage. Objectives are:

- To identify in vivo and during mechanical ventilation the structural changes in lung mechanics that give rise to VILI or predispose to it and to establish the regional association of the presence of inflammatory cells and local alteration of lung mechanics; - To assess the neurological and muscular alterations that modify the ventilatory pattern and pave the way to VILI;

- To evaluate new physical and pharmacological treatments on inflammation created by VILI Work Plan: Different experimental sessions and clinical protocols are planned: -Studies on lung microstructure during VILI at Synchrotron facilities; -Laboratory and clinical studies on VILI during assisted ventilation; anesthesia; fluid overload;

-Analysis of intrapulmonary pattern of propagation of Covid-19 infection (retrospective) and location of associated inflammatory cells (prospective). -Laboratory study on lung fibrosis as model of post-Covid lung disease; -Studies of pharmacological and physical treatment. Significance:

VILI is a micromechanic phenomenon and requires a multi-disciplinary approach, featuring experts of image analysis, physiologists, intensivists and translational biologists. This project aims at a collaborative effort including Uppsala University (Hedenstierna Laboratory, Nuclear Medicine, Intensive Care, Radiology, Translational PET Imaging group), Lund University (Department of Translational Sciences), Karolinska Institute (Danderyd Anesthesia and Intensive Care), Sahlgrenska Academy (Intensive Care).

Given the large number of patients who are treated by respirators, even a small improvement that leads to fewer complications will result in a significant improvement in healthcare.