The DIASPORA Study
Diaphragm Structure and Pathobiology in Patients Being Bridged to Lung Transplant
Study Investigators
Dr. Ewan Goligher (ext. 6810, ewan.goligher@uhn.ca)
Dr. Shaf Keshavjee
Study Contact
Jenna Wong (ext. 7613, jenna.wong@uhn.ca)
Samira Fard (samira.fard@uhn.ca)
Study Summary
A prospective observational cohort study of changes in diaphragm structure and function during ventilation (MV or ECLS) in patients being bridged to lung transplant.
Study Population
We will enroll 30 patients receiving respiratory support (MV or ECLS) as a bridge to transplant (“Cases”), 5 patients undergoing elective lung transplantation, and 5 patients without prior history of chronic respiratory disease undergoing elective thoracic surgery.
Study Objectives
Establish whether the degree of diaphragm atrophy and injury differs according to the duration of exposure to different forms of respiratory support (MV vs. ECLS).
Correlate changes in the diaphragm on ultrasound to histological findings.
Explore the biological mechanisms underlying the development of diaphragm atrophy and injury during mechanical ventilation and extracorporeal life support.
Study Interventions
In Cases, diaphragm ultrasound and biomarkers of muscle injury (skeletal troponin-I) and systemic inflammation (inflammatory cytokines) will be measured daily. Diaphragm strength will be assessed at baseline and prior to transplantation. In all patients, diaphragm biopsies will be obtained at the time of transplantation or thoracic surgery. Myofibre cross-sectional area, fibre type, cellular infiltration and features of muscle injury will be assessed on histology. Muscle ultrastructure will be characterized by electron microscopy. Cellular signalling pathways and gene network regulation will be evaluated by transcriptomics.
Why it Matters
Lung and diaphragm injury is common during mechanical ventilation and substantially increase the risk of death, prolonged ICU admission, and long-term functional disability. The purpose of the study is to determine whether different forms of respiratory support (mechanical ventilator vs. artificial lung support) lead to different degrees of diaphragm injury, as well as to compare changes in the diaphragm seen on ultrasound to changes in the diaphragm tissues under a microscope. These insights will help us to design new strategies for mechanical ventilation that prevent diaphragm injury and improve outcomes.