Caroline de Gracia Lux, Ph.D., Assistant Professor of Radiology, has been awarded the 2021 Haberecht Wildhare-Idea Research Grant for investigating a potential game-changing strategy to improve the outcomes of patients with acute respiratory distress syndrome, or ARDS, a type of lung damage that can be caused by COVID-19.
UT Southwestern’s Haberecht Grant supports a speculative idea that, if proven, constitutes a breakthrough in biomedical research. Dr. de Gracia Lux’s project was chosen for the one-year, $25,000 award from among 24 proposals received from UT Southwestern faculty, postdoctoral fellows, and graduate students.
Human lungs contain over half a billion tiny air sacs whose surface covers over 1,000 square feet to adequately oxygenate the blood traveling in their walls. When the chest expands to breathe, it creates a vacuum that sucks air to fill the tiny air sacs that promptly empty when the chest recoils.
In normal lungs, this is an effortless task because the air sacs produce a fluid called surfactant that coats their surface to markedly reduce the pressure needed to fill and empty. When less surfactant is produced – as in premature or injured lungs as seen with COVID-19 patients – the air sacs collapse, making it difficult to breathe without ventilator assistance.
Ventilators push air in to inflate the lungs, and like clown balloons that are difficult to inflate at first, more pressure is needed to inflate collapsed lungs. Because positive pressure can overinflate some air sacs, overinflation can cause ventilator-induced lung injury. Many interventions proposed over the past decades to decrease inflation pressures, and by extension overinflation, failed to do so. One of these is partial liquid ventilation with perfluorocarbon (PFC). Because PFC liquids weigh twice as much as water, when lungs are partially filled to the volume present after passive exhalation, the liquid, although introduced in the trachea, preferentially fills the dependent air sacs, and because it can dissolve 15 times more oxygen than water, adequate gas exchange is maintained, although some positive pressure was still needed to ventilate through liquid. However, clinical trials were abandoned since they failed to show superiority over pressure gas ventilation.
The goal of Dr. de Gracia Lux’s research is to decrease the required inflation pressure and obviate mechanical ventilation’s complications related to longer times on a ventilator using PFC given as a liquid emulsion intravenously. This approach to facilitating better and safer gas exchange represents a departure from current ARDS management. If successful, this strategy could decrease the amount of time that artificial breathing is needed and even represents a simple and scalable method for improving outcomes of patients with ARDS.
Dr. de Gracia Lux received her doctorate in chemistry from the University of Strasbourg in France under the mentorship of Dr. Marie Pierre Krafft. There, she began to learn about the fascinating properties of fluorinated molecules. Dr. de Gracia Lux then completed postdoctoral training at the University of California, San Diego, focusing on the design and formulation of degradable nanoparticles using synthetic polymers engineered to fall apart upon remote on-demand activation or in response to disease biomarkers.
In 2015, she came to UT Southwestern to join the newly formed Translational Research in Ultrasound Theranostics (TRUST) program in the Department of Radiology. The TRUST team, directed by Dr. Robert Mattrey, Professor of Radiology and in the Advanced Imaging Research Center, develops new strategy, with a focus on ultrasound-based agents, to improve clinicians’ ability to treat and image cancer and other diseases more accurately to ultimately improve patient care.
“I am honored by this award and excited about the groundbreaking step it will be if our hypotheses are proven correct and grateful for my colleagues, including Dr. Robert Mattrey, Assistant Professor of Radiology Dr. Jacques Lux, and Associate Professor of Internal Medicine Dr. Matthew Leveno for their help and support,” Dr. de Gracia Lux said.