Abstract
Acute respiratory distress syndrome (ARDS) is characterized by increased permeability of the alveolar–capillary membrane, a thin barrier composed of adjacent monolayers of alveolar epithelial and lung microvascular endothelial cells. This results in pulmonary edema and severe hypoxemia and is a common cause of death after both viral (e.g., SARS-CoV-2) and bacterial pneumonia. The involvement of the lung in ARDS is notoriously heterogeneous, with consolidated and edematous lung abutting aerated, less injured regions. This makes treatment difficult, as most therapeutic approaches preferentially affect the normal lung regions or are distributed indiscriminately to other organs. In this review, we describe the use of thoracic ultrasound and microbubbles (USMB) to deliver therapeutic cargo (drugs, genes) preferentially to severely injured areas of the lung and in particular to the lung endothelium. While USMB has been explored in other organs, it has been under-appreciated in the treatment of lung injury since ultrasound energy is scattered by air. However, this limitation can be harnessed to direct therapy specifically to severely injured lungs. We explore the cellular mechanisms governing USMB and describe various permutations of cargo administration. Lastly, we discuss both the challenges and potential opportunities presented by USMB in the lung as a tool for both therapy and research.
Highlights
Endothelial cells line the entire vascular system and are the interface between blood and tissue [1]
Therapies that decrease endothelial permeability would be of particular interest in the lung, where acute respiratory distress syndrome (ARDS, called acute lung injury) is characterized by disrupted alveolar endothelial and epithelial barriers, leading to pulmonary edema and arterial hypoxemia [5]
We first briefly review some fundamental determinants of endothelial activation and permeability; subsequently, we focus our discussion on how the combination of thoracic ultrasound and intravenously administered microbubbles (USMB) may permit preferential delivery of therapeutic cargoes to the lung endothelium in the most damaged regions of the lung [3,8]
Summary
Endothelial cells line the entire vascular system and are the interface between blood and tissue [1]. A primary role of the microvascular endothelium is to regulate the flux of molecules between the vascular lumen and the surrounding tissue parenchyma. Therapies that decrease endothelial permeability would be of particular interest in the lung, where acute respiratory distress syndrome (ARDS, called acute lung injury) is characterized by disrupted alveolar endothelial and epithelial barriers, leading to pulmonary edema and arterial hypoxemia [5]. It occurs in nearly 10% of all intensive care unit (ICU) admissions and results in a mortality rate of up to 40% despite the best supportive care [6]. We first briefly review some fundamental determinants of endothelial activation and permeability; subsequently, we focus our discussion on how the combination of thoracic ultrasound and intravenously administered microbubbles (USMB) may permit preferential delivery of therapeutic cargoes to the lung endothelium in the most damaged regions of the lung [3,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
