A materials science approach to treating respiratory distress syndromes and advanced COVID-19 infections

Abstract

Lung Surfactant (LS) is a mixture of lipids and proteins lining the air/water interface in the alveoli. LS facilitates breathing, mainly by reducing the air/water interfacial tension, and thus the energy required to breathe. The lack of functional LS is associated with two pathological conditions: Neonatal Respiratory Distress Syndrome (NRDS) and Acute Respiratory Distress Syndrome (ARDS). NRDS occurs in premature infants who have not developed LS secretion system, while ARDS happens when the lung is injured and the inflammatory response leads to LS inactivation. To date, the state-of-art replacement surfactants are extracted from animals, of which the exact composition is not known and could vary from animal to animal. This raises concerns regarding contamination and quality-control. Additionally, the animal-derived LS has not been effective in treating ARDS as the body's innate immune system inactivates LS, both endogenous and exogenous. This lack of quality-controlled, effective LS thus calls for a systematic understanding of clinical lung surfactant formulation, as well as an investigative study into LS inactivation mechanism during ARDS progression and its treatment. The contribution of my PhD work can be divided into three major themes. First, I have developed an understanding of how formulation affects clinical lung surfactant viscoelasticity and subsequent intratracheal delivery to treat neonatal respiratory distress syndrome. Second, I demonstrated that Langmuir trough, a tool classically used to study lipid monolayer, can be used for measurements of dilatational modulus (resistance to area change) of the lung surfactant system and inflammation products. Third, I investigated dynamics of lung surfactant in the presence of inflammation products, and discovered a mechanism by which a potentially fatal lung collapse can take place. Ultimately, the unified understanding of these phenomena will serve as a powerful weapon against the respiratory distress syndromes. This overarching understanding of the LS system can further be extended to other membrane and interfacial phenomena.