Lung Mechanics Lab Spotlight: Exciting Advancements in Studying Acute Respiratory Distress Syndrome
Staying in self-isolation during the peak of the COVID-19 outbreak yielded a unique set of struggles, being stuck at home and learning remotely disengaged me from my studies and interests relating to school. During these times I found myself more involved with binging “Grey’s Anatomy” and napping rather than schlepping my way through learning complex concepts and math via zoom. As the days drew on, I found myself increasingly detached from my academic interests, but something that rekindled my academic passions towards the end of quarantine was my biomedical engineering class. Learning about the pathophysiology and treatment of Acute Respiratory Distress Syndrome (ARDS) revitalized my passion for my major due to its relevance to the current health landscape worldwide.
To understand the importance of this field of research, we first must briefly talk about the anatomy of the lungs. Properly functioning lungs exchange gas through the alveoli, which are lined by thin type I epithelial cells that permit gas exchange and type II cells that secrete surfactant. Pulmonary surfactant is necessary to lower the surface tension of the air/liquid interface, which keeps the lungs compliant. This phenomenon allows them to expand when inflated with air without damaging alveoli.
A healthy Alveoli, filled with air (Modified Figure of Carrie Perlman)
Acute Respiratory Distress Syndrome (ARDS) is extremely dangerous, with about 200,000 cases per year in the United States (1) and a death rate of 27-45% depending on its severity (2). ARDS is a non-cardiogenic pulmonary edema, which is characterized by excess fluid in the tissue and airspace of the lungs. Inflammation from conditions like sepsis, shock, and pneumonia cause blood vessels in the lungs to leak, heterogeneously filling the alveoli with fluid and reducing oxygenation. There is also an overdistention of the flooded alveolus’s air-filled neighbor, which results in stress concentration building up, making these spots more susceptible to damage during both spontaneous breathing and mechanical ventilation. The ventilation decreases, resulting in high carbon dioxide and high pH, causing patients to feel distressed.
Due to its relevance in today’s world, I will note that there are some key differences between regular ARDS and the ARDS associated with COVID-19. The ARDS associated with COVID-19 is different because type II cells are infected by the virus, but they are observed to proliferate, a fascinating phenomenon of unknown origin. The abundant type II cells produce more surfactant, keeping lung compliance and ventilation regular, which keeps carbon dioxide and pH levels normal. This means that patients will feel relatively normal at the beginning of ARDS onset. This is highly dangerous, due to the fact that by the time the patient begins to feel ill, their ARDS is already in the advanced stages and their blood oxygen levels are only half of what they should be!
So who is studying this and what discoveries are being made?
I spoke to Dr. Carrie Perlman, a professor and researcher at Stevens Institute of Technology to learn about the exciting things she has done in this field. She came up with an idea that led her and her team to develop the first method to use confocal microscopy along with other techniques to determine surface tension in flooded alveoli of the lungs. Her knowledge of the Laplace equation assisted in her modeling of the micromechanics of the alveoli, as it relates the surface tension and radius of the alveoli curvature to the pressure. This information can be very useful in this type of modeling because lung injury is proportional to surface tension.
Dr. Perlman and her colleagues Kharge and Wu published a fascinating paper in 2015, where they detailed their discovery that the chemical sulforhodamine B (SRB) lowers surface tension in the lungs. This is an exciting breakthrough because according to Perlman, it has the potential to help ARDS patients avoid mechanical ventilation and help ventilated ARDS patients survive! Although she is still not sure exactly how this mechanism works, Perlman says that SRB works in conjunction with a protein from the blood and together they improve the way the natural pulmonary surfactant works. She said that it was surprising that SRB needed to work with the plasma protein because it was generally believed that the plasma raised surface tension, but Dr. Perlman and her team found that the plasma protein on its own does not alter surface tension.
Another interesting thing going on in the lab is that one of Dr. Perlman’s postdoctoral fellows, Jardim-Neto created a low-cost ventilator system that can support multiple patients. This circuit is described as having “polyvinyl chloride plumbing tubes and connectors, with ball valves and water columns used to control pressures”, meaning that the volume of air is the same for each patient while the pressure is individualized. This is rather primitive compared to standard ventilators, but this is an excellent way to combat ventilator shortages.
As you can see, the Lung Mechanics Lab at Stevens is an interesting place, where you can find novel solutions to challenging healthcare problems that utilize a creative combination of mechanics, biophysics and physiology. Dr. Perlman and her team hope to move forward with their treatments and make a lasting clinical impact. When talking about her career Dr. Perlman remarked that she “couldn’t have predicted how fascinating it would be”, which gives me hope that I will have a similar experience in my biomedical engineering journey.
(1) Harman, Eloise. “Acute Respiratory Distress Syndrome (ARDS).” Background, Pathophysiology, Etiology, 27 Mar. 2020, emedicine.medscape.com/article/165139-overview#a6.
(2) Diamond M, Peniston Feliciano HL, Sanghavi D, et al. Acute Respiratory Distress Syndrome (ARDS) [Updated 2020 Jan 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:https://www.ncbi.nlm.nih.gov/books/NBK436002/
About Dr. Carrie E Perlman:
Dr. Perlman is an associate professor at Stevens Institute Technology's School of Engineering and Science. At the Lung Mechanics lab Dr. Perlman and her team study and develop treatments for Pulmonary Edema. She received her B.S. in mechanical engineering from MIT, M.S. and Ph.D in biomedical engineering from Northwestern University, and completed her Postdoctoral training at the Physiology & Cellular Biophysics and Pulmonary Division, Dept of Medicine, Columbia University.
About the author:
Hi, my name is Julia Caputo and I am a research intern here at EWAAB. I have always been amazed by science and technology. I am a biomedical engineering student from Queens, New York and I am entering my third year at Stevens Institute of Technology. On campus, I am passionately involved in the Society of Women Engineers and Alpha Phi Omega Service Fraternity. I recently got my Emergency Medical Technician license and I hope to go to medical school.