Lung Simulations Could Improve Respiratory Treatment

ARDS is a life-threatening inflammation of the respiratory system that kills 74,000 adults each year in the United States alone. It is most common among patients with lung injury or sepsis, a whole-body inflammation caused by infection. Treatment involves surfactant replacement therapy (SRT) to make it easier for the lungs to inflate, similar to the therapy used in premature babies, who can lack the surfactant necessary to expand their lungs. While SRT has contributed to a dramatic reduction in mortality rates of premature babies, the attempt to implement the technology in adults has been largely unsuccessful.

To try and reveal why, researchers at the University of Michigan (U-M; Ann Arbor, USA) and Ecole Polytechnique (Palaiseau, France) developed a mathematical computer model that provided a three-dimensional (3D) image of exactly how SRT flowed through the lungs of patients in the three key trials that examined the technology. The first (1997) clinical study in adults showed promise, cutting mortality rate from 40% to 20%. But two larger studies in 2004 and 2011 showed no improvement in mortality, and the treatment was abandoned.

The computer model used fluid mechanical principals for 3-D modeling of the lung airway tree in both neonates and adults, showing how a liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, they saw that the SRT plug deposits a coating film on the airway wall, and then splits unevenly at the bifurcation due to gravity. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity.

When the researchers applied this engineering perspective to SRT, they saw one detail that set the successful 1997 study apart; a less concentrated version of medication was used. The SRT used in the 1997 study delivered the same dose of medication as the later studies, but it was dissolved in up to four times more liquid. The additional liquid helped the medication reach the tiny air sacs in the lungs. The study was published on July 13, 2015, in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

“The medication needs to work its way from the trachea to tiny air sacs deep inside the lungs to be effective. This therapy is relatively straightforward in babies but more complex in adults, mostly because adult lungs are much bigger,” said lead author professor of biomedical engineering James Grotberg, MD, PhD, of the U-M College of Engineering. “The modeling technology could be used in other types of research as well, including more precise targeting of other medications in the lungs and projecting results from animal research to humans.”

Related Links:
University of Michigan
Ecole Polytechnique