Published September 2018 | Lung Cellular and Molecular Physiology
Congenital diaphragmatic hernia (CDH) happens once in every 2,000 to 3,000 pregnancies. In this developmental defect, the diaphragm does not form properly in the fetus, which allows the intestines to enter the chest cavity and inhibit lung growth. About 60 percent of babies born with this condition die. Survivors live with respiratory problems, which may require tracheostomy and long-term mechanical ventilation.
An experimental fetal surgery, tracheal occlusion, improves survival and lung growth, but babies still live with substantial respiratory problems. Researchers at Cincinnati Children’s have begun to address the critical need for greater understanding of how this surgery affects lung development.
In tracheal occlusion, a surgeon inserts a balloon in the trachea of the fetus, which causes buildup of lung fluid, lung expansion and growth. The balloon stays in place until a surgeon removes it a few weeks before the expected delivery date.
Researchers led by Brian Varisco, MD, completed a first-of-its-kind proteomic analysis of tracheal fluid in a CDH animal model and compared it to controls. They found that the surgery promotes lung cell growth and AKT-related signaling cascades, a marker of cell growth and proliferation.
However, tracheal occlusion addressed changes in only 11 of the 118 proteins that CDH alters. The discrepancy could help explain some of the respiratory problems that children still endure after the treatment. For example, numbers of crucial ciliated cells that help clear mucus were reduced after the procedure.
“Since this is a relatively new procedure, still in small clinical trials,” says Varisco, “the study helps us see what kind of lung problems—such as mucociliary clearance or recovery from infections—we might anticipate later."