Congenital diaphragmatic hernia is a dangerous malformation of the lungs and diaphragm in which almost a third of affected babies die due to underdevelopment of the lungs. Until now, there have been no concrete approaches to treating this malformation with medication. In an international study, scientists from the Department of Pediatric Surgery at Leipzig University Hospital have been able to show that inflammatory cells play a previously underestimated role in the underdeveloped lungs of children with diaphragmatic hernia before and after birth. The results lay the foundation for potential new treatment approaches and have been published in the renowned American Journal of Respiratory and Critical Care Medicine.
Congenital diaphragmatic hernia is one of the most lethal malformations for newborns. The main problem is the underdeveloped lung. The clinical picture also includes a hole in the diaphragm, which is corrected by pediatric surgeons by surgically closing it in the first week of life. Even after a successful operation, however, children with a hiatal hernia often die due to the underdevelopment of their lungs. This condition, known as lung hypoplasia, has so far been almost impossible to treat. Researchers at the Department of Pediatric Surgery at Leipzig University Medicine therefore wanted to find out which molecular mechanisms cause this maldevelopment - and whether they could be treated in a targeted manner.
"In the current study, we were able to demonstrate in human lungs that certain inflammatory cells - macrophages in particular - appear in greater numbers before and after birth. This could influence the development of the lung structure as we see it in congenital diaphragmatic hernia," explains Richard Wagner, Head of "We were also able to confirm some parallels in the inflammatory processes of diaphragmatic hernia between animal models and human samples - a decisive step towards potentially transferring future therapies to humans," says the senior physician and research group leader for pediatric surgery at Leipzig University Medicine.
The current scientific analyses on the disease of congenital diaphragmatic hernia, which were carried out in collaboration with researchers in Mannheim, Paris, Winnipeg and Boston, show that the inflammatory signaling pathways of the immune system are overactivated. The so-called macrophage migration factor, which is associated with disorders in the lung structure, was also conspicuous.
Increased inflammation a key driver of this severe malformation
Modern research methods were used in the study to analyze a large number of proteins in the fetal lungs using "proteomics" technology. Special microscopic staining and cell measurement methods were also used. The results were analyzed using bioinformatic tools and compared with findings from a stem cell model and animal models. PD Dr. Jan-Hendrik Gosemann, managing senior physician and research group leader in pediatric surgery at the UKL, had already demonstrated in a previous study in animal experiments that more macrophages can be found in the lungs of unborn rats with diaphragmatic hernia.
the current results of our study have the potential to one day be translated into new treatment approaches. If we succeed in specifically slowing down the increased inflammation during pregnancy, we could possibly promote lung development and thus improve the chances of survival and quality of life of affected children. The hope would be to develop an additional drug therapy that could be used before birth," says Wagner.
In order to pursue this approach further, the Leipzig team is currently working on setting up a large DFG-funded research program. The plan is to test various anti-inflammatory substances in animal models and on the patient’s own stem cells, with the aim of preparing clinical trials for prenatal treatment in the long term. "So far, our studies are still molecular and cellular observations. But our ongoing research and the resulting findings in past and current publications are good indications that increased inflammation is a key driver of this severe malformation," emphasizes paediatric surgeon PD Dr. Wagner. "I am particularly pleased that Katinka Sturm, a doctoral student in our department, is a first author on this paper - a great honor for such a young scientist."
Original publication in American Journal of Respiratory and Critical Care Medicine: Macrophages Are Enriched Preand Postnatally in Hypoplastic Lungs from Patients with Congenital Diaphragmatic Hernia. DOI: 10.1164/rccm.202501-0153RL
