What percentage of BPD are genetic
Early diagnosis of severe lung disease in babies
Thanks to medical advances, the number of babies who survived premature birth has increased in recent years. However, the lungs are one of the most recently developed organs in the growing fetus and are not fully developed in premature births before the 35th week of pregnancy. As a result, the young patients' airways are prone to complications. The most common lung disease affecting premature babies is bronchopulmonary dyplasia, or BPD for short. Symptoms can be rapid and labored breathing, a constantly increased need for oxygen and an increased number of infections. At birth, premature infants lack fully developed alveoli and the corresponding blood vessels that absorb oxygen from the alveoli.
Bronchopulmonary dysplasia (BPD) is the most common lung disease that premature babies suffer from. Around 15-30 percent of premature babies with a birth weight of less than 1,000 grams or a gestation period of less than 28 weeks, but also those born later, are affected. It is a chronic but potentially reversible disease. The therapy options available include cortisone, vitamin A and supportive measures such as optimizing fluid intake and the ventilation situation. In the majority of young patients with BPD, symptoms improve significantly in the first year of life. However, they more often suffer from overexcitability of the bronchial system with increased inflammation of the airways in the first years of life. In premature babies with a severe form of BPD, physical, motor, and mental development is often delayed. At school age they have more respiratory problems, a higher risk of allergic asthma and often generally decreased lung function compared to their peers who were carried out to full term.
Artificial respiration as a 'double-edged sword'
Bronchopulmonary dysplasia usually develops when premature babies are ventilated and oxygen therapy has to be carried out until the lungs have matured enough. Although artificial ventilation and treatment with oxygen are often vital, they can damage the infant's lungs and cause inflammation, which can trigger the lung disease BPD. Prenatal factors such as the influence of infections or reduced growth of the child in the womb can also contribute to the development of BPD. "The lung disease BPD mostly affects premature babies, but mature newborns can also develop BPD," explains DZL researcher Dr. Anne Hilgendorff from the Institute for Lung Biology at the Helmholtz Zentrum München. The specialist in pediatric and adolescent medicine deals in her research with diseases of newborns and the treatment of premature babies.
BPD can be a temporary illness - in the majority of young patients with BPD, symptoms improve significantly in the first year of life. In some children, however, symptoms can continue into adulthood, which can increase the risk of respiratory problems and lung diseases such as chronic obstructive pulmonary disease (COPD).
However, the exact causes of BPD have not yet been clarified. In addition to impairments from the artificial ventilation itself and a potentially damaging effect from an excessively high oxygen concentration, characteristic inflammatory processes and the functional and structural immaturity of the lungs are further triggers.
Molecular disease mechanism discovered
In a study that also included a genetic analysis in a total of 1,061 newborns, including 492 diagnosed with “bronchopulmonary dysplasia”, DZL researchers and scientists from other institutions have now discovered a molecular mechanism that makes a decisive contribution to the development of the disease. They found that certain genetic changes, specifically in the gene for the growth factor receptor PDGFR-α (Platelet-Derived Growth Factor Receptor α), significantly increase the risk of the disease. Lung tissue cells that produce PDGFR-α contribute to the formation of the alveoli and the development of the lung structure. The researchers were also able to confirm the genetic abnormalities in cells isolated from the lungs of affected children.
"In a test model that was only established at a few locations worldwide, we were able to show for the first time that a lower production of PDGFR-α in connection with artificial ventilation led to the typical symptoms of BPD," explains study director Hilgendorff. However, the scientists were able to reduce the symptoms of the disease in the experimental model if they artificially increased the signal transmission via PDGFR-α. In further experiments, they were also able to show that the inflammatory messenger substance TGF-β (Transforming Growth Factor β) contributes to the development of BPD: It also reduces the production of PDGFR-α. The signal molecule TGF-β is likely to be released particularly often as a result of mechanical damage to the lungs during artificial ventilation. According to the scientists, this could be genetic as well as mediated by inflammation or made worse. In further studies, they want to check more intensively whether it is possible to intervene therapeutically in this signal chain in a targeted manner and thus open up a way for possible therapies.
Early and reliable diagnosis tangible for the first time
So far, however, doctors have often not been able to identify BPD with certainty and in good time to initiate important therapies after the birth. A research team led by Hilgendorff and Dr. Kai Martin Förster from the Perinatal Center at the University of Munich's Clinic recently developed a method with which for the first time an early and reliable diagnosis of the lung disease appears possible. To do this, the scientists analyzed blood plasma samples from 35 premature babies, which were obtained in the first week of life. In the samples they looked for changes in all recognizable proteins and repeated the examination on the 28th day of life of the infants.
To analyze the data, the scientists developed a statistical model that can be used to determine which proteins in the blood indicate an impending BPD immediately after birth. Three proteins that are already suspected of contributing to the development of the disease became conspicuous in the analysis. They are among the most important disease processes that show the remodeling of the lung structure, the state of vascular development and the inflammatory reaction. In cooperation with the neonatology department of the children's clinic in Giessen, private lecturer Dr. Harald Ehrhardt, the proteins were confirmed in a second group of premature babies and, with the help of a collaboration with the Erasmus University in Rotterdam, were detected in the lung tissue of premature babies.
The researchers now want to check the results in further studies. “If the results are confirmed, a simple test could be developed that only analyzes the three marker proteins and not, as in the complex procedure, all 1,129 proteins. If the procedure took all the hurdles, the early diagnosis would make the therapy of the small patients much easier and promote the success of the possible treatment, ”reports Hilgendorff confidently.
German Center for Lung Research
The German Center for Lung Research (DZL), founded in 2011, is one of the six German Centers for Health Research funded by the Federal Ministry of Education and Research and the federal states. In the DZL, excellent scientists and their teams from university and non-university institutions work together in the field of lung research at five locations. Together they have the goal of developing new approaches for the prevention, diagnosis and therapy of lung diseases. The focus is on eight disease areas: asthma and allergies, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pneumonia and acute lung failure, diffuse parenchymal lung diseases, pulmonary hypertension and end-stage lung diseases.
PD Dr. Anne Hilgendorff
Helmholtz Zentrum München - German Research Center for Health and Environment (GmbH) Institute for Lung Biology & Comprehensive Pneumology Center
Press and public relations
German Center for Lung Research (DZL)
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