Artificial respiration is a life-saving technology, but it can damage the respiratory system. Researchers at the Technion present new aspects of this injury and offer a preliminary treatment that will provide it among respiratory preterm infants and thus improve their health
About one-tenth of the world’s babies are born prematurely, before their body systems have developed properly. One of these systems is the respiratory system, which reaches full maturity at the age of two and is essential for the survival of the baby. When the fetus is in the womb it receives oxygen from its mother through the umbilical cord, but after birth it must breathe on its own. Therefore preterm infants are often characterized by respiratory distress and need support to breathe. Moreover, the earlier the preterm infant is born the more severe the respiratory distress and the longer the respiration period is expected. Sometimes, respiration is done through a respirator that injects air into the lungs through a tube inserted into the trachea.
Despite the continuing improvement in soul technologies and preterm care, morbidity rates among them are still higher than desired. One of the problems stems from the fact that essential treatments for prematurity, including artificial respiration, do prevent death but create damage and side effects that can affect the patient in the long run. These effects and sources of damage to the artificial soul are not yet fully understood. This is the background to the research being done in Prof. Joshua Schnittman from the Faculty of Biomedical Engineering at the Technion.
In a previous study, published last year in the Journal of the Royal Society Interface, Prof. Joshua Schnittman and Dr. Eliram Nof discovered a phenomenon not mentioned at all in the medical literature: pulmonary damage resulting from air jet exiting the tube inserted into the trachea of the premature infant during artificial respiration. Using a physical model (flow mechanics), the two discovered that this jet exerts strong shear forces on the epithelial tissue – the layer of cells that line the airways, which can cause damage to the patient, especially when it is premature.
In a follow-up study, now published in the journal Bioengineering & Translational Medicine, The researchers tested the hypothesis in a new model containing artificial human epithelium. The study was led by Prof. Schnittman, Dr. Eliram Nof and Dr. Arbel Artzi-Schnirman. Pediatricians and otolaryngologists are also involved in the study, including Dr. Liron Bornstein, a faculty member at the Rappaport Faculty of Medicine at the Technion and a senior physician in the Department of Neonatal and Premature Intensive Care at Rambam Medical Campus.
The study was done using a three-dimensional model of the upper airways – the trachea and the bronchi that branch off from it. Within this model, the researchers grew a layer of epithelial cells – the cells that also cover the natural respiratory system – to track the effect of respiration on them. “Today we already know that artificial respiration, which is a life-saving technology, causes various damages to the respiratory system,” explains Prof. Schnittman. “These damages have so far been attributed to mechanical factors such as the entry of air under pressure that causes the lung tissue to stretch. In recent years, insights into more complex sources of damage have been added. A process that underlies lung damage in respiratory preterm infants resulting from airflow and shear forces during respiration. “
In a previous study, Technion researchers found, as mentioned, that the air jet exerts strong shear forces on the epithelial tissue; They have now discovered that the jet causes a change in the balance of cytokines – proteins that form the basis for communication between immune cells. In other words, beyond the mechanical damage – erosion of the epithelium – the invasive respiration also triggers an immune response and this can lead to harmful and even life-threatening inflammatory developments.
Following these findings, the researchers examined the possibility of reducing the said damage through medication, and with the help of their colleagues, the doctors chose a common drug called Montelukast, which is used to treat asthma patients. Indeed, in the three-dimensional model, they found that pretreatment with montlocast moderates epithelial cell mortality and the immune response during respiration.
Prof. Schnittman estimates that the use of models of the type developed in his laboratory may improve the in-vitro pre-clinical trials conducted in laboratories. “If preclinical research in laboratories is more efficient and accurate, we can reach the next stage – preclinical animal experiments – when we are much more focused. That way we can not only accelerate research but also reduce harm to experimental animals.”
As mentioned, this is the first study demonstrating in a laboratory-developed model the effect of an artificial respiration air jet on the immune system. This study offers a new tool for examining clinical trials in search of a solution that may eliminate or at least mitigate inflammatory damage. Prof. Schnittman estimates that these findings may be beneficial, beyond treating preterm infants, also in other contexts such as treating patients with other lung diseases that require artificial respiration, for example COPD and corona.
The study is supported by the European Commission for Research (ERC).
Prof. Joshua Schnittman He is a faculty member in the Faculty of Biomedical Engineering, and heads the Bioflow Laboratory. The laboratory is engaged in the study of the aerodynamics of drugs and particles in the respiratory system. Prof. Schnittman has developed a model of “acinus-on-chip” that allows to assess various health risks and design drugs for the respiratory system.
Dr. Eliram Nof Appointed a researcher at the Memorial Sloan Kettering Cancer Center in New York a few months ago.
Dr. Arbel Artzi–Snirman Recently moderated as head of the Center for Advanced Technologies for Medical Application at Rambam Medical Campus, Haifa.
For an article in the journalBioengineering & Translational Medicine click here
For a video explaining the study, click here