Optimising Postnatal Transition: effects of gradual aeration on IMmature Animal Lungs - a PEEP-based approach (OPTIMAL PEEP)

• Applicant: Dr. Anja Demel
• Subject Area: Pediatric and Adolescent Medicine ; Anatomy and Physiology
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 399182194

The recommendation of the current European Resuscitation Council Guidelines of 2015 suggests respiratory support with the use of continuous positive airway pressure as a non-invasive approach being superior to mechanical ventilation in preterm infants. Non-invasive ventilation, applied via a facemask is accepted as the first choice respiratory care provided to preterm infants in the delivery room.There are different ways of non-invasive aeration modes after birth in comparison to ventilation like using continuous positive airway pressure support, sustained inflation or nasal high-flow-devise to aerate the lung if the preterm infant is not breathing appropriate or spontaneously. Despite many years of intense research in this field, aerating lung strategies relating to the best timing, needed opening pressure, tidal volume or positive end-expiratory pressure level remain controversial.Nevertheless, both methods have not been able to reduce adequately neonatal chronic lung disease, also known as bronchopulmonary dysplasia. Bronchopulmonary dysplasia is the most common complication in premature infants, which highly influences the later neuro-developmental outcome in child- and adulthood and mortality. The following health costs have a huge economic impact and present therefore a global health issue.The respiratory transitional period at birth involves much more than lung aeration, changes in glottic function and breathing activity. Postnatal airway liquid clearance and sustained prevention of liquid efflux into the lungs is one of the major challenges during the first hours of life. Little or no scientific knowledge is available to assess the effectiveness of this approach, how it integrates with the preterm infant’s physiological state and why it sometimes fails. Gradually increasing and continuously sustaining PEEP-based lung recruitment strategies will be investigated comparing different respiratory support devices (Benveniste Valve, Sustained Inflation, High-Flow-Therapy) in well-characterised preterm animal models as intermediate step of translational research.The Benveniste Valve might be superior to establish optimal non-invasive aeration and respiratory support by applying gradually an increasing end-expiratory positive pressure that will lead to reduced cell inflammation followed by a reduction of long-term damage of the immature lung. This may be more the result of considering the postnatal (patho-)physiological mechanisms of lung aeration and successful fluid clearance.Visualising the spatial relationships between fluid clearance and lung aeration after birth through phase-contrast X-ray imaging and histologically analysed lung sections will be mandatory to assess inflammation and injury.The results of the study will influence the future resuscitation guideline recommendation of respiratory support in preterm infants around the world.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Host: Professor Stuart Hooper, Ph.D.