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

2015年现行欧洲复苏理事会指南的建议表明，在早产儿中，使用持续气道正压通气作为一种无创方法的呼吸支持上级优于机械通气。无创通气是早产儿在分娩过程中的首选呼吸护理方式。与通气相比，出生后有不同的无创通气模式，如持续气道正压通气支持、持续充气或鼻高流量装置，以在早产儿呼吸不正常或自主呼吸时为肺部通气。尽管在这一领域进行了多年的深入研究，但与最佳时机、所需开放压力、潮气量或呼气末正压水平相关的肺通气策略仍存在争议。然而，这两种方法都未能充分减少新生儿慢性肺部疾病，也称为支气管肺发育不良。支气管肺发育不良是早产儿最常见的并发症，严重影响儿童和成年后的神经发育结果和死亡率。以下健康成本具有巨大的经济影响，因此是一个全球性的健康问题。出生时的呼吸过渡期涉及的不仅仅是肺通气、声门功能和呼吸活动的变化。出生后气道液体清除和持续防止液体流出到肺部是生命最初几个小时的主要挑战之一。很少或没有科学知识可用于评估这种方法的有效性，它如何与早产儿的生理状态相结合，以及为什么它有时会失败。将研究逐渐增加和持续维持基于PEEP的肺复张策略，比较不同的呼吸支持装置（Benveniste瓣膜，持续充盈，Benveniste瓣膜可能上级于通过逐渐增加终末流量来建立最佳的无创通气和呼吸支持，呼气正压将导致细胞炎症减少，随后减少未成熟肺的长期损伤。这可能更多地是考虑到出生后肺通气和成功的液体清除的（病理）生理机制的结果。X线成像和组织学分析肺切片将是强制性的，以评估炎症和损伤。研究结果将影响未来复苏指南中呼吸支持的建议，世界各地的早产儿。

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.