Long-term management of bronchopulmonary dysplasia: biological, histological, and functional effects of mechanical stretch by non-invasive ventilation on postnatal lung development

Prematurity can impair lung development due to chronic injury and repair, and subsequently lead to bronchopulmonary dysplasia (BPD) and associated life-long consequences. Evolution of care increased the survival of extremely preterm infants and has changed the pathophysiology of BPD resulting in different phenotypes. Later in life, children with BPD have poorer cardiorespiratory, nutritional, and neurodevelopmental outcomes, which generate significant public health costs. The lung is a mechanically active organ, which requires adequate stretching of its structures to ensure fetal and postnatal lung development as well as repair after injury. Extensive research has focused on early screening of risk factors and biomarkers of lung injury as well as on lung protective strategies during resuscitation and early postnatal care. Previous works in the rabbit model of congenital diaphragmatic hernia, which also impairs lung growth and maturation, has demonstrated that several molecules involved in the crucial process of alveolarization were overexpressed concomitantly with stretch-induced lung growth. In preterm infants, early application of continuous positive airway pressure (CPAP) after delivery has shown physiological benefits. Besides, animal studies have demonstrated functional and structural effects of CPAP on lung development. However, in preterm infants, there is a lack of clinical consensus over the best way and timing to achieve the weaning from CPAP. The clinical impact of non-invasive ventilation on lung growth and function at that time is not clear. The present project will be dedicated to the study of long-term postnatal modulation of lung growth and function using different types of non-invasive respiratory support as a source of mechanical forces. The project will be split into an in vivo model of long-term BPD and an clinical part with infants diagnosed with BPD and chronic hypoxemia.