With improved survival of extremely low gestational age newborns, a high incidence of bronchopulmonary dysplasia (BPD) and respiratory morbidities persist throughout childhood. Premature birth results in impaired lung alveolar and vascular growth and airways disease. The standard NIH definition of BPD, as based on the need for oxygen and respiratory support at 36 weeks gestational age, is imprecise and provides a poor surrogate for persistent respiratory problems throughout childhood. Importantly, premature infants even without the BPD diagnosis have persistent respiratory disease. Furthermore, BPD is not a homogenous respiratory disease, but represents a spectrum of airway and parenchymal abnormalities that likely contribute to different clinical phenotypes and to late respiratory morbidities after NICU discharge. However, the relative roles of small airways dysfunction and distal lung and vascular disease to late respiratory outcomes after preterm birth remain unknown. The importance of this problem has been further highlighted at recent NIH Workshops on prematurity and lung disease, which concluded that improved characterization of respiratory phenotypes after preterm birth is necessary to better understand disease heterogeneity and variability in outcomes; to accurately identify at risk infants for late disease; to improve specific therapeutic targets; and to enhance clinical trial design for early interventions. We have previously demonstrated reduced forced expiratory flows (FEF) and pulmonary diffusion capacity (DLCO) in BPD infants compared to full term controls; that decrements in FEF and DLCO are not well correlated with each other; and that each measure likely reflects different contributions to BPD pathophysiology and late respiratory morbidities. Therefore, we hypothesize that infant respiratory morbidities after preterm birth are highly variable due to differential impairment of airway, parenchymal and vascular development that can be characterized as distinct physiologic phenotypes; that the nature and severity of these specific impairments of lung function are strongly associated with increased respiratory morbidities during infancy; and that proteomic biomarkers can enhance the physiologic characterization of phenotype and prediction of late respiratory outcomes.

R01HL145679

2019-03-01

2023-02-28