Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach

Bronchopulmonary dysplasia (BPD) is the most common respiratory consequence of premature birth and contributes to significant short- and long-term morbidity, mortality, and resource utilization. Initially defined as a radiographic, clinical, and histopathologic entity, the chronic lung disease known as BPD has evolved as obstetrical and neonatal care have improved the survival of lower gestational age infants. Now, definitions based on need for supplemental oxygen at 28 days and or 36 weeks provide a useful reference point in the NICU, but are no longer based on histopathologic findings, and are neither designed to predict longer-term respiratory consequences nor to study the evolution of a multifactorial disease. The aims of this review are to critically examine the evolution of the diagnosis of BPD and the challenges inherent to current classifications. We found that the increasing use of respiratory support strategies that administer ambient air without supplemental oxygen confounds oxygen-based definitions of BPD. Furthermore, lack of reproducible, genetic, biochemical, and physiologic biomarkers limits the ability to identify impending BPD for early intervention, quantify disease severity for standardized classification and approaches, and reliably predict the long-term outcomes. More comprehensive, multidisciplinary approaches to overcome these challenges involve longitudinal observation of extremely preterm infants, not only those with BPD, using genetic, environmental, physiologic and clinical data as well as large databases of patient samples. The Prematurity and Respiratory Outcomes Program (PROP) will provide such a framework to address these challenges through high-resolution characterization of both NICU and post-NICU discharge outcomes.