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ABSTRACT

D espite significant advances in perinatal care, bronchopulmonary dysplasia (BPD) remains one of the most common, complex, and intriguing diseases in perinatal medicine. The pathogenesis of BPD remains to be elucidated fully. Defining this disease continues to be imprecise and varies across institutions, and evidence-based guidelines addressing management are lacking. To address these and other knowledge gaps, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) held a workshop on BPD in October 2016. Information presented at the workshop included an overview of BPD providing a definition, epidemiology, pathogenesis pathways, and the strengths and limitations of available management options. The expert panel also discussed a research agenda; the use of advanced technology including medications, respiratory support measures, modern imaging, and management for preventing and treating BPD; and the current approach to the follow-up of these infants. The workshop panel developed a proposal for an updated definition for BPD based on prior definitions and current care practices. This report provides a summary of the workshop proceedings. BPD was first described in 1967 by Northway et al in an era when the mortality from respiratory distress syndrome (RDS) was >50%. Infants who were ventilated and survived the initial phase of RDS often recovered slowly from their pulmonary injury. Northway et al reported the stages of lung injury progression. The authors named the disorder, BPD, a chronic disease with a “prolonged healing phase” of RDS. Oxygen toxicity, positive pressure ventilation, and endotracheal intubation were all implicated as causative factors for the development of BPD. Later, injuries from mechanical ventilation (“ventilatorinduced lung injury”) captured by the catch phrase— “pressure + volume + time”—was emphasized as causative factors for BPD. Initially, researchers included radiologic features and pathologic findings when available to define BPD. As the survival rate of RDS increased with more BPD survivors, a clinical definition for BPD was adopted as “those infants requiring supplemental oxygen on post-natal day 28.” As more immature infants survived, it was felt that day 28 oxygen use could be related to other factors (eg, prematurity) and in 1988, Shennan et al refined the definition to oxygen use at 36 weeks postmenstrual age (PMA). In 2000, a workshop sponsored by the National Heart, Lung and Blood Institute proposed a more comprehensive definition for BPD to help identify varying severity and, thus, they categorized BPD as “none, mild, moderate or severe.” “No BPD” was defined as <28 days of supplemental oxygen. Mild BPD included infants who received oxygen or respiratory support for >28 days but were on room air at 36 weeks PMA. Infants with moderate BPD required supplemental oxygen, <30% fraction of inspired oxygen concentration, at 36 weeks PMA. Finally, severe BPD was classified as the use of >30% oxygen or positive pressure at 36 weeks PMA. After the National Heart, Lung and Blood Institute workshop, a further refinement in the definition included a physiologic challenge of supplemental oxygen withdrawal to test for oxygen need at 36 weeks PMA. Infants were classified as “Yes BPD” by the “Physiologic definition of BPD” if they had an oxygen saturation of <88% within 60 minutes of a “room air challenge test.” Subsequently, the saturation target was

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