Pulmonary Biomarkers of Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia, or BPD, is a chronic pulmonary disorder of premature infants, commonly defi ned as having an oxygen requirement at 36 weeks postmenstrual age. It is an important source of morbidity and mortality in premature neonates. Its' etiology appears to be multifactorial with the most common associations being prematurity, need for mechanical ventilation, and oxygen exposure. Implied in the pathogenesis of BPD is the role of cytokines which are immune mediators produced by most cell types. This is evidenced by studies in which there exist alterations in the levels of "pro-infl ammatory" and "anti-infl ammatory" cytokines. The imbalance of these cytokines have either heralded the onset or predicted the presence of BPD, or indicated a decreased propensity to developing this chronic respiratory disorder of preterm infants. Many other pulmonary markers have been shown to be altered in patients with BPD. These include markers indicative of altered lung repair processes, decreased endothelial integrity, oxidative damage and abnormal fi brinolytic activity, all of which are thought to be mechanisms contributing to the development of BPD.In this review, we will discuss the physiologic role of specifi c biomarkers in the pulmonary tract of the human premature neonate, the perturbations that enable them to be deranged, and their proposed association with BPD.

High-mobility group box-1 protein in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia and steroid therapy

“…1 A recent report has implicated HMGB1 in an animal model of chorioamnionitis. 19 Interestingly, both TNF-a and IL-1b, known to be early-release cytokines in response to injurious stimuli and potent inducers of the late-release cytokine HMGB1, have been implicated in animal models 20,21 and human 22 BPD. Although we were unable to locate any reports of HMGB1 in developmentally appropriate animal models of BPD, HMGB1 has been reported to mediate the inflammatory cascade in an experimental model of necrotizing enterocolitis in neonatal rats.…”

Hyperoxia in the Pathogenesis of Bronchopulmonary Dysplasia

“…Human neonates who developed BPD showed increased levels of tumor necrosis factor alpha (TNFα) in the tracheal aspirates [ 102 ]. Lung tissue of neonatal rat and mice pups exposed to hyperoxia also showed an increase in TNFα [ 15 ].…”

“…This suppresses the secretion of cytokines and the ability of those cells to function as accessory cells for T-cell and NK-cell stimulation [ 97 ]. Serum and tracheal aspirate IL-10 levels were found decreased in those infants who developed BPD [ 102 ].…”

“…These proinfl ammatory agents are elevated very early following exposure to hyperoxia in the human preterm population who ultimately develop BPD [ 102 ].…”

Recurrent copy number variants associated with bronchopulmonary dysplasia

“…Several previous studies have identified an association between candidate gene variants and BPD. Most of these studies have focused on genes for innate immunity, antioxidant defenses, mechanism of vascular remodeling, and genes coding for surfactants proteins (5,10). While many significant findings have been reported, a majority of them have not been replicated in subsequent cohorts (5,6).…”