Epidemiological Characteristics and Resource Use in Neonates With Bronchopulmonary Dysplasia: 1993-2006
To determine the trends in incidence of diagnosis of bronchopulmonary dysplasia (BPD) and associated health services use for the neonatal hospitalization of patients with BPD in an era of changing definitions and management. All neonatal hospitalization records available through the Nationwide Inpatient Sample, 1993-2006, were analyzed. Multivariable regression analyses were performed for incidence of BPD diagnosis and associated hospital length of stay and charges. Multiple models were constructed to assess the roles of changes in diagnosis of very low birth weight (VLBW) neonates and different modalities of respiratory support used for treatment. The absolute incidence of diagnosis of BPD fell 3.3% annually (P = .0009) between 1993 and 2006 coincident with a 3.5-fold increase in the use of noninvasive respiratory support in patients with BPD. When data were controlled for demographic factors, this significant decrease in incidence persisted at a rate of 4.3% annually (P = .0002). All models demonstrated a rise in hospital length of stay and financial charges for the neonatal hospitalization of patients with BPD. The incidence of BPD adjusted for frequency of prolonged mechanical ventilation also decreased but only by 2.8% annually (P = .0075). The incidence of diagnosis of BPD decreased significantly between 1993 and 2006. In well-controlled models, birth hospitalization charges for these patients rose during the same period. Less invasive ventilatory support may improve respiratory outcomes of VLBW neonates.
[Show abstract] [Hide abstract] ABSTRACT: The most common form of newborn chronic lung disease, bronchopulmonary dysplasia (BPD), is thought to be caused by oxidative disruption of lung morphogenesis which results in decreased pulmonary vasculature and alveolar simplification. Although cellular redox status is known to regulate cellular proliferation and differentiation, redox-sensitive pathways associated with these processes in developing pulmonary epithelium are unknown. Redox sensitive pathways are commonly regulated by cysteine thiol modifications. Therefore two thiol oxidoreductase systems, thioredoxin and glutathione, were chosen in order to elucidate the roles of these pathways on cell death. Studies herein indicate thiol oxidation contributes to cell death through impaired activity of glutathione dependent (GSH-dependent) and thioredoxin (Trx) systems and altered signaling through redox sensitive pathways. Free thiol content decreased by 71% with hyperoxic (95% oxygen) exposure. Increased cell death was observed during oxygen exposure when either the thioredoxin (Trx) systems or glutathione dependent were pharmacologically inhibited with aurothioglucose (ATG) or buthionine sulphoximine respectively. However, inhibition of the Trx system yielded the smallest decrease in free thiol content (1.44% with ATG treatment vs 21.33% with BSO treatment). Although, Trx1 protein levels were unchanged, Trx1 function was impaired during hyperoxic treatment as indicated by progressive cysteine oxidation. Overexpression of Trx1 in H1299 cells utilizing an inducible construct increased cell survival during hyperoxia whereas siRNA knockdown of Trx1 during oxygen treatment reduced cell viability. Overall, this indicated a comparatively small pool of proteins rely on Trx redox functions to mediate cell survival in hyperoxia, and the protective functions of Trx1 are progressively lost by its oxidative inhibition. To further elucidate the role of Trx1, potential Trx1 redox protein-protein interactions mediating cytoprotection and cell survival pathways were determined by utilizing a substrate trap (mass action trapping) proteomics approach. With this method, known Trx1 targets were detected including peroxiredoxin-1 as well as novel targets, including two HSP90 isoforms (HSP90AA1 and HSP90AB1). Reactive cysteines within the structure of HSP90 are known to modulate its ATPase dependent chaperone activity through disulfide formation and S-nitrosylation. While HSP90 expression is unchanged at the protein level during hyperoxic exposure, siRNA knockdown significantly increased hyperoxic cell death by 2.5-fold, indicating cellular dependence on HSP90 chaperone functions in response of hyperoxic exposure. These data support the hypothesis that hyperoxic impairment of Trx1 negatively impacts HSP90-oxidative responses critical to cell survival with potential implications on pathways implicated in lung development and the pathogenesis of BPD.0Comments 7Citations
- "Survival of the most premature has increased significantly since the introduction of exogenous surfactants , steroids  , and milder ventilation techniques    . Despite advances in treatment , premature infants exposed to supplemental oxygen often develop bronchopulmonary dysplasia (BPD) 1 , a form of chronic lung disease characterized by alveolar simplification and decreased microvasculature   . Premature infants who develop BPD demonstrate increased markers of oxidative stress when Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/freeradbiomed "
- "Over the years, BPD frequency in ELBW infants has been increasing rapidly, as a significantly increased fraction of them survive [3,5,8910. Emerging evidence seems to show that gentle non-invasive ventilation techniques, particularly nasal continuous positive airway pressure (NCPAP) together with low FiO 2 levels may reduce barotrauma and volutrauma even in ELBW infants, thus decreasing BPD risk; therefore these are being increasingly used in the smallest ELBW infants111213141516. We have reported a very low prevalence of BPD among ELBW infants ≥24 weeks admitted from July 1, 1986 to June 30, 2002 to the neonatal intensive care unit (NICU) of Perrino Hospital, Brindisi, commonly using a minimal handling approach . "
- " Intra-amniotic inflammation is thought to play a major role in the pathogenesis of fetal lung injury, aberrant lung development and the resulting neonatal and adult chronic lung disease. [1,2] Bronchopulmonary dysplasia (BPD) accounts for the vast majority of chronic lung disease in infancy affecting 35% of infants weighing less than 1,500 grams.  Studies have linked elevated cytokines in the amniotic fluid with an increase in BPD and neonatal morbidity/mortality. [1,2,4,5] In surfactant-treated patients, BPD is characterized histologically by some degree of alveolar septal fibrosis, arrest in acinar development, and impaired vascular development. [6,7] Current therapies in the p"