Epidemiological Characteristics and Resource Use in Neonates With Bronchopulmonary Dysplasia: 1993-2006
Division of Newborn Medicine, Kravis Children's Hospital, Mount Sinai Medical Center, New York, NY 10029, USA. PEDIATRICS
(Impact Factor: 5.47).
08/2010; 126(2):291-7. DOI: 10.1542/peds.2009-3456
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.
Available from: Peter Vitiello
- "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 "
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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.
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ABSTRACT: The American Academy of Pediatrics (AAP) recommends that all preterm neonates undergo a period of observation in a car safety seat before discharge, known as the Infant Car Seat Challenge (ICSC), to monitor for respiratory immaturity and the risk of adverse cardiopulmonary events in the upright position. However, no universal guidelines exist to define appropriate cutoffs for failure of the ICSC. We sought to evaluate regional neonatal intensive care unit (NICU) implementation of the ICSC and to evaluate variation in failure criteria.
We contacted level II and III nurseries/NICUs in New York/New England (n = 119) to determine if each performed ICSCs, their inclusion criteria, duration of testing, and failure criteria.
We contacted 119 institutions and had an 87% response rate (n = 103). Of the institutions that responded, 89% (n = 89) perform ICSCs. Of these 89 with current protocols, 17% did not follow AAP guidelines to test all neonates born <37 weeks' gestation, and 45% did not follow guidelines for test duration. Despite wide variation, most units use thresholds for bradycardia of <80 bpm and desaturation of <90% to determine failure.
Despite AAP guidelines, implementation of ICSCs for preterm neonates is not universal in the region studied. Variation in definition of ICSC failure means that neonates are receiving differential care, not on the basis of their clinical characteristics, but on which institution performs the test. We propose standardizing the test to all infants born at <37 weeks' gestation to a duration of at least 90 minutes, along with a failure threshold for bradycardia of <80 bpm for >10 seconds, and for saturation <90% for >10 seconds.
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ABSTRACT: We have determined that murine lung fibroblasts are divisible into two major subpopulations based on expression of Thy 1. Twenty-four to fifty-three percent of freshly isolated lung cells displayed Thy 1 and were separated using FACS into Thy 1+ and Thy 1- fractions for morphologic examination. Analysis by electron microscopy revealed that both the Thy 1+ and Thy 1- fractions contained fibroblasts. Freshly isolated lung cells cultured for 2 wk consisted of greater than 95% fibroblasts, with 28 to 49% displaying Thy 1. These cells were sorted by FACS into Thy 1+ and Thy 1- lines that maintained a stable phenotype over many weeks and that were used as a source to obtain stable fibroblast clones. Adherent pulmonary fibroblasts are not phagocytic and lack the markers of macrophages, dendritic cells, B lymphocytes, and T lymphocytes (with the exception of Thy 1). Interestingly, the Thy 1- fibroblasts spread more and contained a more extensive microfilament and microtubule network than did the spindly and often lipid-containing Thy 1+ population. Both populations of fibroblasts synthesized collagen. Class I MHC expression was very low on Thy 1+ and Thy 1- fibroblasts, but high levels were displayed after gamma-IFN treatment. Most exciting was the unexpected finding that only the Thy 1- lines and clones displayed class II MHC (Ia) in response to treatment with gamma-IFN. Moreover, only the Thy 1- fraction (gamma-IFN-treated) presented antigen to T lymphocyte clones, an observation that suggests that this subset of cells may be involved primarily in promoting chronic lung inflammation, which is associated with developing fibrosis. Thus, two populations of pulmonary fibroblasts exist, defined by the expression of Thy 1, distinguishing morphology, inducibility for Ia expression, and antigen-presenting function. It should now be possible, using these characteristics, to ascertain the role of pulmonary fibroblast subpopulations in developing fibrosis.
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