Apoptosis has been shown to be involved in several processes during embryogenesis, but the ontogeny of apoptosis during lung development ahs not been studied. The goals of the current study were to determine if apoptosis occurs during lung development, and to determine the ontogeny of the changes in apoptosis that occur. We studied the ontogeny of apoptosis in vivo using lungs from 14-18-d gestation fetal rats, newborn rats, and 1-d-, 2-d-, 5-d-, and 10-d-old rat pups. Apoptosis was assessed by electron microscopy and the terminal deoxyribonucleotidyl transferase dUTP nick end-labeling assay. We compared the in vivo results with explants of 14-d gestation fetal rat lung placed in culture for 1-4 d because the biochemical development of the lung in organ culture has been shown to closely parallel the development of the lung in vivo. We found apoptosis of mesenchymal cells at the periphery of distal lung buds in early fetal lung (14-16-d gestation). Apoptosis of both mesenchyme and epithelium was present in later fetal lung (18-d gestation). There were no qualitative differences in apoptosis between in vivo fetal lung and explant cultures of fetal lung. There was a 14-fold increase in apoptosis at birth and in the first postnatal day of life (9-12% of cells) compared with fetal lung (0.6-1% of cells). This was followed by a rapid decline in the percentage of apoptotic cells to fetal levels at postnatal d 2-10. We conclude that apoptosis occurs in a spatially, temporally, and cell-specific manner during lung development. The number of cells undergoing apoptosis increases dramatically in the first day after birth.

BACKGROUND AND OBJECTIVES: Unplanned extubation can be a significant event that places the patient at risk for adverse events. Our goal was to reduce unplanned extubations to <1 unplanned extubation per 100 patient-intubated days. METHODS: All unplanned extubations in the NICU beginning in October 2009 were audited. Data collected included time of day, patient weight, and patient care activity at the time of the event. Bundles of potentially better practices were implemented in sequential Plan-Do-Study-Act cycles. Rates of unplanned extubation (number per patient-intubated day) for each month were analyzed by using control charts, and causes of unplanned extubation were analyzed by using Pareto charts. RESULTS: We found a significant decrease in the unplanned extubation rate after implementation of the first bundle of potentially better practices in May 2010 (2.38 to 0.41 per 100 patient-intubated days). Several more Plan-Do-Study-Act cycles were conducted to sustain this improvement. A persistent reduction in the unplanned extubation rate (0.58 per 100 patient-intubated days) began in February 2013. Causes included dislodgement during care and procedures and variation in the fixation of the endotracheal tube. The majority of events occurred in very low birth weight infants during the daytime shift. CONCLUSIONS: Unplanned extubations in the NICU can be reduced by education of staff and by implementing standard practices of care. Sustainability of any practice change to improve quality is critically dependent on culture change within the NICU. We suggest that the benchmark for unplanned extubation should be a rate <1 per 100 patient-intubated days.

There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are centerspecific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother-newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.

The oleic acid (OA) model of acute lung injury in rats is characterized by a massive and rapid influx of polymorphonuclear neutrophils (PMN) within 1 h, with a peak inflammatory response at 4 h and resolution by 72 h. We hypothesized that PMN apoptosis is involved in the resolution of OA-induced acute lung injury. To test this hypothesis, healthy adult Fischer 344 rats were given 30 microl OA in 0.1% bovine serum albumin (BSA) intravenously; controls were given BSA alone and killed at 1, 4, 24, and 72 h after OA to obtain bronchoalveolar lavage fluid (BALF) and lung tissue. Cell pellets from BALF and formalin-fixed, paraffin-embedded tissue section samples were processed for terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) to identify apoptotic cells. Propidium iodide was used to counterstain nuclei. Percentage of nuclei undergoing apoptosis was counted under a fluorescent microscope. Control rats showed only resident alveolar macrophages (AM) in the BALF with no apoptosis. At the peak of injury, 1 h and 4 h after OA injection, we observed a massive PMN response without any evidence of apoptosis. At 24 h, when the OA injury is clinically and histologically in early resolution, we observed intense apoptosis of PMN nuclei along with evidence of apoptotic bodies in the cytoplasm of AM. Some of the AM also showed apoptotic nuclei at 72 h. Similar observations were made in the lung tissue sections. The results of the TUNEL assay were confirmed by DNA ladders and electron microscopy. We conclude that apoptosis of PMN and clearance by AM is an important mechanism in resolution of OA- induced acute lung injury.

It is well known that exposure to hyperoxia results in lung inflammation and damage, which leads to the development of chronic lung disease. Previous studies have shown increased activities of antioxidant enzymes (AOE) in lung tissue from animals exposed to hyperoxia. We propose the hypothesis that the fetal type II pneumocytes (TIIP) would be resistant to oxygen toxicity by virtue of increasing AOE activity on exposure to hyperoxia. The aim of this study was to measure the activities of catalase, glutathione reductase, glutathione peroxidase (GPX), and cytosolic superoxide dismutase (SOD) in cultures of adult and fetal rat TIIP exposed to 95% oxygen for 24 h. Control cells were incubated in room air. Hyperoxia exposure resulted in 53.4 +/- 1.2% of control viability (mean +/- S.E.M.; p = 0.001) in the adult TIIP with a significant threefold increase in the activities of all the AOE. The fetal TIIP were more resistant to hyperoxia (99.4 +/- 6.1% of control viability). However, in the fetal TIIP, only SOD and GPX levels were significantly increased (fourfold and 2.3-fold, respectively) compared with fetal controls. We conclude that fetal TIIP are more resistant to hyperoxia than adult TIIP in terms of viability; other protective antioxidant factors might account for the better survival of fetal TIIP in hyperoxia.