Hyperoxia prevents the dynamic neonatal increases in lung mesenchymal cell diversity.

Rapid expansion of the pulmonary microvasculature through angiogenesis drives alveolarization, the final stage of lung development that occurs postnatally and dramatically increases lung gas-exchange surface area. Disruption of pulmonary angiogenesis induces long-term structural and physiologic lung abnormalities, including bronchopulmonary dysplasia, a disease characterized by compromised alveolarization. Although endothelial cells are primary determinants of pulmonary angiogenesis, mesenchymal cells (MC) play a critical and dual role in angiogenesis and alveolarization. Therefore, we performed single cell transcriptomics and in-situ imaging of the developing lung to profile mesenchymal cells during alveolarization and in the context of lung injury. Specific mesenchymal cell subtypes were present at birth with increasing diversity during alveolarization even while expressing a distinct transcriptomic profile from more mature correlates. Hyperoxia arrested the transcriptomic progression of the MC, revealed differential cell subtype vulnerability with pericytes and myofibroblasts most affected, altered cell to cell communication, and led to the emergence of Acta1 expressing cells. These insights hold the promise of targeted treatment for neonatal lung disease, which remains a major cause of infant morbidity and mortality across the world.

Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during postnatal growth.

At birth, the lung is still immature, heightening susceptibility to injury but enhancing regenerative capacity. Angiogenesis drives postnatal lung development. Therefore, we profiled the transcriptional ontogeny and sensitivity to injury of pulmonary endothelial cells (EC) during early postnatal life. Although subtype speciation was evident at birth, immature lung EC exhibited transcriptomes distinct from mature counterparts, which progressed dynamically over time. Gradual, temporal changes in aerocyte capillary EC (CAP2) contrasted with more marked alterations in general capillary EC (CAP1) phenotype, including distinct CAP1 present only in the early alveolar lung expressing Peg3, a paternally imprinted transcription factor. Hyperoxia, an injury that impairs angiogenesis induced both common and unique endothelial gene signatures, dysregulated capillary EC crosstalk, and suppressed CAP1 proliferation while stimulating venous EC proliferation. These data highlight the diversity, transcriptomic evolution, and pleiotropic responses to injury of immature lung EC, possessing broad implications for lung development and injury across the lifespan.

Fat Embolism Syndrome After Knee Arthroscopy in a Pediatric Patient.

Fat embolism syndrome describes a constellation of symptoms that follow an insult and that results in a triad of respiratory distress, neurologic symptoms, and petechia. The antecedent insult usually entails trauma or orthopedic procedure, most frequently involving long bone (especially the femur) and pelvic fractures. The underlying mechanism of injury remains unknown but entails biphasic vascular injury with vascular obstruction from fat emboli followed by an inflammatory response. We present an unusual case of a pediatric patient with acute onset of altered mental status, respiratory distress, hypoxemia, and subsequent retinal vascular occlusions after knee arthroscopy and lysis of adhesions. Diagnostic findings most supportive of the fat embolism syndrome included anemia, thrombocytopenia, pulmonary parenchymal, and cerebral pathologic findings on imaging studies. This case highlights the importance of fat embolism syndrome as a diagnostic consideration after an orthopedic procedure, even absent major trauma or long bone fracture.