A translational cellular model to study the impact of high-frequency oscillatory ventilation on human epithelial cell function.
High-frequency oscillatory ventilation (HFOV) has been proposed as gentle ventilation strategy to prevent lung injury in the preterm infant. High-frequency jet ventilation leads to dimensional and mechanical airway deformation in animal airway models, which is consistent with translational studies demonstrating the impact of oxygen and biophysical stresses on normal airway cellular function. There is an overall paucity of clinical and cellular data on the impact of HFOV on the conducting airway. We developed an innovative method to test the impact of the clinical HFO Ventilator (SensorMedics 3100A) on human epithelial cell function. In this translational model, we were able to study the differential effects of biophysical stress due to HFOV independently and in combination with hyperoxia on a direct cellular level of the conducting airway system. Additionally, we could demonstrate that hyperoxia and pressure by HFOV independently resulted in significant cell dysfunction and inflammation, while the combination of HFOV and hyperoxia had a synergistic effect, resulting in greater cell death.



Traditionally, large-animal models are used to analyze the impact of clinical ventilators on lung cellular function. In our dual-chamber model, we interface high-frequency oscillatory ventilation (HFOV) directly with airway cells to study the effects of HFOV independently and combined with hyperoxia. Therefore, it is possible to study the preclinical impact of interventional factors without the high cost of animal models, thus reducing staff, time, as well as animal sparing.
Department of Neonatology, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania; anja.mowes@drexelmed.edu.|Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania.
Anja
A
Mowes
Department of Neonatology, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania.|Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania.
Beatriz E
BE
de Jongh
Nemours Research Lung Center, Alfred I. duPont Children's Hospital, Wilmington, Delaware.
Timothy
T
Cox
Nemours Research Lung Center, Alfred I. duPont Children's Hospital, Wilmington, Delaware.
Yan
Y
Zhu
Nemours Research Lung Center, Alfred I. duPont Children's Hospital, Wilmington, Delaware.|Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pennsylvania; and.|Department of Pediatrics, Temple University, Philadelphia, Pennsylvania.
Thomas H
TH
Shaffer
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D006612:High-Frequency Ventilation / Q000379:methods; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology; D055370:Lung Injury / Q000378:metabolism / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism; D012119:Respiration
D010100:Oxygen
HFOV; human airway cells; modified chamber