Biology subjects

Waisman, D.

Publications and source records attributed to Waisman, D..

2 recordsLinked to original sources

bioRxiv2021

Ventilation-induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with anti-inflammatory therapeutics

Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite maintenance of blood homeostasis. The biotrauma hypothesis advances that mechanical forces from invasive ventilation trigger immunological factors that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here we show that flow-induced stresses under mechanical ventilation can injure the bronchial epithelium of ventilated in vitro upper airway models and directly modulate inflammatory cytokine secretion associated with pulmonary injury. We identify site-specific susceptibility to epithelial erosion in airways from jet-flow impaction and measure an increase in cell apoptosis and modulated secretions of cytokines IL-6, 8 and 10. We find that prophylactic pharmacological treatment with anti-inflammatory therapeutics reduces apoptosis and pro-inflammatory signaling during ventilation. Our 3D in vitro airway platform points to a previously overlooked origin of lung injury and showcases translational opportunities in preclinical pulmonary research towards protective therapies and improved protocols for patient care.

bioengineering↗

bioRxiv2020

Liquid foam therapy (LiFT) for homogenous distribution of exogenous pulmonary surfactant in ARDS

Lung surfactant dysfunction has a critical role in the pathophysiology of acute respiratory distress syndrome (ARDS). Yet, efforts to treat ARDS patients with liquid instillations of exogenous surfactant have so far failed. One of the ongoing challenges in surfactant therapy is obtaining a homogeneous distribution of surfactant within the lungs despite an inherent tendency to non-uniform spreading, owing amongst others to the influence of gravity. Here, we show that liquid foam therapy (LiFT), where surfactant is foamed prior to intratracheal administration, may improve notably surfactant distribution while maintaining safety and efficacy. We first show quantitatively that a foamed surrogate surfactant solution distributes more uniformly in ex vivo pig lungs compared to endotracheal instillations of the liquid solution, while maintaining pulmonary airway pressures within a safe range. Next, we demonstrate that a foamed commercial surfactant preparation (Infasurf) is effective in an established in vivo rat lung lavage model of ARDS. Our results suggest that LiFT may be more effective than liquid instillations for treating ARDS and serve as a proof-of-principle towards large animal and clinical trials.

pharmacology and toxicology↗