Ex Vivo Perfusion and In Vivo Xenotransplantation of Pig Lungs with Humanized Von Willebrand Factor Demonstrate Reduced Platelet Sequestration

Abstract

Purpose: The COVID-19 pandemic accelerated the need to develop remote monitoring of graft function in lung transplant (LT) recipients. While home spirometry has been used previously in LT, long-term engagement has been poor. We aimed to improve engagement and allow efficient data and symptom collection using Bluetooth enabled home spirometers coupled with a digital chatbot. Methods: We implemented an automated, chat-based mobile health intervention via text message or email paired with Bluetooth-enabled handheld spirometers. The chatbot engaged LT recipients weekly in a personalized, automated chat with symptom assessment, education modules, and spirometer data collection. Clinical team members received automatic notification of concerning symptoms or FEV1 declines of >10%. The correlation between home spirometry FEV1 values and lab-based values were assessed with Pearson's coefficient. Results: We mailed home spirometers to 424 patients. Between 5/4/2020 and 10/21/2020, 311 patients enrolled in the automated chat and, of these, 273 patients submitted ≥1 FEV1 measure, (median 13; IQR 6-23) over 24 weeks. The largest drop in FEV1 engagement came after the first week in each patient's chat experience; 65% of those that submitted an FEV1 at baseline entered a value at week one and 72% at week two. However, after this initial decline, engagement remained stable through 24 weeks (57-72%, Figure 1.A). Home spirometry FEV1 correlated closely with in-lab spirometry (rho = 0.94) (Figure 1.B) Conclusion: LT recipients engaged at high rates with a chatbot mobile health intervention and home spirometers to report their FEV1, allowing reliable home-based monitoring of LT recipients. Further investigation will be needed to improve engagement further. Given the projected need for social distancing, and increasing role of telemedicine for long-term management, a chatbot-linked home spirometer may be a powerful tool to detect early graft dysfunction.

Effects of human TFPI and CD47 expression and selectin and integrin inhibition during GalTKO.hCD46 pig lung perfusion with human blood

“…47,59 Our approach in the current study addressed this issue, predicting that use of a P-selectin inhibitor might attenuate this potentially undesirable side effect of DDAVP administration. At least until alternative methods to overcome porcine vWF-mediated coagulation dysfunction are developed, such as "humanizing" the GPIb binding sites on porcine vWF, 60 we advocate to combine DDAVP with P-selectin inhibition in our future work. 61 Similarly, until the upstream triggers for elaboration of inflammatory molecules are better understood and dependably controlled, our lung work will continue to deploy demonstrably effective lung protective pharmacologic interventions.…”