Protective ventilation strategies for the injured lung currently revolve around the use of low Vt, ostensibly to avoid volutrauma, together with positive end-expiratory pressure to increase the fraction of open lung and reduce atelectrauma. Protective ventilation is currently applied in a one-size-fits-all manner, and although this practical approach has reduced acute respiratory distress syndrome deaths, mortality is still high and improvements are at a standstill. Furthermore, how to minimize ventilator-induced lung injury (VILI) for any given lung remains controversial and poorly understood. Here we present a hypothesis of VILI pathogenesis that potentially serves as a basis upon which minimally injurious ventilation strategies might be developed. This hypothesis is based on evidence demonstrating that VILI begins in isolated lung regions manifesting a Permeability-Originated Obstruction Response (POOR) in which alveolar leak leads to surfactant dysfunction and increases local tissue stresses. VILI progresses topographically outward from these regions in a POOR-get-POORer fashion unless steps are taken to interrupt it. We propose that interrupting the POOR-get-POORer progression of lung injury relies on two principles: 1) open the lung to minimize the presence of heterogeneity-induced stress concentrators that are focused around the regions of atelectasis, and 2) ventilate in a patient-dependent manner that minimizes the number of lung units that close during each expiration so that they are not forced to rerecruit during the subsequent inspiration. These principles appear to be borne out in both patient and animal studies in which expiration is terminated before derecruitment of lung units has enough time to occur.

We have utilized a computational model of semi-infinite air bubble progression in a surfactant-doped, fluid-filled rigid capillary to investigate the continual interfacial expansion dynamics that occur during the opening of collapsed pulmonary airways. This model simulates mixed-kinetic conditions with nonlinear surfactant equations of state similar to those of pulmonary surfactant. Several dimensionless parameters govern the system responses: the capillary number (Ca) that relates viscous to surface tension forces; the elasticity number (El), a measure of the ability of surfactant to modify the surface tension; the bulk Péclet number (Pe), relating bulk convection rates to diffusion rates; the adsorption and desorption Stanton numbers (St_a and St_d) that relate the adsorption/desorption rates to surface convective rates; and finally the adsorption depth (λ), a dimensionless bulk surfactant concentration parameter. We investigated this model by performing detailed parameter variation studies at fixed and variable equilibrium concentrations. We find that the surfactant properties can strongly influence the interfacial pressure drop through modification of the surface tension and the creation of Marangoni stresses that influence the viscous stresses along the interface. In addition, these studies demonstrate that, depending upon the range of parameters, either film thickening or film thinning responses are possible. In particular, we find that when Pe[Gt ]1 (as with pulmonary surfactant) or when sorption rates are low, concentration profiles can substantially differ from near-equilibrium approximations and can result in film thinning. These responses may influence stresses on epithelial cells that line pulmonary airways and the stability of these airways, and may be important to the delivery of exogenous surfactant to deep regions of the lung.

This paper provides a synopsis of discussions related to biomedical engineering core curricula that occurred at the Fourth BME Education Summit held at Case Western Reserve University in Cleveland, Ohio in May 2019. This summit was organized by the Council of Chairs of Bioengineering and Biomedical Engineering, and participants included over 300 faculty members from 100+ accredited undergraduate programs. This discussion focused on six key questions: QI: Is there a core curriculum, and if so, what are its components? QII: How does our purported core curriculum prepare students for careers, particularly in industry? QIII: How does design distinguish BME/BIOE graduates from other engineers? QIV: What is the state of engineering analysis and systems-level modeling in BME/BIOE curricula? QV: What is the role of data science in BME/BIOE undergraduate education? QVI: What core experimental skills are required for BME/BIOE undergrads? s. Indeed, BME/BIOI core curricula exists and has matured to emphasize interdisciplinary topics such as physiology, instrumentation, mechanics, computer programming, and mathematical modeling. Departments demonstrate their own identities by highlighting discipline-specific sub-specialties. In addition to technical competence, Industry partners most highly value our students’ capacity for problem solving and communication. As such, BME/BIOE curricula includes open-ended projects that address unmet patient and clinician needs as primary methods to prepare graduates for careers in industry. Culminating senior design experiences distinguish BME/BIOE graduates through their development of client-centered engineering solutions to healthcare problems. Finally, the overall BME/BIOE curriculum is not stagnant—it is clear that data science will become an ever-important element of our students’ training and that new methods to enhance student engagement will be of pedagogical importance as we embark on the next decade.

The progression of acute respiratory distress syndrome (ARDS) from its onset due to disease or trauma to either recovery or death is poorly understood. Currently, there are no generally accepted treatments aside from supportive care using mechanical ventilation. However, this can lead to ventilator-induced lung injury (VILI), which contributes to a 30 to 40% mortality rate. In this study, we develop and demonstrate a technique to quantify forms of energy transport and dissipation during mechanical ventilation to directly evaluate their relationship to VILI. A porcine ARDS model was used, with ventilation parameters independently controlling lung overdistension and alveolar/airway recruitment/derecruitment (RD). Hourly measurements of airflow, tracheal and esophageal pressures, respiratory system impedance, and oxygen transport were taken for six hours following lung injury to track energy transfer and lung function. The final degree of injury was assessed histologically. Total and dissipated energies were quantified from lung pressure–volume relationships and subdivided into contributions from airflow, tissue viscoelasticity, and RD. Only RD correlated with physiologic recovery. Despite accounting for a very small fraction (2 to 5%) of the total energy dissipation, RD is damaging because it occurs quickly over a very small area. We estimate power intensity of RD energy dissipation to be 100 W/m ² , equivalent to 10% of the Sun’s luminance at the Earth’s surface. Minimizing repetitive RD events may thus be crucial for mitigating VILI.