Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LV) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA).

Ratchet recruitment in the acute respiratory distress syndrome: lessons from the newborn cry.

Patients with acute respiratory distress syndrome (ARDS) have few treatment options other than supportive mechanical ventilation. The mortality associated with ARDS remains unacceptably high, and mechanical ventilation itself has the potential to increase mortality further by unintended ventilator-induced lung injury (VILI). Thus, there is motivation to improve management of ventilation in patients with ARDS.

Full-lung simulations of mechanically ventilated lungs incorporating recruitment/derecruitment dynamics.

This study developed and investigated a comprehensive multiscale computational model of a mechanically ventilated ARDS lung to elucidate the underlying mechanisms contributing to the development or prevention of VILI. This model is built upon a healthy lung model that incorporates realistic airway and alveolar geometry, tissue distensibility, and surfactant dynamics. Key features of the ARDS model include recruitment and derecruitment (RD) dynamics, alveolar tissue viscoelasticity, and surfactant deficiency.

Ventilator-Induced Lung Injury as a Dynamic Balance Between Epithelial Cell Damage and Recovery.

Acute respiratory distress syndrome (ARDS) has a high mortality rate that is due in part to ventilator-induced lung injury (VILI). Nevertheless, the majority of patients eventually recover, which means that their innate reparative capacities eventually prevail. Since there are currently no medical therapies for ARDS, minimizing its mortality thus amounts to achieving an optimal balance between spontaneous tissue repair versus the generation of VILI.

Protective ventilation in a pig model of acute lung injury: timing is as important as pressure.

Ventilator-induced lung injury (VILI) is a significant risk for patients with acute respiratory distress syndrome (ARDS). Management of the patient with ARDS is currently dominated by the use of low tidal volume mechanical ventilation, the presumption being that this mitigates overdistension (OD) injury to the remaining normal lung tissue. Evidence exists, however, that it may be more important to avoid cyclic recruitment and derecruitment (RD) of lung units, although the relative roles of OD and RD in VILI remain unclear.

Preparation and Structural Evaluation of Epithelial Cell Monolayers in a Physiologically Sized Microfluidic Culture Device.

In vitro microfluidic experimentation holds great potential to reveal many insights into the microphysiological phenomena occurring in conditions such as acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). However, studies in microfluidic channels with dimensions physiologically relevant to the terminal bronchioles of the human lung currently face several challenges, especially due to difficulties in establishing appropriate cell culture conditions, including media flow rates, within a given culture environment. The presented protocol describes an image-based approach to evaluate the structure of NCI-H441 human lung epithelial cells cultured in an oxygen-impermeable microfluidic channel with dimensions physiologically relevant to the terminal bronchioles of the human lung.

Electric Cell-Substrate Impedance Sensing (ECIS) as a Platform for Evaluating Barrier-Function Susceptibility and Damage from Pulmonary Atelectrauma.

Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells that occurs in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). This in vitro study was performed using Electric Cell-substrate Impedance Sensing (ECIS) as a noninvasive evaluating technique for repetitive stress stimulus/response on monolayers of the human lung epithelial cell line NCI-H441.

Learning Environments and Evidence-Based Practices in Bioengineering and Biomedical Engineering.

This paper provides a synopsis of discussions related to the Learning Environments track of 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. The Learning Environments track had six interactive workshops that provided facilitated discussion and provide recommendations in the areas of: (1) Authentic project/problem identification in clinical, industrial, and global settings, (2) Experiential problem/project-based learning within courses, (3) Experiential learning in co-curricular learning settings, (4) Team-based learning, (5) Teaching to reach a diverse classroom, and (6) innovative platforms and pedagogy.

Atelectrauma Versus Volutrauma: A Tale of Two Time-Constants.

Objectives: Elucidate how the degree of ventilator-induced lung injury due to atelectrauma that is produced in the injured lung during mechanical ventilation is determined by both the timing and magnitude of the airway pressure profile.

Design: A computational model of the injured lung provides a platform for exploring how mechanical ventilation parameters potentially modulate atelectrauma and volutrauma. This model incorporates the time dependence of lung recruitment and derecruitment, and the time-constant of lung emptying during expiration as determined by overall compliance and resistance of the respiratory system.

The POOR Get POORer: A Hypothesis for the Pathogenesis of Ventilator-induced Lung Injury.

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.

Surfactant-Mediated Airway and Acinar Interactions in a Multi-Scale Model of a Healthy Lung.

We present a computational multi-scale model of an adult human lung that combines dynamic surfactant physicochemical interactions and parenchymal tethering between ~16 generations of airways and subtended acini. This model simulates the healthy lung by modeling nonlinear stress distributions from airway/alveolar interdependency. In concert with multi-component surfactant transport processes, this serves to stabilize highly compliant interacting structures.

Core Competencies for Undergraduates in Bioengineering and Biomedical Engineering: Findings, Consequences, and Recommendations.

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.

Microscale to mesoscale analysis of parenchymal tethering: the effect of heterogeneous alveolar pressures on the pulmonary mechanics of compliant airways.

In the healthy lung, bronchi are tethered open by the surrounding parenchyma; for a uniform distribution of these peribronchial structures, the solution is well known. An open question remains regarding the effect of a distributed set of collapsed alveoli, as can occur in disease. Here, we address this question by developing and analyzing microscale finite-element models of systems of heterogeneously inflated alveoli to determine the range and extent of parenchymal tethering effects on a neighboring collapsible airway.

Flow characteristics of urethral catheters of the same caliber vary between manufacturers.

Background: Clean intermittent catheterization (CIC) is frequently prescribed for bladder dysfunction, either per urethra or via a continent catheterizable channel. Small catheters may be required for infants or continent channels. Success with CIC is highly dependent upon patient and family compliance.

Microscale distribution and dynamic surface tension of pulmonary surfactant normalize the recruitment of asymmetric bifurcating airways.

We investigate the influence of bifurcation geometry, asymmetry of daughter airways, surfactant distribution, and physicochemical properties on the uniformity of airway recruitment of asymmetric bifurcating airways. To do so, we developed microfluidic idealized in vitro models of bifurcating airways, through which we can independently evaluate the impact of carina location and daughter airway width and length. We explore the uniformity of recruitment and its relationship to the dynamic surface tension of the lining fluid and relate this behavior to the hydraulic (P) and capillary (P) pressure drops.

The influence of tethering and gravity on the stability of compliant liquid-lined airways.

This study revolves around two simple questions: 1) how does pulmonary airway recruitment/de-recruitment (RecDer) depend on the tethering support provided by surrounding airways and alveoli, and 2) does airway angle of inclination (θ) influence airway stability? These two questions are critical to understanding the existence and prevention of atelectrauma, which may contribute to ventilator-induced lung injury (VILI). To address these questions, we develop PDMS 2mm ID compliant tubes that mimic pulmonary airways. Airway obstruction is modeled using silicone oil, and recruitment occurs through insufflation with a constant flow of air at Q=0.

Reduced-Dimension Modeling Approach for Simulating Recruitment/De-recruitment Dynamics in the Lung.

Acute respiratory distress syndrome is a pulmonary disease that requires the use of mechanical ventilation for patient recovery. However, this can lead to development of ventilator-induced lung injury caused by the over-distension of alveolar tissue and by the repetitive closure (de-recruitment) and reopening (recruitment) of airways. In this study, we developed a multi-scale model of the lung from a reduced-dimension approach to investigate the dynamics of ventilation in the lung during airway collapse and reopening.

Estimation of the Pressure Drop Required for Lymph Flow through Initial Lymphatic Networks.

Background: Lymphatic function is critical for maintaining interstitial fluid balance and is linked to multiple pathological conditions. While smooth muscle contractile mechanisms responsible for fluid flow through collecting lymphatic vessels are well studied, how fluid flows into and through initial lymphatic networks remains poorly understood. The objective of this study was to estimate the pressure difference needed for flow through an intact initial lymphatic network.

The unusual symmetric reopening effect induced by pulmonary surfactant.

This study investigates the stability of a finger of air as it propagates into a liquid-filled model of a liquid-filled model of a pulmonary bifurcation. We seek to elucidate the stability characteristics of the reopening of daughter airways, an event that may be important to the treatment of acute lung disease. To do so, we investigated the symmetry of reopening under conditions of nearly constant surface tension with 1) purified H2O or 2) an anionic surfactant (sodium dodecyl sulfate).

A model of surfactant-induced surface tension effects on the parenchymal tethering of pulmonary airways.

We developed a computational model of lung parenchyma, which is comprised of individual alveolar chamber models. Each alveolus is modeled by a truncated octahedron. Considering the force balance between the elastin and collagen fibers laying on the alveolar membrane and the pressures acting on the membrane, we computed the deformations of the parenchyma with a finite element method.

Lagrangian transport properties of pulmonary interfacial flows.

Disease states characterized by airway fluid occlusion and pulmonary surfactant insufficiency, such as respiratory distress syndrome, have a high mortality rate. Understanding the mechanics of airway reopening, particularly involving surfactant transport, may provide an avenue to increase patient survival via optimized mechanical ventilation waveforms. We model the occluded airway as a liquid-filled rigid tube with the fluid phase displaced by a finger of air that propagates with both mean and sinusoidal velocity components.