Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension that is caused by persistent obstruction of the pulmonary arteries by organized thrombi and associated microvascular disease. Pulmonary endarterectomy (PEA) is the gold standard treatment, but the extent of small vessel remodeling, which strongly influences treatment outcomes, remains difficult to quantify pre-operatively. We developed a multiscale, structure-based model of the pulmonary circulation using patient-specific vascular geometries from CT pulmonary angiography (CTPA) and haemodynamic data from right heart catheterization (RHC). Eleven CTEPH patients were included. The model estimated individual remodeling burden by fitting simulated to measured preoperative mean pulmonary artery pressure (mPAP). PEA was simulated by removing flow obstructions to predict Postoperative mPAP and pulmonary vascular resistance (PVR), both under pre- and post-PEA boundary conditions. Model predictions of post-PEA mPAP and PVR were in reasonable agreement with measured outcomes, especially when Postoperative boundary conditions were applied. Predicted changes in mPAP (∆mPAP) strongly correlated with clinical values (R = 0.81, p = 0.002), improving further with post-PEA flow parameters (R = 0.84, p = 0.001). The model captured variable haemodynamic responses to PEA, even among patients with similar Postoperative mPAP. This preliminary investigation demonstrates the feasibility of personalized computational modeling to non-invasively estimate the extent of microvascular disease and simulate postsurgical haemodynamic outcomes in CTEPH. The findings support the potential for this approach to serve as a clinical decision-making tool, with future validation in larger cohorts and integration of spatial remodeling and longitudinal data.

Determining the health effects of vaping is challenging due to the constantly evolving landscape of electronic cigarette (EC) products and modes of use. Studying the effect of EC aerosols on health requires in vivo and in vitro experiments, where dose and deposition of aerosol is important. We present a computational approach to predict aerosol dosimetry throughout a realistic airway tree to support experimental dosimetry, providing the ability to predict dosimetry in different subjects, species, vaping products and inhalation conditions. EC aerosol transport was modelled using advection-diffusion equations, and deposition was estimated via the mechanisms of sedimentation, impaction, and Brownian diffusion. The model was applied to determine the impact of particle size, such as with increasing EC device power settings, and comparison of mouth-to-lung (MTL) and direct-to-lung (DTL) vaping regimens. Results showed a bell-shaped trend in deposition efficiency, ranging from 74 % to 72 % over a particle size range of 20 nm to 3.5 mu m, with the lowest deposition (similar to 15 % in DTL and similar to 5 % in MTL vaping) in the mid-particle size range (0.5 mu m). Deposition was higher for DTL vaping compared with MTL. MTL vaping resulted in a higher proportion of deposition in the upper airways, while DTL vaping showed greater deposition in the respiratory airways, due to differences in flow rates and puff volume. The mass of particles deposited throughout the airway tree varied from 1 x 10(-7) mg to 4 x 10(-3) mg indicating large variability and the importance of tailoring dose correctly depending on which part of the airway tree is being studied.

BACKGROUND:Studies have identified important associations between computed tomography (CT) features of the normal-appearing lung tissue and patient outcomes, however, the heterogeneity of normal-appearing tissue has not previously been considered in chronic obstructive pulmonary disease (COPD). METHODS:We aimed to quantify heterogeneity in normal-appearing lung tissue on inspiratory CT imaging and its relationship with lung function and clinical outcomes. We analysed data from 520 participants enroled in the COPDGene study, including never-smokers, current and former smokers without airflow obstruction, and COPD (GOLD1-4). Quadtree decomposition was used to derive spatially-connected heterogeneity metrics for medium (-900 to -750 HU) and low (< -900 HU) density tissues, and for all tissues combined. Medium density included tissue typically classified as normal-appearing by HU thresholding. Associations between heterogeneity, lung function, and respiratory morbidity were tested using multivariable regression. RESULTS:Heterogeneity in medium-density tissue was similar between current and former smokers without airflow obstruction and COPD (0.15±0.05 cf. 0.16±0.06, p=0.11), and was significantly higher than in never-smokers (0.10±0.03, p<0.001). After adjusting for emphysema, age, sex, race, smoking status, and BMI, heterogeneity was independently associated with FEV1 % predicted, St. George's Respiratory Questionnaire score, modified Medical Research Council dyspnoea score, six-minute walk distance, and greater FEV1 decline at follow-up. CONCLUSION:Heterogeneity of normal-appearing lung tissue is associated with respiratory morbidity and disease progression in COPD. This highlights the importance of detecting subtle early changes in tissue architecture in current and former smokers at risk for and with COPD.

Electrical impedance tomography (EIT) is medical imaging technique in which small electrical signals are used to map the electrical impedance distribution within the body. It is safe and non-invasive, which make it attractive for use in continuous monitoring or outpatient applications, but the high cost of commercial devices is an impediment to its adoption. Over the last 10 years, many research groups have developed their own EIT devices, but few designs for open-source EIT hardware are available. In this work, we present a complete open-source EIT system that is designed to be suitable for monitoring the lungs of free breathing subjects. The device is low-cost, wearable, and is designed to comply with the industry accepted safety standard for EIT. The device has been tested in two regimes: Firstly in terms of measurement uncertainty as a voltage measurement system, and secondly against a set of measures that have been proposed specifically for EIT hardware. The voltage measurement uncertainty of the device was measured to be − 0.7 % ± 0.36 mV. The EIT specific performance was measured in a phantom test designed to be as physiologically representative as practicable, and the device performed similarly to other published devices. This work will contribute to increased accessibility of EIT for study and will contribute to consensus on testing methodology for EIT devices.

Acute respiratory distress syndrome (ARDS) patients usually require support from ventilation in the intensive care unit (ICU). Recruitment maneuvers (RMs) with positive-end-expiratory-pressure (PEEP) are a common way to recruit alveoli and improve oxygenation. However, excessive PEEP can worsen alveoli status and thus increase the risk of ventilator-induced lung injury (VILI). To date, standards for optimal patient-specific PEEP determination remain unclear, resulting in variability and uncertainty in care and thus requiring personalized care approaches. This research examines the conventional approach, dynamic elastance (E-dyn), and a validated over-distension index (OD) from prior work identified from pressure-volume curves. Overall, in the studied pilot trial, the optimal PEEP selection outcome matches between E-dyn and OD methods within 0-2cmH(2)O (0-1 PEEP levels) variation for 16 out of 18 patients. The variation in the rest 2 patients are 4cmH(2)O (2 PEEP levels). While possible limitation for E-dyn is addressed and discussed, the over-distention index OD shows greater potential in routine care being more intuitive, general, and predictive. Copyright (C) 2024 The Authors. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Electrical impedance tomography (EIT) is an imaging method that can be used to image electrical impedance contrasts within various tissues of the body. To support development of EIT measurement systems, a phantom is required that represents the electrical characteristics of the imaging domain. No existing type of EIT phantom combines good performance in all three characteristics of resistivity resolution, spatial resolution, and stability. Here, a novel EIT phantom concept is proposed that uses 3D printed conductive material. Resistivity is controlled using the 3D printing infill percentage parameter, allowing arbitrary resistivity contrasts within the domain to be manufactured automatically. The concept of controlling resistivity through infill percentage is validated, and the manufacturing accuracy is quantified. A method for making electrical connections to the 3D printed material is developed. Finally, a prototype phantom is printed, and a sample EIT analysis is performed. The resulting phantom, printed with an Ultimaker S3, has high reported spatial resolution of 6.9 µm, 6.9 µm, and 2.5 µm for X, Y, and Z axis directions, respectively (X and Y being the horizontal axes, and Z the vertical). The number of resistivity levels that are manufacturable by varying infill percentage is 15 (calculated by dividing the available range of resistivities by two times the standard deviation of the manufacturing accuracy). This phantom construction technique will allow assessment of the performance of EIT devices under realistic physiological scenarios.

Several experimental studies have found that females have higher particle deposition in the airways than males. This has implications for the delivery of aerosolized therapeutics and for understanding sex differences in respiratory system response to environmental exposures. This study evaluates several factors that potentially contribute to sex differences in particle deposition, using scale-specific structure-function models of one-dimensional (1-D) ventilation distribution, particle transport, and deposition. The impact of gravity, inhalation flow rate, and dead space are evaluated in 12 structure-based models (7 females; 5 males). Females were found to have significantly higher total, bronchial, and alveolar deposition than males across a particle size range from 0.01 to 10 μm. Results suggest that higher deposition fraction in females is due to higher alveolar deposition for smaller particle sizes and higher bronchial deposition for larger particles. Females had higher alveolar deposition in the lower lobes and slightly lower particle concentration in the left upper lobe. Males were found to be more sensitive to changes due to gravity, showing greater reduction in bronchial deposition fraction. Males were also more sensitive to change in inhalation flow rate and to scaling of dead space due to the larger male baseline airway size. Predictions of sex differences in particle deposition-that are consistent with the literature-suggest that sex-based characteristics of lung and airway size interacting with particle size gives rise to differences in regional deposition.NEW & NOTEWORTHY Sex differences in airway tract particle deposition are analyzed using computational models that account for scale-specific structure and function. We show that sex-related differences in lung and airway size can explain experimental observations of increased deposition fraction in females, with females tending toward enhanced fine particle deposition in the alveolar airways and enhanced bronchial deposition for larger particles.

Rationale and ObjectivesFibrotic scarring in idiopathic pulmonary fibrosis (IPF) typically develops first in the posterior-basal lung tissue before advancing to involve more of the lung. The complexity of lung shape in the costo-diaphragmatic region has been proposed as a potential factor in this regional development. Intrinsic and disease-related shape could therefore be important for understanding IPF risk and its staging. We hypothesized that lung and lobe shape in IPF would have important differences from controls.Materials and MethodsA principal component (PC) analysis was used to derive a statistical shape model (SSM) of the lung for a control cohort aged > 50 years (N = 39), using segmented lung and fissure surface data from CT imaging. Individual patient shape models derived for baseline (N = 18) and follow-up (N = 16) CT scans in patients with IPF were projected to the SSM to describe shape as the sum of the SSM average and weighted PC modes. Associations between the first four PC shape modes, lung function, percentage of fibrosis (fibrosis%) and pulmonary vessel-related structures (PVRS%), and other tissue metrics were assessed and compared between the two cohorts.ResultsShape was different between IPF and controls (P < 0.05 for all shape modes), with IPF shape forming a distinct shape cluster. Shape had a negative relationship with age in controls (P = 0.013), but a positive relationship with age in IPF (P = 0.026). Some features of shape changed on follow-up. Shape in IPF was associated with fibrosis% (P < 0.05) and PVRS% (P < 0.05).ConclusionQuantitative comparison of lung and lobe shape in IPF with controls of a similar age reveals shape differences that are strongly associated with age and percent fibrosis. The clustering of IPF cohort shape suggests that it could be an important feature to describe disease.

Background: Patient work of breathing is a key clinical metric strongly to guide patient care and weaning from mechanical ventilation (MV). Measurement requires added equipment, well-trained clinicians, or/and extra interventions. This study combines a spontaneous breathing effort model using b-spline functions with a nonlinear, predictive MV digital-twin model to monitor patient effort in real-time. Methods: Data from 22 patients for two assisted spontaneous breathing MV modes, NAVA (neurally adjusted ventilatory assist) and PSV (pressure support ventilation), are employed. The patient effort function estimates a pleural pressure ensure identifiability P p is identified with a negative constraint level of 75%. Estimated patient effort is compared to electrical activity of the diaphragm (EAdi) signals from the NAVA naso-gastric tude, airway pressure, and tidal volume ( V T ) as well as physiological and clinical expectations. Results: P p generalizes well across the digital twin model and MV modes in comparison to the original single compartment lung model. Strong neuro-muscular correlations are identified with P p compared to EAdi, V T , and airway pressure in NAVA. They are lower in PSV, as expected, as pressure delivery is not a function of EAdi in this MV mode, while the uncontrolled variable V T shows a stronger association with P p than EAdi. Conclusion: The digital twin model relates patient-specific induced breathing effort, modeled as P p , as well as or better than EAdi in both assisted breathing MV modes. Results differ between NAVA and PSV modes due to the poorer patient-ventilator interaction typical in PSV. The ability to estimate patient work of breathing allows non-invasive, real-time quantification of ventilator unloading, heretofore not possible without extra sensors or maneuvers, to help guide weaning or changes in MV settings for assisted spontaneous breathing (ASB) MV modes. P p surrogate of muscular work of breathing induced pressure. To (c) 2024 Elsevier Ltd. All rights reserved.

Two new biomechanical challenges faced cetacean lungs compared to their terrestrial ancestors. First, hydrostatic pressures encountered during deep dives are sufficient to cause nearly full lung collapse, risking substantial barotrauma during surfacing if air is trapped in the fragile smaller airways. Second, rapid ventilation in large cetaceans requires correspondingly high ventilatory flow rates. In order to investigate how airway geometry evolved in response to these challenges, we characterized airway geometry from 12 species of cetaceans that vary in common dive depth and ventilatory behavior and a domestic pig using computed tomography. After segmenting the major airways, we generated centerline networks models for the larger airways and computed geometric parameters for each tree including mean branching angle, percent volume fraction, and Strahler branching, diameter, and length ratios. When airway geometry was regressed against ventilatory and diving parameters with phylogenetic least squares, neither average branching angle, percent volume fraction, Strahler length ratio or Strahler branching ratio significantly varied with common ventilatory mode or common diving depth. Higher Strahler diameter ratios were associated with slower ventilation and deeper diving depth, suggesting that cetacean lungs have responded to biomechanical pressures primarily with changes in airway diameter. High Strahler diameter ratios lungs in deeper diving species may help to facilitate more complete collapse of the delicate terminal airways by providing for a greater incompressible volume for air storage at depth. On the other hand, lungs with low Strahler diameter ratios would be better for fast ventilation because the gradual decrease in diameter moving distally should keep peripheral flow resistance low, maximizing ventilatory flow rates. ### Competing Interest Statement The authors have declared no competing interest.

INTRODUCTION:During mechanical ventilation, cyclic recruitment and derecruitment (R/D) of alveoli result in focal points of heterogeneous stress throughout the lung. In the acutely injured lung, the rates at which alveoli can be recruited or derecruited may also be altered, requiring longer times at higher pressure levels to be recruited during inspiration, but shorter times at lower pressure levels to minimize collapse during exhalation. In this study, we used a computational model to simulate the effects of airway pressure release ventilation (APRV) on acinar recruitment, with varying inspiratory pressure levels and durations of exhalation.MATERIALS AND METHODS:The computational model consisted of a ventilator pressure source, a distensible breathing circuit, an endotracheal tube, and a porcine lung consisting of recruited and derecruited zones, as well as a transitional zone capable of intratidal R/D. Lung injury was simulated by modifying each acinus with an inflation-dependent surface tension. APRV was simulated for an inhalation duration (Thigh) of 4.0 seconds, inspiratory pressures (Phigh) of 28 and 40 cmH2O, and exhalation durations (Tlow) ranging from 0.2 to 1.5 seconds.RESULTS:Both sustained acinar recruitment and intratidal R/D within the subtree were consistently higher for Phigh of 40 cmH2O vs. 28 cmH2O, regardless of Tlow. Increasing Tlow was associated with decreasing sustained acinar recruitment, but increasing intratidal R/D, within the subtree. Increasing Tlow was associated with decreasing elastance of both the total respiratory system and transitional subtree of the model.CONCLUSIONS:Our computational model demonstrates the confounding effects of cyclic R/D, sustained recruitment, and parenchymal strain stiffening on estimates of total lung elastance during APRV. Increasing inspiratory pressures leads to not only more sustained recruitment of unstable acini but also more intratidal R/D. Our model indicates that higher inspiratory pressures should be used in conjunction with shorter exhalation times, to avoid increasing intratidal R/D.