Reference Equations for Within-Breath Respiratory Oscillometry in White Adults.

BACKGROUND: Within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aimed to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. METHODS: White adults with normal spirometry, BMI ≤30 kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19 Hz, Resmon PRO FULL, RESTECH Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to lambda-mu-sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. RESULTS: A total of 144 subjects (age 20.8-86.3 years; height 146-193 cm; BMI 17.42-29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

Examining lung mechanical strains as influenced by breathing volumes and rates using experimental digital image correlation.

BACKGROUND: Mechanical ventilation is often employed to facilitate breathing in patients suffering from respiratory illnesses and disabilities. Despite the benefits, there are risks associated with ventilator-induced lung injuries and death, driving investigations for alternative ventilation techniques to improve mechanical ventilation, such as multi-oscillatory and high-frequency ventilation; however, few studies have evaluated fundamental lung mechanical local deformations under variable loading. METHODS: Porcine whole lung samples were analyzed using a novel application of digital image correlation interfaced with an electromechanical ventilation system to associate the local behavior to the global volume and pressure loading in response to various inflation volumes and breathing rates. Strains, anisotropy, tissue compliance, and the evolutionary response of the inflating lung were analyzed. RESULTS: Experiments demonstrated a direct and near one-to-one linear relationship between applied lung volumes and resulting local mean strain, and a nonlinear relationship between lung pressures and strains. As the applied air delivery volume was doubled, the tissue surface mean strains approximately increased from 20 to 40%, and average maximum strains measured 70-110%. The tissue strain anisotropic ratio ranged from 0.81 to 0.86 and decreased with greater inflation volumes. Local tissue compliance during the inflation cycle, associating evolutionary strains in response to inflation pressures, was also quantified. CONCLUSION: Ventilation frequencies were not found to influence the local stretch response. Strain measures significantly increased and the anisotropic ratio decreased between the smallest and greatest tidal volumes. Tissue compliance did not exhibit a unifying trend. The insights provided by the real-time continuous measures, and the kinetics to kinematics pulmonary linkage established by this study offers valuable characterizations for computational models and establishes a framework for future studies to compare healthy and diseased lung mechanics to further consider alternatives for effective ventilation strategies.

Induction of dynamic hyperinflation by expiratory resistance breathing in healthy subjects - an efficacy and safety study.

NEW FINDINGS: What is the central question of this study? The study aimed to establish a novel model to study the chronic obstructive pulmonary disease (COPD)-related cardiopulmonary effects of dynamic hyperinflation in healthy subjects. What is the main finding and its importance? A model of expiratory resistance breathing (ERB) was established in which dynamic hyperinflation was induced in healthy subjects, expressed both by lung volumes and intrathoracic pressures. ERB outperformed existing methods and represents an efficacious model to study cardiopulmonary mechanics of dynamic hyperinflation without potentially confounding factors as present in COPD. ABSTRACT: Dynamic hyperinflation (DH) determines symptoms and prognosis of chronic obstructive pulmonary disease (COPD). The induction of DH is used to study cardiopulmonary mechanics in healthy subjects without COPD-related confounders like inflammation, hypoxic vasoconstriction and rarefication of pulmonary vasculature. Metronome-paced tachypnoea (MPT) has proven effective in inducing DH in healthy subjects, but does not account for airflow limitation. We aimed to establish a novel model incorporating airflow limitation by combining tachypnoea with an expiratory airway stenosis. We investigated this expiratory resistance breathing (ERB) model in 14 healthy subjects using different stenosis diameters to assess a dose-response relationship. Via cross-over design, we compared ERB to MPT in a random sequence. DH was quantified by inspiratory capacity (IC, litres) and intrinsic positive end-expiratory pressure (PEEPi, cmH2 O). ERB induced a stepwise decreasing IC (means (95% CI): tidal breathing: 3.66 (3.45-3.88), ERB 3 mm: 3.33 (1.75-4.91), 2 mm: 2.05 (0.76-3.34), 1.5 mm: 0.73 (0.12-1.58) litres) and increasing PEEPi (tidal breathing: 0.70 (0.50-0.80), ERB 3 mm: 11.1 (7.0-15.2), 2 mm: 22.3 (17.1-27.6), 1.5 mm: 33.4 (3.40-63) cmH2 O). All three MPT patterns increased PEEPi, but to a far lesser extent than ERB. No adverse events during ERB were noted. In conclusion, ERB was proven to be a safe and efficacious model for the induction of DH and might be used for the investigation of cardiopulmonary interaction in healthy subjects.

Concomitant experimental coinfection by Plasmodium berghei NK65-NY and Ascaris suum downregulates the Ascaris-specific immune response and potentiates Ascaris-associated lung pathology.

BACKGROUND: Ascariasis and malaria are highly prevalent parasitic diseases in tropical regions and often have overlapping endemic areas, contributing to high morbidity and mortality rates in areas with poor sanitary conditions. Several studies have previously aimed to correlate the effects of Ascaris-Plasmodium coinfections but have obtained contradictory and inconclusive results. Therefore, the present study aimed to investigate parasitological and immunopathological aspects of the lung during murine experimental concomitant coinfection by Plasmodium berghei and Ascaris suum during larvae ascariasis. METHODS: C57BL/6J mice were inoculated with 1 × 104 P. berghei strain NK65-NY-infected red blood cells (iRBCs) intraperitoneally and/or 2500 embryonated eggs of A. suum by oral gavage. P. berghei parasitaemia, morbidity and the survival rate were assessed. On the seventh day postinfection (dpi), A. suum lung burden analysis; bronchoalveolar lavage (BAL); histopathology; NAG, MPO and EPO activity measurements; haematological analysis; and respiratory mechanics analysis were performed. The concentrations of interleukin (IL)-1ß, IL-12/IL-23p40, IL-6, IL-4, IL-33, IL-13, IL-5, IL-10, IL-17A, IFN-γ, TNF and TGF-ß were assayed by sandwich ELISA. RESULTS: Animals coinfected with P. berghei and A. suum show decreased production of type 1, 2, and 17 and regulatory cytokines; low leukocyte recruitment in the tissue; increased cellularity in the circulation; and low levels of NAG, MPO and EPO activity that lead to an increase in larvae migration, as shown by the decrease in larvae recovered in the lung parenchyma and increase in larvae recovered in the airway. This situation leads to severe airway haemorrhage and, consequently, an impairment respiratory function that leads to high morbidity and early mortality. CONCLUSIONS: This study demonstrates that the Ascaris-Plasmodium interaction is harmful to the host and suggests that this coinfection may potentiate Ascaris-associated pathology by dampening the Ascaris-specific immune response, resulting in the early death of affected animals.

Intrathoracic Airway Closure Impacts CO2 Signal and Delivered Ventilation during Cardiopulmonary Resuscitation.

RATIONALE: End-tidal CO2 (EtCO2) is used to monitor cardiopulmonary resuscitation (CPR), but it can be affected by intrathoracic airway closure. Chest compressions induce oscillations in expired CO2, and this could reflect variable degrees of airway patency. OBJECTIVES: To understand the impact of airway closure during CPR, and the relationship between the capnogram shape, airway closure, and delivered ventilation. METHODS: This study had three parts: 1) a clinical study analyzing capnograms after intubation in patients with out-of-hospital cardiac arrest receiving continuous chest compressions, 2) a bench model, and 3) experiments with human cadavers. For 2 and 3, a constant CO2 flow was added in the lung to simulate CO2 production. Capnograms similar to clinical recordings were obtained and different ventilator settings tested. EtCO2 was compared with alveolar CO2 (bench). An airway opening index was used to quantify chest compression-induced expired CO2 oscillations in all three clinical and experimental settings. MEASUREMENTS AND MAIN RESULTS: A total of 89 patients were analyzed (mean age, 69 ± 15 yr; 23% female; 12% of hospital admission survival): capnograms exhibited various degrees of oscillations, quantified by the opening index. CO2 value varied considerably across oscillations related to consecutive chest compressions. In bench and cadavers, similar capnograms were reproduced with different degrees of airway closure. Differences in airway patency were associated with huge changes in delivered ventilation. The opening index and delivered ventilation increased with positive end-expiratory pressure, without affecting intrathoracic pressure. Maximal EtCO2 recorded between ventilator breaths reflected alveolar CO2 (bench). CONCLUSIONS: During chest compressions, intrathoracic airway patency greatly affects the delivered ventilation. The expired CO2 signal can reflect CPR effectiveness but is also dependent on airway patency. The maximal EtCO2 recorded between consecutive ventilator breaths best reflects alveolar CO2.

Airway smooth muscle dysfunction in Pompe (Gaa-/- ) mice.

Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase (GAA), an enzyme responsible for hydrolyzing lysosomal glycogen. Deficiency of GAA leads to systemic glycogen accumulation in the lysosomes of skeletal muscle, motor neurons, and smooth muscle. Skeletal muscle and motor neuron pathology are known to contribute to respiratory insufficiency in Pompe disease, but the role of airway pathology has not been evaluated. Here we propose that GAA enzyme deficiency disrupts the function of the trachea and bronchi and this lower airway pathology contributes to respiratory insufficiency in Pompe disease. Using an established mouse model of Pompe disease, the Gaa-/- mouse, we compared histology, pulmonary mechanics, airway smooth muscle (ASM) function, and calcium signaling between Gaa-/- and age-matched wild-type (WT) mice. Lysosomal glycogen accumulation was observed in the smooth muscle of both the bronchi and the trachea in Gaa-/- but not WT mice. Furthermore, Gaa-/- mice had hyporesponsive airway resistance and bronchial ring contraction to the bronchoconstrictive agents methacholine (MCh) and potassium chloride (KCl) and to a bronchodilator (albuterol). Finally, calcium signaling during bronchiolar smooth muscle contraction was impaired in Gaa-/- mice indicating impaired extracellular calcium influx. We conclude that GAA enzyme deficiency leads to glycogen accumulation in the trachea and bronchi and impairs the ability of lower ASM to regulate calcium and respond appropriately to bronchodilator or constrictors. Accordingly, ASM dysfunction may contribute to respiratory impairments in Pompe disease.

Respiratory mechanics of eleven avian species resident at high and low altitude.

The metabolic cost of breathing at rest has never been successfully measured in birds, but has been hypothesized to be higher than in mammals of a similar size because of the rocking motion of the avian sternum being encumbered by the pectoral flight muscles. To measure the cost and work of breathing, and to investigate whether species resident at high altitude exhibit morphological or mechanical changes that alter the work of breathing, we studied 11 species of waterfowl: five from high altitudes (>3000 m) in Perú, and six from low altitudes in Oregon, USA. Birds were anesthetized and mechanically ventilated in sternal recumbency with known tidal volumes and breathing frequencies. The work done by the ventilator was measured, and these values were applied to the combinations of tidal volumes and breathing frequencies used by the birds to breathe at rest. We found the respiratory system of high-altitude species to be of a similar size, but consistently more compliant than that of low-altitude sister taxa, although this did not translate to a significantly reduced work of breathing. The metabolic cost of breathing was estimated to be between 1 and 3% of basal metabolic rate, as low or lower than estimates for other groups of tetrapods.

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction.

Acute Cl2 exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl2 inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60ppm-hour Cl2 dose, and were euthanized 3, 24 and 48h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24h. Cl2 exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO3(-) or NO2(-). Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl2 exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl2 inhalation.

Simulated obstructive respiratory disease dataset over increasing positive end-expiratory pressure.

The breathing dataset presented is collected from 20 healthy individuals at the University of Canterbury using a device to simulate the pressure and flow profiles of obstructive pulmonary disease. Specifically, the expiratory non-linear resistance, which generates the characteristic expiratory pressure-flow loop lobe seen in obstructive disease. Ethical consent for the trial was granted by the University of Canterbury Human Research Ethics Committee (Ref: HREC 2022/26/LR). Data was collected using an open-source data collection device connected to a Fisher and Paykel Healthcare SleepStyle SPSCAA CPAP. The trial was conducted at CPAP PEEP levels of 4 and 8 cmH2O, as well as at ZEEP (0 cmH2O) with no CPAP attached. The simulation device was a modular device connected to the expiratory pathway, consisting of a free volume diversion and fixed high resistance outlet. Three simulation levels were selected for testing, achieved by changing the size of the elastic free volume. The intended use of this dataset is for the initial validation and development of respiratory pulmonary mechanics models, using data collected from healthy people with simulated disease prior to clinical testing.

A Comparative Study of Ex-Vivo Murine Pulmonary Mechanics Under Positive- and Negative-Pressure Ventilation.

Increased ventilator use during the COVID-19 pandemic resurrected persistent questions regarding mechanical ventilation including the difference between physiological and artificial breathing induced by ventilators (i.e., positive- versus negative-pressure ventilation, PPV vs NPV). To address this controversy, we compare murine specimens subjected to PPV and NPV in ex vivo quasi-static loading and quantify pulmonary mechanics via measures of quasi-static and dynamic compliances, transpulmonary pressure, and energetics when varying inflation frequency and volume. Each investigated mechanical parameter yields instance(s) of significant variability between ventilation modes. Most notably, inflation compliance, percent relaxation, and peak pressure are found to be consistently dependent on the ventilation mode. Maximum inflation volume and frequency note varied dependencies contingent on the ventilation mode. Contradictory to limited previous clinical investigations of oxygenation and end-inspiratory measures, the mechanics-focused comprehensive findings presented here indicate lung properties are dependent on loading mode, and importantly, these dependencies differ between smaller versus larger mammalian species despite identical custom-designed PPV/NPV ventilator usage. Results indicate that past contradictory findings regarding ventilation mode comparisons in the field may be linked to the chosen animal model. Understanding the differing fundamental mechanics between PPV and NPV may provide insights for improving ventilation strategies and design to prevent associated lung injuries.

Pulmonary function testing dataset of pressure and flow, dynamic circumference, heart rate, and aeration monitoring.

Respiratory data was collected from 20 subjects, with an even sex distribution, in the low-risk clinical unit at the University of Canterbury. Ethical consent for this trial was granted by the University of Canterbury Human Research Ethics Committee (Ref: HREC 2023/30/LR-PS). Respiratory data were collected, for each subject, over three tests consisting of: 1) increasing set PEEP from a starting point of ZEEP using a CPAP machine; 2) test 1 repeated with two simulated apnoea's (breath holds) at each set PEEP; and 3) three forced expiratory manoeuvres at ZEEP. Data were collected using a custom pressure and flow sensor device, ECG, PPG, Garmin HRM Dual heartrate belt, and a Dräeger PulmoVista 500 Electrical Impedance Tomography (EIT) machine. Subject demographic data was also collected prior to the trial, in a questionnaire, with measurement equipment available. These data aim to inform the development of pulmonary mechanics models and titration algorithms.

Respiratory monitoring dataset, with rapid expiratory occlusions, over increasing positive airway pressure ventilation.

Resting breathing data was collected from 80 smokers, vapers, asthmatics, and otherwise healthy people in the low-risk clinical unit at the University of Canterbury. Subjects were asked to breathe normally through a full-face mask connected to a Fisher and Paykel Healthcare SleepStyle SPSCAA CPAP device. PEEP (Positive End-Expiratory Pressure) support was increased from 4 to 12 cmH2O in 0.5 cmH2O increments. Data was also collected during resting breathing at ZEEP (0 cmH2O) before and after the PEEP trial. The trial was conducted under University of Canterbury Human Research Ethics Committee consent (Ref: HREC 2023/04/LR-PS). Data was collected by and Dräeger PulmoVista 500 EIT machine and a custom Venturi-based pressure and flow sensor device connected in series with the CPAP and full-face mask. The outlined dataset includes pressure, flow, volume, dynamic circumference (thoracic and abdominal, and cross-sectional aeration. Subject demographic data was self-reported using a questionnaire given prior to the trial.

Unexpected pulmonary mechanics during positive pressure mechanical ventilation in fibrotic lung disease with concomitant flail chest.

Understanding of pulmonary mechanics is essential to understanding mechanical ventilation. Typically, clinicians are mindful of peak and plateau pressures displayed on the ventilator and lung compliance, which is decreased in lung disease such as idiopathic pulmonary fibrosis (IPF). Decreased lung compliance leads to elevated peak and plateau pressures. We present a patient with IPF undergoing mechanical ventilation after cardiac arrest. Despite low lung compliance, he had normal peak and plateau pressures due to the presence of flail chest and increased chest wall compliance. This case highlights the role chest wall compliance plays in total respiratory system compliance and pulmonary mechanics.

Comparison of optimization parametrizations for regional lung compliance estimation using personalized pulmonary poromechanical modeling.

Interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF) or post-COVID-19 pulmonary fibrosis, are progressive and severe diseases characterized by an irreversible scarring of interstitial tissues that affects lung function. Despite many efforts, these diseases remain poorly understood and poorly treated. In this paper, we propose an automated method for the estimation of personalized regional lung compliances based on a poromechanical model of the lung. The model is personalized by integrating routine clinical imaging data - namely computed tomography images taken at two breathing levels in order to reproduce the breathing kinematic-notably through an inverse problem with fully personalized boundary conditions that is solved to estimate patient-specific regional lung compliances. A new parametrization of the inverse problem is introduced in this paper, based on the combined estimation of a personalized breathing pressure in addition to material parameters, improving the robustness and consistency of estimation results. The method is applied to three IPF patients and one post-COVID-19 patient. This personalized model could help better understand the role of mechanics in pulmonary remodeling due to fibrosis; moreover, patient-specific regional lung compliances could be used as an objective and quantitative biomarker for improved diagnosis and treatment follow up for various interstitial lung diseases.

A 64-year-Old patient assigned male at birth with COPD and worsening dyspnea while on estrogen and antiandrogen agents.

Among patients with COPD, ventilatory inefficiency in response to exercise can be due to respiratory muscle dysfunction or expiratory flow limitation causing air-trapping and dynamic hyperinflation. We discuss a case of severe ventilatory limitation in response to exercise due to reduced respiratory muscle mass in the setting of gender-affirming hormone therapy (GAHT), and how the interpretation of pulmonary function testing (PFT) and respiratory symptoms among transgender and gender diverse (TGD) patients can be influenced by GAHT.

Changes in pulmonary mechanics from supine to prone position measured through esophageal manometry in critically ill patients with COVID-19 severe acute respiratory distress syndrome.

OBJECTIVE: To describe changes in pulmonary mechanics when changing from supine position (SP) to prone position (PP) in mechanically ventilated (MV) patients with Acute Respiratory Distress Syndrome (ARDS) due to severe COVID-19. DESIGN: Retrospective cohort. SETTING: Intensive Care Unit of the National Institute of Respiratory Diseases (Mexico City). PATIENTS: COVID-19 patients on MV due to ARDS, with criteria for PP. INTERVENTION: Measurement of pulmonary mechanics in patients on SP to PP, using esophageal manometry. MAIN VARIABLES OF INTEREST: Changes in lung and thoracic wall mechanics in SP and PP RESULTS: Nineteen patients were included. Changes during first prone positioning were reported. Reductions in lung stress (10.6 vs 7.7, p=0.02), lung strain (0.74 vs 0.57, p=0.02), lung elastance (p=0.01), chest wall elastance (p=0.003) and relation of respiratory system elastances (p=0.001) were observed between patients when changing from SP to PP. No differences were observed in driving pressure (p=0.19) and transpulmonary pressure during inspiration (p=0.70). CONCLUSIONS: Changes in pulmonary mechanics were observed when patients were comparing values of supine position with measurements obtained 24h after prone positioning. Esophageal pressure monitoring may facilitate ventilator management despite patient positioning.

A quasi-static poromechanical model of the lungs.

The lung vital function of providing oxygen to the body heavily relies on its mechanical behavior and the interaction with its complex environment. In particular, the large compliance and the porosity of the pulmonary tissue are critical for lung inflation and air inhalation, and the diaphragm, the pleura, the rib cage and intercostal muscles all play a role in delivering and controlling the breathing driving forces. In this paper, we introduce a novel poromechanical model of the lungs. The constitutive law is derived within a general poromechanics theory via the formulation of lung-specific assumptions, leading to a hyperelastic potential reproducing the volume response of the pulmonary mixture to a change of pressure. Moreover, physiological boundary conditions are formulated to account for the interaction of the lungs with their surroundings, including a following pressure and bilateral frictionless contact. A strategy is established to estimate the unloaded configuration from a given loaded state, with a particular focus on ensuring a positive porosity. Finally, we illustrate through several realistic examples the relevance of our model and its potential clinical applications.

CPAP pressure and flow data at 2 positive pressure levels and multiple controlled breathing rates from a trial of 30 adults.

OBJECTIVES: A unique dataset of airway flow/pressure from healthy subjects on Continuous Positive Airway Pressure (CPAP) ventilation was collected. This data can be used to develop or validate models of pulmonary mechanics, and/or to develop methods to identify patient-specific parameters which cannot be measured non-invasively, during CPAP therapy. These models and values, particularly if available breath-to-breath in real-time, could assist clinicians in the prescription or optimisation of CPAP therapy, including optimising PEEP settings. DATA DESCRIPTION: Data was obtained from 30 subjects for model-based identification of patient-specific lung mechanics using a specially designed venturi sensor system comprising an array of differential and gauge pressure sensors. Relevant medical information was collected using a questionnaire, including: sex; age; weight; height; smoking history; and history of asthma. Subjects were tasked with breathing at five different rates (including passive), matched to an online pacing sound and video, at two different levels of PEEP (4 and 7 cmH2O) for between 50 and 180 s. Each data set comprises ~ 17 breaths of data, including rest periods between breathing rates and CPAP levels.

Towards a multi-scale computer modeling workflow for simulation of pulmonary ventilation in advanced COVID-19.

Physics-based multi-scale in silico models offer an excellent opportunity to study the effects of heterogeneous tissue damage on airflow and pressure distributions in COVID-19-afflicted lungs. The main objective of this study is to develop a computational modeling workflow, coupling airflow and tissue mechanics as the first step towards a virtual hypothesis-testing platform for studying injury mechanics of COVID-19-afflicted lungs. We developed a CT-based modeling approach to simulate the regional changes in lung dynamics associated with heterogeneous subject-specific COVID-19-induced damage patterns in the parenchyma. Furthermore, we investigated the effect of various levels of inflammation in a meso-scale acinar mechanics model on global lung dynamics. Our simulation results showed that as the severity of damage in the patient's right lower, left lower, and to some extent in the right upper lobe increased, ventilation was redistributed to the least injured right middle and left upper lobes. Furthermore, our multi-scale model reasonably simulated a decrease in overall tidal volume as the level of tissue injury and surfactant loss in the meso-scale acinar mechanics model was increased. This study presents a major step towards multi-scale computational modeling workflows capable of simulating the effect of subject-specific heterogenous COVID-19-induced lung damage on ventilation dynamics.