Search

Respiratory disease is one of the main causes for morbidity and mortality in cetaceans, which highlights the importance of understanding normal lung function and how it may impede homeostasis, and diving capacity. In addition, the use of breathing frequency as a proxy for metabolic rate requires a better estimate of the normal range of tidal volume, respiratory flow, and breath durations. In the current study, we use data on clinically healthy bottlenose dolphins (Tursiops spp.) collected over a decade to define how lung function varies with body mass, age, and sex while in water or during voluntary beaching. The data show that tidal volume consistently varies with body mass both during spontaneous and forced breaths both in water and while beached. Both peak expiratory and inspiratory flow varies with body mass, but also in some circumstances with sex and age. Total and inspiratory breath durations only varied with body mass during forced breaths on land. Expired tidal volume varied with both body mass and either total or expiratory breath duration. These data provide baseline for respiratory function in healthy bottlenose dolphins and suggest that either total or expiratory breath duration provide a useful proxy for tidal volume. [ABSTRACT FROM AUTHOR]

Abstract Background Understanding the characteristics of pulmonary resistance and elastance in relation to the location of airway narrowing, e.g., tracheal stenosis vs. intrapulmonary airway obstruction, will help us understand lung function characteristics and mechanisms related to different airway diseases. Methods In this study, we used ex vivo sheep lungs as a model to measure lung resistance and elastance across a range of transpulmonary pressures (5–30 cmH2O) and ventilation frequencies (0.125–2 Hz). We established two tracheal stenosis models by inserting plastic tubes into the tracheas, representing mild (71.8% lumen area reduction) and severe (92.1%) obstructions. For intrapulmonary airway obstruction, we induced airway narrowing by challenging the lung with acetylcholine (ACh). Results We found a pattern change in the lung resistance and apparent lung elastance as functions of ventilation frequency that depended on the transpulmonary pressure (or lung volume). At a transpulmonary pressure of 10 cmH2O, lung resistance increased with ventilation frequency in severe tracheal stenosis, whereas in ACh-induced airway narrowing the opposite occurred. Furthermore, apparent lung elastance at 10 cmH2O decreased with increasing ventilation frequency in severe tracheal stenosis whereas in ACh-induced airway narrowing the opposite occurred. Flow-volume analysis revealed that the flow amplitude was much sensitive to ventilation frequency in tracheal stenosis than it was in ACh induced airway constriction. Conclusions Results from this study suggest that lung resistance and apparent elastance measured at 10 cmH2O over the frequency range of 0.125-2 Hz can differentiate tracheal stenosis vs. intrapulmonary airway narrowing in ex vivo sheep lungs.

Purpose: Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation. Methods: Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure–volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses. Results: HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains. Conclusion: Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans. [ABSTRACT FROM AUTHOR]

Background: Asthmatic children present variable degrees of airway inflammation, remodeling, and resistance, which correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. Objective: To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways. Methods: 39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses. Results: Asthmatic children showed an increased number of blood eosinophils (p < 0.04), basophils (p < 0.04), monocytes (p < 0.002) and lymphocytes (p < 0.03). In addition, asthmatic children showed impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p < 0.0001) and in the serum (p < 0.0001); TGF-beta in the BC (p < 0.0001) and in the serum (p < 0.004); IL-5 in the BC (p < 0.02) and in the serum (p < 0.01); IL-4 in the serum (p < 0.0002). Conclusions: Impulse oscillometry is a sensitive method to detect airway resistance in persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators. [ABSTRACT FROM AUTHOR]

Background: Understanding the characteristics of pulmonary resistance and elastance in relation to the location of airway narrowing, e.g., tracheal stenosis vs. intrapulmonary airway obstruction, will help us understand lung function characteristics and mechanisms related to different airway diseases. Methods: In this study, we used ex vivo sheep lungs as a model to measure lung resistance and elastance across a range of transpulmonary pressures (5–30 cmH2O) and ventilation frequencies (0.125–2 Hz). We established two tracheal stenosis models by inserting plastic tubes into the tracheas, representing mild (71.8% lumen area reduction) and severe (92.1%) obstructions. For intrapulmonary airway obstruction, we induced airway narrowing by challenging the lung with acetylcholine (ACh). Results: We found a pattern change in the lung resistance and apparent lung elastance as functions of ventilation frequency that depended on the transpulmonary pressure (or lung volume). At a transpulmonary pressure of 10 cmH2O, lung resistance increased with ventilation frequency in severe tracheal stenosis, whereas in ACh-induced airway narrowing the opposite occurred. Furthermore, apparent lung elastance at 10 cmH2O decreased with increasing ventilation frequency in severe tracheal stenosis whereas in ACh-induced airway narrowing the opposite occurred. Flow-volume analysis revealed that the flow amplitude was much sensitive to ventilation frequency in tracheal stenosis than it was in ACh induced airway constriction. Conclusions: Results from this study suggest that lung resistance and apparent elastance measured at 10 cmH2O over the frequency range of 0.125-2 Hz can differentiate tracheal stenosis vs. intrapulmonary airway narrowing in ex vivo sheep lungs. [ABSTRACT FROM AUTHOR]

The movement of air into and out of the lungs is facilitated by changes in pressure within the thoracic cavity relative to atmospheric pressure, as well as the resistance encountered by airways. In this process, the movement of air into and out of the lungs is driven by pressure gradients established by changes in lung volume and intra-alveolar pressure. However, pressure never sucks! The concept that pressure never sucks, pressure only pushes encapsulates a fundamental principle in the behavior of gases. This concept challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we explore the essence of this concept and its applications in pulmonary ventilation. Pressure is one of the most important concepts in physics and physiology. Atmospheric pressure at sea level is equal to 1 atmosphere or around 101,325 Pascal [Pa (1 Pa = 1 N/m2)]. This huge pressure is pushing down on everything all the time. However, this pressure is difficult to understand because we do not often observe the power of this incredible force. We used five readily available, simple, and inexpensive demonstrations to introduce the physics and power of pressure. This extraordinarily complex physics concept was approached in a straightforward and inexpensive manner while still providing an understanding of the fundamental concepts. These simple demonstrations introduced basic concepts and addressed common misconceptions about pressure. NEW & NOTEWORTHY: The concept that pressure never sucks, pressure only pushes challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we will explore the essence of this concept and its applications in pulmonary ventilation. Specifically, we used five readily available, simple, inexpensive demonstrations to introduce the physics and power of pressure. [ABSTRACT FROM AUTHOR]

Multiple thoracic imaging modalities have been developed to link structure to function in the diagnosis and monitoring of lung disease. Volumetric computed tomography (CT) renders three-dimensional maps of lung structures and may be combined with positron emission tomography (PET) to obtain dynamic physiological data. Magnetic resonance imaging (MRI) using ultrashort-echo time (UTE) sequences has improved signal detection from lung parenchyma; contrast agents are used to deduce airway function, ventilation-perfusion-diffusion, and mechanics. Proton MRI can measure regional ventilation-perfusion ratio. Quantitative imaging (QI)-derived endpoints have been developed to identify structure-function phenotypes, including air-blood-tissue volume partition, bronchovascular remodeling, emphysema, fibrosis, and textural patterns indicating architectural alteration. Coregistered landmarks on paired images obtained at different lung volumes are used to infer airway caliber, air trapping, gas and blood transport, compliance, and deformation. This document summarizes fundamental good practice stereological principles in QI study design and analysis; evaluates technical capabilities and limitations of common imaging modalities; and assesses major QI endpoints regarding underlying assumptions and limitations, ability to detect and stratify heterogeneous, overlapping pathophysiology, and monitor disease progression and therapeutic response, correlated with and complementary to, functional indices. The goal is to promote unbiased quantification and interpretation of in vivo imaging data, compare metrics obtained using different QI modalities to ensure accurate and reproducible metric derivation, and avoid misrepresentation of inferred physiological processes. The role of imaging-based computational modeling in advancing these goals is emphasized. Fundamental principles outlined herein are critical for all forms of QI irrespective of acquisition modality or disease entity.

Here we demonstrate how data from the clinical pulmonary function lab can help students learn about the principle of airway-parenchymal interdependence. We examined the relationship between airway conductance (Gaw) and lung volume (thoracic gas volume, TGV) in 48 patients: 17 healthy; 20 with emphysema, expected to have reduced airway-parenchymal interdependence; and 11 with pulmonary fibrosis, expected to have increased airway-parenchymal interdependence. Our findings support these expectations, with the slope of Gaw vs. TGV being steeper among those with pulmonary fibrosis and flatter among those with emphysema, compared to the slope of the healthy group. This type of analytic approach, using real-world patient data readily available from any pulmonary function laboratory, can be used to explore other fundamental principles of respiratory physiology. NEW & NOTEWORTHY: This report demonstrates how common data obtained from the clinical pulmonary function testing laboratory can be used to illustrate important principles of respiratory physiology. Here we show how the relationship between airway conductance and lung volume across different disease states reflects intrinsic differences in airway-parenchymal interdependence. [ABSTRACT FROM AUTHOR]

[Display omitted] Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. Gas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system. [ABSTRACT FROM AUTHOR]

Copyright of Automatisierungstechnik is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Due to its ability to induce heterogenous, patient-specific damage in pulmonary alveoli and capillaries, COVID-19 poses challenges in defining a uniform profile to elucidate infection across all patients. Computational models that integrate changes in ventilation and perfusion with heterogeneous damage profiles offer valuable insights into the impact of COVID-19 on pulmonary health. This study aims to develop an in silico hypothesis-testing platform specifically focused on studying microvascular pulmonary perfusion in COVID-19-infected lungs. Through this platform, we explore the effects of various acinar-level pulmonary perfusion abnormalities on global lung function. Our modelling approach simulates changes in pulmonary perfusion and the resulting mismatch of ventilation and perfusion in COVID-19-afflicted lungs. Using this coupled modelling platform, we conducted multiple simulations to assess different scenarios of perfusion abnormalities in COVID-19-infected lungs. The simulation results showed an overall decrease in ventilation-perfusion (V/Q) ratio with inclusion of various types of perfusion abnormalities such as hypoperfusion with and without microangiopathy. This model serves as a foundation for comprehending and comparing the spectrum of findings associated with COVID-19 in the lung, paving the way for patient-specific modelling of microscale lung damage in emerging pulmonary pathologies like COVID-19. [ABSTRACT FROM AUTHOR]

Background: Oscillometry allows for the non-invasive measurements of lung mechanics. In COVID-19 ARDS patients treated with Non-Invasive Oxygen Support (NI-OS), we aimed to (1) observe lung mechanics at the patients' admission and their subsequent changes, (2) compare lung mechanics with clinical and imaging data, and (3) evaluate whether lung mechanics helps to predict clinical outcomes. Methods: We retrospectively analyzed the data from 37 consecutive patients with moderate–severe COVID-19 ARDS. Oscillometry was performed on their 1st, 4th, and 7th day of hospitalization. Resistance (R5), reactance (X5), within-breath reactance changes (ΔX5), and the frequency dependence of the resistance (R5–R19) were considered. Twenty-seven patients underwent computed tomographic pulmonary angiography (CTPA): collapsed, poorly aerated, and normally inflated areas were quantified. Adverse outcomes were defined as intubation or death. Results: Thirty-two patients were included in this study. At the first measurement, only 44% of them had an abnormal R5 or X5. In total, 23 patients had measurements performed on their 3rd day and 7 on their 7th day of hospitalization. In general, their R5, R5–R19, and ΔX decreased with time, while their X5 increased. Collapsed areas on the CTPA correlated with the X5 z-score (ρ = −0.38; p = 0.046), while poorly aerated areas did not. Seven patients had adverse outcomes but did not present different oscillometry parameters on their 1st day of hospitalization. Conclusions: Our study confirms the feasibility of oscillometry in critically ill patients with COVID-19 pneumonia undergoing NI-OS. The X5 z-scores indicates collapsed but not poorly aerated lung areas in COVID-19 pneumonia. Our data, which show a severe impairment of gas exchange despite normal reactance in most patients with COVID-19 ARDS, support the hypothesis of a composite COVID-19 ARDS physiopathology. [ABSTRACT FROM AUTHOR]

Background & objective: Lung atelectasis is a known complication of general anesthesia, and especially in patients undergoing laparoscopic surgical procedures. Respiratory system compliance (Crs) is a measured sign of lung atelectasis in laparoscopic surgery. A protocolized sequential alveolar recruitment maneuver (RM) with positive endexpiratory pressure (PEEP) was compared to a usual management. Methodology: Patients scheduled for elective laparoscopic radical prostatectomy under extreme Trendelenburg position were randomly allocated to one of the two groups; either PEEP plus alveolar RM in every 30 min (RM group) or PEEP only (PEEP group). The primary outcome was the time-dependent differences in Crs between the groups, that was tested using multivariate analysis of variance (MANOVA). Results: Between 19 patients in the RM group and 17 patients in the PEEP group, patients’ demography was balanced. The time depended difference in Crs was significantly higher in the RM group than in the non-RM group. Postoperative atelectasis occurred in one patient in the PEEP group, whose Crs was 34 cmH2O/mL at the time of intubation. In the subgroup with initial low Crs (< 60 cmH2O/mL), the time-dependent difference in Crs was significantly higher in the RM group than the PEEP group. Conclusion: In the subgroup with initial low respiratory system compliance (< 60 cmH2O/mL), the time-dependent difference in respiratory system compliance was significantly higher in the RM group than in the PEEP group, suggesting that the therapeutic target of RM would be initially low respiratory system compliance patients. Abbreviations: Crs - Respiratory system compliance; RM - recruitment maneuver; PEEP - positive end-expiratory pressure [ABSTRACT FROM AUTHOR]

The mechanics of the lung, consisting of high deformation, non-linear, rapid and cyclic loading, remain a critical unknown, hindering advancements in the field despite the pressing urgency of incurable and often fatal pulmonary diseases; such multi-scale ailments impair organ mechanical function by inducing tissue-level alterations. Here, the tensile mechanics of healthy and diseased murine lung parenchyma with induced variable fibrosis and emphysema are compared—exploring multi-rate and directional tissue elasticity and energetics. Remarkably, parenchymal tissue is found to be notably elastic and non-hysteresis prone. Additionally, chronic fibrosis-induced tissues reveal significantly reduced compliance compared to age-matched controls, indicating characteristic stiffening; moreover, maximum stress tends to be greater in exposed than controls. Emphysematous tissues tend to show lower maximum stress than controls, reflective of hallmark tissue destruction and softening. Furthermore, faster loading rate is found to generally yield elevated stiffness and maximum stress, significantly for fibrosis group exposed tissue—this interdependence between loading rate and tissue disease is notable considering the dynamics of breathing. Generally, control tissues are found to be isotropic, as are emphysematous tissues, but fibrosis may lead to increased anisotropy. Additionally, fibrotic and mature-healthy lungs are found to show age effect trends, such as increased strain energy. Along with these findings, this study additionally facilitates future analyses of other diseases by establishing lung biaxial testing protocols for small-scale murine specimens, which can serve as practical and ethical models for exploring human diseases. Overall, this study offers fundamental material characterizations which will enable future formulations of experimentally informed computational models.

Abstract Rationale Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO2) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values. Objectives In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO2-driven CDP optimization. Methods In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO2-guided lung recruitment maneuvers were included in the study. SpO2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDPOpt_SpO2) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDPXrs). Results We studied 40 infants (gestational age at birth = 22+ 6-27+ 5 wk; postnatal age = 1–23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDPOpt_SpO2 and CDPXrs were highly correlated (ρ = 0.71, p

Abstract Background Steep Trendelenburg position combined with capnoperitoneum can lead to pulmonary complications and prolonged affection of postoperative lung function. Changes in pulmonary function occur independent of different modes of ventilation and levels of positive end-expiratory pressure (PEEP). The effect of flow-controlled ventilation (FCV) has not been evaluated yet. We perioperatively measured spirometric lung function parameters in patients undergoing robot-assisted prostatectomy under FCV. Our primary hypothesis was that there is no significant difference in the ratio of the maximal mid expiratory and inspiratory flow (MEF50/MIF50) after surgery. Methods In 20 patients, spirometric measurements were obtained preoperatively, 40, 120, and 240 min and 1 and 5 days postoperatively. We measured MEF50/MIF50, vital capacity (VC), forced expiratory volume in 1 s (FEV1), and intraoperative ventilation parameters. Results MEF50/MIF50 ratio increased from 0.92 (CI 0.73–1.11) to 1.38 (CI 1.01–1.75, p

We measured resting metabolic rate (RMR), tidal volume (VT), breathing frequency (fR), respiratory flow, and end‐expired gases in rough‐toothed dolphins (Steno bredanensis) housed in managed care after an overnight fast and 1–2 hr following a meal. The measured average (± standard deviation) VT (4.0 ± 1.3 L) and fR (1.9 ± 1.0 breaths/min) were higher and lower, respectively, as compared with estimated values from both terrestrial and aquatic mammals, and the average VT was 43% of the estimated total lung capacity. The end‐expired gas levels suggested that this species keep alveolar O2 (10.6% or 80 mmHg) and CO2 (7.6% or 57 mmHg), and likely arterial gas tensions, low and high, respectively, to maximize efficiency of gas exchange. We show that following an overnight fast, the RMR (566 ± 158 ml O2/min) was 1.8 times the estimated value predicted by Kleiber for terrestrial mammals of the same size. We also show that between 1 and 2 hr after ingestion of a meal, the metabolic rate increases an average of 29% (709 ± 126 ml O2/min). Both body mass (Mb) and fR significantly altered the measured RMR and we propose that both these variables should be measured when estimating energy use in cetaceans. [ABSTRACT FROM AUTHOR]

Background: The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (DLCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O2 transfer, a severely impaired DLCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD. Methods: Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing DLCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores. Results: Subjects from the DLCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired DLCO (P < .05). Peak work rate was -45% (vs controls) and -20% (vs DLCO > 40%) lower in the former group, being associated with lower (and flatter) O2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower SpO2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the DLCO < 40% group (P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity (P > .05). Conclusions: A severely reduced DLCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. DLCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities. [ABSTRACT FROM AUTHOR]

There is a need for more individualized treatment of critically ill patients receiving mechanical ventilation (MV). Therefore, this research aims to create a preliminary multi-scale computational modeling framework for MV in critically ill COVID-19 patients as a step toward studying region-specific and overall lung dynamics in these patients. This goal was accomplished by developing proof-of-concept image-based computer models providing insight into airflow redistribution and volume and pressure gradients on a lobe-specific basis. Our in silico multi-scale MV models simulated redistribution of ventilation for up to 20% of air volume from severely damaged lung lobes to the lobes less affected by COVID-19, hence potentially revealing a risk factor of MV-induced volutrauma due to heterogeneity of lung damage distribution in COVID-19. This study lays the foundation for future COVID-19 patient-specific lung models for individualized simulation of MV. [ABSTRACT FROM AUTHOR]

Abstract Background Mechanical power is a major contributor to lung injury and mortality in adults receiving mechanical ventilation. Recent advances in our understanding of mechanical power have allowed the different mechanical components to be isolated. The preterm lung shares many of the same similarities that would indicate mechanical power may be relevant in this group. To date, the role of mechanical power in neonatal lung injury is unknown. We hypothesise that mechanical power maybe useful in expanding our understanding of preterm lung disease. Specifically, that mechanical power measures may account for gaps in knowledge in how lung injury is initiated. Hypothesis-generating data set To provide a justification for our hypothesis, data in a repository at the Murdoch Children’s Research Institute, Melbourne (Australia) were re-analysed. 16 preterm lambs 124–127d gestation (term 145d) who received 90 min of standardised positive pressure ventilation from birth via a cuffed endotracheal tube were chosen as each was exposed to three distinct and clinically relevant respiratory states with unique mechanics. These were (1) the respiratory transition to air-breathing from an entirely fluid-filled lung (rapid aeration and fall in resistance); (2) commencement of tidal ventilation in an acutely surfactant-deficient state (low compliance) and (3) exogenous surfactant therapy (improved aeration and compliance). Total, tidal, resistive and elastic-dynamic mechanical power were calculated from the flow, pressure and volume signals (200 Hz) for each inflation. Results All components of mechanical power behaved as expected for each state. Mechanical power increased during lung aeration from birth to 5 min, before again falling immediately after surfactant therapy. Before surfactant therapy tidal power contributed 70% of total mechanical power, and 53.7% after. The contribution of resistive power was greatest at birth, demonstrating the initial high respiratory system resistance at birth. Conclusions In our hypothesis-generating dataset, changes in mechanical power were evident during clinically important states for the preterm lung, specifically transition to air-breathing, changes in aeration and surfactant administration. Future preclinical studies using ventilation strategies designed to highlight different types of lung injury, including volu-, baro- and ergotrauma, are needed to test our hypothesis.

Rationale: Ventilatory demand-capacity imbalance, as inferred based on a low ventilatory reserve, is currently assessed only at peak cardiopulmonary exercise testing (CPET). Peak ventilatory reserve, however, is poorly sensitive to the submaximal, dynamic mechanical ventilatory abnormalities that are key to dyspnea genesis and exercise intolerance. Objectives: After establishing sex- and age-corrected norms for dynamic ventilatory reserve at progressively higher work rates, we compared peak and dynamic ventilatory reserve for their ability to expose increased exertional dyspnea and poor exercise tolerance in mild to very severe chronic obstructive pulmonary disease (COPD). Methods: We analyzed resting functional and incremental CPET data from 275 controls (130 men, aged 19-85 yr) and 359 Global Initiative for Chronic Obstructive Lung Disease patients with stage 1-4 obstruction (203 men) who were prospectively recruited for previous ethically approved studies in three research centers. In addition to peak and dynamic ventilatory reserve (12[ventilation / estimated maximal voluntary ventilation]3100), operating lung volumes and dyspnea scores (0-10 on the Borg scale) were obtained. Results: Dynamic ventilatory reserve was asymmetrically distributed in controls; thus, we calculated its centile distribution at every 20 W. The lower limit of normal (lower than the fifth centile) was consistently lower in women and older subjects. Peak and dynamic ventilatory reserve disagreed significantly in indicating an abnormally low test result in patients: whereas approximately 50% of those with a normal peak ventilatory reserve showed a reduced dynamic ventilatory reserve, the opposite was found in approximately 15% (P,0.001). Irrespective of peak ventilatory reserve and COPD severity, patients who had a dynamic ventilatory reserve below the lower limit of normal at an isowork rate of 40W had greater ventilatory requirements, prompting earlier attainment of critically low inspiratory reserve. Consequently, they reported higher dyspnea scores, showing poorer exercise tolerance compared with those with preserved dynamic ventilatory reserve. Conversely, patients with preserved dynamic ventilatory reserve but reduced peak ventilatory reserve reported the lowest dyspnea scores, showing the best exercise tolerance. Conclusions: Reduced submaximal dynamic ventilatory reserve, even in the setting of preserved peak ventilatory reserve, is a powerful predictor of exertional dyspnea and exercise intolerance in COPD. This new parameter of ventilatory demand-capacity mismatch may enhance the yield of clinical CPET in the investigation of activity-related breathlessness in individual patients with COPD and other prevalent cardiopulmonary diseases. [ABSTRACT FROM AUTHOR]

Current literature reports a wide range of stiffness values and constitutive models for lung tissue across different spatial scales. Comparing the reported lung tissue stiffness values across different spatial scales may provide insights into how well those mechanical properties and the proposed constitutive models represent lung tissue's mechanical behavior. Thus, this study applies in silico modeling to compare and potentially bridge the differences reported in lung tissue mechanical properties at different length scales. Specifically, we predicted the mesoscale mechanical behavior of rat lung tissue based on in situ and in vitro microscale test data using finite element (FE) analysis and compared those computational predictions to the reported data using mesoscale uniaxial experiments. Our simulations showed that microscale-based stiffness values differed from the mesoscale data in the simulated strain range of 0–60%, with the atomic force microscopy (AFM)-based data overestimating the mesoscale data above 15% strain. This research demonstrates that computational modeling can be used as an informative and guiding tool to investigate and potentially bridge the differences in reported lung tissue material properties across length scales. [ABSTRACT FROM AUTHOR]

Sliding between lung lobes along lobar fissures is a poorly understood aspect of lung mechanics. The objective of this study was to test the hypothesis that lobar sliding helps reduce distortion in the lung parenchyma during breathing. Finite element models of left lungs with geometries and boundary conditions derived from medical images of human subjects were developed. Effect of lobar sliding was studied by comparing nonlinear finite elastic contact mechanics simulations that allowed and disallowed lobar sliding. Lung parenchymal distortion during simulated breath-holds and tidal breathing was quantified with the model's spatial mean anisotropic deformation index (ADI), a measure of directional preference in volume change that varies spatially in the lung. Models that allowed lobar sliding had significantly lower mean ADI (i.e., lesser parenchymal distortion) than models that disallowed lobar sliding under simulations of both tidal breathing (5.3% median difference, P = 0.008, n = 8) and lung deformation between breath-holds at total lung capacity and functional residual capacity (3.2% median difference, P = 0.03, n = 6). This effect was most pronounced in the lower lobe where lobar sliding reduced parenchymal distortion with statistical significance, but not in the upper lobe. In addition, more lobar sliding was correlated with greater reduction in distortion between sliding and nonsliding models in our study cohorts (Pearson's correlation coefficient of 0.95 for tidal breathing, 0.87 for breathholds, and 0.91 for the combined dataset). These findings are consistent with the hypothesis that lung lobar sliding reduces parenchymal distortion during breathing. [ABSTRACT FROM AUTHOR]

Background: Steep Trendelenburg position combined with capnoperitoneum can lead to pulmonary complications and prolonged affection of postoperative lung function. Changes in pulmonary function occur independent of different modes of ventilation and levels of positive end-expiratory pressure (PEEP). The effect of flow-controlled ventilation (FCV) has not been evaluated yet. We perioperatively measured spirometric lung function parameters in patients undergoing robot-assisted prostatectomy under FCV. Our primary hypothesis was that there is no significant difference in the ratio of the maximal mid expiratory and inspiratory flow (MEF50/MIF50) after surgery. Methods: In 20 patients, spirometric measurements were obtained preoperatively, 40, 120, and 240 min and 1 and 5 days postoperatively. We measured MEF50/MIF50, vital capacity (VC), forced expiratory volume in 1 s (FEV1), and intraoperative ventilation parameters. Results: MEF50/MIF50 ratio increased from 0.92 (CI 0.73–1.11) to 1.38 (CI 1.01–1.75, p < 0.0001) and returned to baseline within 24 h, while VC and FEV1 decreased postoperatively with a second nadir at 24 h and only normalized by the fifth day (p < 0.0001). Compared to patients with PCV, postoperative lung function changes similarly. Conclusion: Flow-controlled ventilation led to changes in lung function similar to those observed with pressure-controlled ventilation. While the ratio of MEF50/MIF50 normalized within 24 h, VC and FEV1 recovered within 5 days after surgery. [ABSTRACT FROM AUTHOR]

Abstract Historical background The prone position was first proposed on theoretical background in 1974 (more advantageous distribution of mechanical ventilation). The first clinical report on 5 ARDS patients in 1976 showed remarkable improvement of oxygenation after pronation. Pathophysiology The findings in CT scans enhanced the use of prone position in ARDS patients. The main mechanism of the improved gas exchange seen in the prone position is nowadays attributed to a dorsal ventilatory recruitment, with a substantially unchanged distribution of perfusion. Regardless of the gas exchange, the primary effect of the prone position is a more homogenous distribution of ventilation, stress and strain, with similar size of pulmonary units in dorsal and ventral regions. In contrast, in the supine position the ventral regions are more expanded compared with the dorsal regions, which leads to greater ventral stress and strain, induced by mechanical ventilation. Outcome in ARDS The number of clinical studies paralleled the evolution of the pathophysiological understanding. The first two clinical trials in 2001 and 2004 were based on the hypothesis that better oxygenation would lead to a better survival and the studies were more focused on gas exchange than on lung mechanics. The equations better oxygenation = better survival was disproved by these and other larger trials (ARMA trial). However, the first studies provided signals that some survival advantages were possible in a more severe ARDS, where both oxygenation and lung mechanics were impaired. The PROSEVA trial finally showed the benefits of prone position on mortality supporting the thesis that the clinical advantages of prone position, instead of improved gas exchange, were mainly due to a less harmful mechanical ventilation and better distribution of stress and strain. In less severe ARDS, in spite of a better gas exchange, reduced mechanical stress and strain, and improved oxygenation, prone position was ineffective on outcome. Prone position and COVID-19 The mechanisms of oxygenation impairment in early COVID-19 are different than in typical ARDS and relate more on perfusion alteration than on alveolar consolidation/collapse, which are minimal in the early phase. Bronchial shunt may also contribute to the early COVID-19 hypoxemia. Therefore, in this phase, the oxygenation improvement in prone position is due to a better matching of local ventilation and perfusion, primarily caused by the perfusion component. Unfortunately, the conditions for improved outcomes, i.e. a better distribution of stress and strain, are almost absent in this phase of COVID-19 disease, as the lung parenchyma is nearly fully inflated. Due to some contradictory results, further studies are needed to better investigate the effect of prone position on outcome in COVID-19 patients. Graphical Abstract

Background: Obesity is known to induce lung function impairment. Previous studies of decline in lung function associated with obesity are well established. Materials and Methods: In this cross-sectional study, to evaluate the effects of different obesity indices on lung mechanics, healthy subjects (males-23 and females-22) were recruited. Anthropometric parameters like body mass index (BMI), waist circumference (WC), hip circumference (HC) and neck circumference (NC) were measured and waist-hip ratio (WHR) was derived. Spirometry, impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) measurements were performed to assess lung function. Subgroups were divided and analysed. Results: In males, increased WHR is associated with increased total airway resistance (R5). BMI correlates positively with R5, R5% predicted, resistance at 20 Hz (R20) and R20% predicted; likewise, WHR shows a positive correlation with R5. In females, increased WHR has significantly higher R5, R5% predicted, R20, R20% predicted, area of reactance (Ax), resonant frequency (Fres) and decreased reactance at 5 Hz (X5), reactance at 20 Hz (X20), X20% predicted. The female group with higher WC shows significantly increased R5, R5% predicted, R20, R20% predicted, Ax, Fres and lower fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), X5, X20, X20% predicted. The group with higher NC has a lower FEV1/FVC ratio. WHR positively correlated with R5% predicted and Fres while WC correlated positively with R5, R5% predicted, Ax and Fres; same way, NC with X5% predicted. Conclusion: Obesity/overweight causes significant changes in lung volumes, capacity and airway mechanics, Higher WC and WHR are associated with significant changes in lung mechanics, which are more prominent in females than in males. NC is not associated with changes in lung mechanics.

Abstract Background Lung ultrasound allows lung aeration to be assessed through dedicated lung ultrasound scores (LUS). Despite LUS have been validated using several techniques, scanty data exist about the relationships between LUS and compliance of the respiratory system (Crs) in restrictive respiratory failure. Aim of this study was to investigate the relationship between LUS and Crs in neonates and adults affected by acute hypoxemic restrictive respiratory failure, as well as the effect of patients’ age on this relationship. Methods Observational, cross-sectional, international, patho-physiology, bi-center study recruiting invasively ventilated, adults and neonates with acute respiratory distress syndrome (ARDS), neonatal ARDS (NARDS) or respiratory distress syndrome (RDS) due to primary surfactant deficiency. Subjects without lung disease (NLD) and ventilated for extra-pulmonary conditions were recruited as controls. LUS, Crs and resistances (Rrs) of the respiratory system were measured within 1 h from each other. Results Forty adults and fifty-six neonates were recruited. LUS was higher in ARDS, NARDS and RDS and lower in control subjects (overall p

Background Most patients admitted to the intensive care unit with coronavirus disease (COVID-19) develop severe respiratory failure. Understanding lung mechanics helps to guide protective mechanical ventilation, improve oxygenation, and reduce the ventilator induce lung injury. This study aims to describe lung mechanics characteristics of patients with COVID -19 related acute respiratory distress syndrome (CARDS) and to compare them with non-COVID-19 associated ARDS. Methods We performed a retrospective observational study of lung mechanics: plateau pressure (Pplat), Driving pressure (DP), Mechanical power (MPw), Elastic (dynamic) power (EdPw), Total ventilatory power (TPw), and oxygenation parameters (ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), the ratio of arterial oxygen partial pressure to fractional inspired oxygen multiplied by PEEP [PaO2/(FiO2 x PEEP)], arterial and venous carbon dioxide partial pressure (PaCO2, PvCO2), and Ventilation dead space (VD) were measured and compared between the two groups after initiation of mechanical ventilation. Results 30 CARDS and 10 ARDS patients fulfilled the study requirements. We observed a significant higher MPw in the CARDS group (29.17 ± 8.29 J/min vs 15.78 ± 4.45 J/min, P 0.007), similarly observed with EdPw (256.7 ± 84.06 mJ/min vs 138.1 ± 39.15 mJ/min, P 0.01) and TPw (289.1 ± 84.51 mJ/min vs 161.5 ± 45.51, P 0.007). Inside the CARDS group, we found 2 subgroups, a low shunt subgroup and a higher shunt (Qs/Qt (%): 6.61 ± 2.46 for vs 40.3 ± 20.6, P 0.0009), however, between these two subgroups we didn’t find statistical differences on lung mechanic parameters but only in oxygenation parameters (PaO2/FiO2 and PaO2/FiO2*PEEP). When comparing these two subgroups with ARDS patients, we found more similarity between the low shunt CARDS and the ARDS patients on MP (R2 0.99, P 0.001), EdPw (R2 0.89, P 0.05) and TPw (R2 0.99, P 0.0009). Conclusions Our study suggests important differences between CARDS and ARDS regarding mechanical parameters that could lead to more complicated management of CARDS patients and a higher prevalence of VILI. However due to the study limitations, a bigger study is necessary to corroborate our findings.

Abstract Background Video-assisted surgery has become an increasingly used surgical technique in patients undergoing major thoracic and abdominal surgery and is associated with significant perioperative respiratory and cardiovascular changes. The aim of this study was to investigate the effect of intraoperative pneumoperitoneum during video-assisted surgery on respiratory physiology in patients undergoing robotic-assisted surgery compared to patients undergoing classic laparoscopy in Trendelenburg position. Methods Twenty-five patients undergoing robotic-assisted surgery (RAS) were compared with twenty patients undergoing classic laparoscopy (LAS). Intraoperative ventilatory parameters (lung compliance and plateau airway pressure) were recorded at five specific timepoints: after induction of anesthesia, after carbon dioxide (CO2) insufflation, one-hour, and two-hours into surgery and at the end of surgery. At the same time, arterial and end-tidal CO2 values were noted and arterial to end-tidal CO2 gradient was calculated. Results We observed a statistically significant difference in plateau pressure between RAS and LAS at one-hour (26.2 ± 4.5 cmH2O vs. 20.2 ± 3.5 cmH2O, p = 0.05) and two-hour intervals (25.2 ± 5.7 cmH2O vs. 17.9 ± 3.1 cmH2O, p = 0.01) during surgery and at the end of surgery (19.9 ± 5.0 cmH2O vs. 17.0 ± 2.7 cmH2O, p = 0.02). Significant changes in lung compliance were also observed between groups at one-hour (28.2 ± 8.5 mL/cmH2O vs. 40.5 ± 13.9 mL/cmH2O, p = 0.01) and two-hour intervals (26.2 ± 7.8 mL/cmH2O vs. 54.6 ± 16.9 mL/cmH2O, p = 0.01) and at the end of surgery (36.3 ± 9.9 mL/cmH2O vs. 58.2 ± 21.3 mL/cmH2O, p = 0.01). At the end of surgery, plateau pressures remained higher than preoperative values in both groups, but lung compliance remained significantly lower than preoperative values only in patients undergoing RAS with a mean 24% change compared to 1.7% change in the LAS group (p = 0.01). We also noted a more significant arterial to end-tidal CO2 gradient in the RAS group compared to LAS group at one-hour (12.9 ± 4.5 mmHg vs. 7.4 ± 4.4 mmHg, p = 0.02) and two-hours interval (15.2 ± 4.5 mmHg vs. 7.7 ± 4.9 mmHg, p = 0.02), as well as at the end of surgery (11.0 ± 6.6 mmHg vs. 7.0 ± 4.6 mmHg, p = 0.03). Conclusion Video-assisted surgery is associated with significant changes in lung mechanics after induction of pneumoperitoneum. The observed changes are more severe and longer-lasting in patients undergoing robotic-assisted surgery compared to classic laparoscopy.

Asthma is a multifactorial disease of origin characterized by airway hyperresponsiveness (AHR) and airway remodeling. Several pieces of evidence from other pathologies suggest that Kisspeptins (Kp) regulate cell proliferation, migration, and invasion, mechanisms that are highly relevant to asthma. Our recent in vitro studies show Kp‐10 (active peptide of Kp), via its receptor, KISS1R, inhibits human airway smooth muscle cell proliferation. Here, we hypothesize a crucial role for Kp‐10 in regulating AHR and airway remodeling in vivo. Utilizing C57BL/6J mice, we assessed the effect of chronic intranasal Kp‐10 exposure on mixed allergen (MA)‐induced mouse model of asthma. MA‐challenged mice showed significant deterioration of lung function compared to those exposed to vehicle (DPBS); Kp‐10 treatment significantly improved the MA‐altered lung functions. Mice treated with Kp‐10 alone did not show any notable changes in lung functions. MA‐exposed mice showed a significant reduction in KISS1R expression as compared to vehicle alone. MA‐challenged mice showed significant alterations in immune cell infiltration in the airways and remodeling changes. Proinflammatory cytokines were significantly increased upon MA exposure, an effect abrogated by Kp‐10 treatment. Furthermore, biochemical and histological studies showed Kp‐10 exposure significantly reduced MA‐induced smooth muscle mass and soluble collagen in the lung. Overall, our findings highlight the effect of chronic Kp‐10 exposure in regulating MA‐induced AHR and remodeling. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: Mechanical power is a major contributor to lung injury and mortality in adults receiving mechanical ventilation. Recent advances in our understanding of mechanical power have allowed the different mechanical components to be isolated. The preterm lung shares many of the same similarities that would indicate mechanical power may be relevant in this group. To date, the role of mechanical power in neonatal lung injury is unknown. We hypothesise that mechanical power maybe useful in expanding our understanding of preterm lung disease. Specifically, that mechanical power measures may account for gaps in knowledge in how lung injury is initiated. Hypothesis-generating data set: To provide a justification for our hypothesis, data in a repository at the Murdoch Children's Research Institute, Melbourne (Australia) were re-analysed. 16 preterm lambs 124–127d gestation (term 145d) who received 90 min of standardised positive pressure ventilation from birth via a cuffed endotracheal tube were chosen as each was exposed to three distinct and clinically relevant respiratory states with unique mechanics. These were (1) the respiratory transition to air-breathing from an entirely fluid-filled lung (rapid aeration and fall in resistance); (2) commencement of tidal ventilation in an acutely surfactant-deficient state (low compliance) and (3) exogenous surfactant therapy (improved aeration and compliance). Total, tidal, resistive and elastic-dynamic mechanical power were calculated from the flow, pressure and volume signals (200 Hz) for each inflation. Results: All components of mechanical power behaved as expected for each state. Mechanical power increased during lung aeration from birth to 5 min, before again falling immediately after surfactant therapy. Before surfactant therapy tidal power contributed 70% of total mechanical power, and 53.7% after. The contribution of resistive power was greatest at birth, demonstrating the initial high respiratory system resistance at birth. Conclusions: In our hypothesis-generating dataset, changes in mechanical power were evident during clinically important states for the preterm lung, specifically transition to air-breathing, changes in aeration and surfactant administration. Future preclinical studies using ventilation strategies designed to highlight different types of lung injury, including volu-, baro- and ergotrauma, are needed to test our hypothesis. [ABSTRACT FROM AUTHOR]

The increased application of mechanical ventilation, the recognition of its harms and the interest in individualization raised the need for an effective monitoring. An increasing number of monitoring tools and modalities were introduced over the past 2 decades with growing insight into asynchrony, lung and chest wall mechanics, respiratory effort and drive. They should be used in a complementary rather than a standalone way. A sound strategy can guide a reduction in adverse effects like ventilator-induced lung injury, ventilator-induced diaphragm dysfunction, patient-ventilator asynchrony and helps early weaning from the ventilator. However, the diversity, complexity, lack of expertise, and associated cost make formulating the appropriate monitoring strategy a challenge for clinicians. Most often, a big amount of data is fed to the clinicians making interpretation difficult. Therefore, it is fundamental for intensivists to be aware of the principle, advantages, and limits of each tool. This analytic review includes a simplified narrative of the commonly used basic and advanced respiratory monitors along with their limits and future prospective. [ABSTRACT FROM AUTHOR]

Breathing involves fluid-solid interactions in the lung; however, the lack of experimental data inhibits combining the mechanics of air flow to airway deformation, challenging the understanding of how biomaterial constituents contribute to tissue response. As such, lung mechanics research is increasingly focused on exploring the relationship between structure and function. To address these needs, we characterize mechanical properties of porcine airways using uniaxial tensile experiments, accounting for bronchial orientation- and location- dependency. Structurally-reinforced constitutive models are developed to incorporate the role of collagen and elastin fibers embedded within the extrafibrillar matrix. The strain-energy function combines a matrix description (evaluating six models: compressible NeoHookean, unconstrained Ogden, uncoupled Mooney-Rivlin, incompressible Ogden, incompressible Demiray and incompressible NeoHookean), superimposed with non-linear fibers (evaluating two models: exponential and polynomial). The best constitutive formulation representative of all bronchial regions is determined based on curve-fit results to experimental data, accounting for uniqueness and sensitivity. Glycosaminoglycan and collagen composition, alongside tissue architecture, indicate fiber form to be primarily responsible for observed airway anisotropy and heterogeneous mechanical behavior. To the authors best knowledge, this study is the first to formulate a structurally-motivated constitutive model, augmented with biochemical analysis and microstructural observations, to investigate the mechanical function of proximal and distal bronchi. Our systematic pulmonary tissue characterization provides a necessary foundation for understanding pulmonary mechanics; furthermore, these results enable clinical translation through simulations of airway obstruction in disease, fluid-structure interaction insights during breathing, and potentially, predictive capabilities for medical interventions. STATEMENT OF SIGNIFICANCE: The advancement of pulmonary research relies on investigating the biomechanical response of the bronchial tree. Experiments demonstrating the non-linear, heterogeneous, and anisotropic material behavior of porcine airways are used to develop a structural constitutive model representative of proximal and distal bronchial behavior. Calibrated material parameters exhibit regional variation in biomaterial properties, initially hypothesized to originate from tissue constituents. Further exploration through biochemical and histological analysis indicates mechanical function is primarily governed by microstructural form. The results of this study can be directly used in finite element and fluid-structure interaction models to enable physiologically relevant and more accurate computational simulations aimed to help diagnose and monitor pulmonary disease.

The measurement of pleural (or intrathoracic) pressure is a key element for a proper setting of mechanical ventilator assistance as both under- and over-assistance may cause detrimental effects on both the lungs and the diaphragm. Esophageal pressure (Pes) is the gold standard tool for such measurements; however, it is invasive and seldom used in daily practice, and easier, bedside-available tools that allow for rapid and continuous monitoring are greatly needed. The tidal swing of central venous pressure (CVP) has long been proposed as a surrogate for pleural pressure (Ppl); however, despite the wide availability of central venous catheters, this variable is very often overlooked in critically ill patients. In the present narrative review, the physiological basis for the use of CVP waveforms to estimate Ppl is presented; the findings of previous and recent papers that addressed this topic are systematically reviewed, and the studies are divided into those reporting positive findings (i.e., CVP was found to be a reliable estimate of Pes or Ppl) and those reporting negative findings. Both the strength and pitfalls of this approach are highlighted, and the current knowledge gaps and direction for future research are delineated. [ABSTRACT FROM AUTHOR]

Abstract Background Patient-specific lung mechanics during mechanical ventilation (MV) can be identified from measured waveforms of fully ventilated, sedated patients. However, asynchrony due to spontaneous breathing (SB) effort can be common, altering these waveforms and reducing the accuracy of identified, model-based, and patient-specific lung mechanics. Methods Changes in patient-specific lung elastance over a pressure–volume (PV) loop, identified using hysteresis loop analysis (HLA), are used to detect the occurrence of asynchrony and identify its type and pattern. The identified HLA parameters are then combined with a nonlinear mechanics hysteresis loop model (HLM) to extract and reconstruct ventilated waveforms unaffected by asynchronous breaths. Asynchrony magnitude can then be quantified using an energy-dissipation metric, E asyn , comparing PV loop area between model-reconstructed and original, altered asynchronous breathing cycles. Performance is evaluated using both test-lung experimental data with a known ground truth and clinical data from four patients with varying levels of asynchrony. Results Root mean square errors for reconstructed PV loops are within 5% for test-lung experimental data, and 10% for over 90% of clinical data. E asyn clearly matches known asynchrony magnitude for experimental data with RMS errors 50% for Patient 1 and 13% for Patient 2. Patient 3 only presents 20% breaths with E asyn > 10%. Patient 4 has E asyn = 0 for 96% breaths showing accuracy in a case without asynchrony. Conclusions Experimental test-lung validation demonstrates the method’s reconstruction accuracy and generality in controlled scenarios. Clinical validation matches direct observations of asynchrony in incidence and quantifies magnitude, including cases without asynchrony, validating its robustness and potential efficacy as a clinical real-time asynchrony monitoring tool.

Distal airways commonly obstruct in lung disease and despite their importance, their mechanical properties are vastly underexplored. The lack of bronchial experiments restricts current airway models to either assume rigid structures, or extrapolate the material properties of the trachea to represent the small airways. Furthermore, past works are exclusively limited to uniaxial testing; investigating the multidirectional tensile loads of both the proximal and distal pulmonary airways is long overdue. Here we present comprehensive mechanical and viscoelastic properties of the porcine airway tree, including the trachea, trachealis muscle, large bronchi, and small bronchi, via measures of elasticity, extensibility, and energetics to explore regional and directional dependencies, cross-examining strain rate and preconditioning effects using planar equibiaxial tensile tests for the first time. We find bronchial regions are notably heterogeneous, where the trachea exhibits greater stiffness, energy loss, and preconditioning sensitivity than the smaller airways. Interestingly, the trachealis muscle is similar to the distal bronchi, despite being anatomically located adjacent to the proximal ring. Tissues are anisotropic and axially stiffer under initial loading, losing more energy with greater stress relaxation circumferentially. Strain rate dependency is also noted, where tissues are more energetically efficient at the faster strain rate, likely attributable to the microstructure. Findings highlight assumptions of homogeneity and isotropy are inadequate, and enable the improvement of aerosol flow and dynamic airway deformation computational predictive models. These results provide much needed fundamental material properties for future explorations contrasting healthy versus diseased pulmonary airway mechanics to better understand the relationship between structure and lung function. We present comprehensive multiaxial mechanical tensile experiments of the proximal and distal airways via measures of maximum stress, initial and ultimate moduli, strain and stress transitions, hysteresis, energy loss, and stress relaxation, and further assess preconditioning and strain rate dependencies to examine the relationship between lung function and structure. The mechanical response of the bronchial tree demonstrates significant anisotropy and heterogeneity, even within the tracheal ring, and emphasizes that contrary to past studies, the behavior of the proximal airways cannot be extended to distal bronchial tree analyses. Establishing these material properties is critical to advancing our understanding of airway function and in developing accurate computational simulations to help diagnose and monitor pulmonary diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Lung ultrasound allows lung aeration to be assessed through dedicated lung ultrasound scores (LUS). Despite LUS have been validated using several techniques, scanty data exist about the relationships between LUS and compliance of the respiratory system (Crs) in restrictive respiratory failure. Aim of this study was to investigate the relationship between LUS and Crs in neonates and adults affected by acute hypoxemic restrictive respiratory failure, as well as the effect of patients' age on this relationship. Methods: Observational, cross-sectional, international, patho-physiology, bi-center study recruiting invasively ventilated, adults and neonates with acute respiratory distress syndrome (ARDS), neonatal ARDS (NARDS) or respiratory distress syndrome (RDS) due to primary surfactant deficiency. Subjects without lung disease (NLD) and ventilated for extra-pulmonary conditions were recruited as controls. LUS, Crs and resistances (Rrs) of the respiratory system were measured within 1 h from each other. Results: Forty adults and fifty-six neonates were recruited. LUS was higher in ARDS, NARDS and RDS and lower in control subjects (overall p < 0.001), while Crs was lower in ARDS, NARDS and RDS and higher in control subjects (overall p < 0.001), without differences between adults and neonates. LUS and Crs were correlated in adults [r = − 0.86 (95% CI − 0.93; − 0.76), p < 0.001] and neonates [r = − 0.76 (95% CI − 0.85; − 0.62), p < 0.001]. Correlations remained significant among subgroups with different causes of respiratory failure; LUS and Rrs were not correlated. Multivariate analyses confirmed the association between LUS and Crs both in adults [B = − 2.8 (95% CI − 4.9; − 0.6), p = 0.012] and neonates [B = − 0.045 (95% CI − 0.07; − 0.02), p = 0.001]. Conclusions: Lung aeration and compliance of the respiratory system are significantly and inversely correlated irrespective of patients' age. A restrictive respiratory failure has the same ultrasound appearance and mechanical characteristics in adults and neonates. [ABSTRACT FROM AUTHOR]

Objectives: To identify short-term repeatability of forced oscillation technique (FOT) measurement of lung function, assess the lung function response to bronchodilators (BDs) by FOT, and prove the concept that only some very preterm infants manifest a change in lung mechanics in response to BD.Study Design: We retrospectively analyzed respiratory system resistance and respiratory system reactance measured by FOT (Fabian HFOi). The measurement short-term repeatability was assessed in 43 patients on 60 occasions; BD responsiveness was assessed using a different data set, including 38 measurements in 18 infants. The coefficient of repeatability was calculated as twice the SD of differences between measurements performed 15 minutes apart. We assessed BD responsiveness by measuring respiratory system resistance and respiratory system reactance before and 15 minutes after administering 200 mcg/kg of nebulized salbutamol. A positive response was defined as an improvement in respiratory system resistance or respiratory system reactance greater than the identified coefficient of repeatability.Results: The coefficient of repeatability was 7.5 cmH2O∗s/L (21%) for respiratory system resistance and 6.3 cmH2O∗s/L (21%) for respiratory system reactance. On average, respiratory system resistance did not change significantly following BD administration, though respiratory system reactance increased significantly (from -32.0 [-50.2, -24.4] to -27.9 [-38.1, -22.0] cmH2O∗s/L, P < .001). Changes in respiratory system resistance or respiratory system reactance after BD were greater than the identified coefficient of repeatability in 8 infants (44%) on 13 (34%) occasions.Conclusions: We identified a threshold to assess BD responsiveness by FOT in preterm infants. We speculate that FOT could be used to assess and personalize treatment with BD. [ABSTRACT FROM AUTHOR]

Background: Video-assisted surgery has become an increasingly used surgical technique in patients undergoing major thoracic and abdominal surgery and is associated with significant perioperative respiratory and cardiovascular changes. The aim of this study was to investigate the effect of intraoperative pneumoperitoneum during video-assisted surgery on respiratory physiology in patients undergoing robotic-assisted surgery compared to patients undergoing classic laparoscopy in Trendelenburg position. Methods: Twenty-five patients undergoing robotic-assisted surgery (RAS) were compared with twenty patients undergoing classic laparoscopy (LAS). Intraoperative ventilatory parameters (lung compliance and plateau airway pressure) were recorded at five specific timepoints: after induction of anesthesia, after carbon dioxide (CO2) insufflation, one-hour, and two-hours into surgery and at the end of surgery. At the same time, arterial and end-tidal CO2 values were noted and arterial to end-tidal CO2 gradient was calculated. Results: We observed a statistically significant difference in plateau pressure between RAS and LAS at one-hour (26.2 ± 4.5 cmH2O vs. 20.2 ± 3.5 cmH2O, p = 0.05) and two-hour intervals (25.2 ± 5.7 cmH2O vs. 17.9 ± 3.1 cmH2O, p = 0.01) during surgery and at the end of surgery (19.9 ± 5.0 cmH2O vs. 17.0 ± 2.7 cmH2O, p = 0.02). Significant changes in lung compliance were also observed between groups at one-hour (28.2 ± 8.5 mL/cmH2O vs. 40.5 ± 13.9 mL/cmH2O, p = 0.01) and two-hour intervals (26.2 ± 7.8 mL/cmH2O vs. 54.6 ± 16.9 mL/cmH2O, p = 0.01) and at the end of surgery (36.3 ± 9.9 mL/cmH2O vs. 58.2 ± 21.3 mL/cmH2O, p = 0.01). At the end of surgery, plateau pressures remained higher than preoperative values in both groups, but lung compliance remained significantly lower than preoperative values only in patients undergoing RAS with a mean 24% change compared to 1.7% change in the LAS group (p = 0.01). We also noted a more significant arterial to end-tidal CO2 gradient in the RAS group compared to LAS group at one-hour (12.9 ± 4.5 mmHg vs. 7.4 ± 4.4 mmHg, p = 0.02) and two-hours interval (15.2 ± 4.5 mmHg vs. 7.7 ± 4.9 mmHg, p = 0.02), as well as at the end of surgery (11.0 ± 6.6 mmHg vs. 7.0 ± 4.6 mmHg, p = 0.03). Conclusion: Video-assisted surgery is associated with significant changes in lung mechanics after induction of pneumoperitoneum. The observed changes are more severe and longer-lasting in patients undergoing robotic-assisted surgery compared to classic laparoscopy. [ABSTRACT FROM AUTHOR]

Mechanical ventilation is commonly used in the pediatric intensive care unit. This paper reviews studies of pediatric mechanical ventilation published in 2021. Topics include physiology, ventilator modes, alarms, disease states, airway suctioning, ventilator liberation, prolonged ventilation, and others. [ABSTRACT FROM AUTHOR]

Beyond the common comorbidities related to obesity, such as type 2 diabetes and cardiovascular diseases, impaired lung function is already known, but whether the fat distribution (sub-cutaneous, visceral) affects the lung function and pulmonary immune response are poorly known. Few evidence has shown that visceral fat is associated with insulin resistance, low-grade inflammation, and reduced lung function. In the present study, the body composition and fat distribution were evaluated by multi-frequency octopolar bioimpedance. This study demonstrated a possible association of increased visceral fat with impaired lung function in obesity grade I (n = 28; 45.46 ± 10.38 years old) women that was not observed in normal weight (n = 20; 43.20 ± 10.78 years old) and in overweight women (n = 30; 47.27 ± 10.25 years old). We also identified a negative correlation in FVC% (R 2 = 0.9129; p < 0.0236), FEV1% (R 2 = 0.1079; p < 0.0134), PEF% (R 2 = 0.1673; p < 0.0018), and VC IN% (R 2 = 0.1330; p < 0.0057) in the obesity grade I group, clearly demonstrating that higher levels of visceral fat correlate with reduced lung function, but not with sub-cutaneous fat. In addition, for the first time, a negative correlation among anti-fibrotic protein klotho (R 2 = 0.09298; p < 0.0897) and anti-inflammatory IL-10 (R 2 = 0.1653; p < 0.0487) in plasma was observed, in contrast to increased visceral fat. On the contrary, in breath condensate, a positive correlation for adiponectin (R 2 = 0.5665; p < 0.0120), IL1-Ra (R 2 = 0.2121; p < 0.0544), and IL1-Beta (R 2 = 0.3270; p < 0.0084) was found. Thus, increased visceral fat directly influences the impairment of lung function and the systemic and pulmonary immune response of women with obesity grade I.

The airways smaller than 2 mm diameter are named small airways. They are essential for the transport and exchange of oxygen and carbon dioxide and at the same time play a relevant role in pulmonary mechanics, contributing to the subdivision of lung volumes. Measurement of small airway function is, therefore, crucial in patients with respiratory disease. This overview focuses on the physiological aspects of the small airways, considered as air ducts as well as determinants of pulmonary mechanics, the most common tools for evaluating their function and treatment implications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Determining the respiratory system's mechanical properties with minimal patient effort has been an important field of investigation addressing patients unable to perform pulmonary function testing and in light of the preventive measures due to the recent pandemic. The current study aimed to present an alternative method for total respiratory resistance measurement during tidal breathing, compare it with airway resistance (Raw), measured by body plethysmography, and validate the procedure in three groups of subjects with normal, constrictive and obstructive respiratory patterns in spirometry. PATIENTS AND METHODS: We developed an alternative method of assessing total respiratory resistance during quiet breathing. After manufacturing the appropriate hardware apparatus, we applied a steady extrinsic resistance (R) for 100-200 m/s during tidal breathing. theoretical mathematical model allowed measurement of total respiratory resistance (Rtot) during inspiration (Rin) and expiration (Rex). To validate the method, 15 individuals were enrolled and assigned to the normal, obstructive and restrictive groups based on their spirometry patterns. All groups participated in two sets of measurements, the plethysmographic and novel method. Finally, respiratory resistance measurements were compared between groups and methods. RESULTS: The method was successfully developed, and Rtot measurements were recorded in five normal subjects and in five obstructive and restrictive subjects. Mean Rin and mean Rex were 4.99 cm H2O/L/sec and 4.42 cm H2O/L/sec in the healthy, 4.87 cm H2O/L/sec, and 6.63 cm H2O/L/sec in the obstructive and 5.97 cm H2O/L/sec and 4.12 cm H2O/L/sec in the restrictive group, respectively. Rex was notably higher than Rin in the obstructive group and was positively correlated with Raw (p<0.005, r=0.47). CONCLUSIONS: This method provides the theoretical background for a plausible alternative tool for accessing a mechanical parameter of the respiratory system, which is easy to perform and requires only passive patient cooperation while enabling rough differentiation between obstructive and restrictive disorders. The model's feasibility potential in a real-life setting was studied in a small sample, and additional implementation and validation of the method in a larger population are guaranteed. [ABSTRACT FROM AUTHOR]

Background: In response to COVID-19 global crisis and arising from social responsibility, efforts have been exerted to promptly research, develop and manufacture ICU ventilators locally to meet the spike in demand. This study aimed at: Evaluating the safety and performance of a newly developed mechanical ventilator; EZVent compared to a commercial ventilator regarding hemodynamics, arterial blood gases (ABG), lung inflammatory markers, and histopathology in a healthy pig model using three different ventilation modes. Methods: Eight adult male pigs were anesthetized and randomly assigned into two equal groups: Commercial vent and EZVent group, the animals of which were ventilated using a standard commercial ventilator and EZVent, respectively. On every animal, three ventilation modes were tested, each mode for 30 min: CMV-VC, CMV-PC, and CPAP-PS modes. Vital signs, ECG, Lung Mechanics (LM), and ABG were measured before ventilation and after 30 min of ventilation of each mode. After animals’ euthanasia, histological examinations of lung samples including morphometric assessment of alveolar edema, alveolar wall thickening, and the mean number of inflammatory cellular infiltrate/cm2 of lung tissue were analyzed. TNF-α and Il-6 expression and localization in lung tissue were assessed by western blot and immunohistochemistry. Results: The vital signs, LM, ABG, morphometric analysis, and histopathological score during the different ventilation modes showed non-significant differences between the study groups. TNF-α and IL-6 were minimally expressed in the bronchiolar epithelium and the alveolar septa. Their increased expression level was insignificant. Conclusion: EZVent is equivalent to the commercial ventilator regarding its safety and efficacy.

Many preterm infants require mechanical ventilation as life-saving therapy. However, ventilation-induced overpressure can result in lung diseases. Considering the lung as a viscoelastic material, positive pressure inside the lung results in increased hydrostatic pressure and tissue compression. To elucidate the effect of positive pressure on lung tissue mechanics and cell behavior, we mimic the effect of overpressure by employing an uniaxial load onto fetal and adult rat lungs with different deformation rates. Additionally, tissue expansion during tidal breathing due to a negative intrathoracic pressure was addressed by uniaxial tension. We found a hyperelastic deformation behavior of fetal tissues under compression and tension with a remarkable strain stiffening. In contrast, adult lungs exhibited a similar response only during compression. Young’s moduli were always larger during tension compared to compression, while only during compression a strong deformation-rate dependency was found. In fact, fetal lung tissue under compression showed clear viscoelastic features even for small strains. Thus, we propose that the fetal lung is much more vulnerable during inflation by mechanical ventilation compared to normal inspiration. Electrophysiological experiments with different hydrostatic pressure gradients acting on primary fetal distal lung epithelial cells revealed that the activity of the epithelial sodium channel (ENaC) and the sodium-potassium pump (Na,K-ATPase) dropped during pressures of 30 cmH2O. Thus, pressures used during mechanical ventilation might impair alveolar fluid clearance important for normal lung function.

Activity-related dyspnea in chronic lung disease is centrally related to dynamic (dyn) inspiratory constraints to tidal volume expansion. Lack of reference values for exertional inspiratory reserve (IR) has limited the yield of cardiopulmonary exercise testing in exposing the underpinnings of this disabling symptom. One hundred fifty apparently healthy subjects (82 males) aged 40–85 underwent incremental cycle ergometry. Based on exercise inspiratory capacity (IC dyn), we generated centile-based reference values for the following metrics of IR as a function of absolute ventilation: IR dyn1 ([1-(tidal volume/IC dyn)] x 100) and IR dyn2 ([1-(end-inspiratory lung volume/total lung capacity] x 100). IR dyn1 and IR dyn2 standards were typically lower in females and older subjects (p <0.05 for sex and age versus ventilation interactions). Low IR dyn1 and IR dyn2 significantly predicted the burden of exertional dyspnea in both sexes (p <0.01). Using these sex and age-adjusted limits of reference, the clinician can adequately judge the presence and severity of abnormally low inspiratory reserves in dyspneic subjects undergoing cardiopulmonary exercise testing. • Proper interpretation of exertional inspiratory constraints requires reference values. • Females and older subjects showed higher inspiratory constraints at iso-ventilation. • Sex- and age-adjusted standards are provided for clinical use. • These norms might improve the yield of CPET in assessing exertional dyspnea. [ABSTRACT FROM AUTHOR]