Mechanical Properties Of Lungs Research Articles

Biomechanical Properties and Cellular Responses in Pulmonary Fibrosis.

Pulmonary fibrosis is a fatal lung disease affecting approximately 5 million people worldwide, with a 5-year survival rate of less than 50%. Currently, the only available treatments are palliative care and lung transplantation, as there is no curative drug for this condition. The disease involves the excessive synthesis of the extracellular matrix (ECM) due to alveolar epithelial cell damage, leading to scarring and stiffening of the lung tissue and ultimately causing respiratory failure. Although multiple factors contribute to the disease, the exact causes remain unclear. The mechanical properties of lung tissue, including elasticity, viscoelasticity, and surface tension, are not only affected by fibrosis but also contribute to its progression. This paper reviews the alteration in these mechanical properties as pulmonary fibrosis progresses and how cells in the lung, including alveolar epithelial cells, fibroblasts, and macrophages, respond to these changes, contributing to disease exacerbation. Furthermore, it highlights the importance of developing advanced in vitro models, based on hydrogels and 3D bioprinting, which can accurately replicate the mechanical and structural properties of fibrotic lungs and are conducive to studying the effects of mechanical stimuli on cellular responses. This review aims to summarize the current understanding of the interaction between the progression of pulmonary fibrosis and the alterations in mechanical properties, which could aid in the development of novel therapeutic strategies for the disease.

Back to the future: the novel art of digital auscultation applied in a prospective observational study of critically ill Covid-19 patients

BackgroundThe Covid-19 pandemic has caused immense pressure on Intensive Care Units (ICU). In patients with severe ARDS due to Covid-19, respiratory mechanics are important for determining the severity of lung damage. Lung auscultation could not be used during the pandemic despite its merit. The main objective of this study was to investigate associations between lung auscultatory sound features and lung mechanical properties, length of stay (LOS) and survival, in adults with severe Covid-19 ARDS.MethodsConsecutive patients admitted to a large ICU between 2020 and 2021 (n = 173) were included. Digital stethoscopes obtained auscultatory sounds and stored them in an on-line database for replay and further processing using advanced AI techniques. Correlation and regression analysis explored relationships between digital auscultation findings and lung mechanics or the ICU outcome. The resulting annotated lung sounds database is also publicly available as supplementary material.ResultsThe presence of squawks was associated with the ICU LOS, outcome and 90-day mortality. Other features (age, SOFA score & oxygenation index upon admission, minimum crackle entropy) had significant impact on outcome. Additional features affecting the 90-d survival were age and mean crackle entropy. Multivariate logistic regression showed that survival was affected by age, baseline SOFA, baseline oxygenation index and minimum crackle entropy.ConclusionsRespiratory mechanics were associated with various adventitious sounds, whereas the lung sound analytics and the presence of certain adventitious sounds correlated with the ICU outcome and the 90-d survival. Spectral features of crackles sounds can serve as prognostic factors for survival, highlighting the importance of digital auscultation.

Lung mechanics showing sex-based differences and circadian time-of-day response to bleomycin-induced lung injury in mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that impairs lung mechanical properties due to dysregulated extracellular matrix remodeling. Lung function assessment is an important physiological endpoint in the mouse model of pulmonary fibrosis (PF) that has gained a broader scientific acceptance in the field. IPF pathophysiology shows sex-based differences, disproportionately affecting more men compared to women. Prior reports suggest that the circadian clock is perturbed during the pathogenesis of PF. We have comprehensively assessed the sex-based differences and time-of-day response (at Zeitgeber time: ZT0/6:00 a.m. or ZT12/6 p.m.) in lung mechanics among sham (control) versus bleomycin (BLM)-challenged female and male (C57BL/6: WT) mice using Flexi-vent. BLM challenge altered lung function significantly in males in both total lung (reduced dynamic compliance, and increased resistance and elastance) as well as lung tissue-specific parameters (increased tissue elastance and tissue damping) but less pronounced in females. BLM-challenged mice showed a time-of-day response in lung function at ZT0 versus ZT12, which was pronounced in the ZT0 BLM group. Overall, these findings provide a comprehensive analysis of altered lung function in female and male mice and the time-of-day difference in lung function parameters following BLM-induced lung fibrosis.

Magnetic Resonance Elastography (MRE) of Bleomycin-Induced Pulmonary Fibrosis in an Animal Model.

Idiopathic pulmonary fibrosis is responsible for 40,000 deaths annually in the United States. A hallmark of idiopathic pulmonary fibrosis is elevated collagen deposition, which alters lung stiffness. Clinically relevant ways to measure changes in lung stiffness during pulmonary fibrosis are not available, and new noninvasive imaging methods are needed to measure changes in lung mechanical properties. Magnetic resonance elastography (MRE) is an in vivo magnetic resonance imaging technique proven to detect changes in shear stiffness in different organs. This study used MRE, histology, and bronchoalveolar lavage (BAL) to study changes in the mechanical and structural properties of the lungs after bleomycin-induced pulmonary fibrosis in pigs. Pulmonary fibrosis was induced in 9 Yorkshire pigs by intratracheal instillation of 2 doses of bleomycin into the right lung only. Magnetic resonance elastography scans were performed at baseline and week 4 and week 8 postsurgery in a 1.5 T magnetic resonance imaging scanner using a spin-echo echo planar imaging sequence to measure changes in lung shear stiffness. At the time of each scan, a BAL was performed. After the final scan, whole lung tissue was removed and analyzed for histological changes. Mean MRE-derived stiffness measurements at baseline, week 4, and week 8 for the control (left) lungs were 1.02 ± 0.27 kPa, 0.86 ± 0.29 kPa, and 0.68 ± 0.20 kPa, respectively. The ratio of the shear stiffness in the injured (right) lung to the uninjured control (left) lung at baseline, week 4, and week 8 was 0.98 ± 0.23, 1.52 ± 0.41, and 1.64 ± 0.40, respectively. High-dose animals showed increased protein in BAL fluid, elevated inflammation observed by the presence of patchy filtrates, and enhanced collagen and α-smooth muscle actin staining on histological sections. Low-dose animals and the control (left) lungs of high-dose animals did not show significant histopathological changes. This study demonstrated that MRE can be used to detect changes in lung stiffness in pigs after bleomycin challenge.

Associating local strains to global pressure-volume mouse lung mechanics using digital image correlation.

Pulmonary diseases alter lung mechanical properties, can cause loss of function, and necessitate use of mechanical ventilation, which can be detrimental. Investigations of lung tissue (local) scale mechanical properties are sparse compared to that of the whole organ (global) level, despite connections between regional strain injury and ventilation. We examine ex vivo mouse lung mechanics by investigating strain values, local compliance, tissue surface heterogeneity, and strain evolutionary behavior for various inflation rates and volumes. A custom electromechanical, pressure–volume ventilator is coupled with digital image correlation to measure regional lung strains and associate local to global mechanics by analyzing novel pressure–strain evolutionary measures. Mean strains at 5 breaths per minute (BPM) for applied volumes of 0.3, 0.5, and 0.7 ml are 5.0, 7.8, and 11.3%, respectively, and 4.7, 8.8, and 12.2% for 20 BPM. Similarly, maximum strains among all rate and volume combinations range 10.7%–22.4%. Strain values (mean, range, mode, and maximum) at peak inflation often exhibit significant volume dependencies. Additionally, select evolutionary behavior (e.g., local lung compliance quantification) and tissue heterogeneity show significant volume dependence. Rate dependencies are generally found to be insignificant; however, strain values and surface lobe heterogeneity tend to increase with increasing rates. By quantifying strain evolutionary behavior in relation to pressure–volume measures, we associate time‐continuous local to global mouse lung mechanics for the first time and further examine the role of volume and rate dependency. The interplay of multiscale deformations evaluated in this work can offer insights for clinical applications, such as ventilator‐induced lung injury.

Mouse lung mechanical properties under varying inflation volumes and cycling frequencies

Respiratory pathologies alter the structure of the lung and impact its mechanics. Mice are widely used in the study of lung pathologies, but there is a lack of fundamental mechanical measurements assessing the interdependent effect of varying inflation volumes and cycling frequency. In this study, the mechanical properties of five male C57BL/6J mice (29–33 weeks of age) lungs were evaluated ex vivo using our custom-designed electromechanical, continuous measure ventilation apparatus. We comprehensively quantify and analyze the effect of loading volumes (0.3, 0.5, 0.7, 0.9 ml) and breathing rates (5, 10, 20 breaths per minute) on pulmonary inflation and deflation mechanical properties. We report means of static compliance between 5.4–16.1 µl/cmH2O, deflation compliance of 5.3–22.2 µl/cmH2O, percent relaxation of 21.7–39.1%, hysteresis of 1.11–7.6 ml•cmH2O, and energy loss of 39–58% for the range of four volumes and three rates tested, along with additional measures. We conclude that inflation volume was found to significantly affect hysteresis, static compliance, starting compliance, top compliance, deflation compliance, and percent relaxation, and cycling rate was found to affect only hysteresis, energy loss, percent relaxation, static compliance and deflation compliance.

Lung and chest wall mechanical properties in metformin-treated and untreated models of type 2 diabetes

The adverse respiratory consequences of type 2 diabetes mellitus (T2DM) may reflect compromised lung function and/or alterations of the chest wall because of skeletal muscle stiffening. We assessed the separate contributions of these compartments to respiratory complications in diabetes and explored the effects of metformin on respiratory abnormalities. Experiments were performed in untreated rats (control, n = 7), high-fat diet-fed rats receiving streptozotocin (T2DM, n = 7), and metformin-treated diabetic rats (MET, n = 6). Newtonian resistance, tissue damping, and elastance were separately assessed for lung and chest wall components by measuring the esophageal pressure during forced oscillations at low (0 cmH2O), medium (3 cmH2O), and high positive end-expiratory pressure (PEEP) (6 cmH2O). Tissue hysteresivity was calculated as damping/elastance. Blood gas parameters were used to assess gas exchange, and lung histology was performed to characterize collagen expression. T2DM at low PEEP compromised airway and lung tissue mechanics in association with gas-exchange defects and collagen overexpression. Abnormal chest wall mechanics in T2DM was indicated only by decreased tissue hysteresivity. No difference in lung or chest wall mechanics, gas exchange, or lung histology was observed between the MET and control groups. These findings suggest the primary involvement of the pulmonary system in the respiratory consequences of T2DM, with chest wall properties only disturbed by a shift toward the dominance of elastic forces at low PEEP. The adequacy of metformin to treat the adverse respiratory consequences of diabetes was also revealed, in addition to its well-established beneficial effects on other organs.NEW & NOTEWORTHY The present study examined the contributions of the lungs and chest wall to respiratory complications in a rat model of diabetes and clarified the effects of metformin on these changes. At low positive end-expiratory pressure, type 2 diabetes was linked to dysfunctional airway and lung tissue mechanics in relation with gas-exchange defects and collagen overexpression, whereas decreased tissue hysteresivity was manifested in the chest wall abnormalities. Metformin treated all adverse respiratory consequences of diabetes.

In asthma positive phase III slopes can result from structural heterogeneity of the bronchial tree.

We have previously identified bronchial generations 5-7 as the locus of maximum contribution to the convective portion of the phase III slope in computed tomography (CT)-based lung models of patients with asthma. In the present study, we examined how phase III slope is generated locally, by specifically interrogating at individual branch points, the necessary condition for a phase III slope to occur: some degree of convective flow sequencing between any two daughter branches that have a heterogeneity in gas washout concentration between them. Flow sequencing at individual branch points showed a wide range of values, including branch points where flow sequencing was such that phase III slopes were negative locally. Yet, the net effect in the 24 bronchial trees that we studied was that flow sequencing between pairs of less and better ventilated units most frequently drove positive phase III slopes in generations 5-7. By investigating the link of local flow sequencing between any two daughter branches to the corresponding heterogeneity of mechanical lung properties, heterogeneity of compliance was seen to be a major determinant of flow sequencing. In these bronchial structures, compliance heterogeneity was essentially brought about by volume asymmetry resulting from terminating pathways within the three-dimensional (3-D) confines of the lung contours. We conclude that the serial and parallel combination of lung mechanical properties at individual branch points in an asymmetrical branching network generates flow sequencing in mid-range conductive airways, leading to a positive at-mouth phase III slope.NEW & NOTEWORTHY Conceptually, the simplest way to obtain a sloping phase III during a washout exhalation is when there is convective flow sequencing between two lung units, such that the better ventilated unit contributes relatively more to exhaled flow at the beginning of phase III in the exhalation. Here, we show how compliance heterogeneity across the serial and parallel arrangement of branch points in bronchial trees of patients with asthma leads to flow sequencing, and thus phase III slopes of positive sign at the patient's mouth.

Evaluation of the influence of individualized protective ventilation on the lung mechanical properties

The work is devoted to the study of the influence of individualized protective ventilation support on pulmonary mecha-nics. The study included 47 patients who underwent open abdominal surgery under general anesthesia. All patients had a moderate to high risk of developing postoperative pulmonary complications by the ARISCAT scale. Intraoperatively, the impact of individualized protective ventilation on respiratory mechanics, namely Ppeak, Pplat, Pdrive, dynamic pulmonary compliance was assessed. Individualized protective respiratory support was ventilation with a tidal volume of 7 ml/kg of ideal body weight, with the selection of the optimal level of positive pressure at the end of exhalation (PEEP), focusing on dynamic pulmonary compliance and performing recruiting maneuver, and then in the case of a decrease in dynamic pulmonary compliance by more than 20 %, followed by re-selection of PEEP. The studied parameters were recorded before and after the recruiting maneuver, as well as on the 30th, 60th, 90th, 120th, 150th, 180th minutes after the recruiting maneuver, depending on the duration of the operation. The use of alveolar straightening techniques led to an improvement in pulmonary mechanics, namely, an increase in dynamic pulmonary compliance by 16 % and a decrease in Pdrive by 17 %. The intraoperative level of PEEP averaged 4 [4; 5] cm of water. No cases of hypoxemia or recurrence of recruiting maneuver were reported. The obtained results indicate that chosen technique of recruiting maneuver is effective and safe, and its use allows reducing the negative impact of mechanical ventilation. The study did not find a statistically significant correlation between the level of PEEP and the value of dynamic pulmonary compliance. Such data prove the need for individual selection of ventilation parameters according to the characteristics of the mechanical properties of each patient.

Non-destructive vacuum-assisted measurement of lung elastic modulus

In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of soft tissue mechanics, which can improve our understanding of disease and inform therapeutic development. In particular, accurate measurement of lung mechanical properties has been especially challenging due to the anatomical and mechanobiological complexities of the lung. Discrepancies between measured mechanical properties of dissected lung tissue samples and intact lung tissues in vivo has limited the ability to accurately characterize integral lung mechanics. Here, we report a non-destructive vacuum-assisted method to evaluate mechanical properties of soft biomaterials, including intact tissues and hydrogels. Using this approach, we measured elastic moduli of rat lung tissue that varied depending on stress-strain distribution throughout the lung. We also observed that the elastic moduli of enzymatically disrupted lung parenchyma increased by at least 64%. The reported methodology enables assessment of the nonlinear viscoelastic characteristics of intact lungs under normal and abnormal (i.e., injured, diseased) conditions and allows measurement of mechanical properties of tissue-mimetic biomaterials for use in therapeutics or in vitro models. Statement of significanceAccurate quantification of tissue stiffness is critical for understanding mechanisms of disease and developing effective therapeutics. Current modalities to measure tissue stiffness are destructive and preclude accurate assessment of lung mechanical properties, as lung mechanics are determined by complex features of the intact lung. To address the need for alternative methods to assess lung mechanics, we report a non-destructive vacuum-based approach to quantify tissue stiffness. We applied this method to correlate lung tissue mechanics with tissue disruption, and to assess the stiffness of biomaterials. This method can be used to inform the development of tissue-mimetic materials for use in therapeutics and disease models, and could potentially be applied for in-situ evaluation of tissue stiffness as a diagnostic or prognostic tool.

Paradoxical Effect of Chest Wall Compression on Respiratory System Compliance: A Multicenter Case Series of Patients With ARDS, With Multimodal Assessment

Paradoxical Effect of Chest Wall Compression on Respiratory System Compliance: A Multicenter Case Series of Patients With ARDS, With Multimodal Assessment

Established severe BPD: is there a way out? Change of ventilatory paradigms.

Improved survival of extremely preterm newborn infants has increased the number of infants at risk for developing bronchopulmonary dysplasia (BPD). Despite efforts to prevent BPD, many of these infants still develop severe BPD (sBPD) and require long-term invasive mechanical ventilation. The focus of research and clinical management has been on the prevention of BPD, which has had only modest success. On the other hand, research on the management of the established sBPD patient has received minimal attention even though this condition poses large economic and health problems with extensive morbidities and late mortality. Patients with sBPD, however, have been shown to respond to treatments focused not only on ventilatory strategies but also on multidisciplinary approaches where neurodevelopmental support, growth promoting strategies, and aggressive treatment of pulmonary hypertension improve their long-term outcomes. In this review we will try to present a physiology-based ventilatory strategy for established sBPD, emphasizing a possible paradigm shift from acute efforts to wean infants at all costs to a more chronic approach of stabilizing the infant. This chronic approach, herein referred to as chronic phase ventilation, aims at allowing active patient engagement, reducing air trapping, and improving ventilation-perfusion matching, while providing sufficient support to optimize late outcomes. IMPACT: Based on pathophysiological aspects of evolving and established severe BPD in premature infants, this review presents some lung mechanical properties of the most severe phenotype and proposes a chronic phase ventilatory strategy that aims at reducing air trapping, improving ventilation-perfusion matching and optimizing late outcomes.

Non-Destructive Vacuum-Assisted Measurement of Lung Elastic Modulus

In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of soft tissue mechanics, which can improve our understanding of disease and inform therapeutic development. In particular, accurate measurement of lung mechanical properties has been especially challenging due to the anatomical and mechanobiological complexities of the lung. Discrepancies between measured mechanical properties of dissected lung tissue samples and intact lung tissues in vivo has limited the ability to accurately characterize integral lung mechanics. Here, we report a non-destructive vacuum-assisted method to evaluate the stiffness of soft biomaterials, including intact tissues and hydrogels. Using this approach, we determined that the elastic modulus of rat lung ranges from 4.44 ± 0.61 to 13.17 ± 3.85 kPa depending on pre-loading conditions. We also observed that the elastic modulus of acutely injured lung tissue increased by at least 64%. The reported methodology enables assessment of the biophysical properties of intact lungs under normal and abnormal (i.e., injured, diseased) conditions and allows measurement of mechanical properties of tissue-mimetic biomaterials for use in therapeutics or in vitro models.

Characterisation of Baseline and Chronic Lung Allograft Dysfunction by Airway Oscillometry: Results of a Multi-Centre Cross-Sectional Study

<h3>Purpose</h3> Baseline and chronic lung allograft dysfunction (BLAD & CLAD) are leading causes of reduced patient survival. Airway oscillometry characterises the lung's mechanical properties with greater sensitivity than spirometry. This study aims to characterise BLAD and CLAD with airway oscillometry. <h3>Methods</h3> Oscillometry was performed on all bilateral lung transplant (LTx) recipients at 2 Australian centres between Jan-Oct 2020 with the TremoFlo C-100 device to obtain resistance (R₅, R_19-5), reactance (X₅), and reactance area (A_x). Patients with acute lung allograft dysfunction were excluded. CLAD was diagnosed/staged using spirometry as per ISHLT 2019 Consensus Criteria. BLAD was defined as failure to ever achieve >80%-pred FEV₁ and FVC. Multivariate logistic regression measured the association between oscillometry risk of CLAD. <h3>Results</h3> A total of 179 LTx recipients [47% males; median age 54 (IQR 25); duration post-LTx 5 years (IQR 7)] were recruited. 112/179 (63%) patients had no CLAD and of these 27 (24%) patients had BLAD. There was a significant difference in median X₅ (-1.64 vs -1.20, p<0.01) and A_x (7.33 vs 4.71, p=0.03) between patients with BLAD compared to those without. There were no significant differences in median R₅, R_5-19 between patients with BLAD compared to those without. R₅, R_5-19, X₅, A_x, were independently associated with CLAD (p<0.01) with A_x being the strongest predictor (aOR 1.14/1-unit increase, AUROC 0.82). There was a significant difference in each median oscillometry parameter in each CLAD stage, p<0.01 <b>Figure 1</b> <h3>Conclusion</h3> BLAD is characterised by abnormal reactance (X₅ & A_x), yet resistive airway properties (R₅ & R_5-19) are similar to patients without BLAD. The association between oscillometry parameters and CLAD demonstrates that oscillometry provides complimentary information about lung dysfunction after transplant. Longitudinal studies are required to determine whether oscillometry has a role in earlier detection of CLAD.

B-spline modelling of inspiratory drive in NAVA-ventilated patients

Abstract Model-based approaches are often used to estimate mechanical properties of lungs, such as elastance (E) and airway resistance (R), during invasive and non-invasive mechanical ventilation (MV). Current models are less effective when spontaneous breathing is present. This analysis utilises b-spline functions within a single compartment model framework to identify patient-specific inspiratory driving pressure. A series of 2nd-order, constrained b-spline basis functions are used to identify inspiratory driving pressure breath to breath alongside single E and R using inspiration and expiration data from n=20 breaths for 10 patients ventilated using NAVA. Median [IQR] per patient RMS error for n = 20 breaths was 0.75 [0.6 – 0.9] cmH2O, with elastance ranging from 2.1 – 29.8 cmH20/L, and per-patient median peak driving pressure ranging from -1.9 to -7.9 cmH2O. Inspiratory driving pressure profiles matched esophageal pressures from literature and its value at peak nervous signal to the diaphragm (Eadi) was correlated with peak Eadi (R2=0.25-0.86). Average trans-pulmonary pressure remained consistent between breaths for each patient, despite differences in peak Eadi and peak airway pressure. Overall, the model-based approach resulted in physiologically reasonable inspiratory driving pressures, with trends with electrical activity and matched literature data showing neuro-muscular decoupling as a function of pressure and/or volume.

Reliability of impulse oscillometry parameters in healthy children and in children with cystic fibrosis.

Impulse oscillometry system (IOS) is an instrument developed to evaluate the mechanical lung properties. It has been reported that to analyse the exam in a proper way it is necessary to carry out more than one measure. However, studies addressing the standardisation are still scarce. The objective was to determine within trial reliability of three measures in IOS parameters in healthy children and children with cystic fibrosis (CF). Weight, height, body mass index, forced spirometric and the oscillometric parameters (resistance, respiratory impedance, respiratory reactance and resonance frequency) data were collected, in a way that all participants performed three IOS measures. To evaluate, the reproducibility was used the intraclass correlation coefficient [two-way mixed model, absolute agreement definition, ICC]. The response stability was appraised using the standard error of measurements (SEM) in three repetitions of the IOS in the healthy children group (HCG) and in the cystic fibrosis group (CFG). About 95 subjects participated, in each group with a mean age of 10.89±2.21years old in the HCG and 9.73±2.43years old in the CFG, having been 41 and 43 boys and 54 and 52 girls, in the respectively group. In both groups, all IOS parameters evaluated in the three measures presented an ICC of 0.9, which is a high reproducibility. The IOS parameters are reproducible for healthy children and CF children in three measures. However, according to the population studied, the performance of only one measure is sufficient to assess respiratory mechanics, whereas the SEM were low, except for Fres, in both groups.

Lung mechanics in type L CoVID-19 pneumonia: a pseudo-normal ARDS

BackgroundThis study was conceived to provide systematic data about lung mechanics during early phases of CoVID-19 pneumonia, as long as to explore its variations during prone positioning.MethodsWe enrolled four patients hospitalized in the Intensive Care Unit of “M. Bufalini” hospital, Cesena (Italy); after the positioning of an esophageal balloon, we measured mechanical power, respiratory system and transpulmonary parameters and arterial blood gases every 6 hours, just before decubitus change and 1 hour after prono-supination.ResultsBoth respiratory system and transpulmonary compliance and driving pressure confirmed the pseudo-normal respiratory mechanics of early CoVID-19 pneumonia (respectively, CRS 40.8 ml/cmH2O and DPRS 9.7 cmH2O; CL 53.1 ml/cmH2O and DPL 7.9 cmH2O). Interestingly, prone positioning involved a worsening in respiratory mechanical properties throughout time (CRS,SUP 56.3 ml/cmH2O and CRS,PR 41.5 ml/cmH2O – P 0.37; CL,SUP 80.8 ml/cmH2O and CL,PR 53.2 ml/cmH2O – P 0.23).ConclusionsDespite the severe ARDS pattern, respiratory system and lung mechanical properties during CoVID-19 pneumonia are pseudo-normal and tend to worsen during pronation.Trial registrationRestrospectively registered.

Predictors of extracorporeal membrane oxygenation efficacy in patients with acute respiratory failure

The purpose of this article is to describe the problem of predicting the lung function recovery in patients with extracorporeal membrane oxygenation for acute respiratory distress syndrome. Data from CESAR and EOLIA clinical trials on the efficacy of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome have been reviewed and some controversial results discussed. The prognostic PRESERVE and RESP scores developed as prognostic tools on the basis of the results of these studies, are presented, the limitations of their applicability in various forms of acute respiratory distress syndrome are discussed. We propose to subdivide the predictors of the extracorporeal membrane oxygenation outcome in patients with acute respiratory distress syndrome into 4 following groups: 1. Lung injury severity criteria, including parameters of their lung mechanical and functional properties. 2. Time from acute respiratory failure onset to extracorporeal membrane oxygenation initiation, which reflects the rate of pathological processes in lungs and timing of decision to initiate extracorporeal membrane oxygenation. 3. The etiology of pulmonary disorders, directly affecting the reversibility of pathological processes in the lungs. 4. The severity of the patient's general condition, including the severity of manifestations of multiple organ failure, the degree of decompensation of concomitant chronic diseases, including oncological and associated with immunosuppression. Several diseases are associated with a higher risk of specific complications, particularly hemorrhagic, during extracorporeal membrane oxygenation.

A Microfluidic System to Measure Neonatal Lung Compliance Over Late Stage Development as a Functional Measure of Lung Tissue Mechanics.

Premature birth interrupts the development of the lung, resulting in functional deficiencies and the onset of complex pathologies, like bronchopulmonary dysplasia (BPD), that further decrease the functional capabilities of the immature lung. The dysregulation of molecular targets has been implicated in the presentation of BPD, but there is currently no method to correlate resultant morphological changes observed in tissue histology with these perturbations to differences in function throughout saccular and alveolar lung development. Lung compliance is an aggregate measure of the lung's mechanical properties that is highly sensitive to a number of molecular, cellular, and architectural characteristics, but little is known about compliance in the neonatal mouse lung due to measurement challenges. We have developed a novel method to quantify changes in lung volume and pressure to determine inspiratory and expiratory compliance throughout neonatal mouse lung development. The compliance measurements obtained were validated against compliance values from published studies using mature lungs following enzymatic degradation of the extracellular matrix (ECM). The system was then used to quantify changes in compliance that occurred over the entire span of neonatal mouse lung development. These methods fill a critically important gap connecting powerful mouse models of development and disease to measures of functional lung mechanics critical to respiration and enable insights into the genetic, molecular, and cellular underpinnings of BPD pathology to improve lung function in premature infants.

Hypoxemia in COVID-19 patients: An hypothesis

The current SARS-Cov-2 virus pandemic challenges critical care physicians and other caregivers to find effective treatment for desperately ill patients — especially those with sudden and extreme hypoxemia. Unlike patients with other forms of Acute Respiratory Distress Syndrome, these patients do not exhibit increased lung stiffness or dramatic dyspnea., even in the presence of arterial blood oxygen levels lower than that seen normally in mixed venous blood. Urgent intubation and mechanical ventilation with high inflation pressures and raised inhaled oxygen concentration have proved unhelpful or worse, but why? Our Hypothesis is that sudden opening of a previously undetected probe-patent foramen ovale (PPFO) may explain this mystery. As hypoxemia without acidosis is a rather weak stimulus of dyspnea or increased ventilation, and opening of such an intracardiac shunt would not worsen lung mechanical properties, the absence of dramatic symptom changes would not be surprising. We point out the high frequency of PFO both in life and at autopsy, and the physiological evidence of large shunt fractions found in Covid-19 patients. Published evidence of hypercoagulability and abundant evidence of pulmonary emboli found at autopsy are in accord with our hypothesis, as they would contribute to raised pressure in the pulmonary arteries and right heart chambers, potentially causing a shunt to open. We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein. Search for an open PFO after a large drop in arterial oxygen saturation can be performed at the bedside with a variety of well-established techniques including bedside echocardiography, nitrogen washout test, and imaging studies. Potential treatments might include balloon or patch closure of the shunt, and various drug treatments to lower pulmonary vascular resistance.