Pulmonary Mechanics Research Articles

GAA Deficiency Disrupts Distal Airway Cells in Pompe Disease

Pompe disease is an autosomal recessive glycogen storage disease caused by mutations in alpha‐glucosidase (GAA) ‐ an enzyme responsible of hydrolyzing lysosomal glycogen. GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption. Skeletal muscle, motor neuron pathology and airway smooth muscle cells are known to contribute to respiratory insufficiency in Pompe disease, but the role of distal airway cells including alveolar type 1 and type 2 cells (AT1 and AT2, respectively) has not been evaluated. AT1 cells depend on lysosomes for cellular homeostasis to maintain a thin barrier for gas exchange whereas AT2 cells depend on lysosomal structures for surfactant production. Using an established mouse model of Pompe disease, the Gaa−/− mouse, we compared lung histology using Periodic acid‐Schiff staining, quantification of immunohistochemistry staining and electron microscopy, and pulmonary mechanics using forced oscillometry FlexiVent system, between Gaa−/− and age‐matched wild‐type (WT) mice. We also perfomed single cell‐RNA seq (scRNA‐seq) on the distal airways of Gaa‐/‐ mice. Lysosomal glycogen accumulation and engorged lamellar bodies were observed in the AT2 cells in Gaa−/− but not WT mice. Furthermore, AT2 positive surfactant protein‐C (SPC) staining and lysosomal positive lysosomal associated membrane protein 1 (LAMP1) staining is more evident with increased colocalization of LAMP1 with the type 2 cell marker after quantification of each marker in Gaa−/− airway cells. The Gaa−/− mice exhibited a significant decrease in total and central airway resistance (Rrs and Rn, respectively), as well as a significant increase in lung compliance (Crs) versus WT mice. Moreover, in the dimensionless and volume‐independent shape constant k that describes the curvature of the upper portion of the deflation limb of the Pressure‐Volume curves, a statistically significant change was observed in Gaa−/− mice. This indicates a change in the intrinsic elastic properties of the respiratory system in Pompe disease. Finally, a robust transcriptomic dysregulation in AT1 and AT2 cells was detected scRNA‐seq in Gaa‐/‐mice relative to WT mice. We conclude that GAA enzyme deficiency leads to glycogen accumulation in the distal airway stem cells that may contribute to respiratory impairments in Pompe disease. Our findings will inform the clinical care of patients with Pompe disease and will provide essential information for the development of novel therapies in Pompe disease that will address this airway pathology.

Memory CD4+ T-Cell Lymphocytic Angiopathy in Fatal Forms of COVID-19 Pulmonary Infection.

The immunopathological pulmonary mechanisms leading to Coronavirus Disease (COVID-19)-related death in adults remain poorly understood. Bronchoalveolar lavage (BAL) and peripheral blood sampling were performed in 74 steroid and non-steroid-treated intensive care unit (ICU) patients (23–75 years; 44 survivors). Peripheral effector SARS-CoV-2-specific T cells were detected in 34/58 cases, mainly directed against the S1 portion of the spike protein. The BAL lymphocytosis consisted of T cells, while the mean CD4/CD8 ratio was 1.80 in non-steroid- treated patients and 1.14 in steroid-treated patients. Moreover, strong BAL SARS-CoV-2 specific T-cell responses were detected in 4/4 surviving and 3/3 non-surviving patients. Serum IFN-γ and IL-6 levels were decreased in steroid-treated patients when compared to non-steroid treated patients. In the lung samples from 3 (1 non-ICU and 2 ICU) additional deceased cases, a lymphocytic memory CD4 T-cell angiopathy colocalizing with SARS-CoV-2 was also observed. Taken together, these data show that disease severity occurs despite strong antiviral CD4 T cell-specific responses migrating to the lung, which could suggest a pathogenic role for perivascular memory CD4 T cells upon fatal COVID-19 pneumonia.

Pemafibrate attenuates pulmonary fibrosis by inhibiting myofibroblast differentiation

Background and ObjectiveIdiopathic pulmonary fibrosis is a chronic progressive disease associated with substantial morbidity and mortality despite advances in medical therapy. Increasing evidence suggests that peroxisome proliferator-activated receptors (PPARs) play important roles in the fibrosis-related diseases and their agonists may become effective therapeutic targets. Pemafibrate is a selective PPARα agonist, but the efficacy against pulmonary fibrosis and mechanisms involved have not been systematically evaluated. Thus, the aims of this study were to explore the role of PPARα in the pulmonary fibrosis and to assess the effect of pemafibrate in vivo and in vitro. MethodsThe effects of pemafibrate were evaluated in bleomycin-challenged murine pulmonary fibrosis model and transforming growth factor-beta 1 (TGF-β1) stimulated lung fibroblasts. ResultsBleomycin instillation induced body weight loss, declined lung function, pulmonary fibrosis, and extensive collagen deposition in the mice, accompanied with decreased pulmonary expression of PPARα, all of which were partially improved by pemafibrate at a dose of 2 mg/kg. Besides, pemafibrate effectively inhibits TGF-β1-induced myofibroblast differentiation and extracellular matrix (ECM) production in vivo and in vitro. Furthermore, we showed that pemafibrate not only inhibited pulmonary expression of NLRP3 and cleaved caspase-1 in bleomycin-inhaled mice, but also repressed activation of NLRP3/caspase-1 axis in TGF-β1 stimulated lung fibroblasts. ConclusionOur data suggest that pemafibrate exerts a marked protection against from the development of pulmonary fibrosis, which could constitute a novel candidate for the treatment for pulmonary fibrosis.

Sleep Disorders in Adults with Prader-Willi Syndrome: Review of the Literature and Clinical Recommendations Based on the Experience of the French Reference Centre.

Prader–Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients’ caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects.

Estimation of Regional Pulmonary Compliance in Idiopathic Pulmonary Fibrosis Based on Personalized Lung Poromechanical Modeling.

Pulmonary function is tightly linked to the lung mechanical behavior, especially large deformation during breathing. Interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF), have an impact on the pulmonary mechanics and consequently alter lung function. However, IPF remains poorly understood, poorly diagnosed, and poorly treated. Currently, the mechanical impact of such diseases is assessed by pressure-volume curves, giving only global information. We developed a poromechanical model of the lung that can be personalized to a patient based on routine clinical data. The personalization pipeline uses clinical data, mainly computed tomography (CT) images at two time steps and involves the formulation of an inverse problem to estimate regional compliances. The estimation problem can be formulated both in terms of "effective", i.e., without considering the mixture porosity, or "rescaled," i.e., where the first-order effect of the porosity has been taken into account, compliances. Regional compliances are estimated for one control subject and three IPF patients, allowing to quantify the IPF-induced tissue stiffening. This personalized model could be used in the clinic as an objective and quantitative tool for IPF diagnosis.

The Impact of Mechanical Ventilation Modes on Complications of Fiberoptic Bronchoscopy in Critically Ill Patients.

OBJECTIVEThe effects of fiberoptic bronchoscopy are not elucidated in different mechanical ventilation modes. The present study aimed to evaluate the effects of fiberoptic bronchoscopy on lung mechanics, ventilation parameters, and gas exchange in 2 often-used modes, volume control and pressure control, in invasively ventilated patients followed up in the intensive care unit.MATERIAL AND METHODSEligible patients were screened and included in the study after intensive care unit-fiberoptic bronchoscopy database search. Patients who underwent fiberoptic bronchoscopy under volume control and pressure control mechanical ventilation modes were compared. The primary outcome was the occurrence of any complication within the first 24 hours after the procedure, and secondary outcomes were changes in lung mechanics (dynamic lung compliance and airway resistance) and gas exchange (arterial partial pressures of oxygen and carbon dioxide).ResultsA total of 61 patients (median age: 69 years, 60.7% male) were included. Twenty-nine (47.5%) patients were ventilated in volume control mode and 32 (52.5%) in pressure control mode during the fiberoptic bronchoscopy procedure, and the median (interquartile range) duration of the procedure was 9 [8-11] minutes. Baseline dynamic lung compliance, airway resistance, arterial partial pressures of oxygen and carbon dioxide, and the fraction of inspired O2 were similar in both groups. After fiberoptic bronchoscopy, dynamic lung compliance decreased in both groups, and airway resistance and peak airway pressures increased but reached pre-fiberoptic bronchoscopy values at the 1st hour after the procedure. No significant differences were detected in both groups in terms of blood gas values and lung mechanics in the 1st and 24th hours after the procedure. In both groups, the 24th hour fraction of inspired O2 was the same as the pre-fiberoptic bronchoscopy values, but the ratio of arterial partial pressure of oxygen and the fraction of inspired O2 improved. No complications developed in patients within 24 hours after the procedure.ConclusionNo differences were detected in terms of gas exchange and pulmonary mechanics, and complications in volume control and pressure control modes in critically ill intubated patients.

Compromised Cardiopulmonary Function in Fibulin-5 Deficient Mice.

Competent elastic fibers are critical to the function of the lung and right circulation. Murine models of elastopathies can aid in understanding the functional roles of the elastin and elastin-associated glycoproteins that constitute elastic fibers. Here, we quantify together lung and pulmonary arterial structure, function, and mechanics with right heart function in a mouse model deficient in the elastin-associated glycoprotein fibulin-5. Differences emerged as a function of genotype, sex, and arterial region. Specifically, functional studies revealed increased lung compliance in fibulin-5 deficiency consistent with a histologically observed increased alveolar disruption. Biaxial mechanical tests revealed that the primary branch pulmonary arteries exhibit decreased elastic energy storage capacity and wall stress despite only modest differences in circumferential and axial material stiffness in the fibulin-5 deficient mice. Histological quantifications confirm a lower elastic fiber content in the fibulin-5 deficient pulmonary arteries, with fragmented elastic laminae in the outer part of the wall - likely the reason for reduced energy storage. Ultrasound measurements confirm sex differences in compromised right ventricular function in the fibulin-5 deficient mice. These results reveal compromised right heart function, but opposite effects of elastic fiber dysfunction on the lung parenchyma (significantly increased compliance) and pulmonary arteries (trend toward decreased distensibility), and call for further probing of ventilation-perfusion relationships in pulmonary pathologies. Amongst many other models, fibulin-5 deficient mice can contribute to our understanding of the complex roles of elastin in pulmonary health and disease.

Abstract No.: ABS1737: Relationship of Lung Ultra-sound Score with oxygenation and pulmonary mechanics in mechanically ventilated patients in the intensive care unit

Background and Aims:Lung ultra-sonography is a technique to recognise impaired alveolar air content and increased interstitial and alveolar fluid. The ultra-sound waves reflect lung aeration beyond parietal pleura, indicating underlying lung pathology. This study ascertains the relationship of Lung Ultra-sound Score (LUSS) with oxygenation and dynamic compliance.Methods:One hundred and one lung ultra-sounds were performed in 50 patients aged 18–60 years, requiring mechanical ventilation in the intensive care unit for at least 24 hours to study the relationship between LUSS and PaO2/FiO2 and pulmonary mechanics. The twelve-region method was used; the number of B lines was counted in each inter-costal space, and the score was awarded. At the same time, ventilator parameters and arterial blood gases were noted. The correlation between variables was evaluated using the Spearman coefficient.Table 1Ventilatory charactersticsParametersNo. of scansMedian (range)SIMV/PS91ASV5PC5FiO21010.5 (0.3-1)PEEP (cm H2O)8 (5-14)PIP (cm H2O)20 (12-32)COMPLIANCE (ml/cm H2O)22 (7.4-42)RESISTANCE (cm H2O/l/sec)2.2 (1-4.5)Pplat (cm H2O)13 (6-20)Pressure support (cm H2O)12 (8-14)Table 2Compliance, resistance, and LUSS by PaO2/FiO2Ratio <200 Mean±SD median (range)Ratio ≥200 Mean±SD median (range) P No. of USG3863Compliance (ml/cm H2O) (7.4-42)18.01±5.0726.24±6.140.000Resistance (cm H2O/l/sec) (1-4.5)2.94±0.911.95±0.740.000LUSS24.5 (12-36)7 (0-11)0.000Results:LUSS showed a negative correlation with PaO2/FiO2 ratio (R2 = 0.607, p < 0.0001) and lung compliance (R2 = 0.354, p < 0.0001) but a positive linear correlation with lung resistance (R2 = 0.406, p < 0.0001).Conclusion:LUSS is an easy and effective bedside tool to measure lung parameters in mechanically ventilated patients, and LUSS correlates significantly with oxygenation, lung compliance, and resistance.

Trajectories of hypoxemia and pulmonary mechanics of COVID-19 ARDS in the NorthCARDS dataset

BackgroundUnderstanding heterogeneity seen in patients with COVIDARDS and comparing to non-COVIDARDS may inform tailored treatments.MethodsA multidisciplinary team of frontline clinicians and data scientists worked to create the Northwell COVIDARDS dataset (NorthCARDS) leveraging over 11,542 COVID-19 hospital admissions. The data was then summarized to examine descriptive differences based on clinically meaningful categories of lung compliance, and to examine trends in oxygenation.FindingsOf the 1536 COVIDARDS patients in the NorthCARDS dataset, there were 531 (34.6%) who had very low lung compliance (< 20 ml/cmH2O), 970 (63.2%) with low-normal compliance (20–50 ml/cmH2O), and 35 (2.2%) with high lung compliance (> 50 ml/cmH2O). The very low compliance group had double the median time to intubation compared to the low-normal group (107.3 h (IQR 25.8, 239.2) vs. 39.5 h (IQR 5.4, 91.6)). Overall, 68.8% (n = 1057) of the patients died during hospitalization. In comparison to non-COVIDARDS reports, there were less patients in the high compliance category (2.2% vs. 12%, compliance ≥ 50 mL/cmH20), and more patients with P/F ≤ 150 (59.8% vs. 45.6%). There is a statistically significant correlation between compliance and P/F ratio. The Oxygenation Index is the highest in the very low compliance group (12.51, SD(6.15)), and lowest in high compliance group (8.78, SD(4.93)).ConclusionsThe respiratory system compliance distribution of COVIDARDS is similar to non-COVIDARDS. In some patients, there may be a relation between time to intubation and duration of high levels of supplemental oxygen treatment on trajectory of lung compliance.

Photobiomodulation Therapy Restores IL-10 Secretion in a Murine Model of Chronic Asthma: Relevance to the Population of CD4+CD25+Foxp3+ Cells in Lung.

It is largely known that photobiomodulation (PBM) has beneficial effects on allergic pulmonary inflammation. Our previous study showed an anti-inflammatory effect of the PBM in an acute experimental model of asthma, and we see that this mechanism is partly dependent on IL-10. However, it remains unclear whether the activation of regulatory T cells is mediated by PBM in a chronic experimental model of asthma. In this sense, the objective of this study was to verify the anti-inflammatory role of the PBM in the pulmonary inflammatory response in a chronic experimental asthma model. The protocol used for asthma induction was the administration of OVA subcutaneously (days 0 and 14) and intranasally (3 times/week, for 5 weeks). On day 50, the animals were sacrificed for the evaluation of the different parameters. The PBM used was the diode, with a wavelength of 660 nm, a power of 100 mW, and 5 J for 50 s/point, in three different application points. Our results showed that PBM decreases macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid (BALF). Moreover, PBM decreased the release of cytokines by the lung, mucus, and collagen in the airways and pulmonary mechanics. When we analyzed the percentage of Treg cells in the group irradiated with laser, we verified an increase in these cells, as well as the release of IL-10 in the BALF. Therefore, we conclude that the use of PBM therapy in chronic airway inflammation attenuated the inflammatory process, as well as the pulmonary functional and structural parameters, probably due to an increase in Treg cells.

Interventional Management of Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension is a distinct form of pulmonary hypertension characterized by the nonresolution of thrombotic material in the pulmonary tree; whenever feasible and safe, first-line treatment should be pulmonary thromboendarterectomy. In patients who are not operative candidates, balloon pulmonary angioplasty (BPA) has emerged as an effective treatment modality that results in improvements in functional class, symptoms, hemodynamics, 6-minute walk distance, and right ventricular and pulmonary artery mechanics. Careful attention to procedural technique and rapid identification and treatment of complications are critical for a successful BPA program.

Revealing Cavin-2 Gene Function in Lung Based on Multi-Omics Data Analysis Method.

Research points out that it is particularly important to comprehensively evaluate immune microenvironmental indicators and gene mutation characteristics to select the best treatment plan. Therefore, exploring the relevant genes of pulmonary injury is an important basis for the improvement of survival. In recent years, with the massive production of omics data, a large number of computational methods have been applied in the field of biomedicine. Most of these computational methods are devel-oped for a certain type of diseases or whole diseases. Algorithms that specifically identify genes associated with pulmonary injury have not yet been developed. To fill this gap, we developed a novel method, named AdaRVM, to identify pulmonary injury-related genes in large scale. AdaRVM is the fusion of Adaboost and Relevance Vector Machine (RVM) to achieve fast and high-precision pattern recognition of pulmonary injury genetic mechanism. AdaRVM found that Cavin-2 gene has strong potential to be related to pulmonary injury. As we known, the formation and function of Caveolae are mediated by two family proteins: Caveolin and Cavin. Many studies have explored the role of Caveolin proteins, but people still knew little about Cavin family members. To verify our method and reveal the functions of cavin-2, we integrated six genome-wide association studies (GWAS) data related to lung function traits, four expression Quantitative Trait Loci (eQTL) data, and one methylation Quantitative Trait Loci (mQTL) data by Summary data level Mendelian Randomization (SMR). We found strong relationship between cavin-2 and canonical signaling pathways ERK1/2, AKT, and STAT3 which are all known to be related to lung injury.

Local envenomation caused by a bioactive peptide fraction of Bothrops jararaca snake venom induces leukocyte influx in the lung and changes in pulmonary mechanics

The crude venom of the Bothrops jararaca snake (Bj-CV) is a complex mixture of biologically active proteins that includes a variety of peptides in the low molecular weight fraction (Bj-PF). We investigated how an intramuscular injection of Bj-CV (1.2 mg kg−1) and Bj-PF (0.24 mg kg−1) influenced lung mechanics and lung and muscle inflammation in male Swiss mice 15 min, 1, 6, and 24 h after inoculation. Pressure dissipation against lung resistive components (ΔP1) rose significantly from 1 to 24 h after Bj-CV and 6–24 h after Bj-PF inoculation. Both Bj-CV and Bj-PF increased the total pressure variation of the lung (ΔPtot) 24 h after injection. Lung static elastance increased significantly after injection in all time periods investigated by Bj-CV and from 6 to 24 h by Bj-PF. Lung static elastance increased significantly after injection in all time periods investigated by Bj-CV and from 6 to 24 h by Bj-PF. Furthermore, intramuscular inoculation of Bj-CV and Bj-PF resulted in an increase in muscle and pulmonary inflammation, as evidenced by an increase in leukocyte influx when compared to the control group. Finally, both Bj-CV and Bj-PF cause acute lung injury, as shown by pulmonary inflammation and decreased lung mechanics. Furthermore, the fact that Bj-PF produces mechanical alterations in the lungs and muscular inflammation implies that non-enzymatic compounds can cause inflammation.

Small Airways: Not Just Air Ducts - Pathophysiological Aspects and Clinical Implications.

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.

The role of autophagy in idiopathic pulmonary fibrosis: from mechanisms to therapies.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease with an extremely poor prognosis. Autophagy is a fundamental intracellular process involved in maintaining cellular homeostasis and regulating cell survival. Autophagy deficiency has been shown to play an important role in the progression of pulmonary fibrosis. This review focused on the six steps of autophagy, as well as the interplay between autophagy and other seven pulmonary fibrosis related mechanisms, which include extracellular matrix deposition, myofibroblast differentiation, epithelial-mesenchymal transition, pulmonary epithelial cell dysfunction, apoptosis, TGF-β1 pathway, and the renin-angiotensin system. In addition, this review also summarized autophagy-related signaling pathways such as mTOR, MAPK, JAK2/STAT3 signaling, p65, and Keap1/Nrf2 signaling during the development of IPF. Furthermore, this review also illustrated the commonly used autophagy detection methods, the currently approved antifibrotic drugs pirfenidone and nintedanib, and several prospective compounds targeting autophagy for the treatment of IPF.

Tongxinluo prevents chronic obstructive pulmonary disease complicated with atherosclerosis by inhibiting ferroptosis and protecting against pulmonary microvascular barrier dysfunction.

Cardiovascular comorbidities are pervasive in chronic obstructive pulmonary disease (COPD) and often result in serious adverse cardiovascular events. Tongxinluo (TXL) has been clinically verified to treat atherosclerosis (AS), improve lung function and alleviate dyspnoea. The present study aimed to explore the effect of lung microvascular barrier dysfunction on AS in COPD and the potential pulmonary protective mechanisms of TXL in COPD complicated with AS. COPD complicated with AS was induced in mice by cigarette smoke (CS) exposure and high-fat diet (HFD) feeding. The mice were treated with atorvastatin (ATO), TXL or combination therapy (ATO+TXL) for 20 weeks. Pulmonary function, lung pathology, serum lipid levels, atherosclerotic plaque area and indicators of barrier function, oxidative stress and ferroptosis in lung tissue were evaluated. In vitro, human pulmonary microvascular endothelial cells (HPMECs) were pretreated with TXL for 4h and then incubated with cigarette smoke extract (CSE) and homocysteine (Hcy) for 36h to induce barrier dysfunction. Then the indicators of barrier function, oxidative stress and ferroptosis were measured. The results demonstrate that CS aggravated dyslipidaemia, atherosclerotic plaque formation, pulmonary function decline, pathological injury, barrier dysfunction, oxidative stress and ferroptosis in the HFD-fed mice. However, these abnormalities were partially reversed by ATO and TXL. Similar results were observed in vitro. In conclusion, pulmonary microvascular barrier dysfunction plays an important role by which COPD affects the progression of AS, and ferroptosis may be involved. Moreover, TXL delays the progression of AS and reduces cardiovascular events by protecting the pulmonary microvascular barrier and inhibiting ferroptosis.

Respiratory mechanics in late COVID-19 ARDS - arestrictive pattern is strongly associated with death. Acohort study.

COVID-19 is associated with severe respiratory distress and high mortality. We investigated the evolution of the respiratory mechanics in COVID-19 acute respiratory distress syndrome (ARDS) and the occurrence of a restrictive respiratory pattern. A retrospective, single-centre study including patients admitted to the ICU during the first wave of the pandemic (March-April 2020). A total of 141 consecutive patients were included. Many patients developed a restrictive pattern of respiratory mechanics during the course of the disease. Fifty-two patients died in the hospital (36.8%). In 29 cases (58% of the deceased) death was associated with a pattern of pulmonary mechanics, indicating a restrictive evolution of ARDS. Other diagnoses related to death were pulmonary embolism (n = 7, 14%), septic shock (n = 17, 33%), and other causes (n = 10, 20%), with some patients combining at least 2 of these diagnoses. In a multivariate analysis, age (OR = 1.06; 95% CI: 1.01-1.12; P = 0.029) and the administration of steroid pulses (OR = 2.7; 95% CI: 1.1-6.8; P = 0.03) were associated with the development of a restrictive pulmonary pattern and a higher level of plasmatic interleukin-6. COVID-19 ARDS is associated with high mortality associated with a specific pattern of respiratory mechanics and sustained activation of innate immunological response. Age and administration of high-dose steroid pulses are associated with this clinical picture.

The Effects of Different Pressure Pneumoperitoneum on the Pulmonary Mechanics and Surgical Satisfaction in the Laparoscopic Cholecystectomy

Objectives. Inspiratory, hemodynamic and metabolic changes occur in laparoscopic surgery depending on pneumoperitoneum and patient position. This study aims to evaluate the effects of intra-abdominal pressure increase based on CO2 pneumoperitoneum in laparoscopic operations on hemodynamic parameters and respiratory dynamics and satisfaction of surgeon and operative view.Materials and Methods. A total of 116 consecutive, prospective, ASA class I–III cases aged 18–70 years undergoing laparoscopic cholecystectomy were enrolled in this study. Data of 104 patients were analysed. Patients were divided into two groups as the group Low Pressure (&lt;12 mmHg) (Group LP) (n=53) and the group Standard Pressure (&gt;13 mmHg) (Group SP) (n=51). In this study administration of general anesthesia used total intravenous anaesthesia in both groups. All groups had standard and TOF monitorization applied. The anaesthesia methods used in both groups were recorded. Before, during and after peritoneal insufflation, the peroperative ventilation parameters and hemodynamic parameters were recorded. The adequacy of pneumoperitoneum, gastric and the operative view were evaluated by the operating surgeon and recorded.Results. The peripheral oxygen saturation showed no significant difference between the low and standard pressure pneumoperitoneum in view of tidal volume, respiratory rate, end tidal CO2, mean and peak inspiratory pressure, and minute ventilation values. In terms of hemodynamics, when values just after intubation and before extubation were compared, it was observed that in the LP group systolic, diastolic and mean blood pressure values were higher. In terms of heart rate, no significant difference was observed in determined periods between groups. There was no significant difference between the groups in terms of surgical satisfaction and vision.Conclusion. Low pressure pneumoperitoneum provides effective respiratory mechanics and stable hemodynamics for laparoscopic cholecystectomy. It also provides the surgeon with sufficient space for hand manipulations. Anaesthetic method, TIVA and neuromuscular blockage provided good surgery vision with low pressure pneumoperitoneum.

Pathophysiology of coronavirus-19 disease acute lung injury.

Purpose of reviewMore than 230 million people have tested positive for severe acute respiratory syndrome-coronavirus-2 infection globally by September 2021. The infection affects primarily the function of the respiratory system, where ∼20% of infected individuals develop coronavirus-19 disease (COVID-19) pneumonia. This review provides an update on the pathophysiology of the COVID-19 acute lung injury.Recent findingsIn patients with COVID-19 pneumonia admitted to the intensive care unit, the PaO2/FiO2 ratio is typically <26.7 kPa (200 mmHg), whereas lung volume appears relatively unchanged. This hypoxaemia is likely determined by a heterogeneous mismatch of pulmonary ventilation and perfusion, mainly associated with immunothrombosis, endothelialitis and neovascularisation. During the disease, lung weight, elastance and dead space can increase, affecting respiratory drive, effort and dyspnoea. In some severe cases, COVID-19 pneumonia may lead to irreversible pulmonary fibrosis.SummaryThis review summarises the fundamental pathophysiological features of COVID-19 in the context of the respiratory system. It provides an overview of the key clinical manifestations of COVID-19 pneumonia, including gas exchange impairment, altered pulmonary mechanics and implications of abnormal chemical and mechanical stimuli. It also critically discusses the clinical implications for mechanical ventilation therapy.

Murine Neonatal Oxidant Lung Injury: NRF2-Dependent Predisposition to Adulthood Respiratory Viral Infection and Protection by Maternal Antioxidant.

NRF2 protects against oxidant-associated airway disorders via cytoprotective gene induction. To examine if NRF2 is an important determinant of respiratory syncytial virus (RSV) susceptibility after neonate lung injury, Nrf2-deficient (Nrf2−/−) and wild-type (Nrf2+/+) mice neonatally exposed to hyperoxia were infected with RSV. To investigate the prenatal antioxidant effect on neonatal oxidative lung injury, time-pregnant Nrf2−/− and Nrf2+/+ mice were given an oral NRF2 agonist (sulforaphane) on embryonic days 11.5–17.5, and offspring were exposed to hyperoxia. Bronchoalveolar lavage and histopathologic analyses determined lung injury. cDNA microarray analyses were performed on placenta and neonatal lungs. RSV-induced pulmonary inflammation, injury, oxidation, and virus load were heightened in hyperoxia-exposed mice, and injury was more severe in hyperoxia-susceptible Nrf2−/− mice than in Nrf2+/+ mice. Maternal sulforaphane significantly alleviated hyperoxic lung injury in both neonate genotypes with more marked attenuation of severe neutrophilia, edema, oxidation, and alveolarization arrest in Nrf2−/− mice. Prenatal sulforaphane altered different genes with similar defensive functions (e.g., inhibition of cell/perinatal death and inflammation, potentiation of angiogenesis/organ development) in both strains, indicating compensatory transcriptome changes in Nrf2−/− mice. Conclusively, oxidative injury in underdeveloped lungs NRF2-dependently predisposed RSV susceptibility. In utero sulforaphane intervention suggested NRF2-dependent and -independent pulmonary protection mechanisms against early-life oxidant injury.