Improved Lung Mechanics Research Articles

Digital Twins of Acute Hypoxemic Respiratory Failure Patients Suggest a Mechanistic Basis for Success and Failure of Noninvasive Ventilation.

To clarify the mechanistic basis for the success or failure of noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF). We created digital twins based on mechanistic computational models of individual patients with AHRF. Interdisciplinary Collaboration in Systems Medicine Research Network. We used individual patient data from 30 moderate-to-severe AHRF patients who had failed high-flow nasal cannula (HFNC) therapy and subsequently underwent a trial of NIV. Using the digital twins, we evaluated lung mechanics, quantified the separate contributions of external support and patient respiratory effort to lung injury indices, and investigated their relative impact on NIV success or failure. In digital twins of patients who successfully completed/failed NIV, after 2 hours of the trial the mean (sd) of the change in total lung stress was -10.9 (6.2)/-0.35 (3.38) cm H2O, mechanical power -13.4 (12.2)/-1.0 (5.4) J/min, and total lung strain 0.02 (0.24)/0.16 (0.30). In the digital twins, positive end-expiratory pressure (PEEP) produced by HFNC was similar to that set during NIV. In digital twins of patients who failed NIV vs. those who succeeded, intrinsic PEEP was 3.5 (0.6) vs. 2.3 (0.8) cm H2O, inspiratory pressure support was 8.3 (5.9) vs. 22.3 (7.2) cm H2O, and tidal volume was 10.9 (1.2) vs. 9.4 (1.8) mL/kg. In digital twins, successful NIV increased respiratory system compliance +25.0 (16.4) mL/cm H2O, lowered inspiratory muscle pressure -9.7 (9.6) cm H2O, and reduced the contribution of patient spontaneous breathing to total driving pressure by 57.0%. In digital twins of AHRF patients, successful NIV improved lung mechanics, lowering respiratory effort and indices associated with lung injury. NIV failed in patients for whom only low levels of positive inspiratory pressure support could be applied without risking patient self-inflicted lung injury due to excessive tidal volumes.

MODIFIED ULTRAFILTRATION IMPROVES LUNG MECHANICS IN CONGENITAL CARDIAC SURGERY - A FACT OR FUTILE: A PROSPECTIVE, OBSERVATIONAL, SINGLE-CENTER STUDY

Objective: Cardiac surgeries involving cardiopulmonary bypass (CPB) can have adverse effects on patients, potentially increasing morbidity. In infants who possess lower blood volume and are exposed to the more artificial surface and larger prime volumes of the CPB, the harmful effects can be significant. Several studies have indicated that modified ultrafiltration (MUF) may yield beneficial effects in cardiac surgery by reducing inflammatory markers, improving hemodynamics, and decreasing excess body water. Our study seeks to evaluate the impact of MUF on pulmonary mechanics in infants undergoing cardiac surgeries on CPB. Methods: This prospective, observational, single-center study was conducted on 56 infants with congenital heart disease, who underwent cardiac surgery, followed by CPB, were included in this study. The primary outcomes were oxygen saturation (SPO2), hemoglobin (Hb), peak inspiratory pressure (Ppeak), and plateau pressure (Pplat). The secondary outcomes were systolic and diastolic invasive blood pressures (IBPs), mean arterial pressure (MAP), mean airway pressure (Pmean), static lung compliance (C-stat), dynamic lung compliance (C-dyn), expiratory resistance (Re), and work of breathing (WOB). Results: A statistically significant increase in SPO2 (98.7 vs. 99.1), Hb (8.3 vs. 13.3), IBPsystolic (85 vs. 90), IBPdiastolic (56 vs. 61.4), and MAP (66.4 vs. 73.2) was observed in congenital cardiac surgery and CPB patients after MUF (all p<0.05). A statistically significant post-procedural decline in Ppeak (18.8 vs. 18.3), Pplat (18.4 vs. 18.1), Re (79.8 vs. 78), and WOB (1.4 vs. 1.3) was also observed (all p<0.05). However, no significant pre-procedural versus post-procedural differences were observed in Pmean, C-stat, and C-dyn (all p>0.05). Conclusion: MUF effectively improved lung mechanics, oxygen saturation, myocardial contractility, hematocrit, and hemodynamics, and minimized the blood transfusion requirement after CPB in infants with congenital heart disease. Future studies should reinvestigate these outcomes with a larger sample size for an extended follow-up duration.

Antenatal Administration of Extracellular Vesicles Derived From Amniotic Fluid Stem Cells Improves Lung Function in Neonatal Rats With Congenital Diaphragmatic Hernia

BackgroundThe severity of pulmonary hypoplasia is a main determinant of outcome for babies with congenital diaphragmatic hernia (CDH). Antenatal administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs) has been shown to rescue morphological features of lung development in the rat nitrofen model of CDH. Herein, we evaluated whether AFSC-EV administration to fetal rats with CDH is associated with neonatal improvement in lung function. MethodsAFSC-EVs were isolated by ultracentrifugation and characterized by size, morphology, and canonical marker expression. At embryonic (E) day 9.5, dams were gavaged with olive oil (control) or nitrofen to induce CDH. At E18.5, fetuses received an intra-amniotic injection of either saline or AFSC-EVs. At E21.5, rats were delivered and subjected to a tracheostomy for mechanical ventilation (flexiVent system). Groups were compared for lung compliance, resistance, Newtonian resistance, tissue damping and elastance. Lungs were evaluated for branching morphogenesis and collagen quantification. ResultsCompared to healthy control, saline-treated pups with CDH had fewer airspaces, more collagen deposition, and functionally exhibited reduced compliance and increased airway resistance, elastance, and tissue damping. Conversely, AFSC-EV administration resulted in improvement of lung mechanics (compliance, resistance, tissue damping, elastance) as well as lung branching morphogenesis and collagen deposition. ConclusionsOur studies show that the rat nitrofen model reproduces lung function impairment similar to that of human babies with CDH. Antenatal administration of AFSC-EVs improves lung morphology and function in neonatal rats with CDH. Level of EvidenceN/A (animal and laboratory study).

Protective effect of β-glucan on Poly(I:C)-induced acute lung injury/inflammation: Therapeutic implications of viral infections in the respiratory system

AimsAcute lung inflammation, particularly acute respiratory distress syndrome (ARDS), is caused by a variety of pathogens including bacteria and viruses. β-Glucans have been reported to possess both anti-inflammatory and immunomodulatory properties. The current study evaluated the therapeutic effect of β-glucans on polyinosinic:polycytidylic acid (Poly(I:C)) induced lung inflammation in both hamster and mice models. Main methodsPoly(I:C)-induced ALI/inflammation models were developed in hamsters (2.5 mg/kg) and mice (2 mg/kg) by delivering the Poly(I:C) intratracheally, and followed with and without β-glucan administration. After treatment, lung mechanics were assessed and lung tissues were isolated and analyzed for mRNA/protein expression, and histopathological examinations. Key findingsPoly(I:C) administration, caused a significant elevation of inflammatory marker's expression in lung tissues and showed abnormal lung mechanics in mice and hamsters. Interestingly, treatment with β-glucan significantly (p < 0.001) reversed the Poly(I:C)-induced inflammatory events and inflammatory markers expression in both mRNA (IL-6, IL-1β, TNF-α, CCL2 and CCL7) and protein levels (TNF-α, CD68, myeloperoxidase, neutrophil elastase, MUC-5Ac and iNOS). Lung functional assays revealed that β-glucan treatment significantly improved lung mechanics. Histopathological analysis showed that β-glucan treatment significantly attenuated the Poly(I:C) induced inflammatory cell infiltration, injury and goblet cell population in lung tissues. Consistent with these findings, β-glucan treatment markedly reduced the number of neutrophils and macrophages in lung tissues. Our findings further demonstrated that β-glucan could reduce inflammation by suppressing the MAPK pathway. SignificanceThese results suggested that β-glucan may attenuate the pathogenic effects of Poly(I:C)-induced ALI/ARDS via modulating the MAPK pathway, indicating β-glucan as a possible therapeutic agent for the treatment of viral-pulmonary inflammation/injury.

Effect of individualized intraoperative lung recruitment maneuver on postoperative pulmonary complications in patients undergoing upper abdominal surgeries under general anesthesia

ABSTRACT Background The concept of lung protective ventilation (LPV) during general anesthesia (GA) aims at minimizing lung injury and postoperative pulmonary complications (POPCs). Recruitment maneuver (RM) as a part of LPV may improve lung mechanics and oxygenation, but despite extensive research, definitive guidelines for the applications of intraoperative RMs have not been established yet. Methods This study was a prospective, single-blinded, randomized clinical trial. Sixty-six subjects undergoing non-laparoscopic upper abdominal surgeries under GA were randomly assigned into two equal groups. Control group (C) received tidal volume of 8 ml/kg predicted body weight (PBW) and positive end expiratory pressure (PEEP) of 5 cmH2O without RM. Recruitment group (R) received tidal volume of 8 ml/kg PBW with stepwise RMs and individualized PEEP titration after each RM. Compliance, plateau pressure, driving pressure, SpO2 and hemodynamics were monitored at each step of RM. POPCs, length of hospital stay and mortality were recorded postoperatively. Results There was a significant reduction in POPCs in (R) group than in (C) group (P = 0.03). Also, there was a significant increase in compliance before extubation in (R) group (P = 0.001). However, no significant difference was noted between both groups as regards mortality rate and length of hospital stay. Conclusion Individualized stepwise lung RM significantly decreases the incidence of POPCs when added to LPV in patients undergoing non-laparoscopic upper abdominal surgeries under GA.

Serum from patients with asthma potentiates macrophage phagocytosis and human mesenchymal stromal cell therapy in experimental allergic asthma

Background/AimsAlthough several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma. MethodshMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed. ResultsSerum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-β, interleukin (IL)-10, tumor necrosis factor-α–stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs. ConclusionsSerum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs.

Dehydrozingerone alleviates pulmonary fibrosis via inhibition of inflammation and epithelial-mesenchymal transition by regulating the Wnt/β-catenin pathway

In idiopathic pulmonary fibrosis (IPF), excessive collagen deposition predisposes to irreversible lung function decline, respiratory failure, and ultimately death. Due to the limited therapeutic efficacy of FDA-approved medications, novel drugs are warranted for better treatment outcomes. Dehydrozingerone (DHZ) is an analogue of curcumin that has been investigated against pulmonary fibrosis using a bleomycin-induced pulmonary fibrosis model in rats. In in vitro, TGF-β-induced differentiation models (using NHLF, LL29, DHLF and A549 cells) were adopted to assess fibrotic markers expression and explored the mechanism of action. DHZ administration attenuated the bleomycin-induced elevation of lung index, inflammatory cell infiltrations, and hydroxyproline levels in lung tissues. Furthermore, treatment with DHZ mitigated the bleomycin-mediated elevation of extracellular matrix (ECM), epithelial-to-mesenchymal-transition (EMT), and collagen deposition markers and improved lung mechanics. In addition, treatment with DHZ significantly suppressed the BLM-induced apoptosis and rescued the BLM-induced pathological abnormalities in lung tissues. In vitro assays revealed that DHZ suppressed the expression of TGF-β-elevated collagen deposition, EMT and ECM markers in both mRNA/protein levels. Our findings showed that DHZ has anti-fibrotic effect against pulmonary fibrosis by modulating Wnt/β-catenin signaling, suggesting that DHZ may serve as a potential treatment option for IPF.

Effects of 2 modes of positive pressure ventilation on respiratory mechanics and gas exchange in foals.

Continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) can improve respiratory mechanics and gas exchange, but different airway pressures have not been compared in foals. Assess the effect of different airway pressures during CPAP and PSV have on respiratory function in healthy foals with pharmacologically induced respiratory insufficiency. We hypothesized that increased airway pressures would improve respiratory mechanics and increased positive end-expiratory pressure (PEEP) would be associated with hypercapnia. Six healthy foals from a university teaching herd. A prospective, 2-phase, 2-treatment, randomized cross-over study design was used to evaluate sequential interventions in sedated foals using 2 protocols (CPAP and PSV). Outcome measures included arterial blood gases, spirometry, volumetric capnography, lung volume and aeration assessed using computed tomography (CT). Sedation and dorsal recumbency were associated with significant reductions in arterial oxygen pressure (PaO2 ), respiratory rate, and tidal volume. Continuous positive airway pressure was associated with improved PaO2 , without concurrent hypercapnia. Volumetric capnography identified improved ventilation:perfusion (V/Q) matching and increased carbon dioxide elimination during ventilation, and spirometry identified decreased respiratory rate and increased tidal volume. Peak inspiratory pressure was moderately associated with PaO2 and lung volume. Improved pulmonary aeration was evident in CT images, and lung volume was increased, particularly during CPAP. Both CPAP and PSV improved lung mechanics and gas exchange in healthy foals with induced respiratory insufficiency.

Optimizing One-Lung Ventilation in Thoracic Surgery—Does Mode of Ventilation Matter?

Postoperative Hypoxemia After Dual-Controlled vs Volume-Controlled Ventilation in Lung SurgeryThe Annals of Thoracic SurgeryPreviewOne-lung ventilation for thoracic surgery represents a challenge due to the risk for hypoxemia and barotrauma. Dual-controlled ventilation (ie, pressure-regulated volume control [PRVC]) may confer improved lung mechanics compared with conventional ventilation (volume-controlled ventilation [VCV]). Our objective was to determine the association between ventilatory mode and pulmonary outcomes after lung resection surgery. Full-Text PDF

Effect of Bronchoscopy on the Outcome of Patients with Severe Sepsis, Acute Respiratory Distress Syndrome and Complicated by Ventilator Associated Pneumonia from Prolonged Ventilation

Introduction: 65% of patients in Intensive Care Units (ICU) with severe sepsis and/or severe traumatic lung contusion are complicated with pneumonia and respiratory failure, which need long-term ventilation. Sepsis is a common finding in such patients; it is either a cause of ventilator associated pneumonia (VAP) or a complication of VAP. VAP is one of the most common complications of prolonged ventilation. Both diagnostic and therapeutic bronchoscopies could be used to improve the outcome in those patients by controlling septic reactions and improve lung mechanics through the clearing of the small airways from purulent discharge. Aims of Work: To evaluate the effect of the use of bronchoscopy in patients with Acute respiratory distress syndrome (ARDS), severe sepsis and complicated by VAP as regards, improve the general condition of those patients, improve lung mechanics, control all signs of both VAP and sepsis, accelerate weaning from the ventilator, shorten the duration of ICU stays and its effect on mortality rate in those patients. Materials and Methods: 200 patients were selected after 4 days of ventilation because of ARDS due to either severe traumatic lung contusion or a severe lung infection. Those who still showed unresolved ARDS (diagnosed by hypoxic index less than 200, bilateral parenchymatous lung infiltration on the chest X ray, ABG showed PH &gt; 7.30), Severe sepsis diagnosed by &gt;12 SOFA score (Sequential Organ Failure Assessment) and developed VAP diagnosed by &gt;6 CPIS score (clinical pulmonary infection score) were included in two groups of 100 patients in each. Only patients of group B did three bronchoscopies and BAL was sent for culture, while patients of group A continued on the traditional way of management and sputum was sent for culture. Improvement of ARDS &amp; VAP, weaning from ventilation, duration of ICU stay, improvement of one/all parameters of both SOFA &amp; CPIS scores, morbidity, and mortality were recorded and compared within 14 days. Results: Patients of group B showed significant improvement in APACHII score (acute physiological assessment and chronic health evaluation score), GCS (Glasgow coma scale), parameters of both SOFA score and CPIS score, hemodynamics parameters, LDH (lactate dehydrogenase), and C-Reactive protein levels. A significantly higher number of patients were weaned from the ventilator and discharged from ICU. There was no significant difference between the two groups regarding the mortality rate. Conclusion: The use of bronchoscopy can improve general conditions, control all signs of severe sepsis, VAP, improve lung mechanics, improve ARDS, accelerate weaning from the ventilator, and shorten the ICU stay but has no effect on mortality rate in those patients with severe sepsis with ARDS and complicated by VAP from prolonged ventilation. Clinical Trial Registration Number: My study is already registered in the clinical trial, and all the information is present in this study. The clinical trial number is NCT04553367, and is registered by my name.

Safety and efficacy of clinical-grade, cryopreserved menstrual blood mesenchymal stromal cells in experimental acute respiratory distress syndrome.

Background: Treatment for critical care conditions, such as acute respiratory distress syndrome (ARDS), requires ready-to-administer injectable mesenchymal stromal cells (MSCs). A validated cryopreserved therapy based on MSCs derived from menstrual blood (MenSCs) is an attractive option that offers advantages over freshly cultured cells and allows its use as an off-the-shelf therapy in acute clinical conditions. The main goal of this study is to provide evidence on the impact of cryopreservation on different biological functions of MenSCs and to determine the optimal therapeutic dose, safety, and efficacy profile of clinical-grade, cryopreserved (cryo)-MenSCs in experimental ARDS. Methods: Biological functions of fresh versus cryo-MenSCs were compared in vitro. The effects of cryo-MenSCs therapy were evaluated in vivo in ARDS-induced (Escherichia coli lipopolysaccharide) C57BL/6 mice. After 24 h, the animals were treated with five doses ranging from 0.25×105 to 1.25×106 cells/animal. At 2 and 7 days after induction of ARDS, safety and efficacy were evaluated. Results: Clinical-grade cryo-MenSCs injections improved lung mechanics and reduced alveolar collapse, tissue cellularity, and remodelling, decreasing elastic and collagen fiber content in alveolar septa. In addition, administration of these cells modulated inflammatory mediators and promoted pro-angiogenic and anti-apoptotic effects in lung-injured animals. More beneficial effects were observed with an optimal dose of 4×106 cells/Kg than with higher or lower doses. Conclusion: From a translational perspective, the results showed that clinical-grade cryopreserved MenSCs retain their biological properties and exert a therapeutic effect in mild to moderate experimental ARDS. The optimal therapeutic dose was well-tolerated, safe, and effective, favouring improved lung function. These findings support the potential value of an off-the-shelf MenSCs-based product as a promising therapeutic strategy for treating ARDS.

Efficacy of perinatal pharmacotherapeutic actions for survival of very preterm newborn rabbits at 26-day gestation.

Investigation of the pathophysiology of lung impairment and protection in very preterm neonates at birth requires adequate experimental models. This study aimed to elucidate the efficacy and mechanism of perinatal pharmacotherapeutic action in postnatal survival of very preterm rabbits. Pregnant New Zealand White rabbits on 25-day gestation (term 31 days) were given dexamethasone (D), or sham injection as control (C), and cesarean delivered 24 hours later on day 26. Newborns were anesthetized, intratracheally intubated, randomly received either saline or porcine surfactant (S), allocated to four groups (C, S, D, and DS), and ventilated with low tidal volume. Under the identical protocol, another four groups were added with nitric oxide (N) inhalation (CN, SN, DN, and DSN). Survival length, lung mechanics, histopathology, and pathobiology of lung tissue were measured for benefits and injury patterns. DSN had the longest median survival time (ST50, 10.3 h), whereas C had the shortest (3.5 h), with remaining groups in-between. The survival was mainly benefited by S, when additive effects with D and/or N were discernible, by improved lung mechanics and alveolar aeration, ameliorated lung injury severity and pneumothorax, and augmented lung phospholipid pools, with DSN being the most optimal. Variable mRNA expression profiles of alveolar epithelia-associated cytokines and inflammatory mediators further characterized injury and response patterns as phenotyping conditioned in pharmacotherapeutic actions. In conclusion, the combined regimens of perinatal medications achieved remarkable survival in very preterm rabbits with lung protective ventilation strategy, offering a unique model in investigation of very preterm birth-associated respiratory physiology and morbidities.NEW & NOTEWORTHY By establishing a very preterm rabbit model with 26-day gestation (term 31 days), optimal survival length for 50% of animals in groups was achieved by comparing regimens of combined antenatal glucocorticoids, postnatal surfactant and inhaled nitric oxide, with a low tidal volume ventilation strategy. The efficacies of pharmacotherapeutic action were associated with significantly improved lung mechanics, ameliorated lung injury and pneumothorax, and enhanced surfactant phospholipid metabolism, along with variable mRNA expression profiles characterizing the response patterns.

Postoperative Hypoxemia After Dual-Controlled vs Volume-Controlled Ventilation in Lung Surgery

BackgroundOne-lung ventilation for thoracic surgery represents a challenge due to the risk for hypoxemia and barotrauma. Dual-controlled ventilation (ie, pressure-regulated volume control [PRVC]) may confer improved lung mechanics compared with conventional ventilation (volume-controlled ventilation [VCV]). Our objective was to determine the association between ventilatory mode and pulmonary outcomes after lung resection surgery. MethodsA historical cohort (2016-2021) of patients undergoing lung resection surgery was used to identify cases performed with PRVC ventilation (intervention) vs VCV (conventional). Both groups were matched in a 1:1 fashion using propensity scoring based on preoperative oxygen saturation, chronic obstructive pulmonary disease, intraoperative ventilator settings, and surgical approach. Our primary outcome was postoperative hypoxemia (oxygen saturation <92% requiring supplemental oxygen longer than 2 hours). Secondary outcomes included respiratory failure, pneumonia, atelectasis, acute respiratory distress syndrome, pleural effusion, and reintubation. Associations were reported using adjusted odds ratios (aOR). ResultsOf 2107 eligible patients (PRVC = 1587 vs VCV = 520), a total of 774 matched pairs were analyzed (PRVC = 387 vs VCV = 387). The overall incidence of postoperative hypoxemia was 35.5% (95% CI 32.2%-39.0%). Hypoxemia was less likely among patients managed with low tidal volumes (≤6 mL/kg per ideal body weight, aOR 0.73, 95% CI 0.57-0.92, P = .008). No significant association was observed between ventilator mode and postoperative hypoxemia (33.3% in PRVC vs 37.7% in VCV; aOR 0.93, 95% CI 0.71-1.23, P = .627) or secondary pulmonary complications (3.9% in PRVC vs 3.4% in VCV; aOR 0.96, 95% CI 0.47-1.97, P = .909). ConclusionsDual-controlled ventilation was not associated with improved pulmonary outcomes compared with conventional ventilation in lung resection surgery.

Efficacy of proning in acute respiratory distress syndrome on extracorporeal membrane oxygenation.

ObjectivesProning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO).MethodsA single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO.ResultsIn total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged.ConclusionsProning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

Comparison of the efficacy of two alveolar recruitment manoeuvres in improving the lung mechanics and the degree of atelectasis in anaesthetized healthy sheep

The aim of the present study was to evaluate whether the application of two types of alveolar recruitment manoeuvres (ARMs) followed by a positive end-expiratory pressure (PEEP) improved lung mechanics and the degree of atelectasis caused by general anaesthesia. Twenty-one female Merino sheep were divided into three groups: sustained inflation ARM (ARMsust), stepwise ARM (AMRstep), and control (without ARM). Sheep received detomidine-morphine for premedication, propofol for induction, and isoflurane during general anaesthesia in a volume-controlled mode with 100% oxygen during the first 15 min of anaesthesia and 40% the rest of the study. The right jugular vein and metacarpal artery were catheterised for mixed venous and arterial blood sample collection, respectively. The quasistatic compliance (Cqst), oxygenation parameters, and shunt fraction (Qs/Qt) were monitored before ARM application (TpreARM), and at 10 (T10) and 60 min (T60) after ARM application. A pulmonary histopathological study was conducted on five animals from each group. A significant increase in Cqst was observed in both ARM groups at T10 compared to TpreARM (ARMsust: P = 0.001; ARMstep: P = 0.002), although only the ARMsust group showed significant differences compared to the control group. The ARMstep group presented a significant improvement in oxygenation parameters and Qs/Qt fraction (T10: 4.84 (3.26–16.48)%, P = 0.048; T60: 4.40 (4.31–14.16)%, P = 0.004) compared with TpreARM (21.48 (20.61–28.32)%). The ARMstep group had the highest percentage of alveolar area and the most homogeneous values. In conclusion, the application of a stepwise ARM followed by PEEP improved atelectasis caused by isoflurane anaesthesia in healthy sheep.

Radiofrequency therapy improves exercise capacity of mice with emphysema

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in “volume reduction” and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.

Awake Prone Positioning in Sars-CoV-2 (Covid-19) Non-Intubated Patients with Acute Respiratory Failure in Adult Population: A Literature Review.

Objective: This article aims to review the current evidence in Covid-19 patients with acute respiratory failure who required awake prone positioning as a therapeutic intervention.&#x0D; I searched the literature on MEDLINE, PubMed, Cochrane Library, Google Scholar, and other databases. I found several studies that analyzed and shared the data regarding awake prone positioning in the Covid-19 patients, with duration ranging from 12-16 hours.&#x0D; I found that the major criteria used included PaO2/FiO2 ratio, SpO2/FiO2, respiratory rate, heart rate. I also searched the suggested indications, contra-indications, complications, and outcomes of those patients.&#x0D; Awake proning showed improvement in lung mechanics and oxygenation, but no benefit in outcome in the majority of studies. &#x0D; Currently, the data is unclear to determine the overall benefit. Further controlled trials are needed.

Effects of intranasal azithromycin on features of cigarette smoke-induced lung inflammation

Airflow limitation in chronic obstructive pulmonary disease (COPD) is the result of exaggerated airway fibrosis and obliteration of the small airways due to persistent inflammation, and an impaired anti-oxidant response. EMT has been implicated as an active signalling process in cigarette smoke (CS)-induced lung pathology, and macrolide Azithromycin (AZT) use has gained interest in treating COPD. Here, we tested effectiveness of intra-nasal AZT alone and in combination with dexamethasone (DEX) on CS-induced acute lung inflammation. Human alveolar epithelial cells (A549) were treated with CS extract (CSE) for 48 h, and male Balb/c mice were exposed to CS (3 cigarettes-3 times/day) for 4 days. The effects of AZT alone (0.25 and 1.25 μM, in vitro; 0.5 and 5 mg/kg, in vivo) or in combination with DEX (1 μM, in vitro; 1 mg/kg, in vivo) on CS-induced cellular cytotoxicity, oxidative stress, inflammation, and lung function were assessed. AZT alone and in combination with DEX significantly inhibited the CS (E)-induced expression of mesenchymal protein markers and the regulatory protein β-catenin. Furthermore, AZT by itself or in combination with DEX significantly suppressed CS-induced expression of the proinflammtory cytokines TNFα, IL1β and IL6 and prevented pNFkB. Mechanistically, AZT restored the CS-induced reduction in anti-oxidant transcription factor NRF2 and upregulated HDAC2 levels, thereby repressing inflammatory gene expression. Beneficial effects of AZT functionally translated in improved lung mechanics in vivo. Further preclinical and clinical studies are warranted to fully establish and validate the therapeutic efficacy of AZT as a mono- or combination therapy for the treatment of COPD.

Comparison of survival of preterm newborn rabbits at 25-28 days of gestation with perinatal therapies at birth transition.

Eligibility of ventilated preterm rabbit model to investigate extreme pulmonary immaturity at birth transition is unknown. By extending this model to early saccular stage of fetal lung development, we evaluated efficacy in survival, lung maturation, and underlying mechanisms of contemporary perinatal therapies. Pregnant New Zealand White rabbit does were given dexamethasone (DEX), or sham injection as control (NDEX), 48 and 24 h before delivery at gestational age (GA) of 25-28 days. At birth, newborn rabbits were anesthetized and randomly allocated to four groups receiving either surfactant or nonsurfactant for both DEX and NDEX, and mechanically ventilated within low tidal volumes. Ranges of time to maintain survival rate ≥ 50% in GA 25-28 days were 59-136, 138-259, 173-288, and 437 to ≥600 min, respectively, each across the four groups. The benefits of DEX and/or surfactant for survival were more obvious in GA 25-26 days, as judged by improved lung mechanics, lower lung injury scores, higher lung surfactant phospholipid pools, and surfactant protein mRNA expression, with DEX-surfactant combination being the most optimal for the outcome. In contrast, those of GA 27-28 days had variable but meaningful responses to the treatment. Cox regression analysis revealed GA, DEX, and surfactant being independently protective factors whereas pneumothorax was a risk factor. The extremely preterm rabbits at GA 25-26 days markedly responded to the perinatal therapies for longer survival, lung maturation and injury alleviation, and were relevant for study of preterm birth transition-associated morbidities and underlying mechanisms.NEW & NOTEWORTHY An extremely preterm rabbit model with gestational age of 25-26 (term 31) days was established by mechanical ventilation with individually adjusted tidal volume at lower ranges. The administration of antenatal glucocorticoids and/or postnatal surfactant achieved significantly longer duration to maintain 50% survival and facilitated lung maturation and protection at early saccular stage. The usefulness of this model should be validated in future investigation of perinatal and neonatal morbidity and mortality at extremely preterm birth transition.

Mitochondria-Rich Fraction Isolated From Mesenchymal Stromal Cells Reduces Lung and Distal Organ Injury in Experimental Sepsis.

To ascertain whether systemic administration of mitochondria-rich fraction isolated from mesenchymal stromal cells would reduce lung, kidney, and liver injury in experimental sepsis. Animal study. Laboratory investigation. Sixty C57BL/6 male mice. Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. At 24 hours after surgery, cecal ligation and puncture and Sham animals were further randomized to receive saline or mitochondria-rich fraction isolated from mesenchymal stromal cells (3 × 106) IV. At 48 hours, survival, peritoneal bacterial load, lung, kidney, and liver injury were analyzed. Furthermore, the effects of mitochondria on oxygen consumption rate and reactive oxygen species production of lung epithelial and endothelial cells were evaluated in vitro. In vitro exposure of lung epithelial and endothelial cells from cecal ligation and puncture animals to mitochondria-rich fraction isolated from mesenchymal stromal cells restored oxygen consumption rate and reduced total reactive oxygen species production. Infusion of exogenous mitochondria-rich fraction from mesenchymal stromal cells (mitotherapy) reduced peritoneal bacterial load, improved lung mechanics and histology, and decreased the expression of interleukin-1β, keratinocyte chemoattractant, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in lung tissue, while increasing keratinocyte growth factor expression and survival rate in cecal ligation and puncture-induced sepsis. Mitotherapy also reduced kidney and liver injury, plasma creatinine levels, and messenger RNA expressions of interleukin-18 in kidney, interleukin-6, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in liver, while increasing nuclear factor erythroid 2-related factor-2 and superoxide dismutase-2 in kidney and interleukin-10 in liver. Mitotherapy decreased lung, liver, and kidney injury and increased survival rate in cecal ligation and puncture-induced sepsis.