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Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though the presence of neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain. The goal of this study was to elucidate the role of neutrophils in a clinically relevant model of bacterial pneumonia. We investigated the effect of reducing neutrophils in a mouse model of pneumococcal pneumonia treated with antibiotics. Neutrophils were reduced with anti-lymphocyte antigen 6 complex locus G6D (Ly6G) monoclonal antibody 24 h before and immediately preceding infection. Mice were inoculated intranasally with Streptococcus pneumoniae and received ceftriaxone 12 h after bacterial inoculation. Neutrophil reduction in mice treated with ceftriaxone attenuated hypoxemia, alveolar permeability, epithelial injury, pulmonary edema, and inflammatory biomarker release induced by bacterial pneumonia, even though bacterial loads in the distal air spaces of the lung were modestly increased as compared with antibiotic treatment alone. Thus, when appropriate antibiotics are administered, lung injury in the early phase of bacterial pneumonia is mediated in part by neutrophils. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense. NEW & NOTEWORTHY: Neutrophil accumulation is a key feature of ARDS, but their contribution to the pathogenesis is still uncertain. We investigated the effect of reducing neutrophils in a clinically relevant mouse model of pneumococcal pneumonia treated with antibiotics. When appropriate antibiotics were administered, neutrophil reduction with Ly6G antibody markedly attenuated lung injury and improved oxygenation. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense. [ABSTRACT FROM AUTHOR]

Dysregulated neutrophil infiltration and activity in lung tissues are pathogenic features of sepsis-induced acute respiratory distress syndrome (ARDS), an important cause of morbidity and mortality in critically ill patients. Therapeutic reduction of excessive neutrophil transmigration from the vasculature into the distal airspaces to mitigate lung tissue damage and improve survival is an important objective. Human peripheral blood polymorphonuclear neutrophils (PMNs) can be separated into two subsets as recently described: one that readily endocytoses albumin nanoparticles (ANPs) referred to as ANPhigh PMN and another that fails to endocytose ANPs referred to as ANPlow PMN. Here, we tested the hypothesis that targeting ANPhigh human PMNs with ANPs loaded with the drug piceatannol (PANPs), a selective spleen tyrosine kinase (Syk) inhibitor that inhibits β2-integrin signaling, would mitigate lipopolysaccharide (LPS)-induced accumulation of PMNs in human lungs and reduce lung edema. In the present study, human lungs were perfused ex vivo with fresh whole blood containing human PMNs and 6 mg of LPS to induce injury accompanied by PMN infiltration into the lungs. Following the LPS exposure, intravenous injection of PANPs reduced transmigration and accumulation of PMNs in the lungs as determined by bronchoalveolar lavage counts and histologic scoring. A parallel reduction in lung weight gain, a surrogate for pulmonary edema fluid accumulation, suggested protection from edema in this human lung injury model. The results demonstrate the potential of therapeutic drug loading of albumin nanoparticles (PANPs) for targeting an injurious, inflammation-inducing population of PMNs in ARDS patients. [ABSTRACT FROM AUTHOR]

The article reports that prone position reduces mortality in severe acute respiratory distress syndrome (ARDS). Topics include considered that the benefit of prone position is well established during passive mechanical ventilation and the effects of prone position on the determinants of lung injury under spontaneous breathing have not been evaluated yet in ARDS.

Background: Pulmonary embolism (PE) resulting from venous thromboembolism is a leading cause of maternal mortality in pregnancy. In patients with massive PE and hemodynamic instability, the treatment options often considered are thrombolytics, inferior vena caval filters, or embolectomy. We report here the case of a patient with massive PE at 28 weeks' gestation, who underwent emergency pulmonary embolectomy via cardiopulmonary bypass. Case presentation: A 35-year old primigravida with a history of massive PE at 25 weeks of gestation was referred to our hospital at 28 weeks of gestation, following treatment failure after insertion of an inferior vena cava filter and heparin administration. Emergency thrombectomy was performed, and intracardiac echography was used for intraoperative fetal heart rate monitoring. However, the patient developed hemodynamic collapse following anesthesia induction; hence, emergency cardiopulmonary bypass (CPB) was performed via median sternotomy. Thrombectomy and tricuspid valve plication were performed under cardiac arrest. After confirming postoperative hemostasis, heparin administration was resumed. At 40 weeks of gestation, labor was induced under epidural analgesia. Both mother and child were discharged with no complications. Conclusion: In conclusion, intracardiac echography is useful for fetal heart rate monitoring during emergency cardiac surgery in pregnancy. Careful CPB management is important to maintain uteroplacental blood flow. Although there is no consensus on the delivery methods in such cases, epidural analgesia during labor was useful in reducing cardiac load and wound traction. [ABSTRACT FROM AUTHOR]

Background: Vocal cord paralysis (VCP) is a rare complication of thoracic cardiovascular surgery. In severe cases, life-threatening airway obstruction may occur.Objective: To evaluate the incidence and severity of VCP among patients who underwent thoracic cardiovascular surgery and to identify possible risk factors.Design: Single-centre retrospective review of adult patients.Setting: Osaka University Hospital, Suita, Japan, from January 2013 to August 2015.Patients: We included 688 patients in the final analysis. Preoperative, intraoperative and postoperative data were collected from medical records. Patients with preoperative VCP or tracheostomy prior to extubation were excluded. The VCP severity in relation to functional recovery was graded using the following categories: absent; mild, remission at 6 months; moderate, partial or persistent VCP at 6 months; or severe, airway obstruction after extubation requiring reintubation. An otolaryngologist diagnosed all VCP cases.Main Outcome Measures: The incidence and severity of VCP after extubation.Results: The incidence (number) of VCP was 4.7% (32), with those of mild, moderate and severe VCP being 1.7% (12), 1.5% (10) and 1.5% (10), respectively. The ICU stay was significantly longer in patients with severe VCP than in patients without VCP [12.5 days (interquartile range 5.5 to 25.5) vs. 3 days (interquartile range 2 to 5), P = 0.0002]. In our multivariable analysis, type 2 diabetes mellitus [odds ratio (OR) 1.853, P = 0.009], intubation period (OR per 24 h 1.136, P = 0.014), ascending aortic arch surgery with brachiocephalic artery reconstruction (OR 8.708, P < 0.001) and ventricular assist device implantation (OR 3.460, P = 0.005) were independent predictors for VCP.Conclusion: The identification of these risk factors may facilitate screening for VCP before extubation and possibly help anaesthesia personnel to be prepared to treat VCP-related airway obstruction should it occur. [ABSTRACT FROM AUTHOR]

Due to the coronavirus disease 2019 pandemic, the number of coronavirus disease 2019-associated acute respiratory distress syndrome is rapidly increasing. The heterogeneity of coronavirus disease 2019-associated acute respiratory distress syndrome contributes to the complexity of managing patients. Here we described two patients with coronavirus disease 2019-associated acute respiratory distress syndrome showing that the bedside physiological approach including careful evaluation of respiratory system mechanics and visualization of ventilation with electrical impedance tomography was useful to individualize ventilatory management. [ABSTRACT FROM AUTHOR]

With each breath, oxygen diffuses across remarkably thin alveolar type I (AT1) cells into underlying capillaries. Interspersed cuboidal AT2 cells produce surfactant and act as stem cells. Even transient disruption of this delicate barrier can promote capillary leak. Here, we selectively ablated AT1 cells, which uncovered rapid AT2 cell flattening with near-continuous barrier preservation, culminating in AT1 differentiation. Proliferation subsequently restored depleted AT2 cells in two phases, mitosis of binucleated AT2 cells followed by replication of mononucleated AT2 cells. M phase entry of binucleated and S phase entry of mononucleated cells were both triggered by AT1-produced hbEGF signaling via EGFR to Wnt-active AT2 cells. Repeated AT1 cell killing elicited exuberant AT2 proliferation, generating aberrant daughter cells that ceased surfactant function yet failed to achieve AT1 differentiation. This hyperplasia eventually resolved, yielding normal-appearing alveoli. Overall, this specialized regenerative program confers a delicate simple epithelium with functional resiliency on par with the physical durability of thicker, pseudostratified, or stratified epithelia. [ABSTRACT FROM AUTHOR]

Monocyte-derived macrophages recruited to injured tissues induce a maladaptive fibrotic response characterized by excessive production of collagen by local fibroblasts. Macrophages initiate this programming via paracrine factors, but it is unknown whether reciprocal responses from fibroblasts enhance profibrotic polarization of macrophages. We identify macrophage-fibroblast crosstalk necessary for injury-associated fibrosis, in which macrophages induced interleukin 6 ( IL-6 ) expression in fibroblasts via purinergic receptor P2rx4 signaling, and IL-6, in turn, induced arginase 1 ( Arg1 ) expression in macrophages. Arg1 contributed to fibrotic responses by metabolizing arginine to ornithine, which fibroblasts used as a substrate to synthesize proline, a uniquely abundant constituent of collagen. Imaging of idiopathic pulmonary fibrosis (IPF) lung samples confirmed expression of ARG1 in myeloid cells, and arginase inhibition suppressed collagen expression in cultured precision-cut IPF lung slices. Taken together, we define a circuit between macrophages and fibroblasts that facilitates cross-feeding metabolism necessary for injury-associated fibrosis.

Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae ., Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy., Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden., Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae ., Competing Interests: -Competing interests The authors declare that they have no competing interests.

Impaired alveolar fluid clearance (AFC) is an important cause of alveolar edema fluid accumulation in patients with acute respiratory distress syndrome (ARDS). Alveolar edema leads to insufficient gas exchange and worse clinical outcomes. Thus, it is important to understand the pathophysiology of impaired AFC in order to develop new therapies for ARDS. Over the last few decades, multiple experimental studies have been done to understand the molecular, cellular, and physiological mechanisms that regulate AFC in the normal and the injured lung. This review provides a review of AFC in the normal lung, focuses on the mechanisms of impaired AFC, and then outlines the regulation of AFC. Finally, we summarize ongoing challenges and possible future research that may offer promising therapies for ARDS., (© 2023 American Association for Anatomy.)

Background: Vocal cord paralysis (VCP) is a rare complication of thoracic cardiovascular surgery. In severe cases, life-threatening airway obstruction may occur., Objective: To evaluate the incidence and severity of VCP among patients who underwent thoracic cardiovascular surgery and to identify possible risk factors., Design: Single-centre retrospective review of adult patients., Setting: Osaka University Hospital, Suita, Japan, from January 2013 to August 2015., Patients: We included 688 patients in the final analysis. Preoperative, intraoperative and postoperative data were collected from medical records. Patients with preoperative VCP or tracheostomy prior to extubation were excluded. The VCP severity in relation to functional recovery was graded using the following categories: absent; mild, remission at 6 months; moderate, partial or persistent VCP at 6 months; or severe, airway obstruction after extubation requiring reintubation. An otolaryngologist diagnosed all VCP cases., Main Outcome Measures: The incidence and severity of VCP after extubation., Results: The incidence (number) of VCP was 4.7% (32), with those of mild, moderate and severe VCP being 1.7% (12), 1.5% (10) and 1.5% (10), respectively. The ICU stay was significantly longer in patients with severe VCP than in patients without VCP [12.5 days (interquartile range 5.5 to 25.5) vs. 3 days (interquartile range 2 to 5), P = 0.0002]. In our multivariable analysis, type 2 diabetes mellitus [odds ratio (OR) 1.853, P = 0.009], intubation period (OR per 24 h 1.136, P = 0.014), ascending aortic arch surgery with brachiocephalic artery reconstruction (OR 8.708, P < 0.001) and ventricular assist device implantation (OR 3.460, P = 0.005) were independent predictors for VCP., Conclusion: The identification of these risk factors may facilitate screening for VCP before extubation and possibly help anaesthesia personnel to be prepared to treat VCP-related airway obstruction should it occur.