Alveolar Damage Research Articles

Role of biomarkers and molecular signaling pathways in acute lung injury.

Acute lung injury (ALI) is caused by bacterial, fungal, and viral infections. When pathogens invade the lungs, the immune system responds by producing cytokines, chemokines, and interferons to promote the infiltration of phagocytic cells, which are essential for pathogen clearance. Their excess production causes an overactive immune response and a pathological hyper-inflammatory state, which leads to ALI. Until now, there is no particular pharmaceutical treatment available for ALI despite known inflammatory mediators like neutrophil extracellular traps (NETs) and reactive oxygen species (ROS). Therefore, the primary objective of this review is to provide the clear overview on the mechanisms controlling NETs, ROS formation, and other relevant processes during the pathogenesis of ALI. In addition, we have discussed the significance of epithelial and endothelial damage indicators and several molecular signaling pathways associated with ALI. The literature review was done from Web of Science, Scopus, PubMed, and Google Scholar for ALI, NETs, ROS, inflammation, biomarkers, Toll- and nucleotide-binding oligomerization domain (NOD)-like receptors, alveolar damage, pro-inflammatory cytokines, and epithelial/endothelial damage alone or in combination. This review summarized the main clinical signs of ALI, including the regulation and distinct function of epithelial and endothelial biomarkers, NETs, ROS, and pattern recognition receptors (PRRs). However, no particular drugs including vaccine for ALI has been established. Furthermore, there is a lack of validated diagnostic tools and a poor predictive rationality of current therapeutic biomarkers. Hence, extensive and precise research is required to speed up the process of drug testing and development by the application of artificial intelligence technologies, structure-based drug design, in-silico approaches, and drug repurposing.

Postmortem chest computed tomography in COVID-19: A minimally invasive autopsy method

ObjectivesPerforming autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology. MethodsTwenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis. ResultsThere was a positive correlation between patient mean CT and histopathological severity score indexes - Pearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground-glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between ground-glass opacities extension and exudative diffuse alveolar damage in histological slides (R=−0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =−0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p ≥ 0.10). ConclusionsA minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground-glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.

Phenolic-rich fraction of green tea attenuates histamine-mediated cardiopulmonary toxicity by inhibiting Cox-2/NF-κB signaling pathway and regulating oxidant/antioxidant balance

BackgroundHistamine (HIS) has a substantial impact on the development of numerous allergic disorders including asthma. Antihistamines mostly target histamine receptor-1 alone, so it is not entirely effective in the treatment of allergic diseases. In the current investigation, we examine the growing evidence for novel therapeutic strategies that aim to treat histamine-mediated cardiopulmonary toxicity with the phenolic-rich fraction of green tea (PRFGT).ResultsOur findings demonstrated that weekly ingestion of HIS to rats induced oxidant/antioxidant imbalance in both lung and heart homogenates. The histopathological examination demonstrated extensive interstitial pneumonia with progressive alveolar and bronchial damage in HIS receiving groups. Heart sections showed severe myocardial necrosis and hemorrhage. All lesions were confirmed by the immunohistochemical staining that demonstrated strong caspase-3, cyclooxygenase-2 (Cox-2), and tumor necrosis factor-α (TNF-α) protein expressions along with upregulation of the pulmonary m-RNA expression of TNF-α, nuclear factor kappa-B (NF-κB), and interleukin-1β (IL-1β) genes and cardiac levels of many apoptotic genes. Otherwise, the pretreatment of rats with PRFGT had the ability to alleviate all the aforementioned toxicological parameters and return the microscopic picture of both lung and heart sections to normal histology.ConclusionsWe concluded that PRFGT’s powerful antioxidant, anti-inflammatory, and anti-apoptotic properties can reduce cardiopulmonary toxicity caused by HIS. We recommended daily intake of green tea as a beverage or adding it to foods containing elevated levels of HIS to prevent its possible toxicity.

Immune checkpoint inhibitors in patients with lung cancer having chronic interstitial pneumonia.

In interstitial pneumonia (IP)-associated lung cancer, immune checkpoint inhibitor pneumonitis (ICIP) is common with immune checkpoint inhibitor (ICI) treatment. The purpose of the present study was to clarify the safety and efficacy of ICI treatment for patients with lung cancer with IP. This multicentre retrospective observational study was conducted from June 2016 to December 2020 in patients with primary lung cancer with IP who received ICI treatment. A total of 200 patients (median age 70 years; male/female, 176/24) were enrolled from 27 institutions. ICIP occurred in 61 patients (30.5%), pneumonitis grades 3-5 in 32 patients (15.5%) and death in nine patients (4.5%). The common computed tomography pattern of ICIP was organising pneumonia in 29 patients (47.5%). Subsequently, diffuse alveolar damage (DAD) pattern was observed in 19 patients (31.1%) who had a significantly worse prognosis than those with a non-DAD pattern (median progression-free survival (PFS) 115 days versus 226 days, p=0.042; median overall survival (OS) 334 days versus 1316 days, p<0.001). Immune-related adverse events (irAEs) occurred in approximately 50% of patients. Patients with irAEs (n=100) had a better prognosis than those without irAEs (n=100) (median PFS 200 days versus 77 days, p<0.001; median OS 597 days versus 390 days p=0.0074). The objective response rate and disease control rate were 41.3% and 68.5%, respectively. Although ICI treatment was effective for patients with lung cancer with IP, ICIP developed in approximately 30% of patients. Patients with irAEs had a significantly better PFS and OS than those without irAEs.

Progressive pulmonary fibrosis in myositis-specific antibody-positive interstitial pneumonia: a retrospective cohort study.

Idiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP. This descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients' medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia. A total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan-Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936-5.392, p = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072-10.017, p = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974-38.157, p = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115-0.899, p = 0.031). Approximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP.

Investigation of the efficacy of two different laser types in the treatment of lower lip paresthesia after sagittal split ramus osteotomy

Orthognathic surgery involves invasive and major surgical procedures commonly used to correct maxillofacial deformities. Bilateral sagittal split ramus osteotomy (BSSO) is often used to treat dentofacial anomalies related to the mandible, but it can result in various complications, the most common of which is inferior alveolar nerve damage. Nerve damage–induced paresthesia of the lower lip significantly affects patient comfort. Medical treatments such as steroids and vitamin B, low-level laser therapy (LLLT), and platelet-rich fibrin (PRF) can be used as supportive therapies for nerve regeneration after damage. This study aimed to investigate the effectiveness of two different types of lasers in treating lower lip paresthesia after BSSO. This clinical trial was a controlled, single-center, prospective, single-blind, randomized study. Thirty patients were included in the study and randomly assigned to three groups: Group I (laser GRR, n = 10) received transcutaneous and transmucosal GRR laser treatment, Group II (Epic10 laser, n = 10) received transmucosal and transcutaneous Epic10 laser treatment, and Group III (vitamin B, n = 10) received B-complex vitamin tablets orally once a day. Two-point and brush tests were performed six times at specific intervals, and a visual analog scale was used to evaluate pain and sensitivity. Both vitamin B and laser therapies accelerated nerve regeneration. The contribution of the laser groups to the healing rate was better than that of the vitamin B group. Although there was no statistically significant difference between the two laser groups, clinical observations indicated better results in the GRR laser group.

Younger age is associated with cardiovascular pathological phenotype of severe COVID-19 at autopsy.

COVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19. This study included autopsied patients, aged 6 months to 83 years, with confirmed COVID-19 in 2020-2021. We collected tissue samples from deceased patients using a minimally invasive autopsy protocol and assessed pathological data following a systematic approach. Eighty-six patients were included, with a median age of 55 years (IQR 32.3-66.0). We showed that age was significantly lower in patients with acute heart ischemia (p = 0.004), myocarditis (p = 0.03) and lung angiomatosis (p < 0.001), and significantly higher in patients with exudative diffuse alveolar damage (p = 0.02), proliferative diffuse alveolar damage (p < 0.001), lung squamous metaplasia (p = 0.003) and lung viral atypia (p = 0.03), compared to patients without those findings. We stratified patients by their age and showed that cardiovascular findings were more prevalent in children and young adults. We performed principal component analysis and cluster of pathological variables, and showed that cardiovascular variables clustered and covariated together, and separated from pulmonary variables. We showed that age modulates pathological outcomes in fatal COVID-19. Younger age is associated with cardiovascular abnormalities and older age with pulmonary findings.

Vitamin D3 improved hypoxia-induced lung injury by inhibiting the complement and coagulation cascade and autophagy pathway

BackgroundPulmonary metabolic dysfunction can cause lung tissue injury. There is still no ideal drug to protect against hypoxia-induced lung injury, therefore, the development of new drugs to prevent and treat hypoxia-induced lung injury is urgently needed. We aimed to explore the ameliorative effects and molecular mechanisms of vitamin D3 (VD3) on hypoxia-induced lung tissue injury.MethodsSprague–Dawley (SD) rats were randomly divided into three groups: normoxia, hypoxia, and hypoxia + VD3. The rat model of hypoxia was established by placing the rats in a hypobaric chamber. The degree of lung injury was determined using hematoxylin and eosin (H&E) staining, lung water content, and lung permeability index. Transcriptome data were subjected to differential gene expression and pathway analyses. In vitro, type II alveolar epithelial cells were co-cultured with hepatocytes and then exposed to hypoxic conditions for 24 h. For VD3 treatment, the cells were treated with low and high concentrations of VD3.ResultsTranscriptome and KEGG analyses revealed that VD3 affects the complement and coagulation cascade pathways in hypoxia-induced rats, and the genes enriched in this pathway were Fgb/Fga/LOC100910418. Hypoxia can cause increases in lung edema, inflammation, and lung permeability disruption, which are attenuated by VD3 treatment. VD3 weakened the complement and coagulation cascade in the lung and liver of hypoxia-induced rats, characterized by lower expression of fibrinogen alpha chain (Fga), fibrinogen beta chain (Fgb), protease-activated receptor 1 (PAR1), protease-activated receptor 3 (PAR3), protease-activated receptor 4 (PAR4), complement (C) 3, C3a, and C5. In addition, VD3 improved hypoxic-induced type II alveolar epithelial cell damage and inflammation by inhibiting the complement and coagulation cascades. Furthermore, VD3 inhibited hypoxia-induced autophagy in vivo and in vitro, which was abolished by the mitophagy inducer, carbonyl cyanide-m-chlorophenylhydrazone (CCCP).ConclusionVD3 alleviated hypoxia-induced pulmonary edema by inhibiting the complement and coagulation cascades and autophagy pathways.

Minocycline reduces alveolar bone loss and bone damage in Wistar rats with experimental periodontitis.

This study aimed to investigate the impact of minocycline on the alveolar bone in experimental periodontitis in rats. Thirty Wistar rats were randomly assigned to three groups: control without periodontitis; experimental periodontitis induced by ligature; experimental periodontitis + intraperitoneal administration minocycline for seven days. Ligatures remained in place in both periodontitis groups for 14 days. At the end of the experiment, the animals were euthanized and one hemimandible underwent micro-computed tomography (micro-CT) analysis to assess vertical bone loss and alveolar bone quality. Histopathological analysis was performed on the other hemimandible. Statistical analysis was performed using ANOVA with Tukey's post-test (p<0.05). The results showed a significant reduction in vertical bone loss in the animals treated with minocycline compared with untreated animals. Minocycline also preserved the alveolar bone thickness, number, spacing, and bone volume to tissue volume ratio. Histopathological analysis indicated that minocycline reduced bone resorption, decreased inflammatory response, and maintained the bone collagen fibers. This study demonstrated the effectiveness of minocycline in reducing vertical bone loss and preserved bone quality in rats with experimental periodontitis. The results of this study indicate that minocycline has the potential to serve as an additional treatment option for periodontitis. However, further research is warranted to assess the efficacy and safety of minocycline use in patients with periodontitis.

Probiotics improves sepsis-induced acute lung injury in association with intestinal microbiota and pulmonary concentrations of Th17 and Treg

This study aims to assess the immune status of septic acute lung injury (ALI) at various stages and to investigate whether probiotics can mitigate ALI in septic rats. Rats were randomly assigned to sham, caecal ligation and puncture (CLP), and probiotic treatment after CLP (CLP+PT) group. Intestinal contents, bronchoalveolar lavage fluid (BALF), and lung tissue were collected from rats at 6, 24 and 48 h after CLP. Results showed that Th17 level at 24 h in BALF is significantly higher than that at 6 and 48 h. The Treg level increased after CLP and reached its highest point at 48 h. Pathological damage in the alveolar interstitium intensified over time. At 24 h, Th17 percentage of BALF significantly increased in the CLP group while it significantly decreased in the CLP+PT group, and the Treg percentage of BALF at 48 h showed the same alteration trend. Alveolar interstitial pathological damage in the CLP+PT group was reduced at all time points compared to the CLP group. The abundance of Firmicutes was higher and Bacteroidetes lower in the sepsis group compared to the sham group. However, the abundance of these bacteria was similar between the probiotic and pseudo-probiotic groups. Actinomycetes levels differed significantly among the three groups, with the probiotic group exhibiting significantly higher levels. Bifidobacteria levels were significantly higher in the probiotic group compared to the sepsis group. Phenotype prediction indicated a higher proportion of biofilm formation in the probiotic group compared to the sepsis group. In conclusions, significant alterations in Th17 and Treg levels in BALF of septic rats suggest a shift in the distribution of important T lymphocytes in the lungs during sepsis. Probiotics modulated the gut microbiota of septic rats, downregulated the highest value of Th17 and Treg percentage in BAFL, resulting in mitigated lung injury in rats.

Особенности поражения легких при коинфекции ВИЧ/SARS-CoV-2 у пациентов с разной степенью иммунодефицита

Introduction.The development of the COVID-19 pandemic along with the ongoing pandemic of HIV infection has raised the question of how these two diseases interact. This study examines morphological changes that occur in lung tissue during HIV/SARS-CoV-2 coinfection in patients with varying levels of immune status. Materials and methods. The study included 6 deceased HIV-infected patients who had a clinical diagnosis of COVID-19, which was confirmed postmortem by the detection of SARS-CoV-2 RNA in lung samples obtained during biopsy using polymerase chain reaction. Three patients were with newly diagnosed HIV infection; three patients had a relatively intact immune status (CD4+ more than 200 cells/μl) and no opportunistic infection and received effective antiretroviral therapy. To perform histologic examination, we used histochemical stains by Van Gieson, Grocott, Ziehl-Neelsen, PAS reaction as well as immunohistochemistry (IHC) with antibodies against SARS-CoV-2 nucleocapsid and cytomegalovirus. Results. The macroscopic picture in all cases was characterized by a decreased airiness and compaction of the lung tissue. Microscopically, patients with newly diagnosed HIV demonstrated diffuse alveolar damage (DAD) with pneumocystis pneumonia and cytomegalovirus infection. Nucleocapsid of SARS-CoV-2 was revealed in hyaline membranes and alveolar cells. In patients with controlled HIV, we detected manifestations of various phases of DAD and/or disseminated intravascular coagulation (DIC) syndrome with a predominant distribution of SARS-CoV-2 in macrophages and blood vessels. Conclusion. Lung damage in severe HIV-associated immunodeficiency was determined by the combination of direct cytopathic effect of coronavirus and opportunistic pathogens. In controlled HIV and relatively intact immune status, immune mediated action of SARS-CoV-2 could take place manifesting in diffuse alveolar damage and making the morphological picture comparable to that in HIV-negative patients.

Histopathological Profile of Lung Lesions- An Autopsy Study at a Tertiary Care Centre, Kerala, India

Introduction: Autopsy plays a crucial role in understanding and identifying pulmonary pathology, encompassing non neoplastic lesions, neoplastic conditions and the secondary implications of the lungs in terminal events of cardiovascular diseases. Pathological analysis confirms diagnosis and identifies the prevalence of lesions, contributing significantly to medical understanding and patient care. Aim: To estimate the prevalence of lung pathology in autopsy specimens through Histopathological Examination (HPE). Materials and Methods: A cross-sectional one-year study was conducted to determine the histopathological alterations in 132 lung autopsy specimens from Medicolegal autopsies received in the Department of Pathology at a tertiary care centre in Government Medical College, Cochin, Kerala, India from January 2021 to December 2021. Autopsy specimens of the lung were fixed in 10% formalin. Following gross examination, tissue sections were processed with paraffin and subjected to staining, with microscopy findings recorded. The data was numerically coded and entered into a Microsoft Excel spreadsheet. Statistical Package for Social Sciences (SPSS) version 21.0 was used for descriptive statistics and graphical representations of findings. Results: The mean age of the study population, comprising 132 autopsy cases, was 49.41±52.12 years and the male-to- female ratio was 3.71:1. Most cases 97/132 (73.50%) involved sudden deaths where the cause remained unknown. Significant microscopic findings found in 117 (88.63%) cases were as follows: Pulmonary oedema and congestion: 61 (46.21%), Pneumonia: 17 (12.87%), Diffuse Alveolar Damage (DAD): 12 (9.09%), Chronic venous congestion: 8 (6.06%), Tuberculosis: 7 (5.30%), Emphysema: 7 (5.30%), Pulmonary fibrosis: 1 (0.75%), Fat embolism: 1 (0.75%) and Pulmonary arterial hypertension: 1 (0.75%). Neoplastic lesions were identified in 7 (5.30%) cases, with primary lung cancers accounting for 3 (2.27%) cases. There were 10 cases of Real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), positive Coronavirus Disease 2019 (COVID-19) autopsies, of which 6 (60%) exhibited DAD, while 4 (40%) showed changes of bronchopneumonia. Conclusion: Non neoplastic lesions such as pulmonary oedema, DAD and infections contributed to mortality in most cases. DAD was the most common lung finding in more than half of COVID- 19 deaths. The prevalence of pulmonary neoplastic lesions in autopsies underscores their epidemiological significance in a particular geographical area.

Metformin enhanced the effect of pirfenidone on pulmonary fibrosis in mice.

The aim of the study is to observe the anti-inflammatory and antioxidative stress effects of metformin on bleomycin (BLM)-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with pirfenidone, metformin, pirfenidone plus metformin and the NADPH oxidase 4 (NOX4) inhibitor diphenyleneiodonium chloride (DPI). Pathological changes and hydroxyproline (HPO) levels were examined in the lung tissue of mice with pulmonary fibrosis. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels in lung tissue were determined. Compared with pirfenidone, pirfenidone plus metformin could reduce alveolar damage and collagen fibre deposition and alleviate BLM-induced pulmonary fibrosis. Lung HPO levels were significantly lower in the PFD + MET group than in the BLM group (p < 0.05). SOD levels in the lungs of mice were increased in the PFD + MET group than in the BLM group (p < 0.05). Metformin and pirfenidone plus metformin can reduce MDA levels (p < 0.05). Pirfenidone plus metformin could reduce HPO levels, increase SOD levels, and reduce MDA levels in the lungs of mice. There was a significant correlation between the HPO level and the Ashcroft score (r = 0.520, p < 0.001). Metformin enhanced the antifibrotic effects of pirfenidone on BLM-treated mice. Moreover, these findings provide an experimental basis for examining whether metformin can improve the antifibrotic effects of pirfenidone on patients with idiopathic pulmonary fibrosis (IPF). It has broad therapeutic prospects for patients with IPF.

Clinical and laboratory parameters and pathomorphological features of the lungs in patients who have had COVID-19 viral pneumonia

Post-Covid syndrome is characterized by general somatic manifestations, changes in the psycho-emotional sphere, cognitive disorders, disorders of the cardiovascular, respiratory systems and excretory function. However, there is little information in the literature about the mechanisms of thanatogenesis in patients who have had COVID-19. An analysis of clinical and laboratory parameters and pathomorphological changes was carried out in 9 autopsy cases of patients who had previously suffered a new coronavirus infection (COVID-19). The age of the deceased ranged from 80 to 96 years. At the time of hospitalization, the concentration of IgG varied from 32.61 to 1013.5 RLU, IgM - from 0.29 to 16.98 U/ml. The period from clinical diagnosis to death ranged from 12 to 46 days, and the time from clinical recovery (negative polymerase chain reaction) to death ranged from 2 to 30 days. In all cases, unresolved viral pneumonia and diffuse alveolar damage (exudative-proliferative phase) were diagnosed.

BRD3308 suppresses macrophage oxidative stress and pyroptosis via upregulating acetylation of H3K27 in sepsis-induced acute lung injury

Abstract Background Sepsis-induced acute lung injury (ALI) leads to severe hypoxemia and respiratory failure, contributing to poor prognosis in septic patients. Endotoxin dissemination triggers oxidative stress and the release of inflammatory cytokines in macrophages, initiating diffuse alveolar damage. The role of epigenetic histone modifications in organ injury is increasingly recognized. The present study aimed to investigate the use of a histone modification inhibitor to alleviate sepsis-induced ALI, revealing a new strategy for improving sepsis patient survival. Methods In vivo models of ALI were established through the intraperitoneal injection of lipopolysaccharide and cecal ligation and puncture surgery. Furthermore, the disease process was simulated in vitro by stimulating Tamm-Horsfall protein-1 (THP-1) cells with lipopolysaccharide. Hematoxylin and eosin staining, blood gas analysis and pulmonary function tests were utilized to assess the extent of lung tissue damage. Western blot analysis, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence were used to measure the levels and distribution of the indicated indicators within cells and tissues. Reactive oxygen species and autophagic flux alterations were detected using specific probes. Results BRD3308, which is a inhibitor of histone deacetylase 3, improved lung tissue damage, inflammatory infiltration and edema in ALI by inhibiting Nod-like receptor protein3-mediated pyroptosis in macrophages. By upregulating autophagy, BRD3308 improved the disruption of redox balance in macrophages and reduced the accumulation of reactive oxygen species. Mechanistically, BRD3308 inhibited histone deacetylase 3 activity by binding to it and altering its conformation. Following histone deacetylase 3 inhibition, acetylation of H3K27 was significantly increased. Moreover, the increase in H3K27Ac led to the upregulation of autophagy-related gene 5, a key component of autophagosomes, thereby activating autophagy. Conclusions BRD3308 inhibits oxidative stress and pyroptosis in macrophages by modulating histone acetylation, thereby preventing sepsis-induced ALI. The present study provides a potential strategy and theoretical basis for the clinical treatment of sepsis-induced ALI.

A Case of Lipoid Pneumonia - Hydrocarbon Pneumonitis

Lipoid pneumonia is a rare lung disease that occurs when lipid-containing products are aspirated or inhaled.[1] Exogenous lipoid pneumonia is typically caused by the inhalation or aspiration of animal fats, mineral oils, or vegetable oils, while endogenous lipoid pneumonia occurs due to lipid accumulation within intra-alveolar macrophages in the presence of bronchial obstruction, chronic pulmonary infection, pulmonary alveolar proteinosis, or fat storage diseases.[2] The clinical and radiological features of this condition are non-specific, and a careful history is crucial for accurate diagnosis. Organizing pneumonia can also be observed as a non-specific consequence of interstitial inflammatory diseases such as nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing diffuse alveolar damage, vasculitis, or aspiration pneumonia. In this case report, we discuss the presentation of lipoid pneumonia in a 23-year-old male with a history of petroleum ingestion.

Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19

Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Forty patients (32M:8F, age: 22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. UK Research and Innovation/Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust.

CHEST COMPUTED TOMOGRAPHY FINDINGS IN CANNABIS SMOKERS : SYSTEMATIC REVIEW

Introduction: In contrast, cannabinoids and nicotine are chemically distinct compounds, with cannabinoids exhibiting a unique set of effects pertaining to aspects such as gene expression, inflammatory mechanisms, immunological modulation, and cellular energy and survival. Consequently, a comparison between the pulmonary effects of cannabis and tobacco consumption is crucial. As a sensitive and repeatable tool for quantifying the airway alterations and alveolar lung damage that are hallmarks of smoking-related emphysema and COPD, noninvasive lung imaging with HRCT scans has developed. In-depth analyses of HRCT images obtained from cannabis consumers were conducted in only two studies. The aim: This study review chest CT findings in cannabis smokers. Methods: For this systematic review, publications that were published from 2012 to 2023 were taken into account during the search process. This was achieved through the utilization of numerous online reference sources, such as Pubmed and SagePub. The decision was made to exclude review articles, previously published works, and incomplete works. Result: We obtained 54 articles from Pubmed and 76 from SagePub. We extracted were 2 article from Pubmed and 4 articles from SagePub. Conclusion: Research shows that patients can experience pneumothorax with bullae and blebs. Those who smoke marijuana can also experience emphysema and chronic bronchitis.

Histologic Characteristics and Clinical Courses of Primary Viral Pneumonia Other than COVID-19.

Objective To clarify both the histologic changes in primary viral pneumonia other than COVID-19 and whether patients with severe lung injury (SLI) on biopsy specimens progress to severe respiratory insufficiency. Methods Patients with primary viral pneumonia other than COVID-19, who underwent lung tissue biopsy, were retrospectively studied. Patients Forty-three patients (41 living patients and 2 autopsied cases) were included in the study. Results Nine patients had SLI, whereas most of patients who recovered from primary viral pneumonia showed a nonspecific epithelial injury pattern. One patient underwent a biopsy under mechanical ventilation. Two of 8 (25.0%) patients on ambient air or low-flow oxygen therapy progressed to a severe respiratory condition and then to death, while only 1 (3.1%) of 32 patients without SLI progressed to a severe respiratory condition and death (p=0.096). The proportion of patients who required O2 treatment for ≥2 weeks was higher in patients with SLI than in those without SLI (p=0.033). The 2 autopsy cases showed a typical pattern of diffuse alveolar damage, with both showing hyaline membranes. Non-specific histologic findings were present in 32 patients without SLI. Conclusion Some patients with SLI progressed to severe respiratory insufficiency, whereas those without SLI rarely progressed to severe respiratory insufficiency or death. The frequency of patients progressing to a severe respiratory condition or death did not differ significantly between those with and without SLI. The proportion of patients who required longer O2 treatment was higher in SLI group than in those without SLI.

Pulmonary function assessment after COVID-19 in vaccinated healthcare workers

COVID-19 typically presents with flu-like symptoms due to the viral infection itself. The most severe cases are characterised by lung damage, an important factor in fatal outcome due to alveolar damage. In some cases, patients develop a long COVID with persistent symptoms of chest pain and fatigue. Causes, including organ damage or inflammation, are being investigated. Clinical outcomes are variable and permanent lung damage is not fully understood, while vaccination is effective against severe infection but its effect on respiratory function in mild cases remains uncertain. This retrospective study aims to analyse changes in lung function in HCWs who had COVID-19 between 2020 and 2022, comparing their spirometric test results before and after the pandemic and taking into account their vaccination status. 321 HCWs were included in the study. The study examined spirometric parameters both before and after the pandemic, and all measured outcomes except the FEV1/FVC ratio showed a significant decrease during the study period. We then assessed the association between SARS-CoV-2 infection and changes in lung function parameters, analysing infections in 2020, 2021 and 2022 separately. We found a statistically significant difference in Forced vital capacity (FVC) between infected and non-infected subjects in 2020 and 2021, but not in 2022. To evaluate the protective effect of SARS-CoV-2 vaccination on respiratory function, a linear regression analysis was performed using changes in FVC, Forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio and Peak expiratory flow (PEF) as dependent variables. The analysis showed that the decline in FVC was significantly lower in subjects who had been vaccinated prior to infection. The study concludes that subclinical SARS-CoV-2 infections in 2020 and 2021 worsened respiratory parameters (FVC and FEV1), but vaccination protected against these effects. Even healthy individuals with previous infections showed respiratory changes, with vaccination providing protection, especially for FVC decline. This highlights the importance of vaccinating healthcare workers against COVID-19.