Hyaline Membrane Formation Research Articles

MgO Nanoparticle Synthesis, Chemical Delivery in Rat Model Induced Lung Injury

Acute lung injury is a disorder of acute inflammation that causes disruption of the lung endothelial and epithelial barriers. Acute Respiratory Distress Syndrome or ARDS is a diffuse inflammatory lung process that frequently manifests in critically ill patients, with an estimated incidence of 3 million people a year. Clinically, ARDS is manifested by bilateral or diffuse radiographic infiltrates, hypoxemia, decreased lung compliance, and increased ventilatory dead space. The histological manifestation of ARDS is diffuse alveolar damage as defined by epithelial injury, hyaline membrane formation and alveolar flooding with proteinaceous fluid, increase alveolar surface area and frequently neutrophilic inflammation. The animal model correlate to ARDS as an acute lung injury (ALI). Models were employed to test potential new therapeutic interventions and to investigate under-lying mechanistic pathways that lead to diffuse lung injury. In this study cage cigarette smoke model was used for an acute lung injury. For that purpose, thirty (30) young albino healthy rats were used, and their duration of trial was 21 days. Each group was given an oral drug administration containing MgO-150mg/kg, MgO-300mg/kg BW for treatment and diet schedule in young albino rats of male sex for the experimental procedure of 0 to 21 days. Mean body weight, BALF, lipid profile, liver profile and lung histology were assessed. Results revealed that MgO nanoparticles exhibited antioxidant capacity at dosages of 300mg/kg, and 150mg/kg. This formulation of selected nanoparticles at high dose exhibited an acute lung injury and antioxidant effects as compared to low dose extract. Additionally, transcriptional factors revealed up-regulation at high dose in contrast to the low dose extract in lung injury treated groups.

The effect of budesonide delivered by high-frequency oscillatory ventilation on acute inflammatory response in severe lung injury in adult rabbits.

The inflammation present in acute respiratory distress syndrome (ARDS) and thereby associated injury to the alveolar-capillary membrane and pulmonary surfactant can potentiate respiratory failure. Even considering the high mortality rate of severe ARDS, glucocorticoids appear to be a reasonable treatment option along with an appropriate route of delivery to the distal lung. This study aimed to investigate the effect of budesonide therapy delivered intratracheally by high-frequency oscillatory ventilation (HFOV) on lung function and inflammation in severe ARDS. Adult New Zealand rabbits with respiratory failure (P/F<13.3 kPa) induced by intratracheal instillation of hydrochloric acid (HCl, 3 ml/kg, pH 1.5) followed by high tidal ventilation (VT 20 ml/kg) to mimic ventilator-induced lung injury (VILI) were treated with intratracheal bolus of budesonide (0.25 mg/kg, Pulmicort) delivered by HFOV (frequency 8 Hz, MAP 1 kPa, deltaP 0.9 kPa). Saline instead of HCl without VILI with HFOV delivered air bolus instead of therapy served as healthy control. All animals were subjected to lung-protective ventilation for 4 h, and respiratory parameters were monitored regularly. Postmortem, lung injury, wet-to-dry weight ratio, leukocyte shifts, and levels of cytokines in plasma and lung were evaluated. Budesonide therapy improved the lung function (P/F ratio, oxygenation index, and compliance), decreased the cytokine levels, reduced lung edema and neutrophils influx into the lung, and improved lung architecture in interstitial congestion, hyaline membrane, and atelectasis formation compared to untreated animals. This study indicates that HFOV delivered budesonide effectively ameliorated respiratory function, and attenuated acid-induced lung injury in a rabbit model of severe ARDS.

The Biochemistry and Pathology Characteristics of Coronavirus Disease 2019

Coronavirus Disease 2019 started appeared in December 2019 China’s, Hubei Province, Wuhan. During the following three months, it spread rapidly to numerous provinces in China and transversely the world. The initial bunch was epidemiologically associated with a seafood wholesale market in Wuhan. Many essential aspects of the pathogenesis, pathology, and pathophysiology of SARS- CoV2 have not yet clear. Here, we offer a comprehensive overview of the biochemistry Characteristics and histopathological results present in various organs and cells and the pathophysiology. In this review we found many damage in some organic system, such as pulmonary edema with hyaline membrane formation, desquamation and hyperplasia of pneumocytes, proteinaceous in Respiratory tract, spleen atrophic, degeneration and focal necrosis of hepatocytes, Esophageal, stomach and bowel in digestive tract. Degenerated or necrosed myocardial cells in Heart. Degeneration and shedding of renal tubules epithelial cells, hyaline casts in Kidneys and other organs.

Comparison of ultrasound signs, computed tomography data and morphological examination of the lungs in patients with coronavirus infection: post hoc analysis

INTRODUCTION: Ultrasound examination (US) of the lungs has shown high efficiency in the diagnosis of COVID-19 pneumonia. The aim of the research was studying the correspondence of computed tomography (CT) US signs of the lungs and morphological data in patients with COVID-19 pneumonia. MATERIALS AND METHODS: The post hoc analysis included 388 patients who simultaneously underwent ultrasound and CT of the lungs. Lung ultrasound was performed according to the 16-zone “Russian Protocol”. Morphological data were obtained from the results of pathoanatomic examination of deceased patients. RESULTS: The comparison of signs detected by CT and ultrasound of the lungs was performed during a multidimensional correspondence analysis. The analysis was carried out using a three-dimensional solution that explained 64.9 % of inertia (p &lt; 0.001). CT signs of “ground glass opacity” (100 %) corresponded to the B-line at ultrasound (100 %), CT of the consolidation sign (44.8 %) — ultrasound signs of consolidation (46.9 %), aerobronchogram of CT (34 %) — aerobronchogram of ultrasound (36.9 %), free liquid CT (11.1 %) — free liquid Ultrasound (13.9 %). CT signs of reticular changes (29.6 %) and “cobblestone pavement” (12.4 %) corresponded to various combinations of ultrasound signs of subpleural consolidation and B-lines. The B-lines were caused by the exudation of fluid and protein molecules into the intraalveolar space against the background of massive death of alveolocytes and formed by the development of intraalveolar edema and the formation of hyaline membranes. The ultrasonic sign of consolidation appeared in the airless zone of the lungs. Subpleural consolidation are caused by thickening and inflammatory infiltration of the pleura, diffuse alveolar damage, with intraalveolar edema, death and decay of alveolocytes, perivascular inflammatory cell reaction/ During treatment for more than 7 days, consolidation in the lung tissue developed due to the disorganization of the organ structure due to the progression of fibrosis. CONCLUSION: Multivariate correspondence analysis showed correlation of CT signs and US signs of the lungs. Morphological analysis showed polymorphism of histological data that caused the formation of ultrasound signs.

Successful Treatment of White Lung in Elderly Patients with COVID-19

Novel coronavirus (SARS-CoV-2, hereby known as COVID-19) has the characteristics of rapid variation and multiple variants, which has caused a huge impact on human health worldwide. At the end of 2022, the Omicron variant was widely spread in China, and the patients infected with COVID-19 were mainly concentrated in the elderly over 80 years old and people with serious basic diseases. Pathologically, diffuse lung injury can be seen in the advanced stage of severe and critical diseases, with a large number of inflammatory cells and fibrous mucus exudation, alveolar epithelial cells shedding and necrosis, severe pulmonary edema, hyaline membrane formation, and diffuse ground-glass shadow or consolidation on imaging, which is manifested as “white lung” [1], and its mortality rate has significantly increased. This study reported two cases of elderly patients admitted to the Affiliated Hospital of Hebei University for the treatment of COVID-19.

Pathological findings in congenital diaphragmatic hernia on necropsy studies: A single-center case series.

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidities. The objective of this study was to delineate the histopathological features observed in necropsies of CDH patients and correlate these with their clinical manifestations. We retrospectively reviewed the postmortem findings and corresponding clinical characteristics in eight CDH cases from 2017 to July 2022. The median survival time was 46 (8-624) hours. Autopsy reports showed that diffuse alveolar damage (congestion and hemorrhage) and hyaline membrane formation were the primary pathological lung changes observed. Notably, despite significant reduction in lung volume, the lung development appeared normal in 50% of the cases, while lobulated deformities were present in three (37.5%) cases. All patients displayed a large patent ductus arteriosus (PDA) and a patent foramen ovale, resulting in increased right ventricle (RV) volume, and myocardial fibers appeared slightly congested and swollen. The pulmonary vessels indicated thickening of the arterial media and adventitia. Lung hypoplasia and diffuse lung damage resulted in impaired gas exchange, while PDA and pulmonary hypertension led to RV failure, subsequent organ dysfunction and ultimately death. Patients with CDH typically succumb to cardiopulmonary failure, a condition driven by a complex interplay of pathophysiological factors. This complexity accounts for the unpredictable response to currently available vasodilators and ventilation therapies.

Cardio-Pulmonary Histopathology with Clinical Correlations of Deceased Patients with COVID-19: A Case Series in Tehran, Iran.

SARS-CoV-2 may affect vital organs. The present study investigated the histopathology of pulmonary and cardiac tissues with clinical correlation in deceased patients with COVID-19. We obtained pulmonary and cardiac tissues from 30 deceased patients with COVID-19 in Tehran, Iran, from January to May 2021. Sampling was performed through a percutaneous needle biopsy. After slide preparation, two expert pathologists studied them. We assessed the correlation between clinical and pathological data by Fisher's exact test. The mean age of the patients was 73.8±13.4 years, and the male-to-female ratio was 23/7. The most common underlying disease was hypertension (HTN) in 25 patients (83%). Fifty-five tissue samples were achieved, including 28 pulmonary and 27 cardiac samples. Our results showed that all patients (100%) developed diffuse alveolar damage (DAD), and 26 (93%) developed hyaline membrane formation. The most common phase of DAD was the exudative-proliferative phase in 16 (57.1%). Three cardiac samples (11%) revealed myocarditis, and seven (26%) showed cardiomyocyte hypertrophy. In univariate analysis using Fischer's exact test, myocarditis had significant relationships with C-reactive protein (CRP) levels higher than 80 mg/dL (P=0.008) and elevated cardiac troponin levels higher than two-fold (P=0.01). COVID-19 can affect the major vital organs. However, only myocarditis had a significant relationship with the circulating levels of inflammatory factors.

Lung Expression of Macrophage Markers CD68 and CD163, Angiotensin Converting Enzyme 2 (ACE2), and Caspase-3 in COVID-19.

Background and Objectives: The coronavirus (SARS-CoV-2) damages all systems and organs. Yet, to a greater extent, the lungs are particularly involved, due to the formation of diffuse exudative inflammation in the form of acute respiratory distress syndrome (ARDS) with next progression to pulmonary fibrosis. SARS-associated lung damage is accompanied by the pronounced activation of mononuclear cells, damage of the alveoli and microvessels, and the development of organized pneumonia. To study the expression of macrophage markers (CD68 and CD163), angiotensin-converting enzyme-2 (ACE2), and caspase-3 on the results of two fatal clinical observations of COVID-19. Materials and Methods: In both clinical cases, the female patients died from complications of confirmed COVID-19. Conventional morphological and immunohistochemical methods were used. Results: There was an acute exudative hemorrhagic pneumonia with the formation of hyaline membranes, focal organization of fibrin, stromal sclerosis, stasis, and thrombus formation in the lung vessels. Signs such as the formation of hyaline membranes, organization, and fibrosis were more pronounced in severe disease activity. The activation of CD68+/CD163+ macrophages could cause cell damage at an early stage of pneumonia development, and subsequently cause fibrotic changes in lung tissue. ACE2 expression in lung tissue was not detected in severe pneumonia, while in moderate pneumonia, weak expression was noted in individual cells of the alveolar epithelium and vascular endothelium. Conclusions: This finding could show the dependence of ACE2 expression on the severity of the inflammatory process in the lungs. The expression of caspase-3 was more pronounced in severe pneumonia.

Effect of Pulmonary Rehabilitation on Exercise Capacity in Post Hospitalized Covid-19 Patients: An Experimental Study

Introduction: COVID-19 is a systemic disease; the lungs are most commonly affected, with histopathological findings that may include diffuse alveolar epithelium destruction, capillary damage or bleeding, hyaline membrane formation, alveolar septal fibrous proliferation, and pulmonary consolidation. Method: This study was designed as experimental, randomized double-blinded study. Participate divided into two groups- the pulmonary rehabilitation group(Group A) and control group(Group B). The inclusion criteria were patient with confirmed case of infection of COVID-19 was defined by RT-PCR assay on nasopharyngeal swab; aged 20 to 55 years; Hospitalised due to severity of covid-19 symptoms, persistent high grade fever&gt;1000 F, breathlessness, increase in dry cough), ≥3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilator support., Any persistent sequel of COVID- 19. All participants were explained the study protocol and they were enrolled in protocol after their written consent for this study. 6 minute walk test (6 MWT) was taken before and after the study protocol. Within group analysis using Wilcoxon signed Rank test. Between group analysis using Mann-Whitney Test. Level of significance was kept at p&lt;0.005. Results: Within group analysis showed statistically significant difference in Group A (Z=-5.076,p=0.0001) whereas no statistically difference in Group B (Z=-2.160 ,p=0.078). Comparison of end of 8 weeks intervention data which shows that there is statistically significant difference in both the groups(U=45, p =0.001) Conclusion: Pulmonary rehabilitation is possible and effective therapeutic strategy to improve the aerobic capacity and improve quality of life post-hospitalized COVID-19 patients. Keywords: COVID-19, Pulmonary Rehabilitation, Aerobic capacity

THE OUTLOOKS FOR THE SURFACTANT REPLACEMENT THERAPY OF COVID-19 INDUCED RESPIRATORY DISTRESS SYNDROME IN CHILDREN

Nearly 6.5 million people have died worldwide from the COVID-19 pandemic. Improvement of pediatric patients survival depends on the continued provision of basic health services to women and children all over the world. The world scientific community must start more scientific clinical investigations and receive more data in order to know the impact of COVID-19 on children`s health andmortality, and to ensure that children and adolescents do not die from preventable events. Such trends in the spread of morbidity and mortality from COVID-19 require an interdisciplinary approach as soon as possible tofurther contain the spread of the disease and prevent complications in order to improve the quality of life. Insufficiently studied molecular changes in lung morpho-biology due to the action of COVID-19 complicate its clinical treatment. An in-depth genetic mechanisms investigation during pathogenetic disorders caused by virus can help in the development of new treatment methods, in articular, the use of surfactant drugs as a component of basic therapy. Recently, it became known that COVID-19-associated lung damage is characterized by typical pathophysiological changes for RDS. Diffuse alveolar damage occurs due to edema of the interstitium, the formation of hyaline membranes, as well as the proliferation of fibroblasts at the stage of recovery. When COVID-19 affects the lungs, surfactantsynthesis is dysregulated, as viral proteins suppress the expression of regulatory genes. Changes during the reparation process also lead to loss of surfactant function. Surfactant replacement therapy can be an alternative in the treatment of patients with COVID-19-associated lung damage, there are a number of studies that prove the effectiveness of such therapy in other infections. COVID-19 can be especially dangerous for children with chronic lung disease, congenital malformations, previously undiagnosed genetic defects in thesurfactant production system. However, timely use of surfactant replacement therapy can prevent one of the worst complications duringmechanical ventilation - air leakage syndrome.

SARS-CoV-2-Infection (COVID-19): Clinical Course, Viral Acute Respiratory Distress Syndrome (ARDS) and Cause(s) of Death.

SARS-CoV-2-infected symptomatic patients often suffer from high fever and loss of appetite which are responsible for the deficit of fluids and of protein intake. Many patients admitted to the emergency room are, therefore, hypovolemic and hypoproteinemic and often suffer from respiratory distress accompanied by ground glass opacities in the CT scan of the lungs. Ischemic damage in the lung capillaries is responsible for the microscopic hallmark, diffuse alveolar damage (DAD) characterized by hyaline membrane formation, fluid invasion of the alveoli, and progressive arrest of blood flow in the pulmonary vessels. The consequences are progressive congestion, increase in lung weight, and progressive hypoxia (progressive severity of ARDS). Sequestration of blood in the lungs worsens hypovolemia and ischemia in different organs. This is most probably responsible for the recruitment of inflammatory cells into the ischemic peripheral tissues, the release of acute-phase mediators, and for the persistence of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autopsy studies have been performed mostly in patients who died in the ICU after SARS-CoV-2 infection because of progressive acute respiratory distress syndrome (ARDS). In the death certification charts, after respiratory insufficiency, hypovolemic heart failure should be mentioned as the main cause of death.

The CHARTER-Ireland trial: can nebulised heparin reduce acute lung injury in patients with SARS-CoV-2 requiring advanced respiratory support in Ireland: a study protocol and statistical analysis plan for a randomised control trial

BackgroundCOVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS, hastens recovery and is safe in non-COVID ARDS. Unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents entry into mammalian cells. Nebulisation of heparin may therefore limit fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. Based on these findings, we designed the CHARTER-Ireland Study, a phase 1b/2a randomised controlled study of nebulised heparin in patients requiring advanced respiratory support for COVID-19 pneumonia.MethodsThis is a multi-centre, phase 1b/IIa, randomised, parallel-group, open-label study. The study will randomise 40 SARs-CoV-2-positive patients receiving advanced respiratory support in a critical care area. Randomisation will be via 1:1 allocation to usual care plus nebulised unfractionated heparin 6 hourly to day 10 while receiving advanced respiratory support or usual care only. The study aims to evaluate whether unfractionated heparin will decrease the procoagulant response associated with ARDS up to day 10. The study will also assess safety and tolerability of nebulised heparin as defined by number of severe adverse events; oxygen index and respiratory oxygenation index of intubated and unintubated, respectively; ventilatory ratio; and plasma concentration of interleukin (IL)-1β, IL6, IL-8, IL-10 and soluble tumour necrosis factor receptor 1, C-reactive protein, procalcitonin, ferritin, fibrinogen and lactate dehydrogenase as well as the ratios of IL-1β/IL-10 and IL-6/IL-10. These parameters will be assessed on days 1, 3, 5 and 10; time to separation from advanced respiratory support, time to discharge from the intensive care unit and number tracheostomised to day 28; and survival to days 28 and 60 and to hospital discharge, censored at day 60. Some clinical outcome data from our study will be included in the international meta-trials, CHARTER and INHALE-HEP.DiscussionThis trial aims to provide evidence of potential therapeutic benefit while establishing safety of nebulised heparin in the management of ARDS associated with SARs-CoV-2 infection.Trial registrationClinicalTrials.govNCT04511923. Registered on 13 August 2020.Protocol version 8, 22/12/2021Protocol identifier: NUIG-2020-003EudraCT registration number: 2020-003349-12 9 October 2020

A Case Report on Histomorphological Features in Death Due to H1N1 Influenza

Swine influenza strain can be transmitted from human to human and causes normal symptoms of influenza. Transmission mainly occurs between pigs and pigs and humans. Our present study is of a 72yrs old male who died of H1N1 infection. Postmortem findings showed congested and edematous lungs with patchy areas of consolidation. Histopathological findings in lung revealed edema, pneumonic changes, hyaline membrane formation and focal cytophagocytosis.

Radiation Induced Lung Injury (RILI) and COVID-19 Pneumonia: Are There Similarities by The Radiation Oncologist’s Point of View?

Coronavirus disease 2019 (COVID-19), is a novel infectious disease responsible for a severe acute respiratory syndrome due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, which was firstly reported in January 2020 in Wuhan, Hubei Province, China, and then rapidly spread to other countries beyond China with a pandemic proportion in these last two years. In its severe lung expression, disease onset may result in death due to massive alveolar damage and progressive respiratory failure due to acute lung injury (ALI) which predisposes to fatal acute respiratory distress syndrome (ARDS). Autopsies reports describe a diffuse alveolar damage with vascular congestion, inflammatory cell population entrapped, thrombosis with hyaline membrane formation in the alveolar walls allowing to an irreversible lung destruction. Altogether these findings remind the radiation oncologists many similarities with radiation induced lung injury which is a well-known side effect of radiotherapy for lung cancer. A fascinating hypothesis is that a common inflammatory paradoxical response of lung could be underlying the injury whatever the causes may be, virus, drugs or ionizing radiation. In this paper we will review the similarities between these two illnesses just going through the mechanisms of ALI-ARDS and the role of the most important immune cells and cytokines involved.

Histological Changes in the Lung Tissue in Association with COVID-19: Review Article

Background: It has been shown that SARS-CoV-2 is a multi-systemic virus and can affect number of body systems including the respiratory tract, the gastro-intestinal tract, the liver, the kidney and the nervous system. Despite the high mortality rate, there is little literature on postmortem findings of this unique virus, perhaps due to its highly contagious nature, inadequate information on prevention, and a lack of robust infrastructure for appropriate management of infected cases at various centers throughout the world. Aim of the study: The aim of the current study was to review and list the main histological changes seen in patients died because of COVID-19. Methods: A systemic search was carried out including Google Scholar, PubMed, and MEDLINE and the Google search Engine in order to scan all available published articles dealing with histological changes affection the lung in patients with documented COVID-19. The following key words were used to accomplish the search mission: COVID-19, SARS-CoV-2, Lung Histology, Pulmonary Histology, Histopathology. The search was limited to articles written in English language. Any article published between the end of 2019 and the time of initiating the current work was reviewed. The information in the current review is totally based on reviewed articles that are mentioned in the section of references. Results: The main sources of lung tissues were Whole lung biopsy, Postmortem study, Core needle biopsy and Ultrasound based samples from autopsy. The exudative changes include injury to pneumocytes, congestion of capillaries, giant cell formations, dilation of alveolar ducts, thickening of capillaries, edema of interstitium and formation of hyaline membrane. The proliferative changes include hyperplasia of Type-2 pneumocytes with some reactive atypia with proliferation of myofibroblastic cells leading to granulation tissue formation, thickening of alveolar wall accumulation of alveolar macrophages, interstitial thickening which harbors collections of proliferating fibroblasts together with foci of hemorrhage and lymphocytic infiltration. Conclusion: The main histopathological changes in lung of patients with COVID-19 can be grouped into three main phases, exudative, proliferative and fibrotic phases in addition to changes involving vascular tissues, bronchi and bronchioles and the main changes are the diffuse alveolar damage seen in exudative and proliferative phases.

ELECTRON MICROSCOPIC STUDY OF THE LUNGS OF DECEASED PATIENTS WITH COVID-19

TYPE: Late Breaking Abstract TOPIC: Imaging PURPOSE: To visualize the ultrastructural pulmonary damage in patients deceased from SARS-CoV-2 infection. METHODS: An observational study was performed from March 15th 2020 to December 31st 2021 at the Fundación Jiménez Díaz (Spain). Epidemiological and analytical data were obtained. Ultrasound-guided post-mortem percutaneous biopsies were performed with a 33-mm 14G automatic gun, for their histological examination, and for electron microscopy observation. RESULTS: Five patients (80% women) were included. Mean age was 86 years (84-88); 60% had two medical conditions (HT, DM, obesity). The median length of hospitalization was three days (range 1-16). Percutaneous biopsies were performed at the bedside in the first hour after death. Diffuse alveolar damage was present in all patients, with increased alveolar wall thickness. Loss of lung structure and cell lysis and vacuolization were observed in endothelial cells and in pneumocytes of both types. In type II pneumocytes, images consistent with coronavirus viral particles included inside vesicles as well as extracellular particles close to membrane remnants, were identified. Although every patient received at least one prophylactic dose of heparin, 66% had a DD above 3,000 μg/L. Fibrin microthrombi, mainly in alveolar capillaries, were identified in all patients, with no signs of vasculitis. CONCLUSIONS: Pulmonary microthrombosis was observed in all patients, in spite of anticoagulant treatment. A more detailed study under EM showed frequent formation of hyaline membranes as well as severe cellular damage in both type II pneumocytes and endothelial cells. CLINICAL IMPLICATIONS: Microthrombosis seems to be present from the onset even in patients treated with anticoagulation. DISCLOSURE: No significant relationships. KEYWORD: Electron microscopic

Angiopteris cochinchinensis de Vriese Ameliorates LPS-Induced Acute Lung Injury via Src Inhibition.

Growing demand for treatment options against acute lung injury (ALI) emphasizes studies on plant extracts harboring anti-inflammatory effects. According to GC-MS analysis, Angiopteris cochinchinensis de Vriese consists of various flavonoids with anti-inflammatory activities. Thus, in this study, the anti-inflammatory effects of an extract of Angiopteris cochinchinensis de Vriese (Ac-EE) were assessed using RAW264.6 murine macrophages and a lipopolysaccharide (LPS)-induced ALI model. Ac-EE reduced the nitric oxide production in murine macrophages increased by LPS induction. Moreover, protective effects of Ac-EE on lung tissue were demonstrated by shrinkage of edema and lung injury. Reduced neutrophil infiltration and formation of hyaline membranes were also detected in lung tissues after H&E staining. Semiquantitative RT-PCR, quantitative real-time PCR, and ELISA showed that Ac-EE inhibits the production of proinflammatory mediators, including iNOS and COX-2, and cytokines, such as TNF-α, IL-1β, and IL-6. An Ac-EE-mediated anti-inflammatory response was derived from inhibiting the NF-κB signaling pathway, which was evaluated by luciferase reporter assay and Western blotting analysis. A cellular thermal shift assay revealed that the prime target of Ac-EE in alleviating inflammation was Src. With its direct binding with Src, Angiopteris cochinchinensis de Vriese significantly mitigates lung injury, showing possibilities of its potential as an effective botanical drug.

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury.

Background and Objective: Lung-protective mechanical ventilation is known to attenuate ventilator-associated lung injury (VALI), but often at the expense of hypoventilation and hypercapnia. It remains unclear whether the main mechanism by which VALI is attenuated is a product of limiting mechanical forces to the lung during ventilation, or a direct biological effect of hypercapnia. Methods: Acute lung injury (ALI) was induced in 60 anesthetized rats by the instillation of 1.25 M HCl into the lungs via tracheostomy. Ten rats each were randomly assigned to one of six experimental groups and ventilated for 4 h with: 1) Conventional HighV E Normocapnia (high VT, high minute ventilation, normocapnia), 2) Conventional Normocapnia (high VT, normocapnia), 3) Protective Normocapnia (VT 8 ml/kg, high RR), 4) Conventional iCO 2 Hypercapnia (high VT, low RR, inhaled CO2), 5) Protective iCO 2 Hypercapnia (VT 8 ml/kg, high RR, added CO2), 6) Protective endogenous Hypercapnia (VT 8 ml/kg, low RR). Blood gasses, broncho-alveolar lavage fluid (BALF), and tissue specimens were collected and analyzed for histologic and biologic lung injury assessment. Results: Mild ALI was achieved in all groups characterized by a decreased mean PaO2/FiO2 ratio from 428 to 242 mmHg (p < 0.05), and an increased mean elastance from 2.46 to 4.32 cmH2O/L (p < 0.0001). There were no differences in gas exchange among groups. Wet-to-dry ratios and formation of hyaline membranes were significantly lower in low VT groups compared to conventional tidal volumes. Hypercapnia reduced diffuse alveolar damage and IL-6 levels in the BALF, which was also true when CO2 was added to conventional VT. In low VT groups, hypercapnia did not induce any further protective effect except increasing pulmonary IL-10 in the BALF. No differences in lung injury were observed when hypercapnia was induced by adding CO2 or decreasing minute ventilation, although permissive hypercapnia decreased the pH significantly and decreased liver histologic injury. Conclusion: Our findings suggest that low tidal volume ventilation likely attenuates VALI by limiting mechanical damage to the lung, while hypercapnia attenuates VALI by limiting pro-inflammatory and biochemical mechanisms of injury. When combined, both lung-protective ventilation and hypercapnia have the potential to exert an synergistic effect for the prevention of VALI.

Pathology of COVID-19

Coronavirus infection 2019 (COVID-19) has become a challenge for the health care system around the world due to the progressive increase in the number of cases with severe manifestations of the disease. Autopsy findings are fundamental and critical to better understanding how infection affects the human body. These data are needed to improve diagnostic and treatment methods, as well as to stratify risk groups.&#x0D; The purpose of the review is to analyze and summarize the pathological data available to date related to COVID-19. In COVID-19, the lungs are usually severe and swollen. Histologically, the most frequent is the detection of both exudative and proliferative diffuse alveolar injury with the formation of hyaline membranes, inflammatory cell infiltration, and stagnant small vessels. There is also evidence that SARS-CoV-2 causes endothelial dysfunction. There is still insufficient data to reflect the complete pathophysiological picture of SARS-CoV-2 infection.&#x0D; Almost all of the articles reviewed in this review focused on pulmonary macro- and microscopic changes; there is little data on the features of the virus affecting other organs and its systemic effect. Despite the tremendous attention and investment in the fight against the new coronavirus infection, diagnosis of most of the deaths associated with COVID-19 is difficult.&#x0D; It is necessary to conduct further pathological studies, the purpose of which should be the development of a standardized diagnostic method, as well as the isolation of pathognomonic signs of the disease.

Persistent Lung Injury and Prothrombotic State in Long COVID.

Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is to investigate the basis of pulmonary susceptibility during sequelae and the possibility that prothrombotic states may influence long-term pulmonary symptoms of COVID-19. The patient’s lungs remain vulnerable during the recovery stage due to persistent shedding of the virus, the inflammatory environment, the prothrombotic state, and injury and subsequent repair of the blood-air barrier. The transformation of inflammation to proliferation and fibrosis, hypoxia-involved vascular remodeling, vascular endothelial cell damage, phosphatidylserine-involved hypercoagulability, and continuous changes in serological markers all contribute to post-discharge lung injury. Considering the important role of microthrombus and arteriovenous thrombus in the process of pulmonary functional lesions to organic lesions, we further study the possibility that prothrombotic states, including pulmonary vascular endothelial cell activation and hypercoagulability, may affect long-term pulmonary symptoms in long COVID. Early use of combined anticoagulant and antiplatelet therapy is a promising approach to reduce the incidence of pulmonary sequelae. Essentially, early treatment can block the occurrence of thrombotic events. Because impeded pulmonary circulation causes large pressure imbalances over the alveolar membrane leading to the infiltration of plasma into the alveolar cavity, inhibition of thrombotic events can prevent pulmonary hypertension, formation of lung hyaline membranes, and lung consolidation.