Pulmonary Interstitium Research Articles

СORONAVIRUS INFECTION WITH AN OBESITY

Summary. Relevance of the topic: most of the world is obese and there are enough cases of the impact of this pathology on the development of a complicated and severe course of novel coronavirus (COVID-19) infection. Purpose of the study: to study literature data on the effect of obesity on the course of novel coronavirus infection. Objectives : 1. To consider obesity as a factor contributing to the intensification of inflammatory reactions. 2. To study the etiology and pathogenesis of COVID-19 infection. 3. To establish the relationship between obesity and complications arising from coronavirus infection. Results. The most common feature of COVID-19 is severe acute respiratory syndrome caused by progressive lung consolidation. There is a positive correlation between the duration of COVID-19 infection and the degree of interstitial fibrosis. Extensive pulmonary fibrosis is one of the main causes of pulmonary consolidation due to the excessive extracellular matrix component produced by activated myofibroblasts [7]. Pulmonary lipofibroblasts are a special type of adipocytes that contain typical lipid droplets and are close to the second type of alveolar epithelial cells of the pulmonary interstitium. Lipofibroblasts may result from ectopic fat deposition, which plays a vital role in the progression of COVID-19 in these patients. When exposed to various stimulants, such as hyperoxia and infection of lung lipofibroblasts, a transdifferentiated myogenic phenotype called myofibroblasts occurs, which causes pulmonary fibrosis [10]. A significant number of obese patients have impaired glucose metabolism, which is considered a risk factor and leads to death. SARS infection has been found to cause hyperglycemia in some patients due to dysfunction of the islets of the pancreas as a result of a viral attack. A similar effect occurs after infection with SARS-COV-2. This explains why 52% of those infected with SARS-COV-2 had hyperglycemia. The level of glucose increase in metabolic disorders in obese patients can be much higher. Hyperglycemia leads to a number of complications, including osmotic imbalance of fluid and electrolytes, hyperosmolar non-ketonemic coma, worsening skeletal muscle catabolism, impaired wound healing, altered coagulation, and increased susceptibility to infections [4]. In addition, hyperglycemia impairs the body's immune function. All of this worsens the clinical outcome of COVID-19. Notably, proper blood glucose control reduces mortality in critically ill patients, highlighting the importance of blood glucose control. Conclusion. The relationship between obesity as a factor complicating the course of SARS-COV-2 infection has been shown. This mainly concerns the development of a cytokine storm due to the release of IL-1, IL-6, IL-10 by adipose tissue, as well as TNF- α . It should be noted that obesity affects the occurrence of concomitant metabolic diseases in patients, such as type 2 diabetes mellitus, coronary heart disease, atherosclerosis, etc., leading to acute myocardial infarction, increased thrombus formation and many other serious conditions. In addition, it is difficult for obese patients to provide specialized medical care when connecting to a ventilator, preventing pressure ulcers and attaching a secondary infection.

СORONAVIRUS INFECTION WITH AN OBESITY

Summary. Relevance of the topic: most of the world is obese and there are enough cases of the impact of this pathology on the development of a complicated and severe course of novel coronavirus (COVID-19) infection. Purpose of the study: to study literature data on the effect of obesity on the course of novel coronavirus infection. Objectives : 1. To consider obesity as a factor contributing to the intensification of inflammatory reactions. 2. To study the etiology and pathogenesis of COVID-19 infection. 3. To establish the relationship between obesity and complications arising from coronavirus infection. Results. The most common feature of COVID-19 is severe acute respiratory syndrome caused by progressive lung consolidation. There is a positive correlation between the duration of COVID-19 infection and the degree of interstitial fibrosis. Extensive pulmonary fibrosis is one of the main causes of pulmonary consolidation due to the excessive extracellular matrix component produced by activated myofibroblasts [7]. Pulmonary lipofibroblasts are a special type of adipocytes that contain typical lipid droplets and are close to the second type of alveolar epithelial cells of the pulmonary interstitium. Lipofibroblasts may result from ectopic fat deposition, which plays a vital role in the progression of COVID-19 in these patients. When exposed to various stimulants, such as hyperoxia and infection of lung lipofibroblasts, a transdifferentiated myogenic phenotype called myofibroblasts occurs, which causes pulmonary fibrosis [10]. A significant number of obese patients have impaired glucose metabolism, which is considered a risk factor and leads to death. SARS infection has been found to cause hyperglycemia in some patients due to dysfunction of the islets of the pancreas as a result of a viral attack. A similar effect occurs after infection with SARS-COV-2. This explains why 52% of those infected with SARS-COV-2 had hyperglycemia. The level of glucose increase in metabolic disorders in obese patients can be much higher. Hyperglycemia leads to a number of complications, including osmotic imbalance of fluid and electrolytes, hyperosmolar non-ketonemic coma, worsening skeletal muscle catabolism, impaired wound healing, altered coagulation, and increased susceptibility to infections [4]. In addition, hyperglycemia impairs the body's immune function. All of this worsens the clinical outcome of COVID-19. Notably, proper blood glucose control reduces mortality in critically ill patients, highlighting the importance of blood glucose control. Conclusion. The relationship between obesity as a factor complicating the course of SARS-COV-2 infection has been shown. This mainly concerns the development of a cytokine storm due to the release of IL-1, IL-6, IL-10 by adipose tissue, as well as TNF- α . It should be noted that obesity affects the occurrence of concomitant metabolic diseases in patients, such as type 2 diabetes mellitus, coronary heart disease, atherosclerosis, etc., leading to acute myocardial infarction, increased thrombus formation and many other serious conditions. In addition, it is difficult for obese patients to provide specialized medical care when connecting to a ventilator, preventing pressure ulcers and attaching a secondary infection.

Caprine Arthritis Encephalitis Virus Is Associated with Renal Lesions.

Caprine arthritis encephalitis virus (CAEV) is a monocyte/macrophage-tropic lentivirus that primarily infects goats resulting in a well-recognized set of chronic inflammatory syndromes focused on the joint synovium, tissues of the central nervous system, pulmonary interstitium and mammary gland. Clinically affected animals generally manifest with one or more of these classic CAEV-associated tissue lesions; however, CAEV-associated renal inflammation in goats has not been reported in the peer-reviewed literature. Here we describe six goats with chronic, multisystemic CAEV infections in conjunction with CAEV-associated renal lesions. One of the animals had CAEV antigen-associated thrombotic arteritis resulting in infarction of both the kidney and heart. These goats had microscopic evidence of inflammatory renal injury (interstitial nephritis) with detectable renal immunolabeling for CAEV antigen in three of six animals and amplifiable proviral sequences consistent with CAEV in all six animals. Cardiac lesions (vascular, myocardial or endocardial) were also identified in four of six animals. Within the viral promoter (U3) region, known transcription factor binding sites (TFBSs) were generally conserved, although one viral isolate had a duplication of the U3 A region encoding a second gamma-activated site (GAS). Despite the TFBS conservation, the isolates demonstrated a degree of phylogenetic diversity. At present, the clinical consequence of CAEV-associated renal injury is not clear.

Severe Hydroxyapatite Deposition Disease in Binturongs (Arctictis binturong).

In a collection of 6 young binturongs (Arctictis binturong), 3 presented with anorexia, lethargy, and footpad swelling diagnosed by surgical biopsy as calcinosis circumscripta. Despite supportive care over the next 4 years, affected binturongs had progressive weight loss, hyperphosphatemia, and hyperkalemia and developed large radiodense deposits in tissues adjacent to appendicular joints, thoracolumbar vertebrae, and the sternum. Two binturongs died and necropsies showed severe periarticular mineral deposition with fibrosis and granulomatous inflammation. Additionally, binturongs had mineralization of distal renal tubules, mineralization of the renal interstitium, and marked mineralization of the pulmonary interstitium and peribronchiolar smooth muscle. Foot biopsies from the surviving binturong were evaluated by spectroscopic microanalysis and were positive for hydroxyapatite, Ca10(PO4)6(OH)2. Periarticular and footpad mineralization in these binturongs is consistent with hydroxyapatite deposition disease, which is rarely described in humans and animals as a primary familial condition or a secondary condition often associated with renal injury.

COVID-19 associated spontaneous barotrauma: a literature review

Reports of spontaneous pneumothorax and pneumomediastinum as a complication of coronavirus disease (COVID-19) have been increasing. COVID-19 causes inflammatory disease mainly affecting the respiratory system. Severity varies from asymptomatic pulmonary findings on imaging to acute respiratory distress syndrome along with pleural effusions, consolidations and spontaneous pneumomediastinum and pneumothorax. The aim of this paper was to review the literature to explore the association between pneumomediastinum/pneumothorax and COVID-19 respiratory disease, both in patients on ventilators and without ventilators, on a spontaneous basis. To this end, we conducted a comprehensive online literature search using PubMed for articles published with the key words of ‘spontaneous pneumothorax’, ‘pneumomediastinum’ and ‘COVID-19’. Further references were obtained through cross-referencing the bibliographies cited in each publication. We found that spontaneous barotrauma is one of the complications associated with COVID-19 infection and has been observed in patients with and without mechanical ventilation. The process of pneumomediastinum and pneumothorax development is not well understood, especially in patients without underlying lung disease or on mechanical ventilation. We identified various factors that predispose to barotrauma. First, the direct infection of the Type I and Type II pneumocytes by the virus. Second, the pressure gradient between the alveoli and the pulmonary interstitium. Finally, barotrauma can occur secondary to the severe inflammatory response from the COVID-19-related cytokine storm. These conditions are all associated with severe alveolar damage and rupture of the alveolar wall that can produce pneumomediastinum and pneumothorax, both in mechanically ventilated patients and non-ventilated patients. COVID-19 is associated complications result in prolonged mechanical ventilation and length of stay, as well as overall increase in morbidity and mortality. Spontaneous pneumothorax and pneumomediastinum are two serious complications. Education regarding the adjustment of ventilation settlings in the ventilator-dependent COVID-19 patient may perhaps offset the iatrogenic component of barotrauma seen in some such patients.

Polyvinylpyrrolidone functionalization induces deformable structure of graphene oxide nanosheets for lung-targeting delivery

Nanomaterials (NMs) as lung-targeted drug delivery vehicles have attracted great attentions. Recent studies indicated that elastic or deformable property of NMs could play a vital role in biomedical applications. Herein, polyvinylpyrrolidone (PVP) functionalized graphene oxide (GO-PVP) via a facile one-pot method and PEGylated GO (GO-PEG) nanosheets (NSs) were synthesized at room temperature. By using rare earth elemental labeling method, we quantitatively revealed that GO-PVP NSs were targeting retention in the lung that after 4 h intravenous injection, the lung/liver and lung/spleen ratios in GO-PVP treated mice were about 230-fold and 30-fold higher of those in GO-PEG treated mice, respectively, especially a considerable amount was retained in the lower respiratory tract including pulmonary interstitium and alveolar region as fibril-like shapes. The florescence imaging and in situ confocal Raman microscopy combining with laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) elemental imaging analysis further confirmed that a more amount of GO-PVP than GO-PEG retention in the pulmonary interstitium. Utilizing atomic force microscopy PeakForce quantitative nanomechanical mapping technique, the nanomechanical property investigation shows that GO-PVP NSs are softer, more adhesive and deformable than GO-PEG NSs. Further, the molecular dynamics simulations illustrate that GO-PVP has deformable structure due to the hydrogen-bond interaction at basal plane between PVP and GO that cause GO-PVP surface roughness and to possess low solvent accessible surface area (SASA), comparatively, the GO-PEG owns relatively firm structure and higher SASA. This study indicates that the well dispersion property and deformable structure of GO-PVP in the lung contribute to its filtration of the endothelial/epithelial barrier and retention in the interstitium and alveolar region. Importantly, the study inspires us to design elastic or deformable NMs in response to the lung disease especially those have occurred in the lower respiratory tract.

Role of bovine respiratory syncytial virus in etiology of respiratory diseases on milk farms

Bovine respiratory syncytial virus (BRSV) is one of the etiological agents of respiratory diseases. The agent spreads widely in all the countries with intensive livestock farming and can cause pathologic changes in respiratory system either alone or in combination with other viruses and bacteria. It is a matter of crucial importance to study spread of the agent on large milk farms, to detect it in the internal organs of infected animals, and to quantify virus accumulation in them. The purpose of the research was to study peculiarities of RS infection spread, frequency of the virus detection in biomaterial samples (both alone and in associations with infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea/mucosal disease viruses (BVDV) and with Pasteurellaceae bacteria) on large milk farms affected by respiratory animal diseases; and to determine virus concentration in the respiratory organs. BRSV alone was reported in 9.2% of the tested biomaterial samples, as associated with IBR and BVDV it was reported in 1.4% and 5.2% of samples, correspondingly. The number of samples containing simultaneously BRSV and Pasteurellaceae bacteria was 10.8%. The virus was reported in a maximum of 26.6% of the tested samples. With the help of real-time PCR the virus genome was detected in lungs (13.1%), in exudate from trachea, bronchi and nasal sinuses (6.0%), in nasal discharge (4.0%) and in bronchi (1.7%). The virus was seldom detected in trachea and bronchial mucosa (1.1%) and in pulmonary lymph nodes (0.8%). Quantification of BRSV RNA demonstrated that maximum virus accumulation was observed in lungs and nasal charges and it confirms data on its tropism to pulmonary interstitium.

Regulatory mechanisms of neutrophil migration from the circulation to the airspace.

The neutrophil, a short-lived effector leukocyte of the innate immune system best known for its proteases and other degradative cargo, has unique, reciprocal physiological interactions with the lung. During health, large numbers of ‘marginated’ neutrophils reside within the pulmonary vasculature, where they patrol the endothelial surface for pathogens and complete their life cycle. Upon respiratory infection, rapid and sustained recruitment of neutrophils through the endothelial barrier, across the extravascular pulmonary interstitium, and again through the respiratory epithelium into the airspace lumen, is required for pathogen killing. Overexuberant neutrophil trafficking to the lung, however, causes bystander tissue injury and underlies several acute and chronic lung diseases. Due in part to the unique architecture of the lung’s capillary network, the neutrophil follows a microanatomic passage into the distal airspace unlike that observed in other end-organs that it infiltrates. Several of the regulatory mechanisms underlying the stepwise recruitment of circulating neutrophils to the infected lung have been defined over the past few decades; however, fundamental questions remain. In this article, we provide an updated review and perspective on emerging roles for the neutrophil in lung biology, on the molecular mechanisms that control the trafficking of neutrophils to the lung, and on past and ongoing efforts to design therapeutics to intervene upon pulmonary neutrophilia in lung disease.

Wells’ syndrome associated with eosinophilic granulomatosis with polyangiitis − A case report

Introduction. Wells` syndrome (eosinophilic cellulitis) is a chronic, recurrent disease characterized by episodes of erythematous and edematous plaques or nodules with occasional development of hemorrhagic bullae on the trunk and limbs. Eosinophilic granulomatosis with polyangiitis, formerly known as Churg-Strauss syndrome, is a specific variant of the group of diseases characterized by necrotizing vasculitis of small to medium-sized blood vessels affecting multiple organ systems. The association of Wells` syndrome and eosinophilic granulomatosis with polyangiitis is very rare, and to our knowledge has been reported in only ten patients. Case report. We present a case of a 34-year-old woman with a 3-year history of periodical onset of erythematous plaques on the trunk and edematous plaques clinically resembling cellulitis on her lower limbs. The patient reported a one-year history of asthma, rhinosinusitis, and nasal polyposis. Skin biopsy revealed the presence of diffuse eosinophilic infiltrates in the dermis accompanied by characteristic ?flame figures?. Further investigation showed peripheral blood eo-sinophilia (22.6%), bilateral maxillary sinusitis, presence of eosinophil infiltrates and microabscesses in the bron-chial wall, and pericapillary eosinophil infiltrates in the pulmonary interstitium shown by bronchoscopy and transbronchial biopsy, respectively. Treatment was started with methylprednisolone 0.5 mg/kg/day, and the dose was gradually tapered for the following twelve weeks. Complete remission of skin changes was achieved, but new lesions appeared in the past two years, which required repeated treatment. Conclusion. Association of these syndromes is unusual and may be based on the common pathogenetic background. We hypothesize that Wells` syndrome could be a stage preceding eosinophilic granulomatosis with polyangiitis, and that patients should be evaluated for eosinophilic granulomatosis with polyangiitis, since these two diseases overlap in clinical and laboratory findings.

A krónikus obstruktív tüdőbetegség és kezelési lehetőségei

[Chronic obstructive pulmonary disease (COPD) is prognosticated to become the 3rd most prevalent cause of early lethality. It’s main etiology is long-term smoking which induces chronic inflammation and obstruction of the airways as well as elastolysis of the pulmonary interstitium which lead to emphysema. Increased resistance of the intrathoracic airways and emphysema induce hyperinflation of the lung and chest which increases the work-load of the respi­ratory muscles. COPD patients are typically hypoxaemic and normocapnic. Finally, fatigue of the respiratory muscles cause the development of global respiratory failure (hypercapnia and severe hypoxaemia). Most effective intervention is smoking cessation. Maintanance treatment includes inhalational long-acting bronchodilators with or without inhalational corticosteroids. Acute exacerbation is treated with O2 supplementation, inhalational bronchodilators, systemic steroids and/or antiobiotics. Frequency and severity of acute exacerbations prognosticate shorter survival. In chronic respiratory failure long-term home O2 therapy can be provided.]

Suberose- a Doença Profissional mais Portuguesa

Introduction/ background/ objectives Portugal is the world’s largest producer of cork. It is derived from the cork oak (quercus suber) and consists of dead cells with cellulose. The tasks with the highest load are usually assigned to the male and the most repetitive to the female; this implies a different occupational exposure, meaning that exposures of higher risk generally occur almost exclusively in male positions. The first reference to Suberose (cork = suber) was in 1947. However, most studies in the sector were carried out in companies with good working conditions, so the conclusions may not be easily extrapolated to most cork workers. The aim of this bibliographic review is to summarize the most relevant information about the topic. Methodology This is a Bibliographic Review, initiated through a survey conducted in October 2020 in the databases “CINALH plus with full text, Medline with full text, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Nursing and Allied Health Collection: comprehensive, MedicLatina and RCAAP ”. Content The first articles related to the Cork sector highlight the role that some microorganisms have, like Penicillium glabrum (formerly known as frequentans); more recent documents add Chrysonilia Sitophila and Mucor. In places with less humidity the fungal concentration decreases. Workers with Suberosis had skin reactions to the fungus in question and the inhalation of the respective aerosols caused the characteristic symptoms. Some authors also believe that some mites may have some relevance in cork asthma (such as P notatum, Cladosporium, A fumigatus, Alternaria alternata, Acarus siro and Tyrophagus putrescentiae). The suberin found abundantly in cork, may also be associated with some symptoms. Workers are also exposed to cork dust; yet it is less prevalent in the workplace than fungi. Suberose is a pathology of the pulmonary interstitium caused by repeated exposure to dust and mold from cork; in fact, it is the most prevalent disease of the pulmonary interstitium in the north of the country. However, Asthma may also be associated with a lower prevalence. Depending on the size of the fungal spores, Asthma or Hypersensitivity Pneumonitis will be more likely, that is, if smaller (1 to 2 micromers), an alveolar response (alveolitis) will appear more frequently; if larger, a bronchial response, like asthma, can occur. Conclusions The cork industry is reasonably developed in some areas of the country, but knowledge about Suberosis is not always abundant. It would be relevant that all professionals in the Occupational Health Teams with clients in this area were comfortable in the way how to approach the sector; in addition, it is very relevant to develop recent research, disseminating it internationally, not least because Portugal is the country that most developed the sector, worldwide.

The multispiral computed tomography in the early diagnosis of pneumonia caused by SARS-CoV-2

The high informative value of chest computed tomography in the diagnosis of pneumonia caused by SARS-CoV-2 is generally recognized, but there is no enough data on the diagnostic capabilities of this method within 5 first days of the clinical manifestations of the disease. The paper presents the results of chest multispiral (multislice) computed tomography (MSCT) of 56 patients with COVID-19 pneumonia in the early days of the disease. The aim of the study was to analyze the semiotics of pathological changes in the lungs in the first days of the onset of clinical symptoms of COVID-19 and to clarify the methodology for conducting MSCT. Methods. The data of chest MSCT of 56 patients with clinical symptoms of a new coronavirus infection SARS-CoV-2 were analyzed. MSCT was carried out in the first 4 – 5 days of the disease. Results. Five variants for the development of the disease were revealed, including atypical, characterized by the prevalence and CT semiotics of lung damage and apparently due to the different response of the patients to SARS-CoV-2 infection. The leading signs of COVID-19 pneumonia in the early stages of the disease were foci of ground glass opacification (GGO), multifocal lesions of the lungs, edema of the interalveolar pulmonary interstitium, which distinguishes it from pneumonia of another etiology. Conclusion. Comparison of MSCT data and the clinical picture of the disease during the first 5 days suggests with high confidence the pneumonia associated with COVID-19. A prerequisite for conducting MSCT in case of suspicion of this type of pneumonia is the implementation of thin 0.5 – 1.5 mm sections, MSCT performance at suspended full inspiration, post-processing of unenhanced tomogram data in MinIP mode.

COMMON VARIABLE IMMUNODEFICIENCY-ASSOCIATED GRANULOMATOUS-LYMPHOCYTIC INTERSTITIAL LUNG DISEASE DIAGNOSED ON TRANSBRONCHIAL LUNG CRYOBIOPSY

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) is a rare entity involving granulomatous and lymphoproliferative inflammation of the small airways and pulmonary interstitium. Imaging reveals lower lung predominant ground glass and/or consolidative opacities and nodules. Histopathology may have features of lymphocytic interstitial pneumonia, follicular bronchiolitis and/or organizing pneumonia. GLILD is often seen as a manifestation of common variable immunodeficiency (CVID). Diagnosis requires lung biopsy as imaging findings are nonspecific. Surgical lung biopsy (SLB) is the gold standard in diagnosing interstitial lung disease. However, the relatively new, less invasive approach of transbronchial lung cryobiopsy (TBLC) has been increasingly considered for diagnostic purposes for diffuse parenchymal lung disease (DPLD). CASE PRESENTATION: A 58 year old male with a history of idiopathic thrombocytopenic purpura status-post splenectomy and rituximab presented with dyspnea on exertion, chest pressure and a chronic cough. CT chest revealed areas of consolidation and ground glass opacities in a lower lung distribution on a background of pulmonary fibrosis. Pulmonary function tests showed mild restriction and low diffusing capacity. He underwent outpatient TBLC with histopathologic findings of organizing pneumonia, patchy chronic inflammation, fibrosis and peribronchial lymphoid hyperplasia. Labs revealed low IgG and IgA, absence of member B cells, and deficiency of T cells. The patient was diagnosed with GLILD in setting of CVID. He was started on prednisone and IVIG with improvement in imaging findings and symptoms. DISCUSSION: GLILD is a granulomatous and lymphoproliferative disorder that occurs in 8-25% of patients with CVID. Patients may have shortness of breath and cough, as well as splenomegaly, cytopenia, and adenopathy. The constellation of signs and imaging findings are suggestive but not specific. Biopsy is needed for diagnosis. SLB is associated with relatively higher morbidity and mortality compared to TBLC, and necessitates hospitalization. TBLC has been proposed as a less invasive alternative to SLB. Advantages include lower mortality and complication rate, and no requirement for hospitalization. In this case, we demonstrate the utility of TBLC done as an outpatient in obtaining a diagnostic tissue sample, with clinical improvement on steroids and IVIG. There is no standard treatment for GLILD, but corticosteroids are recommended as first line therapy. Success has also been shown with azathioprine, ritxumab and IVIG. CONCLUSIONS: Transbronchial lung cryobiopsy is emerging as a less invasive alternative modality for obtaining tissue with less morbidity, less mortality and the advantage of being performed in the outpatient setting. Further studies regarding safety, diagnostic accuracy and yield in SLB versus TBLC are required to establish TBLC as common practice. Reference #1: Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CIVD). Park JH, Levinson AI. Clin Immunol. 2010; 134(2):97. Reference #2: Transbronchial Lung Cryobiopsy in Idiopathic Pulmonary Fibrosis: A State of the Art Review. Adv Ther (2019) 36:2193-2204. Reference #3: British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders. Hurst JR, Verma N. Lowe D, Daxendale HE, Jolles S, Kelleher P, Longhurst HJ, Patel Sy, Renzoni EA, Sander CR, Avery GR, Babar JL, Buckland MS, Burns S, Egner W, Gompels MM, Gordins P, Haddock JA, Hart SP, Hayman GR, Herriot R, Hoyles RK, Huissoon AP, Jacob J, Nicholson AG, Rassl DM, Sargur RB, Savic S, Seneviratne SL, Sheaff M, Vaailta PM, Walters GI, Whitehouse JL, Wright PA, Condliffe AM. J Allergy Clin Immunol Pract. 2017;5(4):938. Epub 2017 Mar 25. DISCLOSURES: No relevant relationships by Lawrence Benjamin, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria No relevant relationships by Houda Boucekkine, source=Web Response No relevant relationships by Scott Oh, source=Web Response

DIFFUSE PULMONARY MENINGOTHELIOMATOSIS DIAGNOSED BY TRANSBRONCHIAL CRYOBIOPSY

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Minute pulmonary meningothelial-like nodules (MPMNs) are typically asymptomatic, solitary lesions incidentally noted on pathologic evaluation of lung tissue. However, diffuse, bilateral pulmonary involvement, termed diffuse pulmonary meningotheliomatosis (DPM), is exceedingly rare and has only been described in a small number of case studies. We report a case of a patient diagnosed with DPM via transbronchial cryobiopsy. CASE PRESENTATION: A 67-year-old non-smoking female with a history of scleroderma was referred for diffuse bilateral pulmonary nodules found on computed tomography (CT) scan of the chest with mosaicism concerning for diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). Pulmonary function testing was notable for an isolated reduction in diffusing capacity at 58% with a normal echocardiogram. Two transbronchial cryobiopsy samples were obtained from the right lower lobe. Pathology revealed a meningothelial nodule. Immunohistochemistry was positive for epithelial membrane antigen (EMA) as well as progesterone receptor (PR) and negative for synaptophysin and chromogranin. Follow up imaging at 1 year demonstrated stability. Taken in context with her radiographic findings, the patient was diagnosed with DPM. DISCUSSION: DPM is an extremely rare condition characterized by MPMNs diffusely involving lung parenchyma. It predominantly affects females (2.2:1) with a median age of 59-62. DPM has no predilection for specific lobes, and it can be mistaken for metastatic or interstitial disease. Histologically, MPMNs appear as epithelioid cells arranged in small nests in pulmonary interstitium. Immunochemically, MPMNs tend to be positive for vimentin, EMA and PR and negative for S-100 protein, chromogranin A, and synaptophysin. Though the clinical significance of DPM is still unclear, prior studies have noted higher incidence among patients with underlying lung disease, particularly thromboembolism and malignancy. CONCLUSIONS: In summary, we present a case of DPM diagnosed by transbronchial cryobiopsy to highlight the importance of considering DPM in the differential of bilateral micronodular lung disease. Reference #1: Korn D, Bensch K, Liebow AA, Castleman B. Multiple minute pulmonary tumors resembling chemodectomas. Am J Pathol. 1960;37(6):641–672. Reference #2: Gaffey MJ, Mills SE, Askin FB. Minute pulmonary meningothelial-like nodules. A clinicopathologic study of so-called minute pulmonary chemodectoma. Am J Surg Pathol 1988; 12: 167-175. Reference #3: Gleason JB, Valentin R, Almedia P, Martinez N, Bejarano PA. Diffuse pulmonary meningotheliomatosis: a literature review of a rare diffuse parenchymal lung disease with unclear clinical significance. J Assoc Chest Physic 2017; 5: 18-25. DISCLOSURES: Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria No relevant relationships by I. Obi Emeruwa, source=Web Response No relevant relationships by Scott Oh, source=Web Response No relevant relationships by Megan Trieu, source=Web Response

The therapeutic effect of carnosine combined with dexamethasone in the lung injury of seawater-drowning

Objective: To explore the therapeutic effect of carnosine and dexamethasone in lung injury caused by seawater drowning. Methods: The in vitro experiments with A549 cells were divided into 5 groups: blank control group (C), seawater injury group (S), seawater injury+dexamethasone treatment group (S+D), seawater injury+carnosine treatment group (S+C), seawater injury dexamethasone and carnosine combined therapy(S+D+C) group. The optimal therapeutic dose of drugs for the treatment of seawater drowning lung injury was tested in vitro. Based on the optimal dose, the levels of TNF-α and IL-6 in each group at different time points were detected at the cell level by ELISA. The level of apoptosis was detected by flow cytometry. The in vivo experiments with SD rats were randomly divided into 5 groups (n=8 each): blank control group (RC),seawater drowning injury group (RS),seawater drowning injury+dexamethasone treatment group (RSD),seawater drowning injury+carnosine treatment group (RSC),seawater drowning injury+dexamethasone+carnosine combined treatment group (RSDC). The animal model with seawater inhalation acute lung injury was made by intratracheal infusion (4 ml/kg). The pathological changes of the lungs were observed. The expression of superoxide dismutase (SOD) in each group was detected by Western blot. Results: The results of in vitro experiments showed significant increase of apoptosis after seawater injury. The normal cell rate in group C was 98.3% while the apoptosis rate was 1.7%. The normal cell in group S was 18.8%, and the apoptosis rate was 81% (P<0.01). TNF-α and IL-6 levels in group S increased to 180.25 ng/L and 61.56 ng/L, respectively, which were statistically significant compared with group C (P<0.01). After drug protection, apoptosis was reduced in S+D group, S+C group and S+D+C group, with apoptosis rates of 65.4%, 70.9% and 42.6%, respectively. The contents of TNF-α and IL-6 also decreased in the S+D+C group (P<0.01). The results of in vivo experiments showed obvious lung injury and disordered lung tissue structures in the RS group at 4 h after modeling. There was hemorrhage in the pulmonary interstitium and a large number of inflammatory cells. Results of western blot showed that the expression of SOD increased in the RS group. Compared with RS group, the treatment alleviated acute lung injury and decreased the expression level of SOD in RSD, RSC and RSDC groups (P<0.01). Conclusion: Dexamethasone and carnosine reduced the influence of seawater inhalation on the lung in the rat model. The positive effect of combination of these two drugs on lung injury caused by seawater inhalation was stronger than a single drug.

Serum surfactant protein A as a surrogate biomarker of a negative heart sign among patients with interstitial lung disease.

ABSTRACTThe mechanisms underlying interstitial lung disease (ILD) are characterized by variable inflammation or fibrosis of the pulmonary interstitium. A negative heart sign (NHS) on 67Ga scintigrams of patients with ILD is due to considerably increased inflammatory activity in the lungs. We retrospectively analyzed relationships between NHS and established biomarkers of disease severity in patients with ILD. Among 81 consecutive non-smoking patients with ILD (mean age, 63 years) who had been hospitalized between April 2009 and October 2011, we selected 52 who had been assessed by 67Ga scintigraphy. We then evaluated relationships between NHS and blood biomarkers, pulmonary function and high-resolution computed tomography (HRCT). Among these 52 patients, 10 showed idiopathic pulmonary fibrosis and 42 had other ILD. Multivariate analysis with stepwise variable selection, serum surfactant protein (SP)-A (OR (odds ratio), 1.026; 95%CI (confidence interval), 1.003–1.050; P = 0.024) and inflammation index calculated from HRCT findings (OR, 1.358; 95%CI, 1.079–1.709; P = 0.009) were significant predictors of an NHS. Serum SP-A offered 85% sensitivity and 75% specificity for predicting NHS at an optimal cut-off of 45.8 ng/mL. Serum SP-A concentrations correlated positively with inflammation index (r = 0.344, P = 0.015). In conclusion, serum SP-A might serve as a surrogate biomarker for predicting an NHS in patients with ILD.

Balneotherapy and hydrotherapy in chronic respiratory disease.

Chronic respiratory diseases (CRD) belong to major noncommunicable diseases (NCD) targeted by World Health Organization (WHO) NCD Action Plan and United Nations (UN) Sustainable Development Goal (STG) 3.4 to achieve 30% decline of mortality by the year 2030. Strong evidence is now available in the literature for therapeutic aquatic exercise interventions in improving health status of chronic obstructive pulmonary diseases (COPD) patients. However, gym-based exercises can be difficult for patients with COPD who are mainly elderly and often have co-morbidities—such as severe arthritis and obesity—which may impair their ability to exercise at an adequate intensity. Besides improving respiratory function and health status in COPD, exercise in water helps overcoming patient’s fears and promote socialization, contrasting the risk of depression, which is a major condition often associated with long term COPD condition. Susceptibility to respiratory infections plays a role in exacerbations of COPD. Sulphur-rich water inhalations improve muco-ciliary clearance, reduce inflammatory cytokines production and inflammatory mucosal infiltration, reduce elastase secretion by neutrophils, preserving elastic properties of pulmonary interstitium and thus facilitating expectoration. Repeated cold water stimulations in COPD also reduce frequency of infections. Finally, sauna bathing reduces the risk of pneumonia. On the other side, hydrotherapy/balneotherapy also help obesity control, which is one of the most difficult NCD risk factors to modify and consequently is an important component of the WHO preventive strategy to achieve STG 3.4. Along with high prevalence and mortality, CRD cause increasing pharmaceutical and hospital costs. In this perspective, Health Resort Medicine should not be ignored as a resource in the WHO NCD strategy and Universal Health Coverage, providing a multi-stakeholder platform (including the network of health resorts and their facilities) able to give a real help to the achievement of UN goal STG 3.4 by the year 2030.

CT features of COVID-19 patients with two consecutive negative RT-PCR tests after treatment

The objective of this study is to expound the CT features of COVID-19 patients whose throat swab samples were negative for two consecutive nucleic acid tests after treatment. We retrospectively reviewed 46 COVID-19 patients with two consecutive negative RT-PCR tests after treatment. The cases were divided into moderate group and severe/critical group according to disease severity. Clinical and CT scanning data were collected. CT signs of pulmonary lesions and the score of lung involvement were expounded. Thirty-nine moderate cases and seven severe/critical cases were included. Residual pulmonary lesions were visible in CT images. Moderate patients showed peripheral lesions while severe/critical cases exhibited both central and peripheral lesions with all lobes involvement. Mixed ground glass opacity (GGO) and pulmonary consolidation were noted. A larger proportion of severe patients showed reticular pulmonary interstitium thickening. Air bronchogram, pleural effusion, vascular enlargement, bronchial wall thickening, bronchiectasis, pleural thickening and pleural adhesion were more frequently observed in severe/critical group. The severe/critical group showed higher CT score. Pulmonary lesions persisted even after twice consecutive negative nucleic acid tests. We strongly recommended regular follow-up of CT scans after nucleic acid tests conversion. Evaluation of complete remission should base on chest CT.

Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice

BackgroundPneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model.MethodsThe network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP-induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (ribavirin or ceftriaxone sodium injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Proteins expression was quantified by western blotting.ResultsThe network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway.ConclusionOur findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.

Transcription factor YY1 inhibits the expression of THY1 to promote interstitial pulmonary fibrosis by activating the HSF1/miR-214 axis

Interstitial pulmonary fibrosis (IPF) is a progressive disease of diverse etiology manifesting with proliferation of lung fibroblasts and accumulation of extracellular matrix deposition in pulmonary interstitium. Recent studies show aberrant expression of mRNAs and microRNAs (miRNAs) in human embryonic pulmonary fibroblasts (HEPFs). In this study, we investigated effects of the YY1/HSF1/miR-214/THY1 axis on the functions of HEPFs and IPF. Loss- and gain-of-function tests were conducted to identify roles of YY1, HSF1, miR-214, and THY1 in IPF. As determined by RT-qPCR or western blot assay, silencing YY1 down-regulated HSF1 expression and attenuated the expression of pro-proliferative and fibrosis markers in HEPFs. Meanwhile, viability of HEPFs was impeded by YY1 knockdown. The binding relationship between miR-214 and THY1 was verified using dual-luciferase reporter assay. In HEPFs, down-regulation of HSF1 reduced miR-214 expression to repress proliferation and fibrogenic transformation of HEPFs, while inhibition of miR-214 expression could restrain the fibrogenic transformation property of HEPFs by up-regulating THY1. Subsequently, IPF model in mice was induced by bleomycin treatment. These animal experiments validated the protective effects of YY1 knockdown against IPF-induced lung pathological manifestations, which could be reversed by THY1 knockdown. Our study demonstrates the important involvement of YY1/HSF1/miR-214/THY1 axis in the development of IPF.