Type Of Interstitial Pneumonia Research Articles

LncRNA-mediated ceRNA network reveals the mechanism of action of Saorilao-4 decoction against pulmonary fibrosis.

Introduction: Pulmonary fibrosis (PF), a type of interstitial pneumonia with complex etiology and high mortality, is characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. In this study, we screened for potential biomarkers in PF and clarified the role of the lncRNA-miRNA-mRNA ceRNA network in the inhibitory effect of SRL-4 on PF. Methods: Healthy male SPF SD rats were randomly divided into three groups, namely, CON, MOD, and SRL-4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to determine the biological functions of the target genes. A visualized lncRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, while key genes in the network were identified using the cytoNCA plugin. Results: Seventy-four differentially expressed lncRNAs and 118 differentially expressed mRNAs were identified. Gene Ontology analysis revealed that the target genes were mainly enriched in the cell membrane and in response to organic substances, while Kyoto Encyclopedia of Genes and Genomes analysis showed that the target genes were mainly enriched in the AMPK, PPAR, and cAMP signaling pathways. We elucidated a ceRNA axis, namely, Plcd3-OT1/rno-miR-150-3p/Fkbp5, with potential implications in PF. Key genes, such as AABR07051308.1-201, F2rl2-OT1, and LINC3337, may be important targets for the treatment of PF, while the AMPK, PPAR, and cAMP signaling pathways are potential key targets and important pathways through which SRL-4 mitigates PF. Conclusion: Our findings suggest that SRL-4 improves PF by regulating the lncRNA-miRNA-mRNA network.

Evaluation of lung protection of Sanghuangporus sanghuang through TLR4/NF-κB/MAPK, keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 signaling pathways mediating apoptosis and autophagy

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial pneumonia characterized by chronic and progressive fibrosis with an unknown etiology. Previous pharmacological studies have shown that Sanghuangporus sanghuang possesses various beneficial properties including immunomodulatory, hepatoprotective, antitumor, antidiabetic, anti-inflammatory, and neuroprotective effects. This study used a bleomycin (BLM)-induced IPF mouse model to illustrate the possible benefits of SS in ameliorating IPF. BLM was administered on day 1 to establish a pulmonary fibrosis mouse model, and SS was administered through oral gavage for 21 d. Hematoxylin and eosin (H&E) and Masson’s trichrome staining results showed that SS significantly reduced tissue damage and decreased fibrosis expression. We observed that SS treatment resulted in a substantial lowering in the level of pro-inflammatory cytokines like TGF-β, TNF-α, IL-1β, and IL-6 as well as MPO. In addition, we observed a notable increase in glutathione (GSH) levels. Western blot analysis of SS showed that it reduces inflammatory factors (TWEAK, iNOS, and COX-2), MAPK (JNK, p-ERK, and p-38), fibrosis-related molecules (TGF-β, SMAD3, fibronectin, collagen, α-SMA, MMP2, and MMP9), apoptosis (p53, p21, and Bax), and autophagy (Beclin-1, LC3A/B-I/II, and p62), and notably increases caspase 3, Bcl-2, and antioxidant (Catalase, GPx3, and SOD-1) levels. SS alleviates IPF by regulating the TLR4/NF-κB/MAPK, Keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 pathways. These results suggest that SS has a pharmacological activity that protects the lungs and has the potential to improve pulmonary fibrosis.

Effect of the 2020 hypersensitivity pneumonitis guideline on the pathologic diagnosis of interstitial pneumonia

It was reported that the 2020 guideline for hypersensitivity pneumonitis (HP) might result in the overdiagnosis of fibrotic HP (fHP). fHP and other types of interstitial pneumonias have several overlapping characteristics, and a high diagnostic concordance rate of fHP is rarely obtained. Therefore, we investigated the impact of the 2020 HP guideline on the pathological diagnosis of cases previously diagnosed as interstitial pneumonia. We identified 289 fibrotic interstitial pneumonia cases from 2014 to 2019 and classified them into four categories according to the 2020 HP guideline: typical, probable, and indeterminate for fHP and alternative diagnosis. The original pathological diagnosis of 217 cases were compared to their classification as either typical, probable, or indeterminate for fHP according to the 2020 guideline. The clinical data, including serum data and pulmonary function tests, were compared among the groups. Diagnoses changed from non-fHP to fHP for 54 (25%) of the 217 cases, of which, 8 were typical fHP and 46 were probable fHP. The ratio of typical and probable fHP cases to the total number of VATS cases was significantly lower when using transbronchial lung cryobiopsy (p < 0.001). The clinical data of these cases bore a more remarkable resemblance to those diagnosed as indeterminate for fHP than to those diagnosed as typical or probable. The pathological criteria in the new HP guidelines increase the diagnosis of fHP. However, it is unclear whether this increase leads to overdiagnosis, and requires further investigation. Transbronchial lung cryobiopsy may not be helpful when using the new criteria to impart findings for fHP diagnosis.

GROUND GLASS OPACITIES: SIGN OF CAUTION IN TYPICAL INTERSTITIAL PNEUMONIA

Typical interstitial pneumonia (IP) is mainly the fibrotic form of interstitial lung disease. In some cases with typical IP, a certain amount of ground-glass opacity (GGO) can be detected on high-resolution computed tomography, however, some important issues, such as the co-existence of GGO and typical IP, still require further investigation by biopsy. After the diagnosis of typical IP, anti-fibrosis treatment is usually considered. Here, we hypothesized that GGO in typical IP could be a manifestation of an acute inflammatory attack requiring immunosuppressive therapy or an indicator of ongoing contact with trigger factors that initiate pathological reactions in typical IP.

Exploring the Value of Features of Lung Texture in Distinguishing Between Usual and Nonspecific Interstitial Pneumonia

This article aims to explore the potential use of lung texture assessed in CT images in distinguishing between the usual interstitial pneumonia and the nonspecific interstitial pneumonia. A retrospective analysis of 96 cases of interstitial pneumonia was performed. Among these cases, there were 40 cases of usual interstitial pneumonia (UIP) and 56 cases of the nonspecific interstitial pneumonia (NSIP) . All of the patients underwent computed tomography (CT) scans. A lung intelligence kit (LK) was utilized to perform lung segmentation and texture feature extraction. The significant variables were determined by variance analysis, least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Finally, a multivariate logistic regression model was established to distinguish between the two types of interstitial pneumonia. Receiver operating characteristic (ROC) curves, area under the curve (AUC) values, sensitivity, and specificity were used to evaluate the performance of the established model. A total of 100 texture features were extracted from the whole lung that was segmented by LK, and 8 features remained after feature reduction. The AUC, sensitivity, and specificity of the multivariate logistic regression model in the training group and the test group were 0.952 and 0.838, 0.821 and 0.667, and 0.949 and 0.824, respectively. It is possible to distinguish between UIP and NSIP using lung texture features obtained from CT images.

An Overview of Herbal Medicines for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung scarring condition with the histological characteristic of typical interstitial pneumonia. Injury to alveolar epithelial cells is a critical precursor in the pathogenesis of this disease. The prevalence of IPF is growing exponentially, with substantial morbidity and mortality rates increasing the burden on economic healthcare costs. A multidisciplinary approach for diagnosis is used to rule out the alternative causes of interstitial lung disease. Pirfenidone and nintedanib, two innovative antifibrotic medicines introduced in recent years, have provided therapeutic benefits to many IPF patients, and several IPF medications are in the early phases of clinical trials. However, available medications can cause unpleasant symptoms such as nausea and diarrhoea. More efforts have been made to uncover alternative treatments towards a more personalised patient-centred care and hence improve the outcomes in the IPF patients. Through a multi-level and multi-target treatment approach, herbal medicines, such as Traditional Chinese Medicine (TCM), have been identified as revolutionary medical treatment for IPF. Due to their natural properties, herbal medicines have shown to possess low adverse effects, stable therapeutic impact, and no obvious drug dependencies. Herbal medicines have also shown anti-inflammatory and anti-fibrotic effects, which make them a promising therapeutic target for IPF. A growing number of formulas, herbal components, and various forms of Chinese herbal medicine extracts are available for IPF patients in China. This review summarises the role of herbal medicines in the prevention and treatment of IPF.

Interstitial pneumonia and diffuse alveolar damage in domestic animals.

Classification of pneumonia in animals has been controversial, and the most problematic pattern is interstitial pneumonia. This is true from the gross and histologic perspectives, and also from a mechanistic point of view. Multiple infectious and noninfectious diseases are associated with interstitial pneumonia, all of them converging in the release of inflammatory mediators that generate local damage and attract inflammatory cells that inevitably trigger a second wave of damage. Diffuse alveolar damage is one of the more frequently identified histologic types of interstitial pneumonia and involves injury to alveolar epithelial and/or endothelial cells, with 3 distinct stages. The first is the "exudative" stage, with alveolar edema and hyaline membranes. The second is the "proliferative" stage, with hyperplasia and reactive atypia of type II pneumocytes, infiltration of lymphocytes, plasma cells, and macrophages in the interstitium and early proliferation of fibroblasts. These stages are reversible and often nonfatal. If damage persists, there is a third "fibrosing" stage, characterized by fibrosis of the interstitium due to proliferation of fibroblasts/myofibroblasts, persistence of type II pneumocytes, segments of squamous metaplasia of alveolar epithelium, plus inflammation. Understanding the lesion patterns associated with interstitial pneumonias, their causes, and the underlying mechanisms aid in accurate diagnosis that involves an interdisciplinary collaborative approach involving pathologists, clinicians, and radiologists.

High complement protein C1q levels in pulmonary fibrosis and non-small cell lung cancer associated with poor prognosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common type of interstitial pneumonia. Lung cancer, mainly non-small cell lung cancer (NSCLC), is a complication of idiopathic pulmonary fibrosis. IPF is also an independent risk factor of lung cancer. Some studies have shown that the complement system can promote the progression of interstitial pulmonary fibrosis. In addition, C1q has also demonstrated to exert a tumor-promoting effect in many tumors. However, the role of C1q in idiopathic pulmonary fibrosis and lung cancer still remain unclear.MethodsWe selected common differentially expressed genes in IPF and non-small cell lung cancer using datasets from GEO, and investigated common hub gene. The hub genes were validated in IPF by establishing mouse model of IPF and using another four datasets from the GEO. Multiple databases were analyzed including those of Kaplan–Meier Plotter, Tumor Immune Estimation Resource (TIMER2.0) and the Human Protein Atlas (HPA) for NSCLC.ResultsIn this study, 37 common DEGs were identified in IPF and NSCLC including 32 up-regulated genes and 5 down-regulated genes, and C1q was identified as common hub gene. The methylation status of C1q decreased and the expression levels of C1q increased in both lung cancer and idiopathic pulmonary fibrosis. The prognosis of non-small cell lung cancer and IPF patients with high levels of C1q is poor.ConclusionsThese results show that C1q participates in pulmonary fibrosis and non-small cell lung cancer, and may be a potential diagnostic / prognostic biomarker or a therapeutic target.

Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case\u2013control study

PurposeThe immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia—idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis.MethodsEleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects.ResultsThe odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03–0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease.ConclusionThe administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

FEATURES OF THE COURSE AND TIMING OF DIAGNOSIS OF PLEUROPULMONARY COMPLICATIONS OF CORONAVIRUS INFECTION

Coronavirus infection in most cases is of the type of interstitial pneumonia. According to the literature, the most common complications are thrombotic complications of the lungs, myocardium, central nervous system, liver, and kidneys. There are only isolated reports of pleural complications. The aim. To study the features of the course and term of diagnosis of pleuropulmonary complications, specifying the possibilities of their prevention and exclusion of errors. Materials and methods. Under our supervision, there were 23 patients with various complications of pleuropulmonary character. Among these patients, there were 15 males, 8 – females. There were ten patients under the age of 50 and 13 over the age of 50. The interstitial background in all patients was interstitial changes in the lung parenchyma. Results and discussion. Deterioration of patients (increased temperature, shortness of breath, cough, and decreased blood oxygenation) forced doctors to resort to additional examination and consultation with specialists after a certain period of observation (4–5 days). Pulmonary and pleural hemorrhage occurred in 2 (8,72 %) subjects, spontaneous pneumothorax, including and 1 bilateral, occurred in 5 (21,7 %) patients, pneumohydrothorax – in 4 (14,4 %), pneumomediastinum – in 2 (8,7 %), severe pneumothorax – in 7 (30,4 %) people. The most serious complications were the impression of the pleura with a violation of the integrity of the cortical lungs (pneumohydrothorax, intense pneumothorax), which led to death in 6 (26,1 %) people. The period before the diagnosis of complications was in the range of 4–6 days. Conclusions. Physical control of patients with signs of respiratory failure should be performed every 2 hours, ultrasound – three times a day, examination and lateral radiography – with the duration of shortness of breath more than two days or its increase, without waiting for the time suggested by the radiologist.

The long non-coding RNA PFI protects against pulmonary fibrosis by interacting with splicing regulator SRSF1.

Pulmonary fibrosis (PF) is a type of interstitial pneumonia with complex etiology and high mortality, characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. Recently, there has been growing appreciation of the importance of long non-coding RNAs (lncRNAs) in organ fibrosis. The aim of this study was to investigate the role of lncRNAs in lung fibrosis. We used a qRT-PCR assay to identify dysregulated lncRNAs in the lungs of mice with experimental, bleomycin (BLM)-induced pulmonary fibrosis, and a series of molecular assays to assess the role of the novel lncRNA NONMMUT060091, designated as pulmonary fibrosis inhibitor (PFI), which was significantly downregulated in lung fibrosis. Functionally, knockdown of endogenous PFI by smart silencer promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in primary mouse lung fibroblasts (MLFs). In contrast, overexpression of PFI partially abrogated TGF-β1-induced fibrogenesis both in MLFs and in the human fetal lung fibroblast MRC-5 cells. Similarly, PFI overexpression attenuated BLM-induced pulmonary fibrosis compared with wild type (WT) mice. Mechanistically, using chromatin isolation by RNA purification-mass spectrometry (ChIRP-MS) and an RNA pull-down assay, PFI was found to directly bind Serine/arginine-rich splicing factor 1 (SRSF1), and to repress its expression and pro-fibrotic activity. Furthermore, silencing of SRSF1 inhibited TGF-β1-induced proliferation, differentiation, and ECM deposition in MRC-5 cells by limiting the formation of the EDA+Fn1 splicing isoform; whereas forced expression of SRSF1 by intratracheal injection of adeno-associated virus 5 (AAV5) ablated the anti-fibrotic effect of PFI in BLM-treated mice. Overall, these data reveal that PFI mitigated pulmonary fibrosis through negative regulation of the expression and activity of SRSF1 to decrease the formation of the EDA+Fn1 splicing isoform, and suggest that PFI and SRSF1 may serve as potential targets for the treatment of lung fibrosis.

Radiološka slika KOVID-19 pneumonije

Interstitial pneumonia is the main manifestation of the COVID-19 disease. The aim of this paper is to present the spectrum of typical radiological findings (CT - computed tomography, and radiographic) in COVID-19 pneumonia, the different CT examination techniques, the types and evolution of inflammatory lesions in the lungs, the criteria for assessing the probability of COVID-19 pneumonia in comparison to other types of interstitial pneumonia, and the scoring systems for determining the extent of COVID-19 pneumonia, based on CT findings and radiography. The standard CT examination protocol is a native CT examination of the chest, and, due to high sensitivity of low-dose CT protocols for detecting lung lesions, this imaging technique has become widely used in radiological practice during the COVID-19 pandemic. Bilateral, multiple, round or confluent zones of ground-glass density, predominantly localized subpleurally, peripherally and posteriorly, usually most extensive in the lower lobes, represent a typical CT presentation of COVID-19 pneumonia. Consolidations may develop at a later stage. A chest X-ray shows homogeneously reduced transparency in the lateral pulmonary fields, circular and irregular cloudlike shadows, and confluent patchy shadows, usually most extensive basally and laterally. RSNA and CO-RADS criteria are used to assess the probability of COVID-19 pneumonia, based on the criteria of a typical/atypical CT finding. Four stages of COVID-19 pneumonia have been defined, based on the dynamics of inflammatory lung lesion presentation: early, progressive, the phase of consolidation and the phase of organization. To assess the extent and severity of pneumonia, various scoring systems have been proposed, the most widely accepted one being the CT severity scoring system, based on visual semiquantitative assessment of the percentage of lung parenchyma inflammation lesions involvement of each of the five lobes, on a scale of 1 (&lt;5%) to 5 (&gt;75%), whereby the maximum score can be 25.

Effectiveness of polymyxin B hemoperfusion in acute exacerbation of interstitial pneumonia: a retrospective analysis.

Background:Acute exacerbation (AE) of interstitial pneumonia (IP) occurs commonly and has a poor prognosis. Polymyxin B hemoperfusion (PMX-DHP) has a beneficial effect on AE of some types of IPs, particularly idiopathic pulmonary fibrosis (IPF). However, little is known about the efficacy of PMX-DHP in the Korean population. The aim of this study was to examine the effectiveness of PMX-DHP in AE of IP.Methods:We conducted a retrospective study of 12 patients with AE of IP, including two patients with AE of IPF, who were treated with PMX-DHP at our center. Treatment with PMX-DHP was carried out once or twice. We collected and analyzed data on changes in oxygenation with PMX-DHP and survival after AE.Results:In patients with AE of IP, the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, or the P/F ratio, had significantly improved at the end of the treatment with PMX-DHP (87.0 [80.3 – 130.9] to 200.6 [105.0 – 245.5] mmHg, p = 0.019). The white blood cell (WBC) count had significantly reduced at the end of the treatment (12,400 [8,860 – 20,287] to 6,800 [3,950 – 15,775]/mm3, p = 0.050). The 28-day and in-hospital mortality rates of patients after AE of IP were 41.7 % and 75.0 %, respectively.Conclusion:PMX-DHP improved oxygenation and reduced the WBC count in patients with AE, with either steroids alone or steroids and cyclophosphamide. Further studies are required to verify the potential benefits of PMX-DHP for patients with AE of IP.

ORGANIZING PNEUMONIA: A RARE MANIFESTATION OF EARLY-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Systemic Lupus Erythematosus (SLE) affects lungs (30-50%) with pleurisy being the commonest manifestation. Interstitial Pneumonia (IP) related to SLE was found be less reported about 10% and Organizing Pneumonia (OP) type of IP was noted to be very rare (1). Here, we present a rare case of Organizing pneumonia manifesting in SLE CASE PRESENTATION: A 30-year-old female with history of left breast carcinoma status post bilateral mastectomy, adjuvant chemotherapy and radiation therapy completed in March 2019, sickle cell trait and SLE, first presented in January 2020 with dyspnea and cough. CT chest revealed bilateral lower lobe predominant consolidative opacities with air bronchogram and multifocal sub-pleural ground glass opacities throughout both the lungs [Fig 1A], she was treated for pneumonia. On next admission, she also complained of generalized myalgias/arthralgias and unresolving skin rashes on extremities and neck with topical steroids. No other system involvement except for proteinuria. ANA, ds-DNA and lupus anticoagulant were positive with elevated CRP. CT chest slightly worsened compared to previous CT [Fig 1B]. Bronchoscopy revealed normal gross appearance. RLL trans-bronchial biopsy pathology showed mild chronic interstitial inflammation, intra-alveolar macrophages and focal secondary organizing pneumonia with no specific features. She was started on Plaquenil and long-term low dose steroids that controlled her symptoms DISCUSSION: SLE commonly manifests as lung pathology varying from pleurisy (50%), lung parenchymal disease (10-15%) and pulmonary vascular hypertension (1,2). SLE induced IP commonly presents as Chronic IP (63.6%). The most common HRCT finding is unclassifiable and Nonspecific IP (NSIP) is shown to be the most common histopathology (1). Previous articles reported that pulmonary manifestations especially ILD and serositis usually present as a late manifestation or in SLE patients diagnosed at an older age (1,3,4) with no gender predominance. OP has a well-known association with connective tissue disorders like Rheumatoid Arthritis and Myositis but there are only a handful of cases of SLE reported in association with Bronchio-Obliterans Organizing Pneumonia (BOOP), and commonly seen in older women(1). In contrast our patient was young 30-year-old female who had isolated Organizing pneumonia identified as an early manifestation / initial presentation of SLE. Also, it is possible that OP resulted following a predisposing pulmonary insult in SLE – pneumonia and chest radiotherapy. It was noted from metanalysis that NSIP with OP was a favorable prognosis in patients with SLE compared to other histopathology (2,5) CONCLUSIONS: Though rare, Organizing Pneumonia can occur at any age of onset/ duration of SLE and early diagnosis and treatment with steroids and immunosuppression decreases morbidity and mortality from lung manifestations in SLE, given its favorable prognosis Reference #1: 1. Toyoda Y, Koyama K, Kawano H, Nishimura H, Kagawa K, Morizumi S, et al. Clinical features of interstitial pneumonia associated with systemic lupus erythematosus. Respir Investig. 2019;57(5):435–43. Reference #2: 2. Enomoto N, Egashira R, Tabata K, Hashisako M, Kitani M, Waseda Y, et al. Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study. Sci Rep. 2019;9(1):1–11.v Reference #3: 5. Tselios K, Urowitz MB. Cardiovascular and Pulmonary Manifestations of Systemic Lupus Erythematosus. Curr Rheumatol Rev. 2017;13(3):206–18. DISCLOSURES: No relevant relationships by Rathnavali Katragadda, source=Web Response No relevant relationships by Vinod Khatri, source=Web Response No relevant relationships by Leela Krishna Vamsee Miriyala, source=Web Response No relevant relationships by Shanti Pittampalli, source=Web Response

Clinical study of 34 patients with cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation

目的分析异基因造血干细胞移植（allo-HSCT）后巨细胞病毒（CMV）肺炎的临床特点及预后。方法对2016年3月1日至2019年6月30日在上海市第一人民医院血液科接受allo-HSCT后并发CMV肺炎的患者进行回顾性分析。结果①全部411例allo-HSCT患者中，34例（8.3％）移植后发生CMV肺炎，其中男18例，女16例，中位年龄32（8～62）岁；急性髓系白血病14例，急性淋巴细胞白血病10例，骨髓增生异常综合征5例，非霍奇金淋巴瘤3例，再生障碍性贫血2例。②CMV肺炎中位发病时间为移植后53（36～506）d，主要症状为咳嗽（26例，76.5％）、发热（23例，67.6％）及气促（14例，41.2％），仅17.6％（6/34）的患者有咯痰，2例（5.9％）患者早期无明显症状而在常规胸部CT检查时发现。28例（82.4％）患者的影像学表现为小叶中心结节、弥漫毛玻璃影等典型间质性肺炎改变，6例（17.6％）表现为斑片、结节以及实变样不典型影像学改变。③26例（76.5％）患者血浆CMV-DNA阳性，拷贝数低于同期BALF检测结果［1.70×107（5.44×105～4.45×109）拷贝/L对1.45×108（1.10×107～1.10×1011）拷贝/L，P＝0.004］。④13例（38.2％）CMV肺炎患者合并其他下呼吸道病原体感染（真菌10株，细菌6株，腺病毒1株）。⑤所有患者中位随访时间12.8（0.4～46.5）个月，总生存率为58.82％，年龄≥40岁、接受高流量通气是CMV肺炎患者独立预后不良因素（P＝0.049，P＝0.009）。结论气管镜肺泡灌洗液检测有助于提升allo-HSCT后CMV肺炎病原学诊断的准确性。年龄≥40岁及接受高流量通气是CMV肺炎患者独立预后不良因素。

Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.

The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

BackgroundAcute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is devastating with no established treatment. This phenomenon involves disordered coagulation and excessive inflammatory reactions. As recombinant human soluble thrombomodulin (rhsTM) possesses anti-coagulative and anti-inflammatory properties, the medicine is expected to improve the prognosis of the disease. The aim of this study was to summarize current evidence regarding benefits and harms of rhsTM treatment for AE of IPF.MethodPatients with AE of IPF were eligible for the review and all of the other types of interstitial pneumonias were excluded. The effect of rhsTM treatment on the outcomes such as all-cause mortality was estimated in comparison to conventional therapy. Primary studies of any design aside from a case report were reviewed. Electronic databases such as Medline and EMBASE were searched from 2002 through August 14, 2019. Two reviewers independently selected eligible reports and extracted relevant data. A risk of bias of individual studies was assessed similarly. Meta-analysis was conducted for univariate results if at least three studies were available for the same outcome.ResultOut of a total of 390 records identified, eight studies were first deemed eligible and four of them were finally focused for the review. Only one study was a prospective trial and a historical control was employed in all studies. An overall risk of bias was rated as serious in three out of four studies. A total of 169 subjects were included. Two out of three studies that reported 3-month all-cause mortality by univariate analysis demonstrated beneficial effects of rhsTM treatment and a pooled analysis demonstrated that rhsTM treatment improved 3-month all-cause mortality with a risk ratio of 0.50 (95% confidence interval (CI): 0.35–0.72). All two studies reporting multivariate results demonstrated that rhsTM treatment improved 3-month all-cause mortality with odds ratios of 0.21 (95% CI: 0.05–0.91) and 0.25 (95% CI: 0.09–0.68), respectively. There were no serious adverse events.ConclusionThe rhsTM treatment was demonstrated to improve 3-month all-cause mortality of AE of IPF with no serious adverse events. However, these findings should be interpreted with caution due to a small number of studies and serious risk of bias.

Age-related rhesus macaque models of COVID-19.

BackgroundSince December 2019, an outbreak of the Corona Virus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS‐CoV‐2 was a need to explore the possible age‐related phenomena with non‐human primate models.MethodsThree 3‐5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS‐CoV‐2, and then analyzed by clinical signs, viral replication, chest X‐ray, histopathological changes and immune response.ResultsViral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS‐CoV‐2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages.ConclusionSARS‐CoV‐2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS‐CoV‐2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS‐CoV‐2 infection.

Компьютерная томография в диагностике различных форм амиодарон-индуцированной легочной токсичности

Purpose: To determine computed tomography subtypes of amiodarone-induced pulmonary toxicity (AIPT). &#x0D; Material and methods: We included 214 CT exams of 110 patients with history of amiodarone use. AIPT was confirmed in 90 cases. In 81 % of patients we repeat CT exam 2–5 times, observation period till 1 month to 10 years. The mean age of patients was 71 years (21 females, 69 – males). In 52 % of patients lung scintigraphy was done. We included functional lung test, spirometry, heart ultrasound in diagnostic plan.&#x0D; Results: Only in 3 % of cases we detected acute form of AIPT. In 68 % of patients subacute form was revealed, in that cases we indentified different patterns of lung defeat, which mimic oncology disease, different types of interstitial pneumonias, small vessel pulmonary embolism. In other cases chronic form AIPT was suspected. Unilateral changes and craniocaudal gradient were not pathognomic for AIPT. We did not identify consolidation zones and nodules. Honeycombing was not a typical feature of chronic form of AIPT. Appearance of ground-glass opacity pattern was feature of lung toxicity exaxerbation.&#x0D; Conclusion: AIPT diagnose of exclusion because of it’s multiple radiological subtypes. There are no specific histological or cytological markers of the disease. Only CT could identify signs of active process and differentiate different subtypes of AIPT.

Proposed method of histological separation between connective tissue disease-associated interstitial pneumonia and idiopathic interstitial pneumonias.

ObjectivesIdiopathic interstitial pneumonia (IIP) and connective tissue disease -associated interstitial pneumonia (CTD-IP) are the two most common types of interstitial pneumonia. IIP and CTD-IP share common histological features, yet their clinical management is different. Separation of the two conditions based solely on histology can be challenging, and there are no established criteria.Materials and methodsWe selected 105 consecutive cases of IIP (79 usual interstitial pneumonia and 26 non-specific interstitial pneumonia) and 49 cases of CTD-IP for derivation and 32 cases of IIP and 10 cases of CTD-IP for validation. Fourteen histological parameters were evaluated independently by two pathologists for derivation group and graded into 0 to 3. The association between the score for each marker and a diagnosis of CTD was investigated using Fisher’s exact test and stepwise logistic regression analysis. A formula for calculating the probability of IIP and CTD-IP was constructed by the markers identified in the regression test with coefficients for each finding. The formula was confirmed using validation case group.ResultsStepwise logistic regression analysis showed that plasmacytosis, lymphoid follicle with germinal center, and airspace fibrin were suggestive of CTD-IP and that fibroblastic foci, smooth muscle hyperplasia, cellular IP, dense perivascular collagen, and fat metaplasia were suggestive of IIP. The formula used to calculate the probabilities based on estimated values for each finding was created, and user-friendly web based app was composed at www.ctdip.com.On the validation study, 30 out of 32 IIP and eight out of 10 CTD-IPs were distinguished correctly by the app (Specificity: 93%, Sensitivity: 80%).ConclusionsWe identified histological markers and derived a practical formula and user-friendly app to distinguish CTD-IPs from IIP.