Publications by authors named "Yuanhua Yang"

81 Publications

Cell landscape atlas for patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy constructed using single-cell RNA sequencing.

Aging (Albany NY) 2021 Jun 21;13. Epub 2021 Jun 21.

Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine, Beijing 100020, China.

This study aimed to construct an atlas of the cell landscape and comprehensively characterize the cellular repertoire of the pulmonary endarterectomized tissues of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Five pulmonary endarterectomized tissues were collected. 10× Genomics single-cell RNA sequencing was performed, followed by the identification of cluster marker genes and cell types. Gene Ontology (GO) enrichment analysis was conducted. Seventeen cell clusters were characterized, corresponding to 10,518 marker genes, and then classified into eight cell types, including fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, cysteine rich secretory protein LCCL domain containing 2 (CRISPLD2)+ cell, cancer stem cell, and undefined. The specific marker genes of fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, and cancer stem cell were significantly enriched for multiple functions associated with muscle cell migration, endothelial cell migration, T cell activation, neutrophil activation, erythrocyte homeostasis, and tissue remodeling, respectively. No functions were significantly enriched for the marker gene of CRISPLD2+ cell. Our study, for the first time, provides an atlas of the cell landscape of the pulmonary endarterectomized tissues of CTEPH patients at single-cell resolution, which may serve as a valuable resource for further elucidation of disease pathophysiology.
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http://dx.doi.org/10.18632/aging.203168DOI Listing
June 2021

Does urban sprawl exacerbate urban haze pollution?

Environ Sci Pollut Res Int 2021 May 31. Epub 2021 May 31.

School of Public Administration, Guangdong University of Finance & Economics, Guangzhou, 510320, China.

Is rapid urban sprawl increasing environmental pollution while boosting economic development? This study uses panel data of 30 Chinese provinces during 2002-2018 to investigate the impact of urban sprawl on haze pollution with the use of a spatial lag model. Urban built-up area (ba) and urban public facilities occupation (upfo) are used to measure the differential impact of urban sprawl on haze pollution. The main highlights of the results are as follows: (1) there is a nonlinear relationship between urban sprawl and haze pollution. An inverted U-shaped relationship was found between built-up area and haze pollution, while urban public facility occupation and haze pollution have a U-shaped correlation. (2) The impact of urban sprawl on haze pollution shows a significant time-based difference. The relationship between the two was not significant in 2002-2010, but become significant in 2011-2018. (3) Significant regional differences in the impact of urban sprawl on haze pollution were found. The effects of urban sprawl on urban haze levels are more pronounced in the eastern and western regions than in the central region.
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http://dx.doi.org/10.1007/s11356-021-14559-1DOI Listing
May 2021

Trends in risk stratification, in-hospital management and mortality of patients with acute pulmonary embolism: an analysis from China pUlmonary thromboembolism REgistry Study (CURES).

Eur Respir J 2021 May 13. Epub 2021 May 13.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China

Background: Similar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies were not clear in Asian countries.

Objectives: We retrospectively analyzed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicenter registry in China (CURES).

Methods: Adult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analyzed. Risk stratification was retrospectively classified by hemodynamical status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines.

Results: Among overall 7438 patients, the proportions with high (hemodynamically instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. was the widely employed diagnostic approach (87.6%) and anticoagulation was the frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted =0.0003), with a concomitant reduction in use of initial systemic thrombolysis (from 14.8% to 5.0%, <0.0001). The common predictors for all-cause mortality shared by hemodynamically stable and unstable patients were co-existing cancer, older age, and impaired renal function.

Conclusions: The considerable reduction of mortality over years was accompanied by changes of initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.
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http://dx.doi.org/10.1183/13993003.02963-2020DOI Listing
May 2021

Expression of miR-93-5p as a Potential Predictor of the Severity of Chronic Thromboembolic Pulmonary Hypertension.

Biomed Res Int 2021 17;2021:6634417. Epub 2021 Apr 17.

Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.

Background: MicroRNAs (miRNAs) play an important role in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the potential correlation between miRNA expression and the severity of CTEPH remains unclear. Our previous study indicated that miRNAs hsa-let-7b-3p, hsa-miR-17-5p, hsa-miR-106b-5p, hsa-miR-3202, hsa-miR-665, and hsa-miR-93-5p are closely involved in CTEPH. This study assessed the associations between the expression levels of these miRNAs and clinical parameters in CTEPH patients.

Methods: A total of eight CTEPH patients and eight healthy adults as a reference group were included, and clinical data including total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), uric acid (UA), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected. Right heart catheterization was conducted to obtain hemodynamic data including cardiac index (CI). The expression levels of let-7b-3p, miR-17-5p, miR-106b-5p, miR-3202, miR-665, and miR-93-5p were measured by quantitative real-time PCR (qPCR). Correlation analysis was applied to estimate the associations between miRNA expression levels and clinical parameters in CTEPH patients.

Results: Serum TP and Alb levels were decreased, while LDH, HBDH, and UA levels were increased in CTEPH patients compared with the reference group ( < 0.05). miR-3202 and miR-665 were upregulated, whereas let-7b-3p, miR-17-5p, miR-106b-5p, and miR-93-5p were downregulated in CTEPH patients relative to the reference group ( < 0.05). miR-93-5p expression was positively correlated with NT-proBNP level and negatively correlated with CI ( < 0.05). Moreover, let-7b-3p tended to be positively correlated with mean pulmonary arterial pressure.

Conclusions: miR-93-5p expression was associated with the severity of CTEPH and could act as a potential predictor of high-risk CTEPH.
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http://dx.doi.org/10.1155/2021/6634417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075669PMC
May 2021

Refractory pleural effusion as a rare complication of pulmonary vascular stenosis induced by fibrosing mediastinitis: a case report and literature review.

J Int Med Res 2021 May;49(5):3000605211010073

Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Fibrosing mediastinitis (FM) is a progressive, life-threatening disease characterized by extrinsic compression of mediastinal bronchovascular structures, and the clinical manifestations largely depend upon the affected structures. Pleural effusion is rarely reported in patients with FM. We herein describe a 70-year-old man who presented with recurrent breathlessness and refractory left pleural effusion. He was misdiagnosed with and treated for tuberculous pleurisy for several months. Thoracentesis revealed a transudative pleural effusion, and a contrast-enhanced computed tomography scan of the thorax showed an extensive mediastinal soft tissue mass consistent with FM. Pulmonary angiography demonstrated pulmonary artery stenosis on the right side and pulmonary vein stenosis mainly on the left side. After measurement of the pulmonary arterial pressure by right heart catheterization, the patient was diagnosed with pulmonary hypertension associated with FM. He underwent balloon angioplasty and stent implantation of the stenosed pulmonary vessels, which led to long-term improvement in his breathlessness and pleural effusion. Our systematic review of the literature highlights that pleural effusion can be an uncommon complication of FM and requires careful etiological differentiation.
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http://dx.doi.org/10.1177/03000605211010073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113940PMC
May 2021

Risk prediction in medically treated chronic thromboembolic pulmonary hypertension.

BMC Pulm Med 2021 Apr 20;21(1):128. Epub 2021 Apr 20.

Department of Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China.

Background: At present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients.

Methods: Consecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance.

Results: A total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score).

Conclusions: A novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients.

Trial Registration: ClinicalTrials.gov (Identifier: NCT01417338).
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http://dx.doi.org/10.1186/s12890-021-01495-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056726PMC
April 2021

Possible immune regulation mechanisms for the progression of chronic thromboembolic pulmonary hypertension.

Thromb Res 2021 02 2;198:122-131. Epub 2020 Dec 2.

Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine, Beijing 100020, China; Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. Electronic address:

Purpose: This study aimed to screen key genes significantly associated with chronic thromboembolic pulmonary hypertension (CTEPH) and predicted suitable drugs for the treatment of CTEPH from the perspective of immune cells.

Methods: The dataset GSE130391 was used for this analysis. Differentially expressed genes (DEGs) between the CTEPH and control groups were screened. Abundance of infiltrating immune cells was analyzed and immune-related DEGs were identified. Next, the circular RNA (circRNA)-micro RNA (miRNA)-mRNA network was constructed, followed by functional enrichment analysis. Then, the protein-protein interaction (PPI) network was constructed and drug-gene interactions were predicted. Finally, miRNA and circRNA prediction results were verified by our previously published studies.

Results: Five key immune cell-related DEGs [CD83 molecule (CD83), complement c5a receptor 1 (C5AR1), atypical chemokine receptor 1 (ACKR1), profilin 2 (PFN2), and solute carrier family 2 member 3 (SLC2A3)] were identified. Several circRNA-miRNA-mRNA interactions were obtained, including circ_0022342miR-503-5pSLC2A3 and circ_0002062miR-92b-3p/miR-92a-3pmannosidase alpha class 2A member 1 (MAN2A1). Immune cell for SLC2A3 was eosinophils and for MAN2A1 was regulatory T cells (Tregs). Additionally, Glufosfamide and Kifunensine might be suitable as candidate drugs for CTEPH treatment.

Conclusions: SLC2A3 and MAN2A1 may be important genes for the pathogenesis of CTEPH. Possible immune regulation mechanisms in CTEPH may be circ_0022342miR-503-5pSLC2A3 and circ_0002062miR-92b-3p/miR-92a-3pMAN2A1. These results may be helpful for the diagnosis and treatment of CTEPH from the perspective of immunology.
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http://dx.doi.org/10.1016/j.thromres.2020.11.032DOI Listing
February 2021

Extracellular matrix collagen biomarkers levels in patients with chronic thromboembolic pulmonary hypertension.

J Thromb Thrombolysis 2020 Nov 11. Epub 2020 Nov 11.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, Beijing, People's Republic of China.

Limited data exist on changes in the extracellular matrix (ECM) collagen biomarkers levels during chronic thromboembolic pulmonary hypertension (CTEPH) development. This study aimed to investigate ECM collagen biomarkers levels in stable patients with CTEPH. Patients with CTEPH and healthy persons were enrolled. Serum levels of procollagen III N-terminal peptide (PIIINP), carboxyterminal propeptide of type I procollagen (PICP), matrix metalloproteinases (MMP2), MMP9, and tissue inhibitor of metalloproteinases 1(TIMP1) were measured by ELISA. Clinical data coincident with samples were collected. The pulmonary endarterectomy (PEA) and control pulmonary artery tissue samples were analyzed for genetic and immunohistochemical differences. The serum concentrations of PIIINP, PICP, MMP2, and MMP9 decreased significantly in CTEPH patients compared to healthy controls (P < 0.001 for each). CTEPH patients had higher serum concentrations of TIMP1 (median, 111.97 [interquartile range, 84.35-139.93]) compared to healthy controls (74.97 [44.03-108.45] ng/mL, P < 0.001). The MMP2 to TIMP1 ratio was lower in patients than in the controls (P < 0.001). After adjusting for the body mass index (BMI), the MMP2 to TIMP1 ratio correlated negatively with pulmonary vascular resistance (PVR) (r = - 0.327, P = 0.025). Increased TIMP1 (P = 0.04) gene expression was identified in tissues of CTEPH patients. Immunohistochemistry results of vascular walls substantiated qRT-PCR results. This study indicates that ECM collagen biomarkers levels were significantly different in stable patients with CTEPH and healthy controls with significantly increased TIMP1 and decreased MMP2 and MMP9. Differences in TIMP1 expression should be expected not only among healthy controls and patients serum, but also across pathological tissue regions. These findings suggest that the state of vascular remodeling in pulmonary vascular bed in stable patients may be represented by ECM collagen biomarkers levels. We conclude that TIMP1 may play an important role in pulmonary vascular reconstruction in stable CTEPH patients.
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http://dx.doi.org/10.1007/s11239-020-02329-8DOI Listing
November 2020

The dynamic relationship between regional corruption and carbon emissions in China.

Clean Technol Environ Policy 2020 Oct 22:1-14. Epub 2020 Oct 22.

School of Business Administration, Guangdong University of Finance and Economics, Guangzhou, 510320 China.

Abstract: Does regional corruption exacerbate regional carbon emissions? To answer this, based on the spatial Durbin model, this study empirically examines the impact of regional corruption on carbon emission, using panel data from 30 provinces in China during the period 2002-2017. The results show that: (1) there is an indistinctive -shaped relationship between regional corruption and carbon emissions at the national level. Regional corruption tends to initially aggravate carbon emissions, then contributes to emission reduction, and then finally boosts carbon emissions. However, this effect is not statistically significant. The results suggest that the role of regional corruption on carbon emissions is twofold. Corruption can exacerbate and can also inhibit regional carbon emissions. (2) Pronounced regional heterogeneity exists with regard to the influence of corruption on carbon emissions. Regional corruption and carbon emissions show a significant -shaped dynamic relationship in China's central region, while the relationship is not significant in the eastern and western regions. (3) The impact of regional corruption on carbon emissions varies with time. For 2002-2009, regional corruption did not have a significant effect on carbon emissions. For 2010-2017, the direct effect became significant, and an apparent -shaped relationship formed between regional corruption and carbon emissions. Based on the empirical results, this paper proposes several policy recommendations regarding corruption and carbon governance.

Graphic Abstract:
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http://dx.doi.org/10.1007/s10098-020-01965-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581307PMC
October 2020

Characteristics and long-term survival of patients with chronic thromboembolic pulmonary hypertension in China.

Respirology 2021 02 20;26(2):196-203. Epub 2020 Sep 20.

Department of Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background And Objective: The purpose of this study was to report the characteristics and long-term survival of patients with CTEPH treated in three distinct ways: PEA, BPA and medical therapy.

Methods: Patients diagnosed with CTEPH were included in the registry that was set up in 18 centres from August 2009 to July 2018. The characteristics and survival of patients with CTEPH receiving the different treatments were reported. Prognostic factors were evaluated by Cox regression model.

Results: A total of 593 patients with CTEPH were included. Eighty-one patients were treated with PEA, 61 with BPA and 451 with drugs. The estimated survival rates at 1, 3, 5 and 8 years were, respectively, 95.2%, 84.6%, 73.4% and 66.6% in all patients; 92.6%, 89.6%, 87.5% and 80.2% in surgical patients; and 95.4%, 88.3%, 71.0% and 64.1% in medically treated patients. The estimated survival rates at 1, 3, 5 and 7 years in patients treated with BPA were 96.7%, 88.1%, 70.0% and 70.0%, respectively. For all patients, PEA was an independent predictor of survival. Other independent risk factors were CHD, cardiac index, PVR, big endothelin-1, APE and 6MWD.

Conclusion: This is the first multicentre prospective registry reporting baseline characteristics and estimated survival of patients with CTEPH in China. The long-term survival rates are similar to those of patients in the international and Spanish registries. PEA is an independent predictor of survival.
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http://dx.doi.org/10.1111/resp.13947DOI Listing
February 2021

hsa-miR-106b-5p participates in the development of chronic thromboembolic pulmonary hypertension via targeting matrix metalloproteinase 2.

Pulm Circ 2020 Jul-Sep;10(3):2045894020928300. Epub 2020 Jul 10.

Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine, Beijing, China.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by elevated pressure in pulmonary arteries. This study was performed to explore the critical miRNAs and genes affecting the pathogenesis of CTEPH.

Methods: GSE56914 dataset (10 CTEPH whole blood samples and 10 control samples) was downloaded from the Gene Expression Omnibus database. Using limma package, the differentially expressed miRNAs (DE-miRNAs) were acquired. After miRNA-target pairs were obtained using miRWalk2.0 tool, a miRNA-target regulatory network was built by Cytoscape software. Using DAVID tool, significantly enriched pathways involving the target genes were identified. Moreover, the protein-protein interaction network and transcription factor-target regulatory network were built by the Cytoscape software. Additionally, quantitative real-time PCR (qRT-PCR) experiments and luciferase assay were conducted to validate miRNA/gene expression and miRNA-target regulatory relationship, respectively.

Results: There were 25 DE-miRNAs (8 up-regulated and 17 down-regulated) between CTEPH and control groups. The target genes of has-let-7b-3p, has-miR-17-5p, has-miR-3202, has-miR-106b-5p, and has-miR-665 were enriched in multiple pathways such as "Insulin secretion". qRT-PCR analysis confirmed upregulation of hsa-miR-3202, hsa-miR-665, and matrix metalloproteinase 2 () as well as downregulation of hsa-let-7b-3p, hsa-miR-17-5p, and hsa-miR-106b-5p. Luciferase assay indicated that was negatively mediated by hsa-miR-106b-5p.

Conclusions: These miRNAs and genes were associated with the pathogenesis of CTEPH. Besides, hsa-miR-106b-5p was involved in the development of CTEPH via targeting .
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http://dx.doi.org/10.1177/2045894020928300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357097PMC
July 2020

Prevalence and risk factors of small airway dysfunction, and association with smoking, in China: findings from a national cross-sectional study.

Lancet Respir Med 2020 11 26;8(11):1081-1093. Epub 2020 Jun 26.

State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.

Background: Small airway dysfunction is a common but neglected respiratory abnormality. Little is known about its prevalence, risk factors, and prognostic factors in China or anywhere else in the world. We aimed to estimate the prevalence of small airway dysfunction using spirometry before and after bronchodilation, both overall and in specific population subgroups; assess its association with a range of lifestyle and environmental factors (particularly smoking); and estimate the burden of small airway dysfunction in China.

Methods: From June, 2012, to May, 2015, the nationally representative China Pulmonary Health study invited 57 779 adults to participate using a multistage stratified sampling method from ten provinces (or equivalent), and 50 479 patients with valid lung function testing results were included in the analysis. We diagnosed small airway dysfunction on the basis of at least two of the following three indicators of lung function being less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50%, and FEF 75%. Small airway dysfunction was further categorised into pre-small airway dysfunction (defined as having normal FEV and FEV/forced vital capacity [FVC] ratio before bronchodilator inhalation), and post-small airway dysfunction (defined as having normal FEV and FEV/FVC ratio both before and after bronchodilator inhalation). Logistic regression yielded adjusted odds ratios (ORs) for small airway dysfunction associated with smoking and other lifestyle and environmental factors. We further estimated the total number of cases of small airway dysfunction in China by applying present study findings to national census data.

Findings: Overall the prevalence of small airway dysfunction was 43·5% (95% CI 40·7-46·3), pre-small airway dysfunction was 25·5% (23·6-27·5), and post-small airway dysfunction was 11·3% (10·3-12·5). After multifactor regression analysis, the risk of small airway dysfunction was significantly associated with age, gender, urbanisation, education level, cigarette smoking, passive smoking, biomass use, exposure to high particulate matter with a diameter less than 2·5 μm (PM) concentrations, history of chronic cough during childhood, history of childhood pneumonia or bronchitis, parental history of respiratory diseases, and increase of body-mass index (BMI) by 5 kg/m. The ORs for small airway dysfunction and pre-small airway dysfunction were similar, whereas larger effect sizes were generally seen for post-small airway dysfunction than for either small airway dysfunction or pre-small airway dysfunction. For post-small airway dysfunction, cigarette smoking, exposure to PM, and increase of BMI by 5 kg/m were significantly associated with increased risk, among preventable risk factors. There was also a dose-response association between cigarette smoking and post-small airway dysfunction among men, but not among women. We estimate that, in 2015, 426 (95% CI 411-468) million adults had small airway dysfunction, 253 (238-278) million had pre-small airway dysfunction, and 111 (104-126) million had post-small airway dysfunction in China.

Interpretation: In China, spirometry-defined small airway dysfunction is highly prevalent, with cigarette smoking being a major modifiable risk factor, along with PM exposure and increase of BMI by 5 kg/m. Our findings emphasise the urgent need to develop and implement effective primary and secondary prevention strategies to reduce the burden of this condition in the general population.

Funding: Ministry of Science and Technology of China; National Natural Science Foundation of China; National Health Commission of China.
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http://dx.doi.org/10.1016/S2213-2600(20)30155-7DOI Listing
November 2020

Rational and design of the China Pulmonary Thromboembolism Registry Study (CURES): A prospective multicenter registry.

Int J Cardiol 2020 10 6;316:242-248. Epub 2020 Jun 6.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, PR China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, PR China; National Clinical Research Center for Respiratory Disease, Beijing, PR China; Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, PR China; Department of Respiratory Medicine, Capital Medical University, Beijing, PR China. Electronic address:

Background: Epidemiological data on pulmonary embolism (PE) in China needs to be updated and reported. The China Pulmonary Thromboembolism Registry Study (CURES) is designed to provide the cross-sectional spectrum and chronological trends of PE in China, as well as to reveal the intrinsic etiology and pathogenesis of the disease.

Methods And Design: The CURES is an ongoing large prospective multicenter registry, which was originally initiated in January 2009 via enrolling suspected or confirmed PE or PE with DVT (deep venous thrombosis) patients and assessed their in-hospital outcomes. As of July 2011, in order to determine the PE-relevant short-term outcomes, enrolled participants were followed-up for at least three months in a longitudinal manner. Since August 2016, with the launch and development of precision medicine research scheme in China, the main principle investigators of CURES decided to collect enrolled patients' blood samples with regular follow-ups every three or six months for at least two years (for long-term outcomes). Up to 31 December 2019, the CURES has enrolled 14,937 eligible patients and collected 1500 blood samples of patients from 100 medical centers in the China PE-DVT network. The study protocol has been approved by the China-Japan Friendship Hospital ethics committee, and all collaborating centers received approvals from their local ethics committee. All patients provided written or verbal informed consent to their participation.

Conclusions: Findings of the CURES will be valuable for revealing the natural history of PE, and facilitating better disease management in China. Registration Number inClinicalTrials.gov:NCT02943343.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.087DOI Listing
October 2020

Speckle tracking for predicting outcomes of balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

Echocardiography 2020 06 24;37(6):841-849. Epub 2020 May 24.

Department of Echocardiography, Heart Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Background: Right ventricular (RV) function is a prognostic marker of chronic thromboembolic pulmonary hypertension (CTEPH). We used two-dimensional (2D) speckle-tracking echocardiography (STE) to evaluate the therapeutic effects of balloon pulmonary angioplasty (BPA) in CTEPH patients.

Methods: A total of 46 CTEPH patients who underwent 2D STE before and after BPA were enrolled in this retrospective study. The following RV functional parameters were measured: tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), RV index of myocardial performance (RIMP), and free wall longitudinal strain (RVFWLS). Satisfactory BPA was defined as mean pulmonary arterial pressure (mPAP) <25 mm Hg or improvement in mPAP > 10 mm Hg after BPA. Patients were divided into two groups according to mPAP values: group I had satisfactory BPA outcomes; group Ⅱ had unsatisfactory BPA outcomes. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values and the ability of RVFWLS to predict successful BPA outcomes.

Results: After BPA, SPAP measured by echocardiography (SPAP ) and RIMP decreased, but TAPSE, RVFAC, and RVFWLS increased. Before BPA, group Ⅰ had significantly better RV function than group Ⅱ. Multifactor logistic regression analysis identified RVFWLS as an independent factor associated with satisfactory BPA outcomes. The optimal cutoff value for RVFWLS in predicting satisfactory BPA outcomes was -12.2%.

Conclusions: Balloon pulmonary angioplasty improves RV function in CTEPH patients. RVFWLS is a valuable noninvasive tool with which to assess the treatment effects of BPA. CTEPH patients with lower RVFWLS may have limited benefit from BPA.
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http://dx.doi.org/10.1111/echo.14709DOI Listing
June 2020

Anxiety and depression in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a Chinese survey.

Exp Ther Med 2020 Apr 27;19(4):3124-3132. Epub 2020 Feb 27.

Center of Respiratory Medicine, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Peking University Health Science Center, Beijing 100029, P.R. China.

Limited studies have focused on mental symptoms (anxiety and depression) and their impact on quality of life (QoL) in patients with pulmonary hypertension (PH). The objective of the present study was to assess the prevalence of anxiety and depression and their association with QoL in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) in a Chinese population. Patients diagnosed with PH by right heart catheterization between March 2015 and February 2016 were recruited. QoL [short form 36 Health Survey Questionnaire (SF-36)] and depression (Patient Health Questionnaire depression scale-9) and anxiety (Generalized Anxiety Disorder-7) were assessed at baseline. Patients were followed up every 3 months. A total of 36 patients with PAH and 62 patients with CTEPH were enrolled. According to the results of the clinical examination and the questionnaires for depression and anxiety, patients were divided into two groups: Group 1, with depression and/or anxiety (n=65, 66.3%) and group 2, without depression or anxiety (n=33, 33.7%). At baseline, the two groups did not differ in their hemodynamics. Patients with depression and/or anxiety (group 1) had a significantly lower score in all subscales of SF-36 (P<0.05). The impairment of QoL significantly correlated with the severity of depression (P<0.001) and anxiety (P<0.05). During the follow-up period, end-point events (death or admission due to deterioration) occurred in 17 patients (17.3%); 8 patients (8.1%) were lost to follow-up. The end-point event-free survival rate in group 2 was significantly higher than that in group 1. Multivariate logistic regression analysis suggested that the financial situation and right ventricular enlargement were influencing factors of depression and/or anxiety. In conclusion, in patients with PH from a Chinese population, anxiety and depression were frequently encountered and significantly correlated with QoL. The significant relevant factors influencing anxiety/depression were the financial situation and right ventricular enlargement and patients with depression had a worse prognosis than those without.
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http://dx.doi.org/10.3892/etm.2020.8566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086277PMC
April 2020

Prevalence, risk factors, and management of asthma in China: a national cross-sectional study.

Lancet 2019 08 20;394(10196):407-418. Epub 2019 Jun 20.

Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing, China; National Center of Gerontology, Beijing Hospital, Beijing, China.

Background: Asthma is a common chronic airway disease worldwide. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of asthma. We therefore aimed to estimate the national prevalence of asthma in a representative sample of the Chinese population.

Methods: A representative sample of 57 779 adults aged 20 years or older was recruited for the national cross-sectional China Pulmonary Health (CPH) study using a multi-stage stratified sampling method with parameters derived from the 2010 census. Ten Chinese provinces, representative of all socioeconomic settings, from six geographical regions were selected, and all assessments were done in local health centres. Exclusion criteria were temporary residence, inability to take a spirometry test, hospital treatment of cardiovascular conditions or tuberculosis, and pregnancy and breastfeeding. Asthma was determined on the basis of a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. All participants were assessed with a standard asthma questionnaire and were classed as having or not having airflow limitation through pulmonary function tests before and after the use of a bronchodilator (400 μg of salbutamol). Risk factors for asthma were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was assessed by the self-reported history of physician diagnosis, treatments, and hospital visits in people with asthma.

Findings: Between June 22, 2012, and May 25, 2015, 57 779 participants were recruited into the CPH study. 50 991 (21 446 men and 29 545 women) completed the questionnaire survey and had reliable post-bronchodilator pulmonary function test results and were thus included in the final analysis. The overall prevalence of asthma in our sample was 4·2% (95% CI 3·1-5·6), representing 45·7 million Chinese adults. The prevalence of asthma with airflow limitation was 1·1% (0·9-1·4), representing 13·1 million adults. Cigarette smoking (odds ratio [OR] 1·89, 95% CI 1·26-2·84; p=0·004), allergic rhinitis (3·06, 2·26-4·15; p<0·0001), childhood pneumonia or bronchitis (2·43, 1·44-4·10; p=0·002), parental history of respiratory disease (1·44, 1·02-2·04; p=0·040), and low education attainment (p=0·045) were associated with prevalent asthma. In 2032 people with asthma, only 28·8% (95% CI 19·7-40·0) reported ever being diagnosed by a physician, 23·4% (13·9-36·6) had a previous pulmonary function test, and 5·6% (3·1-9·9) had been treated with inhaled corticosteroids. Furthermore, 15·5% (11·4-20·8) people with asthma reported at least one emergency room visit and 7·2% (4·9-10·5) at least one hospital admission due to exacerbation of respiratory symptoms within the preceding year.

Interpretation: Asthma is prevalent but largely undiagnosed and undertreated in China. It is crucial to increase the awareness of asthma and disseminate standardised treatment in clinical settings to reduce the disease burden.

Funding: National Key R&D Program of China, Ministry of Science and Technology of China; the Special Research Foundation for Public Welfare of Health, Ministry of Health of China; the Chinese National Research Program for Key Issues in Air Pollution Control; and the National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S0140-6736(19)31147-XDOI Listing
August 2019

miRNA-PDGFRB/HIF1A-lncRNA CTEPHA1 Network Plays Important Roles in the Mechanism of Chronic Thromboembolic Pulmonary Hypertension.

Int Heart J 2019 Jul 14;60(4):924-937. Epub 2019 Jun 14.

Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University.

Our previous studies have revealed that long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and genes were abnormally expressed in the pulmonary artery tissues of the chronic thromboembolic pulmonary hypertension (CTEPH) patients. We aim to establish the CTEPH-related miRNA-gene-lncRNA network for finding the core genes and associated miRNA and lncRNA in CTEPH patients.Firstly, the target genes of differential miRNAs were predicted by searching TargetScan databases, and the predicted target genes were intersected with the mRNAs from the gene chip. Secondly, the intersective genes were analyzed by the Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway software for obtaining differential intersective genes and then establish the miRNA-gene networks. Thirdly, the possible genes regulated by the differential lncRNAs from the gene chip were intersected with the above-screened mRNA to build the lncRNA-mRNA networks. Subsequently, the miRNA-gene-lncRNA networks were constructed according to the two networks above (miRNA-gene networks and lncRNA-mRNA networks). Finally, the core genes of the networks in the experimental group were screened according to Diffk > 0.6 and used to construct the miRNA-core gene-lncRNA networks of CTEPH.The pathway network, miRNA-mRNA network, lncRNA-mRNA networks, and miRNA-gene-lncRNA networks were successfully constructed. The core genes of the miRNA-gene-lncRNA networks (Diffk > 0.6) were the human Beta-type platelet-derived growth factor receptor (PDGFRB) and hypoxia-inducible factor-1a (HIF-1A), the miRNAs-PDGFRB-lncRNAs and miRNAs-HIF1A-lncRNAs networks were constructed. Finally, miRNA-149-5p-PDGFRB-TCONS_l2_00020587-XLOC_l2_010723 and miRNA-338-5p/miRNA-199b-5p-HIF1A- TCONS_l2_00020587-XLOC_l2_010723 were found in the analysis of the network.miRNA-149-5p-PDGFRB-lncRNA CTEPH-associated 1 (CTEPHA1) (TCONS_l2_00020587-XLOC_l2_010723) and miRNA-338-5p/miRNA-199b-5p-HIF1A-lncRNA CTEPHA1 are related to the development of CTEPH.
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http://dx.doi.org/10.1536/ihj.18-479DOI Listing
July 2019

Identification of Chinese Hospitalized Patients' Risk Profile for Venous Thromboembolism (DissolVE1): A Study Protocol of a Non-Interventional Registry Study.

Adv Ther 2019 08 28;36(8):2180-2190. Epub 2019 May 28.

Chinese PLA General Hospital, Haidian District, Beijing, China.

Introduction: Venous thromboembolism (VTE) is a frequent cause of hospitalization, mortality, and long-term adverse consequence among medical and surgical inpatients. The current study is performed to identify the prophylaxis of patients with VTE risk within the 6 weeks prior to the diagnosis of VTE, and the treatment pattern during 3 months after VTE diagnosis in Chinese patients hospitalized for surgeries or medical illness.

Methods: This multicenter, non-interventional, observational registry plans to enroll 1200 patients from 40 centers in China. The study will retrospectively collect data from patients' hospitalization record within 6 weeks of VTE diagnosis and prospectively follow-up patients for 3 months (in four visits). The primary outcome is to determine the percentage of patients receiving adequate prophylaxis in patients hospitalized within 6 weeks before VTE diagnosis and treatment pattern within 3 months after VTE diagnosis. Important secondary endpoints include determining patients with risk of VTE in the hospital setting, risk factors for VTE, and cost analysis of VTE treatment.

Expected Outcomes: The findings will determine the characteristics of VTE, its treatment practices, cost of treatment, and quality of life in patients; this information may help in building diagnostic and prophylaxis strategies for VTE in China.

Trial Registration: The study is registered in the Venous Thromboembolism Registry in China with study number DIREGL07581.

Funding: Sanofi China.
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http://dx.doi.org/10.1007/s12325-019-00987-6DOI Listing
August 2019

Occurrence of acute pulmonary embolism induced by recombinant erythropoietin during treatment of pure red cell aplasia associated with thymoma: A case report.

Medicine (Baltimore) 2019 Mar;98(10):e14789

Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Rationale: Thymoma is a type of rare tumor in the thymus gland, and among patients with thymoma, less than 10% will develop pure red cell aplasia (PRCA), whereas less than 5% of patients with PRCA have a thymoma. The optimal approach for PRCA in thymoma is immunosuppressive therapy, such as steroids, cyclosporine, and human antithymocyte globulin.

Patient Concerns: A sixty-one-year-old male was diagnosed with thymoma with PRCA after he complained fatigue, tinnitus, and weakness for 1 month, he received therapy with recombinant erythropoietin (rhEPO) for 1 month after the tumor was totally resected and readmitted with pulmonary embolism and received anticoagulation therapy with enoxaparin for 3 months.

Diagnoses: Thymoma, pure red cell aplasia, pulmonary embolism.

Intervention: He received cyclosporine A, prednisone and rhEPO treatment. Two months after the thymectomy and postoperative radiation, he was readmitted with pulmonary embolism.

Outcomes: Thymoma and pulmonary embolism become complete response (CR), PRCA become partial response (PR).

Lessons: Clinicians should be alert to the possibility of the increased risk of thrombosis induced by rhEPO when it used to treat PRCA associated with thymoma. If other medication is effective for managing PRCA, rhEPO should be avoided.
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http://dx.doi.org/10.1097/MD.0000000000014789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417601PMC
March 2019

Comparison of prediction value of four bleeding risk scores for pulmonary embolism with anticoagulation: A real-world study in Chinese patients.

Clin Respir J 2019 Mar 28;13(3):139-147. Epub 2019 Feb 28.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P.R. China.

Background: Major bleeding (MB) and clinically relevant bleeding (CRB) are the most common seen complications associated with anticoagulation treatment for pulmonary embolism (PE) patients. A bleeding risk score (BRS) may help to accurately determine the risk of bleeding and make better decisions for patients in clinical practice.

Methods: Patients diagnosed as acute PE and who met the inclusion criteria in Beijing Chao-Yang Hospital from January 2009 to September 2013 were consecutively enrolled. Baseline data were collected. Four BRS (Kuijer score, RIETE score, Kearon score and Nieuwenhuis score) were assessed and compared using the area under the receiver operating characteristic curve (AUC).

Results: A total number of 563 patients were included in the study. Of which, 16 had MB and 89 had CRB within three months of anticoagulation treatment. Three months' cumulative incidence for MB and CRB events was 0.03 (95% CI 0.01-0.05) and 0.17 (95% CI 0.12-0.21), respectively. In our study population, the AUCs for Kuijer, RIETE, Kearon and Nieuwenhuis scores were 0.57 (95% CI 0.44~0.68), 0.56 (95% CI 0.45-0.71), 0.75 (95% CI 0.60~0.89) and 0.59 (95% CI 0.41~0.74), respectively. In addition, the AUCs of four BRS for CRB were all poor, with values less than 0.65.

Conclusions: Only the Kearon score appeared to have more accuracy in predicting the risk of MB. Further large prospective studies are needed to externally validate a BRS for CRB.
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http://dx.doi.org/10.1111/crj.12993DOI Listing
March 2019

Efficacy and Safety of Bronchial Artery Embolization on Hemoptysis in Chronic Thromboembolic Pulmonary Hypertension: A Pilot Prospective Cohort Study.

Crit Care Med 2019 03;47(3):e182-e189

Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, PR China.

Objectives: Managing hemoptysis in chronic thromboembolic pulmonary hypertension can be challenging due to the difficulties in maintaining coagulation homeostasis in affected patients. In this study, we evaluated the efficacy and safety of bronchial artery embolization in treating hemoptysis in chronic thromboembolic pulmonary hypertension patients.

Design: Pilot, prospective cohort study.

Setting: A large respiratory medical institute.

Patients: From January 1, 2012, to December 31, 2017, hospitalized chronic thromboembolic pulmonary hypertension patients were eligible for inclusion. Patients with pulmonary hypertension caused by other conditions, or who failed to participate in the follow-up were excluded.

Interventions: Hemoptysis in chronic thromboembolic pulmonary hypertension patients was treated with or without bronchial artery embolization based on whether the bleeding could be stopped with medication alone and patient willingness for bronchial artery embolization treatment.

Measurements And Main Results: A total of 328 patients diagnosed with chronic thromboembolic pulmonary hypertension were consecutively collected, 317 patients were completed the follow-up. There were 15 chronic thromboembolic pulmonary hypertension patients with hemoptysis in total, and the occurrence rate of hemoptysis in chronic thromboembolic pulmonary hypertension patients was 4.7%. Among the hemoptysis chronic thromboembolic pulmonary hypertension patients, 10 (67%) underwent bronchial artery embolization, and five (33%) were treated with medication only. The median follow-up period for hemoptysis patients was 7.6 months. In patients underwent bronchial artery embolization treatment, oxygenation index and right heart function showed no significant difference between pre bronchial artery embolization and post bronchial artery embolization. Hemoptysis relapse (20% vs 80%; p = 0.025) and hemoptysis-related mortality (0% vs 40%; p = 0.032) were significantly lower, whereas the overall survival (90% vs 40%; p = 0.040) was higher in patients treated with bronchial artery embolization than in patients treated without bronchial artery embolization.

Conclusions: Bronchial artery embolization procedure demonstrated effectiveness and safety to treat hemoptysis in chronic thromboembolic pulmonary hypertension patients at our center, but further controlled studies are needed before it can be considered as an effective therapy for these patients.
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http://dx.doi.org/10.1097/CCM.0000000000003578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407824PMC
March 2019

Trends in Hospitalization and In-Hospital Mortality From VTE, 2007 to 2016, in China.

Chest 2019 02 9;155(2):342-353. Epub 2018 Nov 9.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center for Respiratory Diseases, Beijing, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. Electronic address:

Background: VTE has emerged as a major public health problem. However, data on VTE burden in China are seldom reported.

Methods: This study collected data on patients with a principal diagnosis of VTE, pulmonary embolism (PE), or DVT by using the International Classification of Diseases, 10th Revision, from 90 hospitals across China. The trends in hospitalization rates, mortality, length of stay (LOS), and comorbidities from 2007 to 2016 were analyzed.

Results: In total, 105,723 patients with VTE were identified. For patients with VTE, the age- and sex-adjusted hospitalization rate increased from 3.2 to 17.5 per 100,000 population, and in-hospital mortality decreased from 4.7% to 2.1% (P < .001). The mean LOS declined from 14 to 11 days (P < .001). In addition, the data in 2016 showed that the hospitalization rate of VTE was higher in elderly male patients (male patients vs female patients, 155.3 vs 125.4 per 100,000 population in patients aged ≥ 85 years; P < .001) and in northern China (north vs south, 18.4 vs 13.4 per 100,000 population; P < .001). Higher mortality rates were found in patients with cancer and Charlson Comorbidity Index scores > 2. Similar trends were also observed in patients with PE and those with DVT. The hospitalization rate in China was much lower than that of the United States or selected sites in Canada and Europe, the LOS was much longer, and the in-hospital mortality rates were similar.

Conclusions: The hospitalization rates of VTE increased steadily, and the mortality declined. This study provides important information on the disease burden of VTE in China.
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http://dx.doi.org/10.1016/j.chest.2018.10.040DOI Listing
February 2019

Incidence and risk factors of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a systematic review and meta-analysis of cohort studies.

J Thorac Dis 2018 Aug;10(8):4751-4763

Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100043, China.

Background: The incidence and risk factors of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE) were still controversial. A systematic review and meta-analysis was conducted to assess the incidence and risk factors of CTEPH after acute PE.

Methods: Embase, Medline, China National Knowledge Infrastructure, Wanfang databases, and various reference lists were searched to identify studies published up to May 2018. Only cohort studies that used right heart catheterization for CTEPH diagnosis were included. The study quality was assessed using the Newcastle-Ottawa Scale (NOS). All analyses were conducted with the meta package in R software (3.2.2).

Results: Fifteen studies met the inclusion criteria. The overall incidence of CTEPH after acute PE, with a median follow-up from 6 to 94.3 months, was 3.13% (95% CI: 2.11-4.63%). The incidence of studies from China [4.46% (95% CI: 1.68-11.32%)] was slightly higher than from Europe [2.82% (95% CI: 1.82-4.34%)]. However, there was no significant difference between these two groups (P=0.39). Subgroup analyses of confirmed diagnostic method showed that compared studies using right heart catheterization [3.25% (95% CI: 2.12-4.97%)], studies using right heart catheterization combined with bundled tests tended to yield a similar data [2.40% (95% CI: 0.97-5.81%), P=0.54]. Previous/recurrent PE or previous VTE, idiopathic PE and right heart dysfunction were considered as risk factors of CTEPH in patients with a previous PE.

Conclusions: CTEPH is not a rare complication of acute PE. Close follow-up and implementation of a comprehensive screening program are important, especially in patients with independent risk factors.
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http://dx.doi.org/10.21037/jtd.2018.07.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129909PMC
August 2018

The prevalence and risk factors of venous thromboembolism in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease.

Clin Respir J 2018 Nov 22;12(11):2573-2580. Epub 2018 Oct 22.

Department of Respiratory Medicine, Capital Medical University, Beijing, 100069, P.R. China.

Introduction: Venous thromboembolism (VTE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not rare, which would affect the patient's prognosis.

Objectives: To examine the prevalence, risk factors and clinical characteristics of AECOPD patients with VTE.

Methods: We performed this multi-center, prospective, observational study that involved 16 hospitals in China. Patients admitted to hospital due to AECOPD were consecutively enrolled. Baseline characteristics, VTE risk factors, symptoms, signs and auxiliary examination results were collected. Lower limb venous ultrasound and computed tomography pulmonary angiography were examined.

Results: Between June 2009 and October 2010, a total of 1144 AECOPD patients (the average age 72.0 ± 9.1 years, 761 males) were enrolled in this study. Seventy-eight (6.8%) were diagnosed with VTE, including 24 PE, 64 DVT, 10 combined PE and DVT. VTE patients were older than non-VTE patients. History of venous thromboembolism and lower extremity varicose vein, and presence of longer immobility (≥3 days), lower limbs problems of swelling, pain and walking difficulties, diuretics use, fever, syncope, higher d-dimer and lower hemoglobin were more common in VTE patients than in non-VTE patients. After adjusting the covariates, venous thrombosis history, prolonged immobility (≥3 days), lower limb pain before hospitalization, higher d-dimer independently associated with VTE development. Regular glucocorticoid use was not associated with increased risk of VTE in this set of patients.

Conclusion: VTE is relatively common among hospitalized AECOPD patients. Conventional prophylactic anticoagulant therapy may be considered for those hospitalized AECOPD patients with risk factors.
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http://dx.doi.org/10.1111/crj.12959DOI Listing
November 2018

Clinical and imaging manifestations of Takayasu's arteritis with pulmonary hypertension: A retrospective cohort study in China.

Int J Cardiol 2019 Feb 15;276:224-229. Epub 2018 Aug 15.

Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, PR China; Beijing Institute of Respiratory Medicine, Beijing 100020, PR China. Electronic address:

Background: Takayasu's arteritis with pulmonary artery involvement (PTA) is uncommon and part of which may be accompanied by pulmonary hypertension (PH). This study herein investigated the clinical presentation, imaging features, and outcomes in PTA patients with and without PH.

Methods: A total of 57 PTA patients were selected at the Beijing Chao-Yang Hospital from January 2011 to July 2017. Patients were placed into two groups, PTA-with-PH or PTA-without-PH. The clinical characteristics, imaging features, and outcomes of patients in these two groups were investigated.

Results: Among the 57 PTA patients, 24 were in the PTA-without-PH group and 33 were in the PTA-with-PH group. The disease duration in PTA-with-PH patients was longer than that of PTA-without-PH patients. The mean follow-up duration of 43 patients was 33.5 ± 20.3 months, while three patients in the PTA-with-PH were deceased. The PTA-with-PH group had significantly higher prevalence of chest tightness and dyspnea, shorter 6-minute walk distance (6MWD) and higher Borg scores after walk than that the PTA-without-PH group. Imaging analyses revealed that patients had five different arterial lesions (stenosis, occlusion, vascular wall thickening, in situ thrombosis, and aneurysm), but aneurysms were only detected in patients in PTA-with-PH patients at 42%. Compared with PTA-without-PH patients, PTA-with-PH patients tended to have occlusion lesions, but less likely to have vascular wall thickening.

Conclusions: Compared with PTA-without-PH patients, PTA-with-PH patients had longer disease duration, more severe symptoms and tended to be deceased during the follow-up time. In addition, PTA-with-PH patients tended to have aneurysm and occlusion vessel lesions.
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http://dx.doi.org/10.1016/j.ijcard.2018.08.047DOI Listing
February 2019

Identification of a low frequency missense mutation in MUC6 contributing to pulmonary artery hypertension by whole-exome sequencing.

Pulm Circ 2018 Jul-Sep;8(3):2045894018794374. Epub 2018 Jul 26.

4 Department of Respiratory and Critical Care Medicine, The China-Japan Friendship Hospital, Beijing, PR China.

Pulmonary arterial hypertension (PAH) represents a progressive disease characterized by abnormally high blood pressure in the pulmonary artery. Although mutations in the bone morphogenetic receptor 2 (BMPR2) are found in 80% of heritable, their low penetrance suggests that other unidentified genetic modifiers are required for this disease. In this report, whole-exome sequencing (WES) and a linkage analysis were performed on genomic DNA isolated from four affected relatives and one non-affected relative in two PAH families. By focusing on meaningful variants which were presented in the four affected family members, but not presented in the non-affected individual, 49 SNP and eight indel variants in 39 genes were identified as candidates. Further high-throughput multiplex genotyping and Sanger sequencing were carried out to confirm the putative causal mutations in 150 individuals (30 idiopathic PAH [IPAH] patients, 30 chronic thromboembolic pulmonary hypertension [CTEPH] patients, and 90 normal controls). A heterozygous and deleterious mutation in the gene MUC6 (p.Pro1716Ser) was confirmed in the IPAH group (20/30, 67%) and CTEPH group (1/30, 3.33%); no variant was detected in the 90 normal controls. MUC6, which is short for mucin 6, encodes high molecular weight glycoprotein produced by many epithelial tissues and forms an insoluble mucous barrier that protects the lumens. We re-confirmed this low frequency mutation with the 1000 Genomes database across all species; no population or frequency data of this allele were acquired. We also found that this mutation site was highly conserved in different species and predicted MUC6 has the protection function of the airway and pneumoangiogram based on genomic sequence data. The compound heterozygous MUC6 gene mutation (p.Pro1716Ser) suggests a novel disease mechanism leading to PAH.
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http://dx.doi.org/10.1177/2045894018794374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104216PMC
July 2018

Tricuspid annular displacement measured by 2-dimensional speckle tracking echocardiography for predicting right ventricular function in pulmonary hypertension: A new approach to evaluating right ventricle dysfunction.

Medicine (Baltimore) 2018 Jul;97(30):e11710

Department of Echocardiography, Heart Center Department of Respiratory and Critical Care Medicine Department of Radiology, Beijing Chao Yang Hospital, Capital Medical University, Beijing, China.

This study aimed to determine the ability of tricuspid annular displacement measured by 2-dimensional speckle tracking echocardiography (STE) to predict right ventricular (RV) dysfunction in pulmonary hypertension (PH) patients. Here, we present a new method for assessing RV function that also employs STE and is based on measurement of tricuspid annular displacement.A total of 225 patients were divided into 2 groups according to the pulmonary artery systolic blood pressure (PASP), estimated by echocardiographic measurement of tricuspid regurgitation: group I (PASP ≥50 mm Hg) and group II (36 mm Hg ≤ PASP <50 mm Hg). The tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC), tissue Doppler-derived tricuspid lateral annular systolic velocity (s'), and the tricuspid annular longitudinal displacement (TMAD) parameters were measured. Thirty patients underwent cardiac magnetic resonance (CMR) examination, and right ventricular ejection fraction (RVEF) was calculated.The conventional parameters as well as the TMAD parameters differed significantly between the 2 groups (all P < .01). Good correlation was observed between the TMAD parameters and CMR-derived RVEF (all P < .01). The TMAD parameters had moderate predictive value for predicting RV dysfunction in PH patients (all P < .01). From receiver operating characteristic curves, we determined the optimal cut-off values for TMAD parameters for detecting RV dysfunction with good sensitivity and specificity.The TMAD parameters can predict the decline of RV function in patients with PH and thus provide new diagnostic indices for clinical management of these patients.
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http://dx.doi.org/10.1097/MD.0000000000011710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078723PMC
July 2018

Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.

Lancet 2018 04 9;391(10131):1706-1717. Epub 2018 Apr 9.

National Clinical Research Center for Respiratory Diseases, Beijing, China; Department of Pathology, Beijing Hospital, Beijing, China; National Center of Gerontology, Beijing, China.

Background: Although exposure to cigarette smoking and air pollution is common, the current prevalence of chronic obstructive pulmonary disease (COPD) is unknown in the Chinese adult population. We conducted the China Pulmonary Health (CPH) study to assess the prevalence and risk factors of COPD in China.

Methods: The CPH study is a cross-sectional study in a nationally representative sample of adults aged 20 years or older from ten provinces, autonomous regions, and municipalities in mainland China. All participants underwent a post-bronchodilator pulmonary function test. COPD was diagnosed according to 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

Findings: Between June, 2012, and May, 2015, 57 779 individuals were invited to participate, of whom 50 991 (21 446 men and 29 545 women) had reliable post-bronchodilator results and were included in the final analysis. The overall prevalence of spirometry-defined COPD was 8·6% (95% CI 7·5-9·9), accounting for 99·9 (95% CI 76·3-135·7) million people with COPD in China. Prevalence was higher in men (11·9%, 95% CI 10·2-13·8) than in women (5·4%, 4·6-6·2; p<0·0001 for sex difference) and in people aged 40 years or older (13·7%, 12·1-15·5) than in those aged 20-39 years (2·1%, 1·4-3·2; p<0·0001 for age difference). Only 12·0% (95% CI 8·1-17·4) of people with COPD reported a previous pulmonary function test. Risk factors for COPD included smoking exposure of 20 pack-years or more (odds ratio [OR] 1·95, 95% CI 1·53-2·47), exposure to annual mean particulate matter with a diameter less than 2·5 μm of 50-74 μg/m (1·85, 1·23-2·77) or 75 μg/m or higher (2·00, 1·36-2·92), underweight (body-mass index <18·5 kg/m; 1·43, 1·03-1·97), sometimes childhood chronic cough (1·48, 1·14-1·93) or frequent cough (2·57, 2·01-3·29), and parental history of respiratory diseases (1·40, 1·23-1·60). A lower risk of COPD was associated with middle or high school education (OR 0·76, 95% CI 0·64-0·90) and college or higher education (0·47, 0·33-0·66).

Interpretation: Spirometry-defined COPD is highly prevalent in the Chinese adult population. Cigarette smoking, ambient air pollution, underweight, childhood chronic cough, parental history of respiratory diseases, and low education are major risk factors for COPD. Prevention and early detection of COPD using spirometry should be a public health priority in China to reduce COPD-related morbidity and mortality.

Funding: Ministry of Health and Ministry of Science and Technology of China.
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http://dx.doi.org/10.1016/S0140-6736(18)30841-9DOI Listing
April 2018

Fibrosing mediastinitis with pulmonary hypertension as a complication of pulmonary vein stenosis: A case report and review of the literature.

Medicine (Baltimore) 2018 Jan;97(4):e9694

Department of Echocardiography, Heart Center.

Introduction: Fibrosingmediastinitis (FM) is caused by a proliferation of fibrous tissue in the mediastinum encasing the mediastinal viscera that results in compression of mediastinal bronchovascular structures. Pulmonary hypertension (PH) is a severe complication of FM caused by extrinsic compression of pulmonary blood vessels.

Case Presentation: Here, we present the case of a 47-year-old man who presented with a 10-year history of progressive hemoptysis and a 2-year history of shortness of breath, in whom a diagnosis of FM was made. Occlusion of the superior pulmonary veins was noted, with stenosis of the inferior pulmonary veins, leading to PH. Because the patient was a poor candidate for interventional catheterization, the preferred treatment for FM, his PH has been managed with diuretics, and he remains stable.

Conclusions: FM is a serious, potentially life-threatening condition that is best managed in specialized centers.
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http://dx.doi.org/10.1097/MD.0000000000009694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794377PMC
January 2018