Pub Date : 2020-09-07DOI: 10.1183/13993003.congress-2020.4464
P. Thoré, B. Girerd, X. Jaïs, L. Savale, M. Ghigna, M. Eyries, M. Levy, C. Ovaert, A. Servettaz, A. Guillaumot, C. Dauphin, C. Chabanne, E. Boiffard, V. Cottin, F. Perros, G. Simonneau, Sitbon Olivier, F. Soubrier, D. Bonnet, M. Remy Jardin, A. Chaouat, M. Humbert, D. Montani
{"title":"Phenotype and outcome of PAH patients carrying a TBX4 mutation","authors":"P. Thoré, B. Girerd, X. Jaïs, L. Savale, M. Ghigna, M. Eyries, M. Levy, C. Ovaert, A. Servettaz, A. Guillaumot, C. Dauphin, C. Chabanne, E. Boiffard, V. Cottin, F. Perros, G. Simonneau, Sitbon Olivier, F. Soubrier, D. Bonnet, M. Remy Jardin, A. Chaouat, M. Humbert, D. Montani","doi":"10.1183/13993003.congress-2020.4464","DOIUrl":"https://doi.org/10.1183/13993003.congress-2020.4464","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81493928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-07DOI: 10.1183/13993003.congress-2020.3973
Robert A. Lewis, I. Armstrong, Carmel Bergbaum, M. Brewis, J. Cannon, A. Charalampopoulos, A. C. Church, J. Coghlan, R. Davies, K. Dimopoulos, C. Elliot, J. Gibbs, W. Gin-Sing, Gulam S. Haji, A. Hameed, L. Howard, Martin Johnson, A. Kempny, D. Kiely, F. Lo Giudice, C. McCabe, Oyinkansola Peleyeju, J. Pepke-Zaba, Gary Polwarth, L. Price, I. Sabroe, B. Schreiber, K. Sheares, D. Taboada, A. Thompson, M. Toshner, Ivy Wanjiku, S. Wort, J. Yorke, R. Condliffe
Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure. 1745 patients with idiopathic or connective tissue disease-associated PAH who had completed emPHasis-10 questionnaires between 2014-17 at 6 UK referral centres were identified. Correlations with exercise capacity and WHO functional class (FC) were assessed, and exploratory risk stratification thresholds were tested. Moderate correlations were seen between emPHasis-10 scores and 6-minute walk distance (r=0.546), incremental shuttle walking distance (r=-0.504) and WHO FC (r=0.497; p all <0.0001). Distribution of emPHasis-10 differed significantly between each WHO FC (p all <0.0001). At multivariate analysis, emPHasis-10, but not WHO FC, was an independent predictor of mortality. In a risk stratification approach, scores of 0-16, 17-33 and 34-50 identified incident patients with oneyear mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO FC III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis10 had improved exercise capacity (p<0.0001), and patients who transitioned risk groups demonstrated similar survival to patients originally in those risk groups. The emPHasis-10 score is an independent prognostic marker in patients with idiopathic or connective tissue disease-associated PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity.
健康相关生活质量(HRQoL)评分评估肺动脉高压(PAH)的症状负担，但有关其在预后和风险分层中的作用的数据有限。我们使用emPHasis-10 HRQoL测量来评估这些关系。1745名特发性或结缔组织病相关的PAH患者在2014- 2017年间在6个英国转诊中心完成了emPHasis-10问卷调查。评估与运动能力和WHO功能分级(FC)的相关性，并测试探索性风险分层阈值。强调-10评分与6分钟步行距离(r=0.546)、增加穿梭步行距离(r=-0.504)和WHO FC (r=0.497;P均<0.0001)。各WHO FC间的强调-10分布差异显著(p均<0.0001)。在多变量分析中，强调-10(而非WHO FC)是死亡率的独立预测因子。在风险分层方法中，0-16分、17-33分和34-50分分别确定了一年死亡率为5%、10%和23%的事件患者。WHO FC III患者的生存可以使用emPHasis-10评分≥34分进一步分层(p<0.01)。在随访中，改善了强调10的患者的运动能力得到了改善(p<0.0001)，并且过渡到危险组的患者的生存率与最初处于这些危险组的患者相似。在特发性或结缔组织病相关PAH患者中，emPHasis-10评分是一个独立的预后指标。除了目前使用的参数外，它还可以用于风险分层。强调-10评分的提高与运动能力的提高有关。
{"title":"EmPHasis-10 health-related quality of life score predicts outcomes in patients with idiopathic and connective tissue disease-associated pulmonary arterial hypertension: results from a UK multi-centre study","authors":"Robert A. Lewis, I. Armstrong, Carmel Bergbaum, M. Brewis, J. Cannon, A. Charalampopoulos, A. C. Church, J. Coghlan, R. Davies, K. Dimopoulos, C. Elliot, J. Gibbs, W. Gin-Sing, Gulam S. Haji, A. Hameed, L. Howard, Martin Johnson, A. Kempny, D. Kiely, F. Lo Giudice, C. McCabe, Oyinkansola Peleyeju, J. Pepke-Zaba, Gary Polwarth, L. Price, I. Sabroe, B. Schreiber, K. Sheares, D. Taboada, A. Thompson, M. Toshner, Ivy Wanjiku, S. Wort, J. Yorke, R. Condliffe","doi":"10.1183/13993003.congress-2020.3973","DOIUrl":"https://doi.org/10.1183/13993003.congress-2020.3973","url":null,"abstract":"Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure. 1745 patients with idiopathic or connective tissue disease-associated PAH who had completed emPHasis-10 questionnaires between 2014-17 at 6 UK referral centres were identified. Correlations with exercise capacity and WHO functional class (FC) were assessed, and exploratory risk stratification thresholds were tested. Moderate correlations were seen between emPHasis-10 scores and 6-minute walk distance (r=0.546), incremental shuttle walking distance (r=-0.504) and WHO FC (r=0.497; p all <0.0001). Distribution of emPHasis-10 differed significantly between each WHO FC (p all <0.0001). At multivariate analysis, emPHasis-10, but not WHO FC, was an independent predictor of mortality. In a risk stratification approach, scores of 0-16, 17-33 and 34-50 identified incident patients with oneyear mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO FC III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis10 had improved exercise capacity (p<0.0001), and patients who transitioned risk groups demonstrated similar survival to patients originally in those risk groups. The emPHasis-10 score is an independent prognostic marker in patients with idiopathic or connective tissue disease-associated PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81133472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-07DOI: 10.1183/13993003.congress-2020.1488
K. Jandl, L. Marsh, J. Hoffmann, A. C. Mutgan, O. Baum, W. Bloch, K. Sinn, W. Klepetko, A. Heinemann, A. Olschewski, H. Olschewski, G. Kwapiszewska
{"title":"Basement membrane, a specialized extracellular matrix, shapes endothelial function in IPAH","authors":"K. Jandl, L. Marsh, J. Hoffmann, A. C. Mutgan, O. Baum, W. Bloch, K. Sinn, W. Klepetko, A. Heinemann, A. Olschewski, H. Olschewski, G. Kwapiszewska","doi":"10.1183/13993003.congress-2020.1488","DOIUrl":"https://doi.org/10.1183/13993003.congress-2020.1488","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75502865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-07DOI: 10.1183/13993003.congress-2020.305
R. Castro, E. Gimeno-Santos, J. Vilaró, M. R. I. Figuls, J. Moisés, J. Barberà, I. Blanco
{"title":"Effect of Pulmonary Hypertension in exercise tolerance in patients with Chronic Obstructive Pulmonary Disease: A systematic review and meta-analysis","authors":"R. Castro, E. Gimeno-Santos, J. Vilaró, M. R. I. Figuls, J. Moisés, J. Barberà, I. Blanco","doi":"10.1183/13993003.congress-2020.305","DOIUrl":"https://doi.org/10.1183/13993003.congress-2020.305","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78046883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-07DOI: 10.1183/13993003.congress-2020.3558
N. Berrebeh, R. Thuillet, L. Tu, Benjamin Le Vely, Amélie Cumont, I. Anegon, A. Huertas, M. Humbert, S. Bailly, C. Guignabert
Introduction: Despite increasing evidence suggesting that the Bone Morphogenetic Protein (BMP)-9 signaling pathway is playing a role in the pulmonary hypertension (PH) pathogenesis, the data in the literature are still controversial. Aims and Objectives: To investigate the role of BMP9 signaling pathway in PH pathophysiology. Methods: Bmp9 KO-/- rats were subjected to 3 distinct well characterized experimental PH models: the chronic hypoxia (CHx), monocrotaline (MCT) and Sugen/hypoxia (SuHx) models. Wild-type littermates were used as controls. We then performed transthoracic echocardiography and right heart catheterization as well as histological analyses in these 3 models: 21 days after CHx and MCT treatment and 8 weeks in the SuHx model. Results: While Bmp9 KO-/- rats did not develop any spontaneous phenotype, they were protected against PH induced in our 3 different PH models, compared with their wild-type littermates, as reflected by lower values of mean pulmonary artery pressure (mPAP), total pulmonary vascular resistance (TPVR), and Fulton index. We also found a less pronounced remodeling of the pulmonary arterioles and collagen accumulation in the right ventricle in these Bmp9 KO-/- rats compared to their wild-type littermates. Finally, we found that the in vitro exposure of human pulmonary endothelial cells (ECs) to BMP9 modulates the secretion of pro- and anti-angiogenic factors. These in vitro observations were confirmed in vivo, with Bmp9 KO-/- rats exhibiting increased serum and lung levels of pro-angiogenic factors. Conclusions: BMP9 deficiency does not lead to spontaneous PH, but attenuates the development of experimental PH.
{"title":"Loss of Bmp9 does not lead to spontaneous pulmonary hypertension, but attenuates vascular remodeling in experimental models","authors":"N. Berrebeh, R. Thuillet, L. Tu, Benjamin Le Vely, Amélie Cumont, I. Anegon, A. Huertas, M. Humbert, S. Bailly, C. Guignabert","doi":"10.1183/13993003.congress-2020.3558","DOIUrl":"https://doi.org/10.1183/13993003.congress-2020.3558","url":null,"abstract":"Introduction: Despite increasing evidence suggesting that the Bone Morphogenetic Protein (BMP)-9 signaling pathway is playing a role in the pulmonary hypertension (PH) pathogenesis, the data in the literature are still controversial. Aims and Objectives: To investigate the role of BMP9 signaling pathway in PH pathophysiology. Methods: Bmp9 KO-/- rats were subjected to 3 distinct well characterized experimental PH models: the chronic hypoxia (CHx), monocrotaline (MCT) and Sugen/hypoxia (SuHx) models. Wild-type littermates were used as controls. We then performed transthoracic echocardiography and right heart catheterization as well as histological analyses in these 3 models: 21 days after CHx and MCT treatment and 8 weeks in the SuHx model. Results: While Bmp9 KO-/- rats did not develop any spontaneous phenotype, they were protected against PH induced in our 3 different PH models, compared with their wild-type littermates, as reflected by lower values of mean pulmonary artery pressure (mPAP), total pulmonary vascular resistance (TPVR), and Fulton index. We also found a less pronounced remodeling of the pulmonary arterioles and collagen accumulation in the right ventricle in these Bmp9 KO-/- rats compared to their wild-type littermates. Finally, we found that the in vitro exposure of human pulmonary endothelial cells (ECs) to BMP9 modulates the secretion of pro- and anti-angiogenic factors. These in vitro observations were confirmed in vivo, with Bmp9 KO-/- rats exhibiting increased serum and lung levels of pro-angiogenic factors. Conclusions: BMP9 deficiency does not lead to spontaneous PH, but attenuates the development of experimental PH.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86830621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-01DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a3872
F. Akoumia
Multi-Omics Analysis of the PDGF Response in Pulmonary Vascular Smooth Muscle Cells from Patients with Pulmonary Arterial Hypertension: Implication of the NMDAR The N-methyl-D-aspartate receptor (NMDAR), expressed by PASMC, has been pointed as a novel therapeutic target in PAH, and is a new player involved in the PDGF-dependent proliferation of PASMC. Decoding the mechanisms of action of NMDAR antagonist is important to validate it as a therapeutic option in PAH. Multi-omics approach was designed to study the transcriptional and translational response to PDGF, with or without NMDAR blockade, in PASMC of PAH patients. PASMC of PAH patients and controls in culture were stimulated with PDGF-BB 10 μM for 24 h and exposed to 100 μM MK-801, a noncompetitive NMDAR antagonist. The transcriptomic analysis was done on a Microarray Scanner DNA chip. Proteomic analysis was done using a high resolution Orbitrap mass spectrometer. Transcriptomics revealed that PDGF induced the expression of genes involved in proliferation, migration and apoptosis resistance in PASMC. Exposure to MK-801 reversed these effects. Proteomics revealed 748 differentially expressed proteins between patient and control PASMC, and highlighted overexpression of a large number of members of the Rab protein family. Their expression was increased in patient PASMC exposed to PDGF and was decreased by MK-801 treatment. Consistent with transcriptomics, PDGF induced pro-proliferative proteins while MK-801 induced anti-proliferative proteins in PASMCs of PAH patients. Multi-omics analysis showed that PDGF induced pro-proliferative gene and protein expression tended to normalize using NMDAR in PASMC. These results further support NMDARs as a therapeutic target for the treatment of PAHs.
{"title":"Multi-Omics Analysis of the PDGF Response in Pulmonary Vascular Smooth Muscle Cells from Patients with Pulmonary Arterial Hypertension: Implication of the NMDAR","authors":"F. Akoumia","doi":"10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a3872","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a3872","url":null,"abstract":"Multi-Omics Analysis of the PDGF Response in Pulmonary Vascular Smooth Muscle Cells from Patients with Pulmonary Arterial Hypertension: Implication of the NMDAR The N-methyl-D-aspartate receptor (NMDAR), expressed by PASMC, has been pointed as a novel therapeutic target in PAH, and is a new player involved in the PDGF-dependent proliferation of PASMC. Decoding the mechanisms of action of NMDAR antagonist is important to validate it as a therapeutic option in PAH. Multi-omics approach was designed to study the transcriptional and translational response to PDGF, with or without NMDAR blockade, in PASMC of PAH patients. PASMC of PAH patients and controls in culture were stimulated with PDGF-BB 10 μM for 24 h and exposed to 100 μM MK-801, a noncompetitive NMDAR antagonist. The transcriptomic analysis was done on a Microarray Scanner DNA chip. Proteomic analysis was done using a high resolution Orbitrap mass spectrometer. Transcriptomics revealed that PDGF induced the expression of genes involved in proliferation, migration and apoptosis resistance in PASMC. Exposure to MK-801 reversed these effects. Proteomics revealed 748 differentially expressed proteins between patient and control PASMC, and highlighted overexpression of a large number of members of the Rab protein family. Their expression was increased in patient PASMC exposed to PDGF and was decreased by MK-801 treatment. Consistent with transcriptomics, PDGF induced pro-proliferative proteins while MK-801 induced anti-proliferative proteins in PASMCs of PAH patients. Multi-omics analysis showed that PDGF induced pro-proliferative gene and protein expression tended to normalize using NMDAR in PASMC. These results further support NMDARs as a therapeutic target for the treatment of PAHs.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84529935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-01DOI: 10.1016/j.jval.2020.04.129
D. Londoño, A. Taborda, C. Chamorro, K. Rojas
{"title":"Burden Study of Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension for Colombia Population","authors":"D. Londoño, A. Taborda, C. Chamorro, K. Rojas","doi":"10.1016/j.jval.2020.04.129","DOIUrl":"https://doi.org/10.1016/j.jval.2020.04.129","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83830347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01DOI: 10.1007/978-3-030-52787-7
H. Ford, G. Heresi, M. Risbano
{"title":"Pulmonary Hypertension: Controversial and Emerging Topics","authors":"H. Ford, G. Heresi, M. Risbano","doi":"10.1007/978-3-030-52787-7","DOIUrl":"https://doi.org/10.1007/978-3-030-52787-7","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78437517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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