Imperial College London

DrStephenWort

Faculty of MedicineNational Heart & Lung Institute

Professor of Practice (Pulmonary Hypertension)
 
 
 
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Contact

 

+44 (0)20 7351 8528s.wort

 
 
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Location

 

305Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

395 results found

Price LC, Kouranos V, Baughman R, Bloom C, Stewart I, Shlobin O, Nathan S, Dimopoulos K, Falconer J, Gupta R, McCabe C, Samaranayake C, Mason T, Mukherjee B, Taube C, Sahni A, Kempny A, Semple T, Renzoni E, Wells A, Wort SJet al., 2024, Use of pulmonary arterial hypertension therapies in patient swith sarcoidosis-associated pulmonary hypertension., Sarcoidosis Vasc Diffuse Lung Dis, Vol: 41

Journal article

Stubbs HD, Cannon J, Knightbridge E, Durrington C, Roddis C, Gin-Sing W, Massey F, Knight DS, Virsinskaite R, Lordan JL, Sear E, Apple-Pinguel J, Morris E, Johnson MK, Wort SJet al., 2024, Sendaway capillary NT-proBNP in pulmonary hypertension., BMJ Open Respir Res, Vol: 11

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac ventricular wall stress that is incorporated into pulmonary hypertension (PH) risk stratification models. Sendaway sampling may enable patients to perform NT-proBNP tests remotely. This UK-wide study aimed to assess the agreement of sendaway NT-proBNP with standard venous NT-proBNP and to assess the effect of delayed processing. METHODS: Reference venous NT-proBNP was collected from PH patients. Samples for capillary and venous sendaway tests were collected contemporaneously, mailed to a reference laboratory and processed at 3 and 7 days using a Roche Cobas e411 device. Differences in paired measurements were analysed with Passing-Bablok regression, percentage difference plots and the % difference in risk strata. RESULTS: 113 patients were included in the study. 13% of day 3 capillary samples were insufficient. Day 3 capillary samples were not equivalent to reference samples (Passing Bablok analysis slope of 0.91 (95% CI 0.88 to 0.93) and intercept of 6.0 (95% CI 0.2 to 15.9)). The relative median difference was -7% and there were acceptable limits of agreement. Day 3 capillary NT-proBNP accurately risk stratified patients in 93.5% of cases. By comparison, day 3 venous results accurately risk stratified patients in 90.1% of cases and were equivalent by Passing-Bablok regression. Delayed sampling of sendaway tests led to an unacceptable level of agreement and systematically underestimated NT-proBNP. CONCLUSIONS: Sendaway NT-proBNP sampling may provide an objective measure of right ventricular strain for virtual PH clinics. Results must be interpreted with caution in cases of delayed sampling.

Journal article

Ulrich A, Wu Y, Draisma H, Wharton J, Swietlik EM, Cebola I, Vasilaki E, Balkhiyarova Z, Jarvelin M, Auvinen J, Herzig K-H, Coghlan JG, Lordan J, Church C, Howard L, Pepke-Zaba J, Toshner M, Wort S, Kiely D, Condliffe R, Lawrie A, Graf S, Morrell N, Wilkins M, Prokopenko I, Rhodes C, Rhodes Cet al., 2024, Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension, Nature Communications, Vol: 15, ISSN: 2041-1723

Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling causing premature death from right heart failure. Established DNA variants influence PAH risk, but susceptibility from epigenetic changes is unknown. We addressed this through epigenome-wide association study (EWAS), testing 865,848 CpG sites for association with PAH in 429 individuals with PAH and 1226 controls. Three loci, at Cathepsin Z (CTSZ, cg04917472), Conserved oligomeric Golgi complex 6 (COG6, cg27396197), and Zinc Finger Protein 678 (ZNF678, cg03144189), reached epigenome-wide significance (p < 10−7) and are hypermethylated in PAH, including in individuals with PAH at 1-year follow-up. Of 16 established PAH genes, only cg10976975 in BMP10 shows hypermethylation in PAH. Hypermethylation at CTSZ is associated with decreased blood cathepsin Z mRNA levels. Knockdown of CTSZ expression in human pulmonary artery endothelial cells increases caspase-3/7 activity (p < 10−4). DNA methylation profiles are altered in PAH, exemplified by the pulmonary endothelial function modifier CTSZ, encoding protease cathepsin Z.

Journal article

Varian F, Dick J, Battersby C, Roman S, Ablott J, Watson L, Binmahfooz S, Zafar H, Colgan G, Cannon J, Suntharalingam J, Lordan J, Howard L, McCabe C, Wort J, Price L, Church C, Hamilton N, Armstrong I, Hameed A, Hurdman J, Elliot C, Condliffe R, Wilkins M, Webb A, Adlam D, Benza RL, Rahimi K, Shojaei-Shahrokhabadi M, Lin NX, Wason JMS, McIntosh A, McConnachie A, Middleton JT, Thompson R, Kiely DG, Toshner M, Rothman Aet al., 2024, Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies., Pulm Circ, Vol: 14, ISSN: 2045-8932

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches.

Journal article

Shlobin OA, Shen E, Wort SJ, Piccari L, Scandurra JA, Hassoun PM, Nikkho SM, Nathan SDet al., 2024, Pulmonary hypertension in the setting of interstitial lung disease: Approach to management and treatment. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative-Group 3 Pulmonary Hypertension., Pulm Circ, Vol: 14, ISSN: 2045-8932

Pulmonary hypertension (PH) due to interstitial lung disease (ILD), a commonly encountered complication of fibrotic ILDs, is associated with significant morbidity and mortality. Until recently, the studies of pulmonary vasodilator therapy in PH-ILD have been largely disappointing, with some even demonstrating the potential for harm. This paper is part of a series of Consensus Statements from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative for Group 3 Pulmonary Hypertension, with prior publications covering pathogenesis, prevalence, clinical features, phenotyping, clinical trials, and impact of PH-ILD. It offers a comprehensive review of and a holistic approach to treatment of PH-ILD, including the management of underlying interstitial lung diseases, importance of treating the comorbidities, emphasis on importance of exercise and palliation of dyspnea, and review of the most up-to-date guidelines for referral for potential lung transplant work up. It also summarizes the prior, ongoing, and possibly future studies in treatment of the vascular derangement of this morbid condition.

Journal article

Gayen SK, Baughman RP, Nathan SD, Wells AU, Kouranos V, Alhamad EH, Culver DA, Barney J, Carmoma EM, Cordova FC, Huitema M, Scholand MB, Wijsenbeek M, Ganesh S, Birring SS, Price LC, Wort SJ, Shlobin OA, Gupta Ret al., 2023, Pulmonary hemodynamics and transplant-free survival in sarcoidosis-associated pulmonary hypertension: Results from an international registry., Pulm Circ, Vol: 13, ISSN: 2045-8932

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan-Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant-free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.

Journal article

Mumby S, Peros F, Grynblat J, Manaud G, Papi A, Casolari P, Caramori G, Humbert M, Wort SJ, Adcock Iet al., 2023, Differential responses of pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1, Respiratory Research, Vol: 24, Pages: 1-16, ISSN: 1465-9921

BackgroundPulmonary arterial hypertension (PAH) encompasses a group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling and inflammation. Bromodomain and extra-terminal (BET) proteins are required for the expression of a subset of NF-κB-induced inflammatory genes which can be inhibited by the BET mimic JQ1+. We hypothesised that JQ+ would supress TNFα-driven inflammatory responses in human pulmonary vascular cells from PAH patients.MethodsImmunohistochemical staining of human peripheral lung tissue (N = 14 PAH and N = 12 non-PAH) was performed for the BET proteins BRD2 and 4. Human pulmonary microvascular endothelial cells (HPMEC) and pulmonary artery smooth muscle cells (HPASMC) from PAH patients (N = 4) and non-PAH controls (N = 4) were stimulated with TNFα in presence or absence of JQ1+ or its inactive isomer JQ1–. IL-6 and -8 mRNA was measured by RT-qPCR and protein levels by ELISA. Chromatin immunoprecipitation analysis was performed using EZ-ChIP™ and NF-κB p65 activation determined using a TransAm kit. MTT assay was used to measure cell viability.ResultsNuclear staining of BRD2 and BRD4 was significantly (p < 0.0001) increased in the lung vascular endothelial and smooth muscle cells from PAH patients compared to controls with normal lung function. TNFα-driven IL-6 release from both HPMECs and HPASMCs was greater in PAH cells than control cells. Levels of CXCL8/IL-8 protein release was higher in PAH HPASMCs than in control cells with similar release observed in HPMECs. TNFα-induced recruitment of activated NF-κB p65 to the IL-6 and CXCL8/IL-8 promoters were similar in both cell types and between subject groups. JQ1+ suppressed TNFα-induced IL-6 and CXCL8/IL-8 release and mRNA expression to a comparable extent in control and PAH HPMECs and HPASMCs. JQ1 had a g

Journal article

Mumby S, Perros F, Grynblat J, Manaud G, Papi A, Casolari P, Caramori G, Humbert M, John Wort S, Adcock IMet al., 2023, Differential responsesof pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1, Respiratory Research, Vol: 24, ISSN: 1465-9921

Background:Pulmonary arterial hypertension (PAH) encompasses a group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling and inflammation. Bromodomain and extra-terminal (BET) proteins are required for the expression of a subset of NF-κB-induced inflammatory genes which can be inhibited by the BET mimic JQ1+. We hypothesised that JQ+ would supress TNFα-driven inflammatory responses in human pulmonary vascular cells from PAH patients.Methods:Immunohistochemical staining of human peripheral lung tissue (N = 14 PAH and N = 12 non-PAH) was performed for the BET proteins BRD2 and 4. Human pulmonary microvascular endothelial cells (HPMEC) and pulmonary artery smooth muscle cells (HPASMC) from PAH patients (N = 4) and non-PAH controls (N = 4) were stimulated with TNFα in presence or absence of JQ1+ or its inactive isomer JQ1–. IL-6 and -8 mRNA was measured by RT-qPCR and protein levels by ELISA. Chromatin immunoprecipitation analysis was performed using EZ-ChIP™ and NF-κB p65 activation determined using a TransAm kit. MTT assay was used to measure cell viability.Results:Nuclear staining of BRD2 and BRD4 was significantly (p < 0.0001) increased in the lung vascular endothelial and smooth muscle cells from PAH patients compared to controls with normal lung function. TNFα-driven IL-6 release from both HPMECs and HPASMCs was greater in PAH cells than control cells. Levels of CXCL8/IL-8 protein release was higher in PAH HPASMCs than in control cells with similar release observed in HPMECs. TNFα-induced recruitment of activated NF-κB p65 to the IL-6 and CXCL8/IL-8 promoters were similar in both cell types and between subject groups. JQ1+ suppressed TNFα-induced IL-6 and CXCL8/IL-8 release and mRNA expression to a comparable extent in control and PAH HPMECs and HPASMCs. JQ1 had

Journal article

Samaranayake CB, Warren C, Rhamie S, Haji G, Wort SJ, Price LC, McCabe C, Hull JHet al., 2023, Chaotic breathing in post-COVID-19 breathlessness: a key feature of dysfunctional breathing can be characterised objectively by approximate entropy, ERJ OPEN RESEARCH, Vol: 9

Journal article

Samaranayake CB, Upham J, Tran K, Howard LS, Nguyen S, Lwin M, Anderson J, Wahi S, Price LC, Wort S, Li W, McCabe C, Keir GJet al., 2023, Right ventricular functional recovery assessment with stress echocardiography and cardiopulmonary exercise testing after pulmonary embolism: a pilot prospective multicentre study, BMJ OPEN RESPIRATORY RESEARCH, Vol: 10

Journal article

Samaranayake CB, Kempny A, Naeije R, Gatzoulis M, Price L, Dimopoulos K, Zhao L, Wort SJ, McCabe Cet al., 2023, Beta-blockade improves right ventricular diastolic function in exercising pulmonary arterial hypertension, European Respiratory Journal, Vol: 61, ISSN: 0903-1936

Journal article

Piccari L, Allwood B, Antoniou K, Chung JH, Hassoun PM, Nikkho SM, Saggar R, Shlobin OA, Vitulo P, Nathan SD, Wort SJet al., 2023, Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative - Group 3 Pulmonary Hypertension, PULMONARY CIRCULATION, Vol: 13, ISSN: 2045-8932

Journal article

Dawes TJW, McCabe C, Dimopoulos K, Stewart I, Bax S, Harries C, Samaranayake CB, Kempny A, Molyneaux PL, Seitler S, Semple T, Li W, George PM, Kouranos V, Chua F, Renzoni EA, Kokosi M, Jenkins G, Wells AU, Wort SJ, Price LCet al., 2023, Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: A Bayesian retrospective observational cohort study, Respirology, Vol: 28, Pages: 262-272, ISSN: 1323-7799

Background and ObjectivePulmonary hypertension is a life-limiting complication of interstitial lung disease (ILD-PH). We investigated whether treatment with phosphodiesterase 5 inhibitors (PDE5i) in patients with ILD-PH was associated with improved survival.MethodsConsecutive incident patients with ILD-PH and right heart catheterisation, echocardiography and spirometry data were followed from diagnosis to death, transplantation or censoring with all follow-up and survival data modelled by Bayesian methods.ResultsThe diagnoses in 128 patients were idiopathic pulmonary fibrosis (n = 74, 58%), hypersensitivity pneumonitis (n = 17, 13%), non-specific interstitial pneumonia (n = 12, 9%), undifferentiated ILD (n = 8, 6%) and other lung diseases (n = 17, 13%). Final outcomes were death (n = 106, 83%), transplantation (n = 9, 7%) and censoring (n = 13, 10%). Patients treated with PDE5i (n = 50, 39%) had higher mean pulmonary artery pressure (median 38 mm Hg [interquartile range, IQR: 34, 43] vs. 35 mm Hg [IQR: 31, 38], p = 0.07) and percentage predicted forced vital capacity (FVC; median 57% [IQR: 51, 73] vs. 52% [IQR: 45, 66], p=0.08) though differences did not reach significance. Patients treated with PDE5i survived longer than untreated patients (median 2.18 years [95% CI: 1.43, 3.04] vs. 0.94 years [0.69, 1.51], p = 0.003) independent of all other prognostic markers by Bayesian joint-modelling (HR 0.39, 95% CI: 0.23, 0.59, p < 0.001) and propensity-matched analyses (HR 0.38, 95% CI: 0.22, 0.58, p < 0.001). Survival difference with treatment was significantly larger if right ventricular function was normal, rather than abnormal, at presentation (+2.55 years, 95% CI: −0.03, +3.97 vs. +0.98 years, 95% CI: +0.47, +2.00, p = 0.04).ConclusionPDE5i treatment in ILD-PH should be investigated by a prospective randomized trial.

Journal article

Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Rådegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery J-L, Vonk Noordegraaf A, Delcroix M, Rosenkranz S, ESCERS Scientific Document Groupet al., 2023, 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension., Eur Respir J, Vol: 61

Journal article

Prapa M, Lago-Docampo M, Swietlik EM, Montani D, Eyries M, Humbert M, Welch CL, Chung WK, Berger RMF, Bogaard HJ, Danhaive O, Escribano-Subias P, Gall H, Girerd B, Hernandez-Gonzalez I, Holden S, Hunt D, Jansen SMA, Kerstjens-Frederikse W, Kiely DG, Lapunzina P, McDermott J, Moledina S, Pepke-Zaba J, Polwarth GJ, Schotte G, Tenorio-Castano J, Thompson AAR, Wharton J, Wort SJ, Megy K, Mapeta R, Treacy CM, Martin JM, Li W, Swift AJ, Upton PD, Morrell NW, Graf S, Valverde Det al., 2022, First Genotype-Phenotype Study in TBX4 Syndrome Gain-of-Function Mutations Causative for Lung Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 206, Pages: 1522-1533, ISSN: 1073-449X

Journal article

Kariotis S, Jammeh E, Swietlik EM, Pickworth JA, Rhodes CJ, Otero P, Wharton J, Iremonger J, Dunning MJ, Pandya D, Mascarenhas TS, Errington N, Thompson AAR, Romanoski CE, Rischard F, Garcia JGN, Yuan JX-J, An T-HS, Desai AA, Coghlan G, Lordan J, Corris PA, Howard LS, Condliffe R, Kiely DG, Church C, Pepke-Zaba J, Toshner M, Wort S, Graf S, Morrell NW, Wilkins MR, Lawrie A, Wang Det al., 2022, Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood, Nature Communications, Vol: 13, Pages: 1-1, ISSN: 2041-1723

Journal article

Diller GP, Vidal MLB, Kempny A, Kubota K, Li W, Dimopoulos K, Arvanitaki A, Lammers AE, Wort SJ, Baumgartner H, Orwat S, Gatzoulis MAet al., 2022, A framework of deep learning networks provides expert-level accuracy for the detection and prognostication of pulmonary arterial hypertension, EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING, Vol: 23, Pages: 1447-1456, ISSN: 2047-2404

Journal article

Constantine A, Condliffe R, Ciift P, Jansen K, Wort SJ, Moledina S, Dimopoulos Ket al., 2022, Macitentan for pulmonary arterial hypertension related to repaired congenital heart disease: real-world UK experience, ESC Congress 2022, Publisher: Oxford University Press, Pages: 1928-1928, ISSN: 0195-668X

Conference paper

Mahomed A, Burke-Gaffney A, Ghazaly M, Naser J, Toe Q, Quinlan G, Wort SJet al., 2022, COX2 expression is downregulated in a shear stress magnitude-dependent manner in BMPR2-silenced HPAECs: implications for prostacyclin deficiency in PAH, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Toe QK, Issitt T, Mahomed A, Sturges C, Wort SJ, Quinlan Get al., 2022, Human pulmonary artery endothelial cells upregulate ACE2 expression in response to ironregulatory elements: potential implications for SARS-CoV-2 infection, ERS International Congress 2022, Publisher: European Respiratory Society, ISSN: 0903-1936

Conference paper

Samaranayake C, Mcniven R, Kempny A, Price LC, Harries C, Gatzoulis M, Dimopoulos K, Wort SJ, Mccabe Cet al., 2022, Ventilatory limitation during cardiopulmonary exercise testing predicts survival in patients with pulmonary arterial hypertension with Eisenmenger physiology, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Samaranayake C, Niglas M, Kempny A, Baxan N, Ashek A, Pinguel J, Dimopoulos K, Price LC, Wort SJ, Zhao L, Mccabe Cet al., 2022, Acute beat blockade improves right ventricular diastolic filling in pulmonary arterial hypertension: a rodent CMR and clinical human pressure-volume study, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Constantine A, Rhodes CJ, Ricci P, Li W, Price LC, Mccabe C, Wharton J, Wilkins MR, Howard LS, Dimopoulos K, Wort SJet al., 2022, Correlation between right ventricular dysfunction and plasma protein profile in pulmonary hypertension, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Samaranayake C, Kempny A, Price LC, Pinguel J, Morris E, Moriarty E, Gummadi M, Dimopoulos K, Wort SJ, Zhao L, Mccabe Cet al., 2022, Metabolic modulation of the right ventricle and pulmonary circulation in pulmonary arterial hypertension: an interventional study using a Glucagon-like-peptide-1 (GLP-1) agonist, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Radegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery J-L, Noordegraaf AV, Delcroix M, Rosenkranz S, Schwerzmann M, Anh-Tuan D-X, Bush A, Abdelhamid M, Aboyans V, Arbustini E, Asteggiano R, Barbera J-A, Beghetti M, Cikes M, Condliffe R, de Man F, Falk V, Fauchier L, Gaine S, Galie N, Gin-Sing W, Granton J, Grunig E, Hassoun PM, Hellemons M, Jaarsma T, Kjellstrom B, Klok FA, Konradi A, Koskinas KC, Kotecha D, Lang I, Lewis BS, Linhart A, Lip GYH, Lochen M-L, Mathioudakis AG, Mindham R, Moledina S, Naeije R, Nielsen JC, Olschewski H, Opitz I, Petersen SE, Prescott E, Rakisheva A, Reis A, Ristic AD, Roche N, Rodrigues R, Selton-Suty C, Souza R, Swift AJ, Touyz RM, Ulrich S, Wilkins MR, Wort SJet al., 2022, 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG), European Heart Journal, Pages: 1-114, ISSN: 0195-668X

Journal article

Piccari L, Wort SJ, Meloni F, Rizzo M, Price LC, Martino L, Salvaterra E, Scelsi L, Lopez Meseguer M, Blanco I, Callari A, Perez Gonzalez V, Tuzzolino F, McCabe C, Rodriguez Chiaradia DA, Vitulo Pet al., 2022, The Effect of Borderline Pulmonary Hypertension on Survival in Chronic Lung Disease, RESPIRATION, Vol: 101, Pages: 717-727, ISSN: 0025-7931

Journal article

Toshner M, Church C, Harbaum L, Rhodes C, Moreschi SSV, Liley J, Jones R, Arora A, Batai K, Desai AA, Coghlan JG, Gibbs JSR, Gor D, Graf S, Harlow L, Hernandez-Sanchez J, Howard LS, Humbert M, Karnes J, Kiely DG, Kittles R, Knightbridge E, Lam B, Lutz KA, Nichols WC, Pauciulo MW, Pepke-Zaba J, Suntharalingam J, Soubrier F, Trembath RC, Schwantes-An T-HL, Wort SJ, Wilkins MR, Gaine S, Morrell NW, Corris PAet al., 2022, Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension (vol 59, 2002463, 2022), EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936

Journal article

McFadyen C, Garfield B, Mancio J, Ridge CA, Semple T, Keeling A, Ledot S, Patel B, Samaranayake CB, McCabe C, Wort SJ, Price S, Price LCet al., 2022, Use of sildenafil in patients with severe COVID-19 pneumonitis, British Journal of Anaesthesia, Vol: 129, Pages: E18-E21, ISSN: 0007-0912

Journal article

Jones RJ, De Bie EMDD, Groves E, Zalewska KI, Swietlik EM, Treacy CM, Martin JM, Polwarth G, Li W, Guo J, Baxendale HE, Coleman S, Savinykh N, Coghlan JG, Corris PA, Howard LS, Johnson MK, Church C, Kiely DG, Lawrie A, Lordan JL, Mackenzie Ross RV, Pepke Zaba J, Wilkins MR, Wort SJ, Fiorillo E, Orrù V, Cucca F, Rhodes CJ, Gräf S, Morrell NW, McKinney EF, Wallace C, Toshner M, UK National PAH Cohort Study Consortiumet al., 2022, Autoimmunity is a significant feature of idiopathic pulmonary arterial hypertension., American Journal of Respiratory and Critical Care Medicine, Vol: 206, Pages: 81-93, ISSN: 1073-449X

RATIONALE: Autoimmunity is thought to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear if this is causative or a bystander of disease and if it carries any prognostic or treatment significance. OBJECTIVE: To study autoimmunity in IPAH using a large cross-sectional cohort. METHODS: Assessment of the circulating immune cell phenotype was undertaken using flow cytometry and the profile of serum immunoglobulins was generated using a standardised multiplex array of 19 clinically validated autoantibodies in 473 cases and 946 controls. Additional GST-fusion array and ELISA data were used to identify a serum autoantibody to BMPR2. Clustering analyses and clinical correlations were employed to determine associations between immunogenicity and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Flow cytometric immune profiling demonstrates IPAH is associated with an altered humoral immune response in addition to raised IgG3. Multiplexed autoantibodies were significantly raised in IPAH, and clustering demonstrated three distinct clusters: 'high autoantibody', 'low autoantibody', and a small 'intermediate' cluster exhibiting high levels of RNP-complex. The high autoantibody cluster had worse haemodynamics but improved survival. A small subset of patients demonstrated immunoglobulin reactivity to BMPR2. CONCLUSIONS: This study establishes aberrant immune regulation and presence of autoantibodies as a key feature in the profile of a significant proportion of IPAH patients and is associated with clinical outcomes. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Journal article

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