317 results found
Howard LS, Rosenkranz S, Frantz RP, et al., 2023, Assessing Daily Life Physical Activity by Actigraphy in Pulmonary Arterial Hypertension Insights From the Randomized Controlled Study With Selexipag (TRACE), CHEST, Vol: 163, Pages: 407-418, ISSN: 0012-3692
- Author Web Link
- Citations: 2
Eichstaedt CA, Belge C, Chung WK, et al., 2023, Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH., Eur Respir J, Vol: 61
Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.
Leong K, Howard L, Giudice FL, et al., 2023, Utility of cardiac magnetic resonance feature tracking strain assessment in chronic thromboembolic pulmonary hypertension for prediction of REVEAL 2.0 high risk status, PULMONARY CIRCULATION, Vol: 13, ISSN: 2045-8932
Daines L, Zheng B, Elneima O, et al., 2023, Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19, ERJ Open Research, Vol: 9, Pages: 1-15, ISSN: 2312-0541
BACKGROUND: Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. METHODS: PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness. RESULTS: We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21). CONCLUSIONS: Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.
Liew F, Talwar S, Cross A, et al., 2023, SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination, EBioMedicine, Vol: 87, Pages: 1-14, ISSN: 2352-3964
Background:Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.Methods:In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.Findings:Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.Interpretation:The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.Funding:This
Mulvaney EP, Renzo F, Adao R, et al., 2022, The thromboxane receptor antagonist NTP42 promotes beneficial adaptation and preserves cardiac function in experimental models of right heart overload, Frontiers in Cardiovascular Medicine, Vol: 9, ISSN: 2297-055X
Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary artery pressure leading to right ventricular (RV) failure. While current PAH therapies improve patient outlook, they show limited benefit in attenuating RV dysfunction. Recent investigations demonstrated that the thromboxane (TX) A2 receptor (TP) antagonist NTP42 attenuates experimental PAH across key hemodynamic parameters in the lungs and heart. This study aimed to validate the efficacy of NTP42:KVA4, a novel oral formulation of NTP42 in clinical development, in preclinical models of PAH while also, critically, investigating its direct effects on RV dysfunction.Methods: The effects of NTP42:KVA4 were evaluated in the monocrotaline (MCT) and pulmonary artery banding (PAB) models of PAH and RV dysfunction, respectively, and when compared with leading standard-of-care (SOC) PAH drugs. In addition, the expression of the TP, the target for NTP42, was investigated in cardiac tissue from several other related disease models, and from subjects with PAH and dilated cardiomyopathy (DCM).Results: In the MCT-PAH model, NTP42:KVA4 alleviated disease-induced changes in cardiopulmonary hemodynamics, pulmonary vascular remodeling, inflammation, and fibrosis, to a similar or greater extent than the PAH SOCs tested. In the PAB model, NTP42:KVA4 improved RV geometries and contractility, normalized RV stiffness, and significantly increased RV ejection fraction. In both models, NTP42:KVA4 promoted beneficial RV adaptation, decreasing cellular hypertrophy, and increasing vascularization. Notably, elevated expression of the TP target was observed both in RV tissue from these and related disease models, and in clinical RV specimens of PAH and DCM.Conclusion: This study shows that, through antagonism of TP signaling, NTP42:KVA4 attenuates experimental PAH pathophysiology, not only alleviating pulmonary pathologies but also reducing RV remodeling, promoting beneficial hypertrophy
Richter MJ, Fortuni F, Alenezi F, et al., 2022, Imaging the right atrium in pulmonary hypertension: A systematic review and meta-analysis., J Heart Lung Transplant
BACKGROUND: Right atrial (RA) imaging has emerged as a promising tool for the evaluation of patients with pulmonary hypertension (PH), albeit without systematic validation. METHODS: PubMed, Web of Science and the Cochrane library were searched for studies investigating the prognostic value of RA imaging assessment in patients with PH from 2000 to June 2021 (PROSPERO Identifier: CRD42020212850). An inverse variance-weighted meta-analysis of univariable hazard ratios (HRs) was performed using a random effects model. RESULTS: Thirty-five studies were included (3,476 patients with PH; 74% female, 86% pulmonary arterial hypertension). Risk of bias was low/moderate (Quality of Prognosis Studies checklist). RA area (HR 1.06; 95% confidence interval [CI] 1.04-1.08), RA indexed area (HR 1.09; 95% CI 1.04-1.14), RA peak longitudinal strain (PLS; HR 0.94; 95% CI 0.91-0.97) and RA total emptying fraction (HR 0.96; 95% CI 0.94-0.98) were significantly associated with combined end-points including death, clinical worsening and/or lung transplantation; RA volume and volume index showed marginal significant associations. RA area (HR 1.06; 95% CI 1.04-1.07), RA indexed area (HR 1.12; 95% CI 1.07-1.17) and RA PLS (HR 0.98; 95% CI 0.97-0.99) showed significant associations with mortality; RA total emptying fraction showed a marginal association. CONCLUSIONS: Imaging-based RA assessment qualifies as a relevant prognostic marker in PH. RA area reliably predicts composite end-points and mortality, which underscores its clinical utility. RA PLS emerged as a promising imaging measure, but is currently limited by the number of studies and different acquisition methods.
Stolfo D, Barbisan D, Ameri P, et al., 2022, PERFORMANCE OF RISK STRATIFICATION SCORES AND ROLE OF COMORBIDITIES IN OLDER VS YOUNGER PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION, Publisher: OXFORD UNIV PRESS, ISSN: 1520-765X
Oliveira RKF, Nyasulu PS, Iqbal AA, et al., 2022, Cardiopulmonary disease as sequelae of long-term COVID-19: Current perspectives and challenges, Frontiers in Medicine, Vol: 9, ISSN: 2296-858X
COVID-19 infection primarily targets the lungs, which in severe cases progresses to cytokine storm, acute respiratory distress syndrome, multiorgan dysfunction, and shock. Survivors are now presenting evidence of cardiopulmonary sequelae such as persistent right ventricular dysfunction, chronic thrombosis, lung fibrosis, and pulmonary hypertension. This review will summarize the current knowledge on long-term cardiopulmonary sequelae of COVID-19 and provide a framework for approaching the diagnosis and management of these entities. We will also identify research priorities to address areas of uncertainty and improve the quality of care provided to these patients.
Kariotis S, Jammeh E, Swietlik EM, et al., 2022, Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood, NATURE COMMUNICATIONS, Vol: 13
- Author Web Link
- Citations: 1
Wojciak-Stothard B, Ainscough AJ, Smith TJ, et al., 2022, An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis, Communications Biology, Vol: 5, Pages: 1-15, ISSN: 2399-3642
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
Pepke-Zaba J, Howard L, Kiely D, et al., 2022, PULMONARY EMBOLISM (PE) TO CHRONIC THROMBOEMBOLIC PULMONARY DISEASE (CTEPD): FINDINGS FROM A SURVEY OF UK PHYSICIANS, Publisher: BMJ PUBLISHING GROUP, Pages: A104-A104, ISSN: 0040-6376
Karia N, Howard L, Johnson M, et al., 2022, Mortality rates and cause of mortality in patients with mildly elevated pulmonary pressures versus PH: insights from the retrospective EVIDENCE-PAH study, Publisher: OXFORD UNIV PRESS, Pages: 1927-1927, ISSN: 0195-668X
Constantine A, Rhodes CJ, Ricci P, et al., 2022, Correlation between right ventricular dysfunction and plasma protein profile in pulmonary hypertension, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Majeed RW, Wilkins MR, Howard L, et al., 2022, Pulmonary vascular research institute GoDeep: a meta-registry merging deep phenotyping datafrom international PH reference centers, Pulmonary Circulation, Vol: 12, ISSN: 2045-8940
The Pulmonary Vascular Research Institute GoDeep meta-registry is a collaboration of pulmonary hypertension (PH) reference centers across the globe. Merging worldwide PH data in a central meta-registry to allow advanced analysis of the heterogeneity of PH and its groups/subgroups on a worldwide geographical, ethnical, and etiological landscape (ClinTrial. gov NCT05329714). Retrospective and prospective PH patient data (diagnosis based on catheterization; individuals with exclusion of PH are included as a comparator group) are mapped to a common clinical parameter set of more than 350 items, anonymized and electronically exported to a central server. Use and access is decided by the GoDeep steering board, where each center has one vote. As of April 2022, GoDeep comprised 15,742 individuals with 1.9 million data points from eight PH centers. Geographic distribution comprises 3990 enrollees (25%) from America and 11,752 (75%) from Europe. Eighty-nine perecent were diagnosed with PH and 11% were classified as not PH and provided a comparator group. The retrospective observation period is an average of 3.5 years (standard error of the mean 0.04), with 1159 PH patients followed for over 10 years. Pulmonary arterial hypertension represents the largest PH group (42.6%), followed by Group 2 (21.7%), Group 3 (17.3%), Group 4 (15.2%), and Group 5 (3.3%). The age distribution spans several decades, with patients 60 years or older comprising 60%. The majority of patients met an intermediate risk profile upon diagnosis. Data entry from a further six centers is ongoing, and negotiations with >10 centers worldwide have commenced. Using electronic interface-based automated retrospective and prospective data transfer, GoDeep aims to provide in-depth epidemiological and etiological understanding of PH and its various groups/subgroups on a global scale, offering insights for improved management.
Evans RA, Leavy OC, Richardson M, et al., 2022, Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study, The Lancet Respiratory Medicine, Vol: 10, Pages: 761-775, ISSN: 2213-2600
BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obes
Jones RJ, De Bie EMDD, Groves E, et 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/).
Toshner M, Church C, Harbaum L, et 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
Badagliacca R, Rischard F, Giudice FL, et al., 2022, Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension., J Heart Lung Transplant, Vol: 41, Pages: 780-790
BACKGROUND: Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined. METHODS: Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed. RESULTS: A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO2 peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO2 peak ≥14 ml/kg/min and SVI >30 ml/m2; Group 2, score between 2 and 5 (112 patients) with VO2 peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m2; Group 3, score >5 (46 patients) with VO2 peak <10 ml/kg/min and SVI <30 ml/m2. The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3. CONCLUSIONS: Combinations of VO2 peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH.
Rhodes C, Wharton J, Swietlik E, et al., 2022, Using the plasma proteome for risk stratifying patients with pulmonary arterial hypertension, American Journal of Respiratory and Critical Care Medicine, Vol: 205, Pages: 1102-1111, ISSN: 1073-449X
Rationale: N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of cardiac origin, is used to risk stratify patients with pulmonary arterial hypertension (PAH). Its limitations include poor sensitivity to early vascular pathology. Other biomarkers of vascular or systemic origin may also be useful in the management of PAH.Objectives: Identify prognostic proteins in PAH which complement NT-proBNP and clinical risk scores.Methods: An aptamer-based assay (SomaScan-V4) targeting 4,152 proteins was used to measure plasma proteins in patients with idiopathic, heritable or drug-induced-PAH from the UK National Cohort of PAH (n=357) and the French EFORT study (n=79). Prognostic proteins were identified in discovery-replication analyses of UK samples. Proteins independent of 6-minute walk distance (6-MWD) and NT-proBNP entered LASSO modelling and the best combination in a single score was evaluated against clinical targets in EFORT.Measurements and Main Results: Thirty-one proteins robustly informed prognosis independent of NT-proBNP and 6-MWD in the UK Cohort. A weighted combination score of 6 proteins was validated at baseline (5-year mortality, AUC:0.73, 95%CI:0.63-0.85) and follow-up in EFORT (AUC:0.84, 95%CI:0.75-0.94, p=9.96x10-6). The protein score risk-stratified patients independent of established clinical targets and risk equations. The addition of the 6-protein model score to NT-proBNP improved prediction of 5-year outcomes from AUC:0.762 (0.702-0.821) to 0.818 (0.767-0.869) by ROC analysis (p=0.00426 for difference in AUC) in the UK replication and French samples combined. Conclusions: The plasma proteome informs prognosis beyond established factors in PAH and may provide a more sensitive measure of therapeutic response.
Kariotis S, Jammeh E, Swietlik EM, et al., 2022, Longitudinal Analysis of Three Major Risk-Associated Transcriptomic Subgroups Within the IPAH Classification, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Errington N, Kariotis S, Jammeh E, et al., 2022, Unsupervised Clustering of PH Using Circulating miRNA - Towards Molecular Classification of PH?, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Harbaum L, Rhodes CJ, Wharton J, et al., 2022, Mining the plasma proteome for insights into the molecular pathology of pulmonary arterial hypertension., American Journal of Respiratory and Critical Care Medicine, Vol: 205, Pages: 1-12, ISSN: 1073-449X
RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by structural remodelling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of circulating proteins. OBJECTIVES: To quantify and analyse the plasma proteome of PAH patients using inherited genetic variation to inform on underlying molecular drivers. METHODS: An aptamer-based assay was used to measure plasma proteins in 357 patients with idiopathic or heritable PAH, 103 healthy volunteers and 23 relatives of PAH patients. In discovery and replication subgroups, the plasma proteomes of PAH and healthy individuals were compared and the relationship to transplantation-free survival in PAH determined. To examine causal relationships to PAH, protein quantitative trait loci (pQTL) that influenced protein levels in the patient population were used as instruments for Mendelian randomisation (MR) analysis. MEASUREMENTS AND MAIN RESULTS: From 4,152 annotated plasma proteins, levels of 208 differed between PAH patients and healthy subjects and 49 predicted long-term survival. MR based on cis-pQTL located in proximity to the encoding gene for proteins that were prognostic and distinguished PAH from health estimated an adverse effect for higher levels of netrin-4 (odds ratio [OR] 1.55, 95%-confidence interval [CI] 1.16-2.08) and a protective effect for higher levels of thrombospondin-2 (OR 0.83, 95%-CI 0.74-0.94) on PAH. Both proteins tracked the development of PAH in previously healthy relatives and changes in thrombospondin-2 associated with pulmonary arterial pressure at disease onset. CONCLUSIONS: Integrated analysis of the plasma proteome and genome implicates two secreted matrix-binding proteins, netrin-4 and thrombospondin-2, in the pathobiology of PAH.
Hull JH, Burns P, Carre J, et al., 2022, BTS clinical statement for the assessment and management of respiratory problems in athletic individuals, THORAX, Vol: 77, Pages: 540-551, ISSN: 0040-6376
- Author Web Link
- Citations: 2
Lichtblau M, Piccari L, Ramjug S, et al., 2022, ERS International Congress 2021: highlights from the Pulmonary Vascular Diseases Assembly, ERJ OPEN RESEARCH, Vol: 8
Howard LSGE, He J, Watson GMJ, et al., 2022, Supplementation with Iron in Pulmonary Arterial Hypertension: Two Randomized Crossover Trials (vol 18, pg 981, 2021), ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 19, Pages: 703-703, ISSN: 1546-3222
Leong K, Howard L, Lo Giudice F, et al., 2022, MRI Feature Tracking Strain in Pulmonary Hypertension: Utility of Combined Left Atrial Volumetric and Deformation Assessment in Distinguishing Post- From Pre-capillary Physiology, FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 9, ISSN: 2297-055X
Constantine A, Rhodes CJ, Ricci P, et al., 2022, PLASMA PROTEIN PROFILE IN EISENMENGER SYNDROME AND OTHER FORMS OF PH: ASSOCIATION WITH MARKERS OF RV REMODELLING, ACC.22, Publisher: ELSEVIER SCIENCE INC, Pages: 1364-1364, ISSN: 0735-1097
Badagliacca R, Rischard F, Lo Giudice F, et al., 2021, Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension, 82nd National Congress of the Italian-Society-of-Cardiology (SIC), Publisher: OXFORD UNIV PRESS, ISSN: 1520-765X
Kariotis S, Jammeh E, Swietlik EM, et al., 2021, Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood, Nature Communications, Vol: 12, Pages: 1-14, ISSN: 2041-1723
Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.