Pulmonary Arterial Hypertension In Systemic Sclerosis: Challenges In D | OARRR - Dove Medical Press
Pulmonary Arterial Hypertension In Systemic Sclerosis: Challenges In D | OARRR - Dove Medical Press |
- Pulmonary Arterial Hypertension In Systemic Sclerosis: Challenges In D | OARRR - Dove Medical Press
- Predicting Survival in Patients With Pulmonary Arterial Hypertension - Physician's Weekly
- Liminal Biosciences's PBI-4050 Reduces Pulmonary Hypertension, Preclinical Data Show - Pulmonary Hypertension News
- Meeting highlights from 2019: Updates in asthma, COPD, PAH and more - Healio
| Pulmonary Arterial Hypertension In Systemic Sclerosis: Challenges In D | OARRR - Dove Medical Press Posted: 26 Dec 2019 04:52 PM PST Didem Saygin,1 Robyn T Domsic2 1Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Correspondence: Robyn T Domsic Abstract: Systemic sclerosis (SSc) is a chronic, multisystem autoimmune disease characterized by vasculopathy, fibrosis and immune system activation. Pulmonary hypertension and interstitial lung disease account for majority of SSc-related deaths. Diagnosis of SSc-PAH can be challenging due to nonspecific clinical presentation which can lead to delayed diagnosis. Many screening algorithms have been developed to detect SSc-associated pulmonary arterial hypertension (SSc-PAH) in early stages. Currently used PAH-specific medications are largely extrapolated from IPAH studies due to smaller number of patients with SSc-PAH. In this review, we discuss the current state of knowledge in epidemiology and risk factors for development of SSc-PAH, and challenges and potential solutions in the diagnosis, screening and management of SSc-PAH. Keywords: scleroderma, pulmonary hypertension, screening
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| Predicting Survival in Patients With Pulmonary Arterial Hypertension - Physician's Weekly Posted: 19 Dec 2019 06:16 AM PST A study has found that an updated risk calculator is a better discriminator of risk than other risk assessment strategies for patients with pulmonary arterial hypertension. When managing pulmonary arterial hypertension (PAH), regular risk assessments are recommended to guide treatment decisions and potentially improve morbidity and mortality. "Risk stratification is important in PAH because it can impact how patients are treated," explains Raymond L. Benza, MD. "Overestimating risks can result in overtreatment and substantially increase costs from therapy. Underestimating risk can result a greater risk of death. As such, ensuring that risk estimates are accurate is paramount in the management of PAH." Data from patient registries have been used to develop algorithms that estimate survival in PAH and to inform treatment guidelines. One such algorithm is the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator, which uses up to 12 clinically relevant variables. Three additional risk assessment tools have also been developed using patient populations from the Swedish Pulmonary Arterial Hypertension Register (SPAHR), the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), and the French Pulmonary Hypertension Registry (FPHR). These risk assessments utilize thresholds in 4 to 8 variables. A Comparative AnalysisTo enhance risk prediction in PAH, a new variable—all-cause hospitalization—and a revised variable—renal function measured by estimated glomerular filtration rate, or eGFR—were added to update the REVEAL risk calculator to REVEAL 2.0. Dr. Benza and colleagues had a study published in Chest that compared REVEAL 2.0 with the original REVEAL calculator and also compared risk discrimination with REVEAL 2.0 versus other contemporary risk assessment strategies. The authors analyzed a subpopulation from the REVEAL registry that survived 1 year or longer after being enrolled. Mortality estimates and discrimination were compared between REVEAL 2.0, COMPERA, and FPHR risk assessment strategies. The SPAHR strategy was not included because it is similar to the COMPERA strategy. A three-category REVEAL 2.0 score was computed in which patients were classified as low-, intermediate-, or high-risk.
Assessing Key FindingsThe study showed that REVEAL 2.0 demonstrated similar discrimination as the original calculator, provided excellent separation of risk among the risk categories, and predicted clinical worsening and mortality. "Importantly, the REVEAL 2.0 three-category score had greater discrimination of risk than COMPERA or FPHR," says Dr. Benza. When compared with REVEAL 2.0, COMPERA and FPHR both underestimated and overestimated risk (Table). In the REVEAL 2.0 low-risk group, COMPERA and FPHR overestimated risk in 51% and 60% of patients, respectively. For the REVEAL 2.0 intermediate-risk group, COMPERA and FPHR underestimated risk in 22% and 15% of patients, and overestimated risk in 4% and 19% of patients, respectively. In the highest risk group, COMPERA and FPHR underestimated risk in 80% and 58% of patients, respectively. Importantly, the REVEAL 2.0 three-category score discriminated risk better than the COMPERA and FPHR risk assessment strategies in a mixed group of patients that included those with newly diagnosed PAH and those with a previous diagnosis. "REVEAL 2.0 is a simple, more pragmatic platform for risk assessment in PAH because it is more discriminatory than other tools," Dr. Benza says. "This information is critical because it can help guide treatment decisions." Looking AheadThe REVEAL 2.0 risk calculator can be a valuable asset to standard clinical assessments because they provide a quantitative measure that can be easily tracked over time. REVEAL 2.0 more accurately stratifies individual patient risk than other assessments because it includes multiple, weighted modifiable and nonmodifiable variables. It also offers the advantage of predicting clinical worsening, which may enhance the ability to identify high-risk patients earlier in the disease course and support more informed treatment decisions. "For clinicians who already routinely use risk assessment algorithms, the REVEAL 2.0 calculator can be a useful addition to patient care," says Dr. Benza. "Other available risk assessment strategies can be used as screening tools in PAH. In the future, efforts are needed to incorporate REVEAL 2.0 into clinical guidelines so that this tool will be used more routinely in clinical practice." ReferencesBenza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting survival in patients with pulmonary arterial hypertension: The REVEAL Risk Score Calculator 2.0 and comparison with ESC/ERS-based risk assessment strategies. Chest. 2019 Feb 14 [Epub ahead of print]. Available at: https://journal.chestnet.org/article/S0012-3692(19)30152-7/fulltext. Benza RL, Lohmueller LC, Kraisangka J, Kanwar M. Risk assessment in pulmonary arterial hypertension patients: the long and short of it. Adv Pulm Hypertens. 2018;16:125-135. Benza RL, Miller DP, Foreman AJ, et al. Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis. J Heart Lung Transplant. 2015;34:356-361. Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142:448-456. Farber HW, Benza RL. Risk assessment tools in pulmonary arterial hypertension. Prognosis for prospective trials? Am J Respir Crit Care Med. 2018;197:843-845. Benza RL, Miller DP, Gomberg-Maitland M, et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation. 2010;122:164-172.  |
| Posted: 27 Nov 2019 12:00 AM PST New preclinical data supports the positive effects of Liminal Biosciences's lead candidate, PBI-4050, in reducing pulmonary hypertension and the abnormal enlargement of the heart's right ventricle muscle. The company presented its latest data on two posters at the American Heart Association 2019 conference, held recently in Philadelphia. The posters are titled "PBI-4050 Reduces Angio-proliferative Pulmonary Arterial Hypertension: Decreased Human Pulmonary Artery Smooth Muscle Cell Proliferation and Microvascular Endothelial Cell Endoplasmic Reticulum Stress," and "Transcriptomics of Lung Molecular Remodeling in Pulmonary Hypertension Due to Left Heart Disease: Benefits of Combined PBI-4050/Valsartan Therapy." PBI-4050 is an oral therapy originally developed to treat idiopathic pulmonary fibrosis (IPF). The therapy helps regulate both inflammation and scarring, or fibrosis, by reducing the level of pro-fibrotic cytokines — chemical signals that promote scarring. Apart from IPF, previous data showed that PBI-4050 reduced pulmonary hypertension (PH) and right ventricular hypertrophy, which is the abnormal enlargement of the heart right ventricle muscle, common among PH patients. In the first study, researchers used a rat model that closely mimics severe pulmonary arterial hypertension (PAH) in humans, called Sugen/chronic hypoxia. The team assessed the effects of PBI-4050 compared with that of sildenafil or a placebo. Sildenafil, marketed by Pfizer as Revatio, is an approved oral medication for PAH that widens the blood vessels of the lungs, lowering blood pressure. The rats were treated with PBI-4050 (200 mg/kg/day), sildenafil (100 mg/kg/day), or placebo for 4 weeks. The results showed that PBI-4050 effectively reduced PAH, right ventricular hypertrophy and dysfunction. It also decreased the scarring of blood vessels. Sildenafil showed comparable effects, but was better at improving certain parameters of right ventricular (RV) function. These parameters include right ventricular systolic pressure, tricuspid annular plane systolic excursion (TAPSE) — a measure of the efficiency of the right ventricle to eject blood — and RV contractility. Contractility is the inherent strength and vigor of the heart's contraction. Genetic analyses of the rats' lungs showed that PBI-4050 decreased the levels of the genes that promote fibrosis, including α-smooth muscle actin (α-SMA). It also decreased the levels of the genes that promote inflammation, which include IL-6 and MCP-1. The analyses also showed that PBI-4050 markedly reduced a specific stress pathway, called ER stress, in endothelial cells, which are the cells lining the blood vessels. Overall, the results showed that PBI-4050 reduced the expression of profibrotic and proinflammatory markers. This supports the therapy's development as a treatment for PAH, the researchers said. In the second poster, the investigators used an animal model to study how PBI-4050 could modulate fibrosis in the lung after a heart attack (myocardial infarction) causing PH. Two days after the heart attack, the team administered PBI-4050, valsartan — an angiotensin receptor blocker that lowers blood pressure — or a combination of the two. This treatment was continued for five weeks. The researchers then analyzed gene activity in the lung tissue after treatment. The results suggested that the combination of PBI-4050 and valsartan improved right ventricular hypertrophy and function. The gene activity seen after treatment mirrored these biological effects. "We showed that, after large MI [myocardial infarction] causing PH, PBI-4050 therapy provides added benefit to valsartan, by … improving RV function and hypertrophy," the researchers said. "Although not a current focus of the Company's research program, this new preclinical data adds to our body of knowledge of our lead compound, PBI-4050," Kenneth Galbraith, CEO of Liminal BioSciences, said in a press release:  Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York. × Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York. Latest Posts  |
| Meeting highlights from 2019: Updates in asthma, COPD, PAH and more - Healio Posted: 23 Dec 2019 05:18 AM PST  Healio Pulmonology has you covered on some of the year's top news from medical meetings. We bring you highlights from the American Thoracic Society International Conference and the CHEST Annual Meeting. Some of the most-read articles from these meetings, published on Healio, focus on new treatment options for COPD, interstitial lung disease and pulmonary artery hypertension. Read more below. If you'd like to see more, all highlights from ATS can be found here and highlights from CHEST can be found here. Initial macitentan, tadalafil combination therapy shows promise for PAH: OPTIMA Initial combination therapy with macitentan and tadalafil yielded hemodynamic and functional improvements and treatment was well tolerated in adults with newly diagnosed pulmonary arterial hypertension, according to data presented at the CHEST Annual Meeting. Read more Inhaler formulary changes may worsen asthma control in children Switching inhaler types due to insurance formulary changes may lead to reduced lung function in children with asthma, researchers reported at the CHEST Annual Meeting. "Insurance formulary changes have been a major reason why many of our children with asthma who were otherwise stable have been switched from one long-term controller to another. Anecdotally, these changes cause considerable confusion for both families and health care professionals," Scott G. Bickel, MD, from the University of Louisville School of Medicine, told Healio Pulmonology. "In doing this study, we sought to provide objective data on how these changes influence prescribing patterns and lung function." Read more Beta-blocker fails to prevent COPD exacerbations In patients with moderate to severe COPD without an established indication for beta-blocker use, treatment with metoprolol did not reduce the risk for exacerbations compared with treatment with placebo, according to data presented at the CHEST Annual Meeting. Read more Four novel sepsis phenotypes identified A new study presented at the American Thoracic Society International Conference identified four clinical phenotypes of sepsis that may allow more precise therapy and improve care of critically ill patients: alpha, beta, gamma and delta. Read more ASCENT-COPD: Aclidinium shows continued success in chronic obstructive pulmonary disease Aclidinium reduces moderate to severe exacerbations without increasing cardiovascular event risk in patients with chronic obstructive pulmonary disease, regardless of beta-blocker use or background treatment with long-acting beta-agonists with or without an inhaled corticosteroid, new data presented at the American Thoracic Society International Conference suggest. Read more Nintedanib slows loss of pulmonary function in systemic sclerosis-associated interstitial lung disease Patients with interstitial lung disease associated with systemic sclerosis treated with the tyrosine kinase inhibitor nintedanib exhibited a 44% reduction in the rate of decline of lung function, as measured by forced vital capacity, at 52 weeks compared with placebo, according to data from the SENSCIS trial presented at the American Thoracic Society International Conference. Read more  |
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