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Correale M, Bevere EML, Tricarico L, Villani D, Granato M, Guerriero E, Capasso R, Rossi L, Rotondo C, Cantatore FP, Corrado A, Iacoviello M, Brunetti ND. How to Assess Pulmonary Circulation and Right Heart Chambers in Systemic Sclerosis Patients? Diagnostics (Basel) 2025; 15:1029. [PMID: 40310415 PMCID: PMC12026199 DOI: 10.3390/diagnostics15081029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/11/2025] [Accepted: 04/13/2025] [Indexed: 05/02/2025] Open
Abstract
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by a widespread accumulation of extracellular matrix components leading to fibrosis of the skin and internal organs. Vascular changes occur in all involved tissues and are responsible for several distinctive clinical manifestations of the disease. This review focuses on the usefulness of various diagnostic tools in clinical practice for the early identification of clinical, functional, and/or structural RV impairment in SSc patients at risk of PH. It aims to identify specific causes of RV dysfunction, describe potential differences in outcome measures, and, ultimately, determine different cut-off values compared to subjects with PH not related to SSc.
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Affiliation(s)
- Michele Correale
- Cardiothoracic Department, Ospedali Riuniti University Hospital, 71100 Foggia, Italy
| | - Ester Maria Lucia Bevere
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Lucia Tricarico
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Deborah Villani
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Mattia Granato
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Erminia Guerriero
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Raffaele Capasso
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Luciano Rossi
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Cinzia Rotondo
- Rheumatology Clinic, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (C.R.); (F.P.C.); (A.C.)
| | - Francesco Paolo Cantatore
- Rheumatology Clinic, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (C.R.); (F.P.C.); (A.C.)
| | - Addolorata Corrado
- Rheumatology Clinic, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (C.R.); (F.P.C.); (A.C.)
| | - Massimo Iacoviello
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
| | - Natale Daniele Brunetti
- Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (E.M.L.B.); (L.T.); (D.V.); (M.G.); (E.G.); (R.C.); (L.R.); (M.I.); (N.D.B.)
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Hu J, Deng Y, Dai P, Xie DW, Lan WF, Tan XL. Prognostic impact of right atrial strain in systemic lupus erythematosus with pulmonary arterial hypertension. Echocardiography 2024; 41:e15921. [PMID: 39254093 DOI: 10.1111/echo.15921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/25/2024] [Accepted: 08/23/2024] [Indexed: 09/11/2024] Open
Abstract
OBJECTIVE The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. METHODS STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. RESULTS A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2 ± 9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr < 33.45% had more adverse long-term outcomes (log rank p < .0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p = .010). CONCLUSION Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.
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Affiliation(s)
- Jie Hu
- Department of Echocardiography of Cardiovascular Disease Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yan Deng
- Department of Echocardiography of Cardiovascular Disease Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Ping Dai
- Department of Echocardiography of Cardiovascular Disease Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Dong-Wei Xie
- Department of Echocardiography of Cardiovascular Disease Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Wei-Fang Lan
- Department of Echocardiography of Cardiovascular Disease Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiao-Lan Tan
- Department of Echocardiography of Cardiovascular Disease Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Mathai SC. Pulmonary Hypertension Associated with Connective Tissue Disease. Rheum Dis Clin North Am 2024; 50:359-379. [PMID: 38942575 DOI: 10.1016/j.rdc.2024.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2024]
Abstract
Pulmonary hypertension (PH), a syndrome characterized by elevated pulmonary pressures, commonly complicates connective tissue disease (CTD) and is associated with increased morbidity and mortality. The incidence of PH varies widely between CTDs; patients with systemic sclerosis are most likely to develop PH. Several different types of PH can present in CTD, including PH related to left heart disease and respiratory disease. Importantly, CTD patients are at risk for developing pulmonary arterial hypertension, a rare form of PH that is associated with high morbidity and mortality. Future therapies targeting pulmonary vascular remodeling may improve outcomes for patients with this devastating disease.
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Affiliation(s)
- Stephen C Mathai
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Room 540, Baltimore, MD 21205, USA.
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Budhram B, Weatherald J, Humbert M. Pulmonary Hypertension in Connective Tissue Diseases Other than Systemic Sclerosis. Semin Respir Crit Care Med 2024; 45:419-434. [PMID: 38499196 DOI: 10.1055/s-0044-1782217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2024]
Abstract
Pulmonary hypertension (PH) is a known complication of certain connective tissue diseases (CTDs), with systemic sclerosis (SSc) being the most common in the Western world. However, PH in association with non-SSc CTD such as systemic lupus erythematous, mixed connective tissue disease, and primary Sjögren's syndrome constitutes a distinct subset of patients with inherently different epidemiologic profiles, pathophysiologic mechanisms, clinical features, therapeutic options, and prognostic implications. The purpose of this review is to inform a practical approach for clinicians evaluating patients with non-SSc CTD-associated PH.The development of PH in these patients involves a complex interplay between genetic factors, immune-mediated mechanisms, and endothelial cell dysfunction. Furthermore, the broad spectrum of CTD manifestations can contribute to the development of PH through various pathophysiologic mechanisms, including intrinsic pulmonary arteriolar vasculopathy (pulmonary arterial hypertension, Group 1 PH), left-heart disease (Group 2), chronic lung disease (Group 3), chronic pulmonary artery obstruction (Group 4), and unclear and/or multifactorial mechanisms (Group 5). The importance of diagnosing PH early in symptomatic patients with non-SSc CTD is highlighted, with a review of the relevant biomarkers, imaging, and diagnostic procedures required to establish a diagnosis.Therapeutic strategies for non-SSc PH associated with CTD are explored with an in-depth review of the medical, interventional, and surgical options available to these patients, emphasizing the CTD-specific considerations that guide treatment and aid in prognosis. By identifying gaps in the current literature, we offer insights into future research priorities that may prove valuable for patients with PH associated with non-SSc CTD.
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Affiliation(s)
- Brandon Budhram
- Division of Respirology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Jason Weatherald
- Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Marc Humbert
- Université Paris-Saclay, Inserm UMR_S 999, Service de Pneumologie et Soins Intensifs Respiratoires, European Reference Network for Rare Respiratory Diseases (ERN-LUNG), Hôpital Bicêtre (Assistance Publique Hôpitaux de Paris), Le Kremlin-Bicêtre, France
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Bendstrup E, Lynn E, Troldborg A. Systemic Lupus Erythematosus-related Lung Disease. Semin Respir Crit Care Med 2024; 45:386-396. [PMID: 38547915 DOI: 10.1055/s-0044-1782653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2024]
Abstract
Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and mortality in SLE. This comprehensive review explores the spectrum of pulmonary disease in SLE, including upper airway manifestations (e.g., laryngeal affection), lower airway conditions (e.g., bronchitis, bronchiolitis, bronchiectasis), parenchymal diseases (e.g., interstitial lung disease, acute lupus pneumonitis, diffuse alveolar hemorrhage), pleural diseases (e.g., serositis, shrinking lung syndrome), and vascular diseases (e.g., pulmonary arterial hypertension, pulmonary embolism, acute reversible hypoxemia syndrome). We discuss diagnostic modalities, treatment strategies, and prognosis for each pulmonary manifestation. With diagnostics remaining a challenge and with the absence of standardized treatment guidelines, we emphasize the need for evidence-based guidelines to optimize patient care and improve outcomes in this complex disease.
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Affiliation(s)
- Elisabeth Bendstrup
- Center for Rare Lung Disease, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Evelyn Lynn
- Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Anne Troldborg
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
- Biomedicine, Aarhus University, Aarhus, Denmark
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Ma J, Li G, Wang H, Mo C. Comprehensive review of potential drugs with anti-pulmonary fibrosis properties. Biomed Pharmacother 2024; 173:116282. [PMID: 38401514 DOI: 10.1016/j.biopha.2024.116282] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 02/02/2024] [Accepted: 02/17/2024] [Indexed: 02/26/2024] Open
Abstract
Pulmonary fibrosis is a chronic and progressive lung disease characterized by the accumulation of scar tissue in the lungs, which leads to impaired lung function and reduced quality of life. The prognosis for idiopathic pulmonary fibrosis (IPF), which is the most common form of pulmonary fibrosis, is generally poor. The median survival for patients with IPF is estimated to be around 3-5 years from the time of diagnosis. Currently, there are two approved drugs (Pirfenidone and Nintedanib) for the treatment of IPF. However, Pirfenidone and Nintedanib are not able to reverse or cure pulmonary fibrosis. There is a need for new pharmacological interventions that can slow or halt disease progression and cure pulmonary fibrosis. This review aims to provide an updated overview of current and future drug interventions for idiopathic pulmonary fibrosis, and to summarize possible targets of potential anti-pulmonary fibrosis drugs, providing theoretical support for further clinical combination therapy or the development of new drugs.
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Affiliation(s)
- Jie Ma
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Gang Li
- Department of Thoracic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Han Wang
- Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Center for RNA Science and Therapeutics, School of Medicine, Cleveland, OH, USA
| | - Chunheng Mo
- The Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
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Erdogan M, Esatoglu SN, Kilickiran Avci B, Hatemi G. Treatment of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review and meta-analysis. Intern Emerg Med 2024; 19:731-743. [PMID: 38378970 PMCID: PMC11039558 DOI: 10.1007/s11739-024-03539-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 01/11/2024] [Indexed: 02/22/2024]
Abstract
The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.
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Affiliation(s)
- Mustafa Erdogan
- Division of Rheumatology, Department of Internal Medicine, Cerrahpaşa Medical School, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Sinem Nihal Esatoglu
- Division of Rheumatology, Department of Internal Medicine, Cerrahpaşa Medical School, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Burcak Kilickiran Avci
- Department of Cardiology, Cerrahpaşa Medical School, Istanbul University-Cerrahpaşa, Cerrahpaşa Campus, Kocamustafapaşa Cad. No: 34/E, Fatih, 34998, Istanbul, Turkey.
| | - Gulen Hatemi
- Division of Rheumatology, Department of Internal Medicine, Cerrahpaşa Medical School, Istanbul University-Cerrahpaşa, Istanbul, Turkey
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Farmakis IT, Baroutidou A, Patsiou V, Arvanitaki A, Doundoulakis I, Hobohm L, Zafeiropoulos S, Konstantinides SV, D'Alto M, Badagliacca R, Giannakoulas G. Contribution of pressure and flow changes to resistance reduction after pulmonary arterial hypertension treatment: a meta-analysis of 3898 patients. ERJ Open Res 2024; 10:00706-2023. [PMID: 38259812 PMCID: PMC10801731 DOI: 10.1183/23120541.00706-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 11/21/2023] [Indexed: 01/24/2024] Open
Abstract
Background Pulmonary arterial hypertension (PAH)-targeted therapies exert significant haemodynamic changes; however, systematic synthesis is currently lacking. Methods We searched PubMed, CENTRAL and Web of Science for studies evaluating mean pulmonary artery pressure (mPAP), cardiac index/cardiac output (CI/CO) and pulmonary vascular resistance (PVR) of PAH-targeted therapies either in monotherapy or combinations as assessed by right heart catheterisation in treatment-naïve PAH patients. We performed a random-effects meta-analysis with meta-regression. Results We included 68 studies (90 treatment groups) with 3898 patients (age 47.4±13.2 years, 74% women). In studies with small PVR reduction (<4 WU), CI/CO increase (R2=62%) and not mPAP reduction (R2=24%) was decisive for the PVR reduction (p<0.001 and p=0.36, respectively, in the multivariable meta-regression model); however, in studies with large PVR reduction (>4 WU), both CI/CO increase (R2=72%) and mPAP reduction (R2=35%) contributed significantly to the PVR reduction (p<0.001 and p=0.01, respectively). PVR reduction as a percentage of the pre-treatment value was more pronounced in the oral+prostanoid intravenous/subcutaneous combination therapy (mean difference -50.0%, 95% CI -60.8- -39.2%), compared to oral combination therapy (-41.7%, -47.6- -35.8%), prostanoid i.v./s.c. monotherapy (-31.8%, -37.6- -25.9%) and oral monotherapy (-21.6%, -25.4- -17.8%). Changes in haemodynamic parameters were significantly associated with changes in functional capacity of patients with PAH as expressed by the 6-min walking distance. Conclusion Combination therapies, especially with the inclusion of parenteral prostanoids, lead to remarkable haemodynamic improvement in treatment-naïve PAH patients and may unmask the contribution of mPAP reduction to the overall PVR reduction in addition to the increase in CO.
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Affiliation(s)
- Ioannis T. Farmakis
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
- Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Amalia Baroutidou
- Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Vasiliki Patsiou
- Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Alexandra Arvanitaki
- Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ioannis Doundoulakis
- Athens Heart Center, Athens Medical Center, Athens, Greece
- First Department of Cardiology, National and Kapodistrian University, “Hippokration” Hospital, Athens, Greece
| | - Lukas Hobohm
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
- Department of Cardiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Stefanos Zafeiropoulos
- Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY, USA
- Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY
| | - Stavros V. Konstantinides
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
- Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece
| | - Michele D'Alto
- Department of Cardiology, University “L. Vanvitelli”-Monaldi Hospital, Naples, Italy
| | - Roberto Badagliacca
- Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - George Giannakoulas
- Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Sanges S, Sobanski V, Lamblin N, Hachulla E, Savale L, Montani D, Launay D. Pulmonary hypertension in connective tissue diseases: What every CTD specialist should know - but is afraid to ask! Rev Med Interne 2024; 45:26-40. [PMID: 37925256 DOI: 10.1016/j.revmed.2023.10.450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 10/15/2023] [Accepted: 10/16/2023] [Indexed: 11/06/2023]
Abstract
Pulmonary hypertension (PH) is a possible complication of connective tissue diseases (CTDs), especially systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). It is defined by an elevation of the mean pulmonary arterial pressure above 20mmHg documented during a right heart catheterization (RHC). Due to their multiorgan involvement, CTDs can induce PH by several mechanisms, that are sometimes intricated: pulmonary vasculopathy (group 1) affecting arterioles (pulmonary arterial hypertension, PAH) and possibly venules (pulmonary veno-occlusive-like disease), left-heart disease (group 2), chronic lung disease (group 3) and/or chronic thromboembolic PH (group 4). PH suspicion is often raised by clinical manifestations (dyspnea, fatigue), echocardiographic data (increased peak tricuspid regurgitation velocity), isolated decrease in DLCO in pulmonary function tests, and/or unexplained elevation of BNP/NT-proBNP. Its formal diagnosis always requires a hemodynamic confirmation by RHC. Strategies for PH screening and RHC referral have been extensively investigated for SSc-PAH but data are lacking in other CTDs. Therapeutic management of PH depends of the underlying mechanism(s): PAH-approved therapies in group 1 PH (with possible use of immunosuppressants, especially in case of SLE or MCTD); management of an underlying left-heart disease in group 2 PH; management of an underlying chronic lung disease in group 3 PH; anticoagulation, pulmonary endartectomy, PAH-approved therapies and/or balloon pulmonary angioplasty in group 4 PH. Regular follow-up is mandatory in all CTD-PH patients.
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Affiliation(s)
- S Sanges
- Université de Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, 59000 Lille, France; Inserm, 59000 Lille, France; CHU de Lille, Département de Médecine Interne et Immunologie Clinique, 59000 Lille, France; Centre National de Référence Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), 59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), 59000 Lille, France.
| | - V Sobanski
- Université de Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, 59000 Lille, France; Inserm, 59000 Lille, France; CHU de Lille, Département de Médecine Interne et Immunologie Clinique, 59000 Lille, France; Centre National de Référence Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), 59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), 59000 Lille, France
| | - N Lamblin
- CHU de Lille, Service de Cardiologie, 59000 Lille, France; Institut Pasteur de Lille, Inserm U1167, 59000 Lille, France
| | - E Hachulla
- Université de Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, 59000 Lille, France; Inserm, 59000 Lille, France; CHU de Lille, Département de Médecine Interne et Immunologie Clinique, 59000 Lille, France; Centre National de Référence Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), 59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), 59000 Lille, France
| | - L Savale
- Université Paris Saclay, School of Medicine, Le Kremlin-Bicêtre, France; AP-HP, Department of Respiratory and Intensive Care Medicine, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Inserm UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France
| | - D Montani
- Université Paris Saclay, School of Medicine, Le Kremlin-Bicêtre, France; AP-HP, Department of Respiratory and Intensive Care Medicine, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Inserm UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France
| | - D Launay
- Université de Lille, U1286, INFINITE, Institute for Translational Research in Inflammation, 59000 Lille, France; Inserm, 59000 Lille, France; CHU de Lille, Département de Médecine Interne et Immunologie Clinique, 59000 Lille, France; Centre National de Référence Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), 59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), 59000 Lille, France
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Tuhy T, Hassoun PM. Clinical features of pulmonary arterial hypertension associated with systemic sclerosis. Front Med (Lausanne) 2023; 10:1264906. [PMID: 37828949 PMCID: PMC10565655 DOI: 10.3389/fmed.2023.1264906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 09/11/2023] [Indexed: 10/14/2023] Open
Abstract
Systemic sclerosis is an autoimmune disorder of the connective tissue characterized by disordered inflammation and fibrosis leading to skin thickening and visceral organ complications. Pulmonary involvement, in the form of pulmonary arterial hypertension and/or interstitial lung disease, is the leading cause of morbidity and mortality among individuals with scleroderma. There are no disease-specific therapies for pulmonary involvement of scleroderma, and pulmonary arterial hypertension in this cohort has typically been associated with worse outcomes and less clinical response to modern therapy compared to other forms of Group I pulmonary hypertension in the classification from the World Symposium on Pulmonary Hypertension. Ongoing research aims to delineate how pathologic microvascular remodeling and fibrosis contribute to this poor response and offer a window into future therapeutic targets.
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Affiliation(s)
| | - Paul M. Hassoun
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
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Smukowska-Gorynia A, Gościniak W, Woźniak P, Iwańczyk S, Jaxa-Kwiatkowska K, Sławek-Szmyt S, Janus M, Paluszkiewicz J, Mularek-Kubzdela T. Recent Advances in the Treatment of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases. Pharmaceuticals (Basel) 2023; 16:1252. [PMID: 37765060 PMCID: PMC10534675 DOI: 10.3390/ph16091252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 08/30/2023] [Accepted: 09/02/2023] [Indexed: 09/29/2023] Open
Abstract
Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to diverse groups: (1) pulmonary arterial hypertension (PAH), (2) PH due to left heart disease, (3) secondary PH due to lung disease and/or hypoxia and (4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis. Therefore, early diagnosis should be established. A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase-five inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs, e.g., sotatercept, have been intensively investigated in clinical trials. We aim to review the literature on recent advances in the treatment strategy and prognosis of patients with PAH-CTD. In this manuscript, we discuss the mechanism of action of PAH-specific drugs and new agents and the latest research conducted on PAH-CTD patients.
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Affiliation(s)
- Anna Smukowska-Gorynia
- 1st Department of Cardiology, Poznan University of Medical Sciences, Długa 1/2 Street, 61-848 Poznan, Poland; (W.G.); (P.W.); (S.I.); (K.J.-K.); (S.S.-S.); (M.J.); (J.P.); (T.M.-K.)
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12
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Kularatne M, Boucly A, Savale L, Solinas S, Cheron C, Roche A, Jevnikar M, Jaïs X, Montani D, Humbert M, Sitbon O. Pharmacological management of connective tissue disease-associated pulmonary arterial hypertension. Expert Opin Pharmacother 2023; 24:2101-2115. [PMID: 37869785 DOI: 10.1080/14656566.2023.2273395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 10/17/2023] [Indexed: 10/24/2023]
Abstract
INTRODUCTION Pulmonary arterial hypertension (PAH) is a severe, progressive pulmonary vasculopathy (Group 1 Pulmonary Hypertension (PH)) that complicates the course of many connective tissue diseases (CTD). Detailed testing is required to differentiate PAH from other types of PH caused by CTD such as left heart disease (Group 2 PH), pulmonary parenchymal disease (Group 3 PH), and chronic thromboembolic pulmonary hypertension (Group 4 PH). PAH is most frequently seen in systemic sclerosis but can also be seen with systemic lupus erythematosus, mixed CTD, and primary Sjogren's syndrome. AREAS COVERED This review discusses the epidemiology of CTD-associated PAH, outlines the complex diagnosis approach, and finishes with an in-depth discussion on the current treatment paradigm. Focus is placed on challenges faced in the treatment of CTD-associated PAH, (decreased efficacy and poorer tolerance of pharmacological therapies) and includes a discussion on the future investigational treatments. EXPERT OPINION Despite significant advances over the past decades with more aggressive treatment algorithms, CTD-associated PAH patients continue to have poorer survival compared to those with idiopathic PAH. This review highlights factors leading to disparate outcomes compared to other forms of PAH, and discusses on further improvements that may increase quality of life and survival for CTD-associated PAH patients.
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Affiliation(s)
- Mithum Kularatne
- Division of Respiratory Medicine, Department of Medicine, University of Calgary, Calgary, Canada
| | - Athénaïs Boucly
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Laurent Savale
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Sabina Solinas
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Céline Cheron
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Anne Roche
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Mitja Jevnikar
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Xavier Jaïs
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - David Montani
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Marc Humbert
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Olivier Sitbon
- Faculty of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Le Kremlin-Bicêtre, France
- AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
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13
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Korman BD, Lachant DJ, Castelino FV. Pulmonary Hypertension: How to Best Treat the Different Scleroderma Phenotypes? Rheum Dis Clin North Am 2023; 49:345-357. [PMID: 37028839 DOI: 10.1016/j.rdc.2023.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2023]
Abstract
Pulmonary hypertension (PH) is a leading cause of morbidity and mortality in systemic sclerosis (SSc). PH is a heterogenous condition and several different forms of PH are associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to interstitial lung disease, PH due to left heart disease, and PH due to thromboembolic disease. Extensive research has led to an improved understanding of the mediators involved in the pathogenesis of SSc-PH. Initial combination therapy is the preferred treatment approach for SSc-PAH and requires coordinated care with a multidisciplinary team including rheumatology, pulmonology, and cardiology.
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Affiliation(s)
- Benjamin D Korman
- Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 695, Rochester, NY 14642, USA.
| | - Daniel J Lachant
- Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 692, Rochester, NY 14642, USA
| | - Flavia V Castelino
- Division of Rheumatology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 4B, Boston, MA 02114, USA
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14
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Brown CE, Steiner JM, Leary PJ, Curtis JR, Engelberg RA. A World of Maximalist Medicine: Physician Perspectives on Palliative Care and End-of-life for Patients With Pulmonary Arterial Hypertension. J Pain Symptom Manage 2023; 65:e329-e335. [PMID: 36521765 PMCID: PMC10023342 DOI: 10.1016/j.jpainsymman.2022.11.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/22/2022] [Accepted: 11/29/2022] [Indexed: 12/15/2022]
Abstract
CONTEXT Physicians who specialize in pulmonary arterial hypertension (PAH) care for patients facing a serious, life-limiting illness. Palliative care is underutilized in patients with PAH, and little is known about how best to provide palliative care to this patient population. OBJECTIVES Using a qualitative approach, assess physicians' perspectives on barriers and facilitators to the use of palliative care in PAH. METHODS Participants were board-certified pulmonologists and cardiologists recruited from the Pulmonary Hypertension Association's list of physician specialists and academic center websites. We performed one-on-one semi-structured interviews that were recorded, transcribed, and analyzed using thematic analysis. RESULTS Twelve physicians participated in the study, with a median age of 48.5 years and 20.5 years of clinical experience caring for patients with PAH. We identified the following themes and associated barriers and facilitators to effective implementation of palliative care for patients with PAH: a tailored approach to the individual patient; a PAH-specialist-led culture of care; effective collaboration with palliative care clinicians; and limitations imposed by health systems. CONCLUSION PAH physicians are open to palliative care for their patients and are willing to partner with palliative care clinicians to implement this effectively and in the right setting. Areas for targeted improvement in enhancing palliative care for patients with PAH exist, especially enhancing collaboration between PAH physicians and palliative care specialists and navigating barriers in health systems.
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Affiliation(s)
- Crystal E Brown
- Division of Pulmonary, Critical Care, and Sleep Medicine (C.E.B., J.M.S., P.J.L., J.R.C., R.A.E.), University of Washington Seattle, WA, USA; Cambia Palliative Care Center of Excellence at UW Medicine (C.E.B., J.M.S., J.R.C., R.A.E.), Seattle, WA, USA; Department of Bioethics and Humanities (C.E.B.), University of Washington, Seattle, WA, USA.
| | - Jill M Steiner
- Cambia Palliative Care Center of Excellence at UW Medicine (C.E.B., J.M.S., J.R.C., R.A.E.), Seattle, WA, USA; Division of Cardiology (C.E.B., J.M.S., P.J.L., J.R.C., R.A.E.), University of Washington, Seattle, WA, USA
| | - Peter J Leary
- Division of Pulmonary, Critical Care, and Sleep Medicine (C.E.B., J.M.S., P.J.L., J.R.C., R.A.E.), University of Washington Seattle, WA, USA; Department of Epidemiology (P.J.L.), University of Washington, Seattle, WA, USA
| | - J Randall Curtis
- Division of Pulmonary, Critical Care, and Sleep Medicine (C.E.B., J.M.S., P.J.L., J.R.C., R.A.E.), University of Washington Seattle, WA, USA; Cambia Palliative Care Center of Excellence at UW Medicine (C.E.B., J.M.S., J.R.C., R.A.E.), Seattle, WA, USA
| | - Ruth A Engelberg
- Division of Pulmonary, Critical Care, and Sleep Medicine (C.E.B., J.M.S., P.J.L., J.R.C., R.A.E.), University of Washington Seattle, WA, USA; Cambia Palliative Care Center of Excellence at UW Medicine (C.E.B., J.M.S., J.R.C., R.A.E.), Seattle, WA, USA
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15
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Systemic Lupus Erythematosus and Pulmonary Hypertension. Int J Mol Sci 2023; 24:ijms24065085. [PMID: 36982160 PMCID: PMC10049584 DOI: 10.3390/ijms24065085] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/23/2023] [Accepted: 02/28/2023] [Indexed: 03/09/2023] Open
Abstract
Pulmonary Hypertension (PH) is a common manifestation in patients with Systemic Lupus Erythematosus (SLE) and varies from asymptomatic to life-threatening disease. PH can result not only from immune system dysregulation, but also from various conditions, including cardiorespiratory disorders and thromboembolic diseases. Most commonly, SLE-related PH presents with non-specific symptoms, such as progressive dyspnea on exertion, generalized fatigue and weakness and eventually dyspnea at rest. Prompt diagnosis of SLE-related PH and early identification of the underlying pathogenetic mechanisms is demanded in order to introduce targeted therapy to prevent irreversible pulmonary vascular damage. In most cases the management of PH in SLE patients is similar to idiopathic pulmonary arterial hypertension (PAH). Furthermore, specific diagnostic tools like biomarkers or screening protocols, to establish early diagnosis seem to be not available yet. Although, the survival rates for patients with SLE-related PH vary between studies, it is evident that PH presence negatively affects the survival of SLE patients.
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16
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Brown CE, Steiner JM, Modes M, Lynch Y, Leary PJ, Curtis JR, Engelberg RA. Palliative Care Perspectives of Patients with Pulmonary Arterial Hypertension. Ann Am Thorac Soc 2023; 20:331-334. [PMID: 36416739 PMCID: PMC9989860 DOI: 10.1513/annalsats.202208-721rl] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
| | | | - Matthew Modes
- University of WashingtonSeattle, Washington
- Cedars-Sinai Medical CenterLos Angeles, California
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Abstract
Systemic sclerosis, also known as scleroderma, is a rare and complex autoimmune connective-tissue disease. Once considered an untreatable and unpredictable condition, research advancements have improved our understanding of its disease pathogenesis and clinical phenotypes and expanded our treatment armamentarium. Early and accurate diagnosis is essential, while ongoing efforts to risk stratify patients have a central role in predicting both organ involvement and disease progression. A holistic approach is required when choosing the optimal therapeutic strategy, balancing the side-effect profile with efficacy and tailoring the treatment according to the goals of care of the patient. This Seminar reviews the multiple clinical dimensions of systemic sclerosis, beginning at a precursor very early stage of disease, with a focus on timely early detection of organ involvement. This Seminar also summarises management considerations according to the pathological hallmarks of systemic sclerosis (eg, inflammation, fibrosis, and vasculopathy) and highlights unmet needs and opportunities for future research and discovery.
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Affiliation(s)
- Elizabeth R Volkmann
- Department of Medicine, Division of Rheumatology, University of California, Los Angeles, CA, USA; David Geffen School of Medicine, Los Angeles, CA, USA.
| | | | - Vanessa Smith
- Department of Internal Medicine and Department of Rheumatology, Ghent University (Hospital), Ghent, Belgium; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Centre, Ghent, Belgium
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18
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Anheyer D, Bugaj TJ, Lüdtke R, Appelbaum S, Trübel H, Ostermann T. No Placebo Effect beyond Regression to the Mean on the Six Minute Walk Test in Pulmonary Arterial Hypertension Trials. Int J Mol Sci 2023; 24:ijms24021069. [PMID: 36674584 PMCID: PMC9865257 DOI: 10.3390/ijms24021069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 01/09/2023] Open
Abstract
In drug studies, patients are often included when the disease activity is high. This will make any treatment appear to lessen disease activity, although the improvement is biased by selection. This effect is known as regression towards the mean (RTM). We aimed at investigating drug trials in Pulmonary Arterial Hypertension (PAH) using the 6-minute walking distance test (6MWD) as a primary outcome for the phenomenon of RTM. An existing registry of 43 open label studies and 23 randomized controlled trials conducted between 1990 and 2009 was used as the data source. Data analysis was carried out for 18 randomized controlled trials (RCTs) and 24 open label studies out of this registry. Data were analyzed for verum and placebo arms of the RCTs separately, as well as for the open label arms. In the verum arms, the overall effect given as 33.2 m (95% CI: 25.7; 40.6]); 6MWD was slightly lower than the effect in the observational studies, with 44.6 m (95% CI: [25.4; 63.8]). After studying and interpreting the data, we found that regression towards the mean plays only a minor role in PAH studies. In particular, placebo effects in the RCTs were negligibly small, with a mean 6MWD of -2.5 m (95% CI: [-9.8; 4.7]) in the placebo arm. Therefore, our analysis indicates that results of non-randomized observational studies can be regarded as valid tools for gaining valid clinical effects in patients with PAH.
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Affiliation(s)
- Dennis Anheyer
- Department for Psychology and Psychotherapy, Witten/Herdecke University, 58458 Witten, Germany
- Institute for General Practice and Interprofessional Care, University Hospital Tübingen, 72076 Tübingen, Germany
| | - Till Johannes Bugaj
- Department of General Internal Medicine and Psychosomatics, University of Heidelberg, Medical Hospital, 69120 Heidelberg, Germany
| | | | - Sebastian Appelbaum
- Department for Psychology and Psychotherapy, Witten/Herdecke University, 58458 Witten, Germany
| | - Hubert Trübel
- Department for Medicine, Witten/Herdecke University, 58458 Witten, Germany
| | - Thomas Ostermann
- Department for Psychology and Psychotherapy, Witten/Herdecke University, 58458 Witten, Germany
- Correspondence:
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19
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Lee SG, Moon KW. Epidemiology and Treatment of Systemic Sclerosis in Korea. JOURNAL OF RHEUMATIC DISEASES 2022; 29:200-214. [PMID: 37476430 PMCID: PMC10351407 DOI: 10.4078/jrd.22.0029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/16/2022] [Accepted: 09/19/2022] [Indexed: 07/22/2023]
Abstract
Systemic sclerosis (SSc), a rare, chronic progressive systemic autoimmune disease of unknown etiology, is characterized by autoimmunity, tissue fibrosis, and obliterative vasculopathy. SSc can affect all major organs including the skin, blood vessels, lung, heart, kidneys, and gastrointestinal tract. Our understanding of its pathogenesis has increased over the past few decades, leading to improved diagnosis and treatment. However, the mortality rate of SSc remains considerable, mainly due to cardiopulmonary causes. A growing body of evidence suggests that geographical, regional, and ethnic differences could affect the epidemiology, clinical characteristics and prognosis of SSc. Although Korean data of this issue are lacking, a considerable amount of research has been published by many Korean researchers. To establish treatment strategies for Korean patients, extensive Korean research data are needed. This review summarizes the prevalence, incidence, mortality, and clinical and laboratory manifestations of Korean patients with SSc and discusses the current trends in evidence-based treatment and recommendations.
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Affiliation(s)
- Seung-Geun Lee
- Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Ki Won Moon
- Division of Rheumatology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
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20
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Pitre T, Su J, Cui S, Scanlan R, Chiang C, Husnudinov R, Khalid MF, Khan N, Leung G, Mikhail D, Saadat P, Shahid S, Mah J, Mielniczuk L, Zeraatkar D, Mehta S. Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis. Eur Respir Rev 2022; 31:31/165/220036. [PMID: 35948391 DOI: 10.1183/16000617.0036-2022] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 05/30/2022] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH. METHODS We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception to December 2021. We performed a frequentist random-effects network meta-analysis on all included trials. We rated the certainty of the evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach. RESULTS We included 53 randomised controlled trials with 10 670 patients. Combination therapy with endothelin receptor antagonist (ERA) plus phosphodiesterase-5 inhibitors (PDE5i) reduced clinical worsening (120.7 fewer events per 1000, 95% CI 136.8-93.4 fewer; high certainty) and was superior to either ERA or PDE5i alone, both of which reduced clinical worsening, as did riociguat monotherapy (all high certainty). PDE5i (24.9 fewer deaths per 1000, 95% CI 35.2 fewer to 2.1 more); intravenous/subcutaneous prostanoids (18.3 fewer deaths per 1000, 95% CI 28.6 fewer deaths to 0) and riociguat (29.1 fewer deaths per 1000, 95% CI 38.6 fewer to 8.7 more) probably reduce mortality as compared to placebo (all moderate certainty). Combination therapy with ERA+PDE5i (49.9 m, 95% CI 25.9-73.8 m) and riociguat (49.5 m, 95% CI 17.3-81.7 m) probably increase 6-min walk distance as compared to placebo (moderate certainty). CONCLUSION Current PAH treatments improve clinically important outcomes, although the degree and certainty of benefit vary between treatments.
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Affiliation(s)
- Tyler Pitre
- Division of Internal Medicine, McMaster University, Hamilton, ON, Canada.,Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Johnny Su
- Division of Internal Medicine, McMaster University, Hamilton, ON, Canada.,Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Sonya Cui
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Ryan Scanlan
- Division of Internal Medicine, McMaster University, Hamilton, ON, Canada.,Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Christopher Chiang
- Division of Internal Medicine, McMaster University, Hamilton, ON, Canada.,Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Renata Husnudinov
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | | | - Nadia Khan
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Gareth Leung
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - David Mikhail
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Pakeezah Saadat
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
| | - Shaneela Shahid
- Health Research Methods Evidence and Impact, McMaster University, Hamilton, ON, Canada
| | - Jasmine Mah
- Dept of Medicine, Dalhousie University, Halifax, NS, Canada
| | | | - Dena Zeraatkar
- Health Research Methods Evidence and Impact, McMaster University, Hamilton, ON, Canada.,Harvard Medical School, Harvard University, Boston, MA, USA.,D. Zeraatkar and S. Mehta contributed equally to this article as senior authors and supervised the work
| | - Sanjay Mehta
- Southwest Ontario PH Clinic, Division of Respirology, Dept of Medicine, Lawson Health Research Institute, London Health Sciences Centre, Schulich School of Medicine, Western University, London, ON, Canada.,PHA Canada, Vancouver, BC, Canada.,D. Zeraatkar and S. Mehta contributed equally to this article as senior authors and supervised the work
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21
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Chen YJ, Lin YJ, Guo MMH. Pediatric Lupus Presenting as Pulmonary Hypertension, Myocarditis, and Massive Pericardial Effusion in an 11-Year-Old Girl: A Case Report and Literature Review. Front Pediatr 2022; 10:772422. [PMID: 35155304 PMCID: PMC8826687 DOI: 10.3389/fped.2022.772422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 01/03/2022] [Indexed: 12/02/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease that may cause vital organ damage. Although not rare for child-onset SLE to have cardiovascular or pulmonary involvement, myocarditis, and pulmonary hypertension are infrequent features and can be life-threatening. In this case report, we describe an 11-year-old girl with SLE who initially presented with fulminant myocarditis pulmonary hypertension, and massive pericardial effusion. Initial immunosuppressive therapy with methylprednisolone pulse therapy, and IVIG were administered, followed by cyclophosphamide, which was ultimately successful, with no residual pulmonary hypertension and no recurrence of myocarditis for over 3 years after the initial episode. Our case highlights the need for clinicians to be aware of systemic lupus erythematosus as a possible diagnostic entity in pediatric patients with severe myocarditis or pulmonary hypertension. Aggressive immunosuppressive therapy should be strongly considered in such cases, as it may lead to good short-term and long-term outcomes.
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Affiliation(s)
- Yu-Jhen Chen
- Department of Pediatric Allergy Immunology and Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ying-Jui Lin
- Department of Pediatric Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Mindy Ming-Huey Guo
- Department of Pediatric Allergy Immunology and Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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22
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Fu W, He W, Li Y, Chen Y, Liang J, Lei H, Fu L, Chen Y, Ren N, Jiang Q, Shen Y, Ma R, Wang T, Wang X, Zhang N, Xiao D, Liu C. Efficacy and safety of novel-targeted drugs in the treatment of pulmonary arterial hypertension: a Bayesian network meta-analysis. Drug Deliv 2021; 28:1007-1019. [PMID: 34060401 PMCID: PMC8172220 DOI: 10.1080/10717544.2021.1927243] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/02/2021] [Accepted: 05/04/2021] [Indexed: 12/24/2022] Open
Abstract
Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1st, 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome.Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs.Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted.Registration PROSPERO CRD42020218818.
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Affiliation(s)
- Wenhai Fu
- Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China
| | - Wenjun He
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Yuexin Li
- Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China
| | - Yangxiao Chen
- Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China
| | - Jingyi Liang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Hui Lei
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Lin Fu
- Department of Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China
| | - Yanghang Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Ni Ren
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Qian Jiang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Yi Shen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Ran Ma
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Tao Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Xinni Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Nuofu Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Dakai Xiao
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Chunli Liu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
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Abstract
Pulmonary hypertension (PH), a syndrome characterized by elevated pulmonary pressures, commonly complicates connective tissue disease (CTD) and is associated with increased morbidity and mortality. The incidence of PH varies widely between CTDs; patients with systemic sclerosis are most likely to develop PH. Several different types of PH can present in CTD, including PH related to left heart disease and respiratory disease. Importantly, CTD patients are at risk for developing pulmonary arterial hypertension, a rare form of PH that is associated with high morbidity and mortality. Future therapies targeting pulmonary vascular remodeling may improve outcomes for patients with this devastating disease.
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Affiliation(s)
- Stephen C Mathai
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Room 540, Baltimore, MD 21205, USA.
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24
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Gupta S, Padhan P, Subhankar S, Singh P. Cardiovascular complications in patients with interstitial lung disease and their correlation with 6-minute walk test and spirometry: A single-center study. J Family Med Prim Care 2021; 10:3330-3335. [PMID: 34760753 PMCID: PMC8565147 DOI: 10.4103/jfmpc.jfmpc_350_21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 07/07/2021] [Accepted: 07/10/2021] [Indexed: 11/04/2022] Open
Abstract
Introduction Pulmonary hypertension and other cardiac complications occur frequently due to chronic hypoxia induced by interstitial lung diseases (ILD) or due to connective tissue disorder itself. Two-dimensional (2D) echocardiography is ideal for identifying abnormalities at a given time. In this study, we tried to detect cardiovascular complications in patients with ILD using 2D echocardiography and correlate them with a 6-minute walk test (6 MWT) and spirometry. Materials and Methods This study was carried out for 18 months including 100 consecutive cases of ILD. The diagnosis was made using the latest criteria as per the disease and high-resolution computed tomography (HRCT) thorax. All patients were evaluated with 2D echocardiography, 6 MWT, and spirometry along with routine investigations. Their results were analyzed using STATA 15.1 software. Result Cardiovascular involvement was detected in 68% of cases. Pulmonary hypertension predominated with a prevalence of 50%. In spirometry, mean Forced expiratory volume in first second (FEV1)and Forced vital capacity (FVC) were found to be 54.96 (L) and 53.49 (L), respectively, with a predominant restrictive pattern (89%). There was a significant correlation between baseline saturation of oxygen (SpO2) and pulmonary arterial systolic pressure (PASP) with a P value of <0.05. Baseline SpO2 and distance covered in 6 MWT had a significant correlation (P = 0.014). Conclusion A baseline or nighttime hypoxia is responsible for developing PAH. Pulmonary arterial hypertension should be suspected in patients unable to perform 6 MWT or having low baseline SpO2. A routine follow-up with a 6 MWT and baseline SpO2 should be performed in each visit to identify early deterioration of the disease.
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Affiliation(s)
- Saurabh Gupta
- Department of Pulmonary Medicine, Kalinga Institute of Medical Sciences, KIIT University, Patia, Bhubaneswar, Odisha, India
| | - Prasanta Padhan
- Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Patia, Bhubaneswar, Odisha, India
| | - Saswat Subhankar
- Department of Pulmonary Medicine, Kalinga Institute of Medical Sciences, KIIT University, Patia, Bhubaneswar, Odisha, India
| | - Pratima Singh
- Department of Pulmonary Medicine, Kalinga Institute of Medical Sciences, KIIT University, Patia, Bhubaneswar, Odisha, India
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25
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Haque A, Kiely DG, Kovacs G, Thompson AAR, Condliffe R. Pulmonary hypertension phenotypes in patients with systemic sclerosis. Eur Respir Rev 2021; 30:30/161/210053. [PMID: 34407977 DOI: 10.1183/16000617.0053-2021] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 05/04/2021] [Indexed: 01/05/2023] Open
Abstract
Pulmonary hypertension (PH) commonly affects patients with systemic sclerosis (SSc) and is associated with significant morbidity and increased mortality. PH is a heterogenous condition and several different forms can be associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to left heart disease and PH due to interstitial lung disease. The incidence of pulmonary veno-occlusive disease is also increased. Accurate and early diagnosis to allow optimal treatment is, therefore, essential. Recent changes to diagnostic haemodynamic criteria at the 6th World Symposium on Pulmonary Hypertension have resulted in therapeutic uncertainty regarding patients with borderline pulmonary haemodynamics. Furthermore, the optimal pulmonary vascular resistance threshold for diagnosing PAH and the role of exercise in identifying early disease require further elucidation. In this article we review the epidemiology, diagnosis, outcomes and treatment of the spectrum of pulmonary vascular phenotypes associated with SSc.
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Affiliation(s)
- Ashraful Haque
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.,Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.,Dept of Rheumatology, Royal Hallamshire Hospital, Sheffield, UK.,Both authors contributed equally
| | - David G Kiely
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.,Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Gabor Kovacs
- Medical University of Graz, Graz, Austria.,Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - A A Roger Thompson
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.,Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Robin Condliffe
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK .,Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.,Both authors contributed equally
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26
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Naranjo M, Hassoun PM. Systemic Sclerosis-Associated Pulmonary Hypertension: Spectrum and Impact. Diagnostics (Basel) 2021; 11:911. [PMID: 34065226 PMCID: PMC8161029 DOI: 10.3390/diagnostics11050911] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 04/12/2021] [Accepted: 04/12/2021] [Indexed: 12/14/2022] Open
Abstract
Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a catastrophic complication of one of the most common and devastating autoimmune diseases. Once diagnosed, it becomes the leading cause of mortality among this patient population. Screening modalities and risk assessments have been designed and validated by various organizations and societies in order to identify patients early in their disease course and promptly refer them to expert centers for a hemodynamic assessment and formal diagnosis. Moreover, several large multicenter clinical trials have now included patients with SSc-PAH to assess their response to therapy. Despite an improved understanding of the condition and significant advances in supportive and targeted therapy, outcomes have remained far from optimal. Therefore, rigorous phenotyping and search for novel therapies are desperately needed for this devastating condition.
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Affiliation(s)
| | - Paul M. Hassoun
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA;
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27
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Giri PC, Stevens GJ, Merrill-Henry J, Oyoyo U, Balasubramanian VP. Participation in pulmonary hypertension support group improves patient-reported health quality outcomes: a patient and caregiver survey. Pulm Circ 2021; 11:20458940211013258. [PMID: 34035896 PMCID: PMC8132099 DOI: 10.1177/20458940211013258] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 03/12/2021] [Indexed: 11/29/2022] Open
Abstract
Support group participation has been shown to be effective in many chronic medical conditions. The evidence for integrating support group into pulmonary hypertension care and its effect on quality of life, physical and psychological well-being is limited. We sought to assess the effect of support group participation on quality of life in patients diagnosed with pulmonary hypertension and their caregivers. The emPHasis-10 questionnaire (a tool validated for quality of life assessment in pulmonary hypertension) was used to evaluate the effect of support group participation. Additional demographic and health-related quality measures were examined. Results showed that 165 subjects were enrolled in the study; 122 (74.4%) were patients with pulmonary hypertension, 41 (25.0%) were their caregivers, and 2 (0.02%) did not respond. The cohort was predominantly female (n = 128, 78%), Caucasian (n = 10, 61%), and the principal self-reported classification of pulmonary hypertension was World Health Organization Group 1 (n = 85, 51.8%) and the self-reported New York Heart Association Functional Class was II and III (n = 43, 57.3%). Most participants (n = 118, 71.5%) attended support groups and of them, a majority (n = 107, 90.6%) stated it helped them. There was no difference in quality of life as assessed by emPHasis-10 scores with support group participation (median score 30 vs 32, p = 0.387). There was self-reported improvement in understanding condition better including procedures such as right heart catheterization, medication compliance, and confidence in self-care (p < 0.05). Using multivariate logistic regression, baseline variables that were independently associated with emPHasis-10 scores for the entire cohort included knowledge of New York Heart Association Functional Class (odds ratio: 1.919, 95% CI: 1.004–3.67, p = 0.04) and greater distance traveled to visit pulmonary hypertension physician (odds ratio: 1.391, 95% CI: 0.998--1.94, p = 0.05). In conclusion, support group participation does not improve quality of life as assessed by emPHasis-10 scores but improves other meaningful health-related quality outcomes.
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Affiliation(s)
- Paresh C Giri
- Pulmonary and Critical Care Department, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Gizelle J Stevens
- Pulmonary and Critical Care Department, Loma Linda University Medical Center, Loma Linda, CA, USA
| | | | - Udochukwu Oyoyo
- Department of Dental Education Services, Loma Linda University School of Dentistry, Loma Linda, CA, USA
| | - Vijay P Balasubramanian
- Pulmonary and Critical Care Department, University of California San Francisco-Fresno, Fresno, CA, USA
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28
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A case of sigmoidectomy for sigmoid colon cancer with severe pulmonary arterial hypertension associated with mixed tissue connected disease: A case report. Int J Surg Case Rep 2021; 83:105906. [PMID: 34023548 PMCID: PMC8164025 DOI: 10.1016/j.ijscr.2021.105906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/13/2021] [Indexed: 11/23/2022] Open
Abstract
Introduction Patients with mixed connective tissue disease (MCTD) have higher rates of pulmonary arterial hypertension (PAH) than the general population. PAH is a risk for perioperative respiratory and heart failure, and marked edema of colonic stoma after sigmoidectomy. We report a case of sigmoidectomy for sigmoid colon cancer in a patient with PAH associated with MCTD for whom perioperative treatment was planned to control pulmonary arterial pressure (PAP), and a surgical strategy to avoid complications attributable to PAH and MCTD was employed. Case presentation A 52-year-old woman with sigmoid cancer and severe PAH associated with MCTD underwent surgery. We controlled PAH by using intravenous epoprostenol. We selected open surgery without laparoscopy and Hartmann's operation. After surgery, severe perioperative complications were not detected, and the patient discharged from hospital 17 days after the operation. Discussion During surgery under general anesthesia, the mortality rate of PAH is high because of heart and respiratory failure. We planned to switch the PAH treatment from an oral agent to intravenous epoprostenol only in the preoperative period, and selected open surgery. We ligated the inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) below the branch of LCA to avoid marked edema of stoma. Consequently, we could avoid severe intraoperative and postoperative complications. Conclusions Controlling PAP using epoprostenol, open surgery, stoma and the ligation level for the IMA and IMV preventing are important to avoid perioperative complications of sigmoid colon cancer complicated by severe PAH.
The patient with PAH complicated by MCTD underwent Hartman’s operation for sigmoid colon cancer. Control of PAH by epoprostenol preoperatively is important to prevent perioperative cardiac complications. The level of ligation of the IMA and the LCA is important to avoid severe edema of stoma.
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29
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Vonk MC, Vandecasteele E, van Dijk AP. Pulmonary hypertension in connective tissue diseases, new evidence and challenges. Eur J Clin Invest 2021; 51:e13453. [PMID: 33216992 PMCID: PMC7988614 DOI: 10.1111/eci.13453] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/08/2020] [Accepted: 11/15/2020] [Indexed: 12/21/2022]
Abstract
Pulmonary arterial hypertension is a lethal complication of different connective tissue diseases such as systemic sclerosis, mixed connective tissue disease and systemic lupus erythematosus. Although the treatment possibilities for patients with pulmonary arterial hypertension have increased in the last two decades and survival of patients with idiopathic pulmonary arterial hypertension has improved, the latter is not the case for patients with pulmonary arterial hypertension associated with connective tissue disease. In this narrative review, we review recent literature and describe the improvement of early diagnostic possibilities, screening modalities and treatment options. We also point out the pitfalls in diagnosis in this patient category and describe the unmet needs and what the focus of future research should be.
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Affiliation(s)
- Madelon C. Vonk
- Department of the Rheumatic diseasesRadboud University Nijmegen Medical CentreNijmegenthe Netherlands
| | | | - Arie P. van Dijk
- Department of CardiologyRadboud University Nijmegen Medical CentreNijmegenthe Netherlands
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30
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Roberts K, Stepanovich G, Bhatt-Mehta V, Donn SM. New Pharmacologic Approaches to Bronchopulmonary Dysplasia. J Exp Pharmacol 2021; 13:377-396. [PMID: 33790663 PMCID: PMC8006962 DOI: 10.2147/jep.s262350] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 02/26/2021] [Indexed: 12/22/2022] Open
Abstract
Bronchopulmonary Dysplasia is the most common long-term respiratory morbidity of preterm infants, with the risk of development proportional to the degree of prematurity. While its pathophysiologic and histologic features have changed over time as neonatal demographics and respiratory therapies have evolved, it is now thought to be characterized by impaired distal lung growth and abnormal pulmonary microvascular development. Though the exact sequence of events leading to the development of BPD has not been fully elucidated and likely varies among patients, it is thought to result from inflammatory and mechanical/oxidative injury from chronic ventilatory support in fragile, premature lungs susceptible to injury from surfactant deficiency, structural abnormalities, inadequate antioxidant defenses, and a chest wall that is more compliant than the lung. In addition, non-pulmonary issues may adversely affect lung development, including systemic infections and insufficient nutrition. Once BPD has developed, its management focuses on providing adequate gas exchange while promoting optimal lung growth. Pharmacologic strategies to ameliorate or prevent BPD continue to be investigated. A variety of agents, to be reviewed henceforth, have been developed or re-purposed to target different points in the pathways that lead to BPD, including anti-inflammatories, diuretics, steroids, pulmonary vasodilators, antioxidants, and a number of molecules involved in the cell signaling cascade thought to be involved in the pathogenesis of BPD.
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Affiliation(s)
- Katelyn Roberts
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Gretchen Stepanovich
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Varsha Bhatt-Mehta
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
- College of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Steven M Donn
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
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31
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Di Bartolomeo S, Alunno A, Carubbi F. Respiratory Manifestations in Systemic Lupus Erythematosus. Pharmaceuticals (Basel) 2021; 14:276. [PMID: 33803847 PMCID: PMC8003168 DOI: 10.3390/ph14030276] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/15/2021] [Accepted: 03/16/2021] [Indexed: 12/11/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by a wide spectrum of clinical manifestations. The respiratory system can be involved in up to 50-70% of patients and be the presenting manifestation of the disease in 4-5% of cases. Every part of the respiratory part can be involved, and the severity can vary from mild self-limiting to life threatening forms. Respiratory involvement can be primary (caused by SLE itself) or secondary (e.g., infections or drug toxicity), acute or chronic. The course, treatment and prognosis vary greatly depending on the specific pattern of the disease. This review article aims at providing an overview of respiratory manifestations in SLE along with an update about therapeutic approaches including novel biologic therapies.
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Affiliation(s)
| | - Alessia Alunno
- Rheumatology Unit, Department of Medicine, University of Perugia, 06123 Perugia, Italy;
| | - Francesco Carubbi
- Internal Medicine and Nephrology Unit, Department of Life, Health & Environmental Sciences, University of L’Aquila and Department of Medicine, ASL 1 Avezzano-Sulmona-L’Aquila, 67100 L’Aquila, Italy
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32
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Amarnani R, Yeoh SA, Denneny EK, Wincup C. Lupus and the Lungs: The Assessment and Management of Pulmonary Manifestations of Systemic Lupus Erythematosus. Front Med (Lausanne) 2021; 7:610257. [PMID: 33537331 PMCID: PMC7847931 DOI: 10.3389/fmed.2020.610257] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 12/07/2020] [Indexed: 12/25/2022] Open
Abstract
Pulmonary manifestations of systemic lupus erythematosus (SLE) are wide-ranging and debilitating in nature. Previous studies suggest that anywhere between 20 and 90% of patients with SLE will be troubled by some form of respiratory involvement throughout the course of their disease. This can include disorders of the lung parenchyma (such as interstitial lung disease and acute pneumonitis), pleura (resulting in pleurisy and pleural effusion), and pulmonary vasculature [including pulmonary arterial hypertension (PAH), pulmonary embolic disease, and pulmonary vasculitis], whilst shrinking lung syndrome is a rare complication of the disease. Furthermore, the risks of respiratory infection (which often mimic acute pulmonary manifestations of SLE) are increased by the immunosuppressive treatment that is routinely used in the management of lupus. Although these conditions commonly present with a combination of dyspnea, cough and chest pain, it is important to consider that some patients may be asymptomatic with the only suggestion of the respiratory disorder being found incidentally on thoracic imaging or pulmonary function tests. Treatment decisions are often based upon evidence from case reports or small cases series given the paucity of clinical trial data specifically focused on pulmonary manifestations of SLE. Many therapeutic options are often initiated based on studies in severe manifestations of SLE affecting other organ systems or from experience drawn from the use of these therapeutics in the pulmonary manifestations of other systemic autoimmune rheumatic diseases. In this review, we describe the key features of the pulmonary manifestations of SLE and approaches to investigation and management in clinical practice.
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Affiliation(s)
- Raj Amarnani
- Department of Rheumatology, University College London Hospital, London, United Kingdom
| | - Su-Ann Yeoh
- Department of Rheumatology, University College London Hospital, London, United Kingdom
- Division of Medicine, Department of Rheumatology, University College London, London, United Kingdom
| | - Emma K. Denneny
- Department of Respiratory Medicine, University College London Hospital, London, United Kingdom
- Leukocyte Trafficking Laboratory, Centre for Inflammation and Tissue Repair, UCL Respiratory, University College London, London, United Kingdom
| | - Chris Wincup
- Department of Rheumatology, University College London Hospital, London, United Kingdom
- Division of Medicine, Department of Rheumatology, University College London, London, United Kingdom
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33
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Yu Y, Jia YY, Wang M, Mu L, Li HJ. PTGER3 and MMP-2 play potential roles in diabetic nephropathy via competing endogenous RNA mechanisms. BMC Nephrol 2021; 22:27. [PMID: 33435900 PMCID: PMC7805187 DOI: 10.1186/s12882-020-02194-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 11/29/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Diabetic nephropathy (DN) is a primary complication of diabetes mellitus (DM). The pathology of DN is still vague, and diagnostic accuracy is not enough. This study was performed to identify miRNAs and genes that have possibilities of being used as therapeutic targets for DN in type 2 DM. METHODS Human miRNA data GSE51674 and gene data GSE111154 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) in the kidney between control and DN patients were screened out. The competing endogenous RNA (ceRNA) network was constructed, and key lncRNA-miRNA-mRNA pairs were selected accordingly. Potential drugs targeting DEGs were screened out and validated using PCR analysis. RESULTS Totally, 83 DEmiRNAs and 293 DEGs were identified in GSE51674 and GSE111154, respectively. Thirteen of the top 20 DEmiRNAs (10 up and 10 down) targeted to 47 DEGs. In the ceRNA network, RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 interaction pairs were identified as the key ceRNA network. Interestingly, PTGER3 and hsa-miR-1237-3p were downregulated, and MMP-2 and hsa-miR-106b-5p were upregulated in the kidney of patients with DN compared with normal controls, respectively. PTGER3 and MMP-2 were targeted by drugs including iloprost, treprostinil, or captopril, and the deregulation of the two genes was confirmed in the plasma samples from patients with DN as compared with controls. CONCLUSIONS We speculated that the RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 networks were associated with diabetic renal injury.
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Affiliation(s)
- Yue Yu
- Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, China
| | - Yuan-Yuan Jia
- China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, China
| | - Meng Wang
- Center of Reproductive Medicine, Center of Prenatal Diagnosis, the First Hospital of Jilin University, Changchun, 130021, Jilin Province, People's Republic of China
| | - Lin Mu
- Department of Radiology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, People's Republic of China
| | - Hong-Jun Li
- Health Management Medical Center, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, 130033, Jilin Province, China.
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Cajas Santana LJ, Florez Suarez JB, Méndez Toro A, Quintana López G. Tratamiento farmacológico de la hipertensión pulmonar asociada a la esclerosis sistémica: revisión sistemática de la literatura. REVISTA COLOMBIANA DE REUMATOLOGÍA 2020; 27:135-145. [DOI: 10.1016/j.rcreu.2020.05.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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Attanasio U, Cuomo A, Pirozzi F, Loffredo S, Abete P, Petretta M, Marone G, Bonaduce D, De Paulis A, Rossi FW, Tocchetti CG, Mercurio V. Pulmonary Hypertension Phenotypes in Systemic Sclerosis: The Right Diagnosis for the Right Treatment. Int J Mol Sci 2020; 21:E4430. [PMID: 32580360 PMCID: PMC7352262 DOI: 10.3390/ijms21124430] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 06/16/2020] [Accepted: 06/19/2020] [Indexed: 02/07/2023] Open
Abstract
Systemic sclerosis is an auto-immune disease characterized by skin involvement that often affects multiple organ systems. Pulmonary hypertension is a common finding that can significantly impact prognosis. Molecular pathophysiological mechanisms underlying pulmonary hypertension in systemic sclerosis can be extremely heterogeneous, leading to distinct clinical phenotypes. In addition, different causes of pulmonary hypertension may overlap within the same patient. Since pulmonary hypertension treatment is very different for each phenotype, it is fundamental to perform an adequate diagnostic work-up to properly and promptly identify the prevalent mechanism underlying pulmonary hypertension in order to start the right therapies. When pulmonary hypertension is caused by a primary vasculopathy of the small pulmonary arteries, treatment with pulmonary vasodilators, often in an initial double-combination regimen, is indicated, aimed at reducing the mortality risk profile. In this review, we describe the different clinical phenotypes of pulmonary hypertension in the scleroderma population and discuss the utility of clinical tools to identify the presence of pulmonary vascular disease. Furthermore, we focus on systemic sclerosis-associated pulmonary arterial hypertension, highlighting the advances in the knowledge of right ventricular dysfunction in this setting and the latest updates in terms of treatment with pulmonary vasodilator drugs.
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Affiliation(s)
- Umberto Attanasio
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
| | - Alessandra Cuomo
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
| | - Flora Pirozzi
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
| | - Stefania Loffredo
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
- Center for Basic and Clinical Immunology Research (CISI), 80131 Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131 Naples, Italy
| | - Pasquale Abete
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
| | - Mario Petretta
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
| | - Gianni Marone
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
- Center for Basic and Clinical Immunology Research (CISI), 80131 Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131 Naples, Italy
| | - Domenico Bonaduce
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
| | - Amato De Paulis
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
- Center for Basic and Clinical Immunology Research (CISI), 80131 Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131 Naples, Italy
| | - Francesca Wanda Rossi
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
- Center for Basic and Clinical Immunology Research (CISI), 80131 Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131 Naples, Italy
| | - Carlo Gabriele Tocchetti
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
| | - Valentina Mercurio
- Department of Translational Medical Sciences. Federico II University, 80131 Naples, Italy; (U.A.); (A.C.); (F.P.); (S.L.); (P.A.); (M.P.); (G.M.); (D.B.); (A.D.P.); (F.W.R.); (C.G.T.)
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Almaaitah S, Highland KB, Tonelli AR. Management of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis. Integr Blood Press Control 2020; 13:15-29. [PMID: 32280271 PMCID: PMC7125406 DOI: 10.2147/ibpc.s232038] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 03/05/2020] [Indexed: 12/25/2022] Open
Abstract
Systemic sclerosis (SSc) is a rare and complex immune-mediated connective tissue disease characterized by multi-organ fibrosis and dysfunction. Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a leading cause of death in this population. Pulmonary arterial hypertension (PAH) can coexist with other forms of pulmonary hypertension in SSc, including pulmonary hypertension related to left heart disease, interstitial lung disease, chronic thromboembolism and pulmonary venous occlusive disease, which further complicates diagnosis and management. Available pulmonary arterial hypertension therapies target the nitric oxide, endothelin and prostacyclin pathways. These therapies have been studied in SSc-PAH in addition to idiopathic PAH, often with different treatment responses. In this article, we discuss the management as well as the treatment options for patients with SSc-PAH.
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Affiliation(s)
- Saja Almaaitah
- Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Kristin B Highland
- Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Adriano R Tonelli
- Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, OH, USA
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Lei Y, Zhang X, Lin H, Feng Y, Wang J, Luo R. The effects of oral treatment for systemic sclerosis related pulmonary arterial hypertension: A systematic review and meta-analysis. Mod Rheumatol 2020; 31:151-161. [PMID: 31829087 DOI: 10.1080/14397595.2019.1704125] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
OBJECTIVES The usage of oral therapies, endothelin receptor antagonists (ERAs), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogs has resulted in improved outcomes in patients with pulmonary arterial hypertension related to systemic sclerosis (SSc-PAH). However, the optimal therapeutics have not been determined. METHODS A systematic searching in the databases of Medline (PubMed), Embase, the Cochrane Library (Central) and unpublished clinical trials (clinicaltrials.gov) was conducted to identify the clinical studies with oral treatment for SSc-PAH patients published before 1 June 2019. The data were extracted and the quality was assessed. The main outcomes are exercise capacity and hemodynamic parameters, which were synthesized and analyzed. RESULTS In total, 27 clinical trials were enrolled for further analysis. It was demonstrated that bosentan treatment, the widely used drug for PAH, might improve the exercise capacity and pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in this clinical setting, although without significant difference. Meanwhile, the usage of prostaglandin analogs could improve the parameters mentioned above. Furthermore, combined therapy with ambrisentan and tadalafil significantly increased the treatment efficacy of key parameters in SSc-PAH patients compared with basic treatment. CONCLUSION This meta-analysis reveals that combination therapy might provide more benefits to exercise capacity and hemodynamic parameters in SSc-PAH patients. Still more RCTs are needed to provide more solid evidence.
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Affiliation(s)
- Yunxia Lei
- Southern Medical University, Guangzhou, China.,Department of Rheumatology and Clinical Immunology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xiao Zhang
- Southern Medical University, Guangzhou, China.,Department of Rheumatology and Clinical Immunology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Haobo Lin
- Department of Rheumatology and Clinical Immunology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yuan Feng
- Department of Rheumatology and Clinical Immunology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jieying Wang
- Department of Rheumatology and Clinical Immunology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Riqiang Luo
- Department of Rheumatology and Clinical Immunology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
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Saygin D, Domsic RT. Pulmonary Arterial Hypertension In Systemic Sclerosis: Challenges In Diagnosis, Screening And Treatment. Open Access Rheumatol 2019; 11:323-333. [PMID: 31920409 PMCID: PMC6939800 DOI: 10.2147/oarrr.s228234] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/15/2019] [Indexed: 12/31/2022] Open
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.
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Affiliation(s)
- Didem Saygin
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Robyn T Domsic
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Wang S, Yu M, Zheng X, Dong S. A Bayesian network meta-analysis on the efficacy and safety of eighteen targeted drugs or drug combinations for pulmonary arterial hypertension. Drug Deliv 2019; 25:1898-1909. [PMID: 30442035 PMCID: PMC6249551 DOI: 10.1080/10717544.2018.1523257] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
Abstract
Pulmonary arterial hypertension (PAH) can be relieved by pharmacological interventions, especially the targeted drug, which is classified into endothelin receptor antagonist, phosphodiesterase 5 inhibitor, prostaglandin I2, soluble guanylate cyclase stimulator and selective non-prostanoid prostacyclin receptor agonist. To solve the contradictions existing in reported trials and provide a comprehensive guideline for clinical practice. PubMed, Embase, Cochrane library, and clinicaltrials.gov were searched. The basic information about the article, trial, arm, intervention, and the detailed data of outcome, including 6 minutes walking distance (6MWD) change, WHO functional class (FC) improvement, Borg dyspnea score (BDS) change, cardiac index (CI) change, mean pulmonary arterial pressure (mPAP) change, mean right arterial pressure (mRAP) change, pulmonary vascular resistance (PVR) change, clinical worsening, hospitalization, death, severe adverse events (SAEs), and withdrawal were extracted. The rank of treatments was estimated. 10,230 cases provided the firsthand comparison data about targeted drugs for treating PAH. For 6MWD, ambrisentan + tadalafil, vardenafil, and sildenafil + bosentan were better than others. Epoprostenol, macitentan, and sildenafil represented a greater WHO FC improvement. Vardenafil and treprostinil were better for BDS. So were bosentan + epoprostenol and bosentan alone for CI. Iloprost plus bosentan, bosentan + epoprostenol, and epoprostenol were better for mPAP. Iloprost plus bosentan, bosentan alone, and selexipag could reduce PVR. Sildenafil, epoprostenol, and vardenafil had the highest probability to reduce the incidence of death and withdrawal. To conclude, vardenafil and iloprost + bosentan showed relatively better performance in both efficacy and safety. However, the therapeutic choice should be made according to both the feature of each therapy and the individual condition.
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Affiliation(s)
- Sumei Wang
- a Department of Emergency , Dongfang Hospital Beijing University of Chinese Medicine , Beijing , China
| | - Miao Yu
- b Department of Emergency , Beijing University of Chinese Medicine Third Affiliated Hospital , Beijing , China
| | - Xiangchun Zheng
- a Department of Emergency , Dongfang Hospital Beijing University of Chinese Medicine , Beijing , China
| | - Shangjuan Dong
- c Department Respiration , Dongfang Hospital Beijing University of Chinese Medicine , Beijing , China
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Zanatta E, Polito P, Famoso G, Larosa M, De Zorzi E, Scarpieri E, Cozzi F, Doria A. Pulmonary arterial hypertension in connective tissue disorders: Pathophysiology and treatment. Exp Biol Med (Maywood) 2019; 244:120-131. [PMID: 30669861 PMCID: PMC6405825 DOI: 10.1177/1535370218824101] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
IMPACT STATEMENT Our article focuses on the pathogenesis and treatment of CTD-PAH. In the latest ESC/ESR guidelines for PAH, the authors underline that although CTD-PAH should follow the same treatment protocol as idiopathic PAH, the therapeutic approach is more complex and difficult in the former. This review throws light on several peculiar aspects of CTD-PAH and the latest findings in the pathogenesis, namely, the role of inflammation in the maladaptive right ventricle remodeling in SSc-PAH where immunosuppressants are classically believed to be ineffective. Furthermore, we discuss the major critical points in the therapy of CTD-PAH which is one of the strengths of our article. To the best of our knowledge, there are no other reviews that exclusively focus on the pathogenesis and treatment of CTD-PAH patients, with an emphasis on the more critical issues. Thus, it is our contention that our work would be of interest to the readers.
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Affiliation(s)
- Elisabetta Zanatta
- Department of Medicine-DIMED, Division of Rheumatology,
University of Padova, 35128 Padova, Italy
| | - Pamela Polito
- Department of Medicine-DIMED, Division of Rheumatology,
University of Padova, 35128 Padova, Italy
| | - Giulia Famoso
- Department of Cardiac, Thoracic and Vascular Sciences,
University of Padova, 35128 Padova, Italy
| | - Maddalena Larosa
- Department of Medicine-DIMED, Division of Rheumatology,
University of Padova, 35128 Padova, Italy
| | - Elena De Zorzi
- Department of Medicine-DIMED, Division of Rheumatology,
University of Padova, 35128 Padova, Italy
| | - Elena Scarpieri
- Department of Medicine-DIMED, Division of Rheumatology,
University of Padova, 35128 Padova, Italy
| | - Franco Cozzi
- Department of Medicine-DIMED, Division of Rheumatology,
University of Padova, 35128 Padova, Italy
| | - Andrea Doria
- Department of Medicine-DIMED, Division of Rheumatology,
University of Padova, 35128 Padova, Italy
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McGoon MD, Ferrari P, Armstrong I, Denis M, Howard LS, Lowe G, Mehta S, Murakami N, Wong BA. The importance of patient perspectives in pulmonary hypertension. Eur Respir J 2019; 53:13993003.01919-2018. [PMID: 30545977 PMCID: PMC6351339 DOI: 10.1183/13993003.01919-2018] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Accepted: 10/09/2018] [Indexed: 12/19/2022]
Abstract
The assessment of objective measurement of cardiopulmonary status has helped us achieve better clinical outcomes for patients and develop new therapies through to the point of market access; however, patient surveys indicate that more can be done to improve holistic care and patient engagement. In this multidisciplinary review, we examine how clinical teams can acknowledge and embrace the individual patient's perspective, and thus improve the care for individual patients suffering from pulmonary hypertension by cultivating the importance and relevance of health-related quality of life in direct clinical care. At the individual level, patients should be provided with access to accredited specialist centres which provide a multidisciplinary approach where there is a culture focused on narrative medicine, quality of life, shared decision making and timely access to palliative care, and where there is participation in education. On a larger scale, we call for the development, expansion and promotion of patient associations to support patients and carers, lobby for access to best care and treatments, and provide input into the development of clinical trials and registries, focusing on the patients’ perspective. Analysis and discussion on the importance of patients' perspectives in pulmonary hypertensionhttp://ow.ly/edOt30mgYoI
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Affiliation(s)
- Michael D McGoon
- Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Pisana Ferrari
- Pulmonary Hypertension Association Europe, Vienna, Austria
| | | | | | - Luke S Howard
- National Pulmonary Hypertension Service, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Gabi Lowe
- Jenna Lowe Trust, Republic of South Africa
| | - Sanjay Mehta
- London Health Sciences Centre, Division of Respirology, Dept of Medicine, Schulich School of Medicine, Western University and Pulmonary Hypertension Association Canada, London, ON, Canada
| | | | - Brad A Wong
- Pulmonary Hypertension Association, Silver Spring, MD, USA
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Guía de práctica clínica para el manejo del lupus eritematoso sistémico propuesta por el Colegio Mexicano de Reumatología. ACTA ACUST UNITED AC 2019; 15:3-20. [DOI: 10.1016/j.reuma.2018.03.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 03/20/2018] [Accepted: 03/21/2018] [Indexed: 12/31/2022]
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Denton CP, Wells AU, Coghlan JG. Major lung complications of systemic sclerosis. Nat Rev Rheumatol 2018; 14:511-527. [DOI: 10.1038/s41584-018-0062-0] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Lin H, Wang M, Yu Y, Qin Z, Zhong X, Ma J, Zhao F, Zhang X. Efficacy and tolerability of pharmacological interventions for pulmonary arterial hypertension: A network meta-analysis. Pulm Pharmacol Ther 2018; 50:1-10. [PMID: 29128622 DOI: 10.1016/j.pupt.2017.11.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 09/22/2017] [Accepted: 11/07/2017] [Indexed: 11/16/2022]
Abstract
PURPOSE This network meta-analysis (NMA) is designed to compare the efficacy and tolerability of various therapies and combinations for pulmonary arterial hypertension (PAH). METHOD We conducted a systematic search in databases PubMed, Embase, and Cochrane Library. Treatment efficacy and tolerability were compared by synthesizing direct and indirect evidence. The surface under the curve ranking area was utilized to rank multiple interventions. RESULT A total of 43 randomized clinical trials were included in our NMA. With regard to efficacy outcomes, including 6 min walking distance (6MWD), functional class amelioration (FCA), death, clinical worsening (CW), pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), cardiac index (CI), and mean right atrial pressure (mRAP), endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitor (PDE-5Is), ERA combined with PDE-5Is (EAP), and prostacyclin analogs (PGI) combined with ERA (PAE) performed better than others. Meanwhile PAP and PGE demonstrated better than others in tolerability. Overall, EAP and PAE showed good efficacy and were well-tolerated among all therapies. CONCLUSION Overall, we recommend EAP as the optimal choice for patients with PAH in clinical practice and PAE as suboptimal in view of their desirable performance in efficacy. Most of the combination therapies performed better than monotherapies.
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Affiliation(s)
- Hongjing Lin
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Mupeng Wang
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Ying Yu
- Department of Hepatobiliary Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Zeyu Qin
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Xin Zhong
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Jiahui Ma
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Fangbo Zhao
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Xueli Zhang
- Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China.
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Pulmonale Hypertonie bei Kollagenosen. Z Rheumatol 2018; 77:219-230. [DOI: 10.1007/s00393-018-0443-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Sanges S, Giovannelli J, Sobanski V, Morell-Dubois S, Maillard H, Lambert M, Podevin C, Lamblin N, De Groote P, Bervar JF, Perez T, Matran R, Rémy-Jardin M, Hatron PY, Hachulla É, Launay D. Factors associated with the 6-minute walk distance in patients with systemic sclerosis. Arthritis Res Ther 2017; 19:279. [PMID: 29246248 PMCID: PMC5732461 DOI: 10.1186/s13075-017-1489-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Accepted: 11/28/2017] [Indexed: 12/13/2022] Open
Abstract
Background There is an ongoing debate regarding the relevance of the 6-minute walking distance (6MWD) in systemic sclerosis (SSc) assessment, widely used as a usual test in these patients as well as an outcome measure in clinical trials. In this work, we aimed to assess the associations between the 6MWD and various disease parameters in patients with SSc. Methods Consecutive patients followed in our SSc National Reference Centre were included in this cross-sectional study if they fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc. Data were systematically collected during a comprehensive standardized evaluation that included a 6-minute walk test, clinical assessment, biological results, pulmonary function tests, transthoracic echocardiography, composite scores (European Scleroderma Study Group Activity Index, Medsger severity score, Health Assessment Questionnaire–Disability Index (HAQ-DI)) and treatments. Associations of the 6MWD with various disease parameters were assessed by linear regression in univariate and multivariate analyses. Results The study population comprised 298 patients (females 81%; mean age 58.2 ± 13.3 years; limited cutaneous SSc 82%; interstitial lung disease (ILD) 42%; pulmonary arterial hypertension (PAH) 6%). The 6MWD was significantly and independently associated with gender, age, body mass index, baseline heart rate (HR), HR variation during the test, PAH, history of arterial thrombosis and C-reactive protein levels, as well as with the HAQ-DI score in a sensitivity analysis. Muscle involvement, joint involvement and ILD were not independently associated with the 6MWD. Conclusions During SSc, the 6MWD is independently associated with initial HR and HR variation; with PAH but not ILD, suggesting that pulmonary vasculopathy may have a greater impact than parenchymal involvement on functional limitation; and with global markers of disease activity and patient disability. These results give clinicians further insight into how to interpret the 6MWD in the context of SSc. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1489-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sébastien Sanges
- University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France.,INSERM U995, F-59000, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - Jonathan Giovannelli
- University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France.,INSERM U995, F-59000, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - Vincent Sobanski
- University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France.,INSERM U995, F-59000, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - Sandrine Morell-Dubois
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - Hélène Maillard
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - Marc Lambert
- University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France.,INSERM U995, F-59000, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - Céline Podevin
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France
| | | | | | | | - Thierry Perez
- CHU Lille, Service d'Explorations Fonctionnelles Respiratoires, F-59000, Lille, France
| | - Régis Matran
- CHU Lille, Service d'Explorations Fonctionnelles Respiratoires, F-59000, Lille, France
| | | | - Pierre-Yves Hatron
- University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France.,INSERM U995, F-59000, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - Éric Hachulla
- University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France.,INSERM U995, F-59000, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France.,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France
| | - David Launay
- University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France. .,INSERM U995, F-59000, Lille, France. .,CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000, Lille, France. .,Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000, Lille, France. .,Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), F-59000, Lille, France.
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Santus P, Radovanovic D, Frassanito F, Cristiano A, Rizzi M. Is the six-minute walk test useful or useless in systemic sclerosis? Eur J Intern Med 2017; 43:e37-e39. [PMID: 28545712 DOI: 10.1016/j.ejim.2017.05.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 05/18/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Pierachille Santus
- Department of Biomedical And Clinical Sciences (DIBIC), University of Milan, Milan, Italy.; Respiratory Unit, " Luigi Sacco" University Hospital; ASST Fatebenefratelli-Sacco, Milan, Italy.
| | - Dejan Radovanovic
- Department of Biomedical And Clinical Sciences (DIBIC), University of Milan, Milan, Italy.; Respiratory Unit, " Luigi Sacco" University Hospital; ASST Fatebenefratelli-Sacco, Milan, Italy.
| | - Francesca Frassanito
- Department of Biomedical And Clinical Sciences (DIBIC), University of Milan, Milan, Italy.; Respiratory Unit, " Luigi Sacco" University Hospital; ASST Fatebenefratelli-Sacco, Milan, Italy.
| | - Andrea Cristiano
- Department of Biomedical And Clinical Sciences (DIBIC), University of Milan, Milan, Italy.; Respiratory Unit, " Luigi Sacco" University Hospital; ASST Fatebenefratelli-Sacco, Milan, Italy.
| | - Maurizio Rizzi
- Respiratory Unit, " Luigi Sacco" University Hospital; ASST Fatebenefratelli-Sacco, Milan, Italy.
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Coghlan JG, Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, Kuwana M, McLaughlin VV, Peacock AJ, Simonneau G, Vachiéry JL, Blair C, Gillies H, Miller KL, Harris JHN, Langley J, Rubin LJ. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Ann Rheum Dis 2017; 76:1219-1227. [PMID: 28039187 PMCID: PMC5530350 DOI: 10.1136/annrheumdis-2016-210236] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 12/02/2016] [Accepted: 12/03/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. OBJECTIVE To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. METHODS This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). RESULTS In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. CONCLUSIONS This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. TRIAL REGISTRATION NUMBER NCT01178073, post results.
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Affiliation(s)
| | - Nazzareno Galiè
- Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy
| | - Joan Albert Barberà
- Department of Respiratory Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
- Biomedical Research Networking Center on Respiratory Diseases, Madrid, Spain
| | | | | | - Marius M Hoeper
- Hannover Medical School and German Center of Lung Research (DZL) Hannover, Hannover, Germany
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | | | | | - Gérald Simonneau
- Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, France
- Département Hospitalo-Universitaire (DHU) Thorax Innovation (TORINO), Service de Pneumologie, AP-HP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Hôpital de Bicêtre, Le Kremlin Bicêtre, France
- Laboratoire d'Excellence (LabEx) en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), UMR_S 999, INSERM, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
| | | | | | - Hunter Gillies
- Former employee of Gilead Sciences, Inc., Foster City, California, USA
| | | | | | | | - Lewis J Rubin
- University of California at San Diego, La Jolla, California, USA
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Abstract
Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are
leading causes of morbidity and mortality in systemic sclerosis (SSc). As
symptoms are often under-reported in SSc, early screening of ILD and PAH is of
paramount importance, and early treatment may be associated with better clinical
outcomes. Serologies are particularly helpful in identifying patients at risk
for pulmonary involvement. Pulmonary function testing, high-resolution computed
tomography of the chest and echocardiography are important tools in the initial
screening of these patients. Extensive research has also led to an improved
understanding of the mediators involved in the pathogenesis of ILD and PAH. As a
result, there have been significant advances in the development of novel
targeted therapeutics and an increase in the number of early-phase clinical
trials in SSc.
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Affiliation(s)
- Sara R Schoenfeld
- Division of Rheumatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Flavia V Castelino
- Division of Rheumatology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 2C-2100, Boston, MA 02114, USA
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50
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Del Pozo R, Hernandez Gonzalez I, Escribano-Subias P. The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med 2017; 11:491-503. [DOI: 10.1080/17476348.2017.1317599] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- R Del Pozo
- Pulmonary Hypertension Unit, Pneumonology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - I Hernandez Gonzalez
- Pulmonary Hypertension Unit, Cardiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - P Escribano-Subias
- Pulmonary Hypertension Unit, Cardiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
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