المؤلفون: Franck F. Rahaghi, Vivien M. Hsu, Robert J. Kaner, Maureen D. Mayes, Ivan O. Rosas, Rajan Saggar, Virginia D. Steen, Mary E. Strek, Elana J. Bernstein, Nitin Bhatt, Flavia V. Castelino, Lorinda Chung, Robyn T. Domsic, Kevin R. Flaherty, Nishant Gupta, Bashar Kahaleh, Fernando J. Martinez, Lee E. Morrow, Teng Moua, Nina Patel, Oksana A. Shlobin, Brian D. Southern, Elizabeth R. Volkmann, Dinesh Khanna

المصدر: Respiratory Research, Vol 24, Iss 1, Pp 1-16 (2023)

مصطلحات موضوعية: Autoimmune diseases, Connective tissue diseases, Pulmonary fibrosis, Drug therapy, Algorithms, Diseases of the respiratory system, RC705-779

الوصف: Abstract Background Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35–52% of patients and accounting for 20–40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD. Methods A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from − 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤ − 2.5 or ≥ + 2.5 with a standard deviation not crossing zero. Results Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants. Conclusions This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1465-993XTest

الوصول الحر: https://doaj.org/article/f0f7c08666254d739a6ca421ab557bf3Test

المؤلفون: Lucilla Piccari, Brian Allwood, Katerina Antoniou, Jonathan H. Chung, Paul M. Hassoun, Sylvia M. Nikkho, Rajan Saggar, Oksana A. Shlobin, Patrizio Vitulo, Steven D. Nathan, Stephen John Wort

المصدر: Pulmonary Circulation, Vol 13, Iss 2, Pp n/a-n/a (2023)

مصطلحات موضوعية: endophenotype, histology, idiopathic pulmonary fibrosis, pathophysiology, pulmonary vascular disease, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the respiratory system, RC705-779

الوصف: Abstract Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-8940Test

الوصول الحر: https://doaj.org/article/73b2d7d3068442c48437e55307419645Test

المؤلفون: Sylvia M. Nikkho, Manuel J. Richter, Eric Shen, Steven H. Abman, Katerina Antoniou, Jonathan Chung, Peter Fernandes, Paul Hassoun, Howard M. Lazarus, Horst Olschewski, Lucilla Piccari, Mitchell Psotka, Rajan Saggar, Oksana A. Shlobin, Norman Stockbridge, Patrizio Vitulo, Carmine Dario Vizza, Stephen J. Wort, Steven D. Nathan

المصدر: Pulmonary Circulation, Vol 12, Iss 3, Pp n/a-n/a (2022)

مصطلحات موضوعية: epidemiology, interstitial lung disease, prognosis, pulmonary hypertension, symptom assessment and management, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the respiratory system, RC705-779

الوصف: Abstract Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in‐depth papers on specific topics pertaining to PH‐ILD.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-8940Test

الوصول الحر: https://doaj.org/article/218979fd55614332832c91abea59ce7cTest

المؤلفون: Thomas Bertero, Yu Lu, Sofia Annis, Andrew Hale, Balkrishen Bhat, Rajan Saggar, Rajeev Saggar, W. Dean Wallace, David J. Ross, Sara O. Vargas, Brian B. Graham, Rahul Kumar, Stephen M. Black, Sohrab Fratz, Jeffrey R. Fineman, James D. West, Kathleen J. Haley, Aaron B. Waxman, B. Nelson Chau, Katherine A. Cottrill, Stephen Y. Chan

المصدر: The Journal of Clinical Investigation, Vol 132, Iss 10 (2022)

مصطلحات موضوعية: Medicine

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1558-8238Test

الوصول الحر: https://doaj.org/article/f75ae1b920ed4388b4b98edd05c4de18Test

المؤلفون: Francesco Ferrara, Luna Gargani, Carla Contaldi, Gergely Agoston, Paola Argiento, William F. Armstrong, Francesco Bandera, Filippo Cademartiri, Rodolfo Citro, Antonio Cittadini, Rosangela Cocchia, Michele D’Alto, Antonello D’Andrea, Philipp Douschan, Stefano Ghio, Ekkehard Grünig, Marco Guazzi, Stefania Guida, Jaroslaw D. Kasprzak, Theodore John Kolias, Giuseppe Limongelli, Alberto Maria Marra, Matteo Mazzola, Ciro Mauro, Antonella Moreo, Francesco Pieri, Lorenza Pratali, Nicola Riccardo Pugliese, Mauro Raciti, Brigida Ranieri, Lawrence Rudski, Rajan Saggar, Andrea Salzano, Walter Serra, Anna Agnese Stanziola, Mani Vannan, Damien Voilliot, Olga Vriz, Karina Wierzbowska-Drabik, Robert Naeije, Eduardo Bossone, On behalf of the RIGHT Heart International NETwork (RIGHT-NET) Investigators

المصدر: Cardiovascular Ultrasound, Vol 19, Iss 1, Pp 1-11 (2021)

مصطلحات موضوعية: Right ventricle, Pulmonary hypertension, Exercise echocardiography, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract Purpose This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. Methods All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S’), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e’) and left ventricular ejection fraction (LVEF) were measured. Results The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e’ = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S’ = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. Conclusions When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1476-7120Test

الوصول الحر: https://doaj.org/article/1ca6343f52564abeb27697098f6dbbaeTest

المؤلفون: Anna-Maria Hoffmann-Vold, S. Samuel Weigt, Rajan Saggar, Vyacheslav Palchevskiy, Elizabeth R. Volkmann, Lloyd L. Liang, David Ross, Abbas Ardehali, Joseph P. Lynch, III, John A. Belperio

المصدر: EBioMedicine, Vol 50, Iss , Pp 379-386 (2019)

مصطلحات موضوعية: Medicine, Medicine (General), R5-920

الوصف: Background: Some interstitial lung disease (ILD) patients develop a progressive fibrosing-ILD phenotype (PF-ILD), with similar persistent lung function decline suggesting common molecular pathways involved. Nintedanib, a tyrosine kinase inhibitor targeting the PDGF, FGF, VEGF and M-CSF pathways, has shown comparable efficacy in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated ILD (SSc-ILD). We hypothesize that Nintedanib targeted molecular pathways will be augmented to a similar degree across PF-ILD regardless of aetiology. Methods: We collected explanted lung tissue at the time of lung transplantation from 130 PF-ILD patients (99 (76%) IPF, 14 (11%) SSc-ILD, 17 (13%) other PF-ILD), and wedge biopsies from 200 donor lungs and measured PDGF, FGF, VEGF and M-CSF concentrations by Luminex. Findings: The concentrations of PDGF-AA, PDGF-BB, FGF-2, VEGF and M-CSF were significantly increased in PF-ILD lungs compared to donor lungs (PDGF-AA 93·0 pg/ml [±97·2] vs. 37·5 pg/ml [±35·4], p

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S235239641930725XTest; https://doaj.org/toc/2352-3964Test

الوصول الحر: https://doaj.org/article/acead5a69b63476e8d773a006e546600Test

المؤلفون: John A. Belperio, Faisal Shaikh, Fereidoun Abtin, Michael C. Fishbein, Rajan Saggar, Edmund Tsui, Joseph P. Lynch, III

المصدر: EClinicalMedicine, Vol 37, Iss , Pp 100966- (2021)

مصطلحات موضوعية: Sarcoidosis, Granulomatous, Cardiac sarcoidosis, Neurosarcoidosis, Immunosuppression, Uveitis, Medicine (General), R5-920

الوصف: Sarcoidosis is a poorly understood granulomatous disease that involves the lungs and/or intrathoracic lymph nodes in more than 90% of cases. Although pulmonary sarcoidosis is the leading cause of mortality in this disease, this review focuses on three sites of extrapulmonary involvement (heart, nervous system, and eyes), since involvement of any of these sites can be catastrophic, leading to death, debilitation, or blindness.Patients with cardiac, ocular and neurosarcoidosis necessitate a multidisciplinary approach with careful and long-term follow-up. Prompt diagnosis with imaging and/or biopsy and treatment is required to avoid irreversible damage. Corticosteroids are the mainstay of therapy and are often associated with rapid and durable remissions. Immunosuppressive or biologic agents are reserved for patients failing or experiencing side effects from steroids. Managing sarcoidosis requires vigilance, judgement, and awareness of the vagaries of this fascinating disease.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589537021002467Test; https://doaj.org/toc/2589-5370Test

الوصول الحر: https://doaj.org/article/23818fe547bd4ea288eeed78f5d4d682Test

المؤلفون: Rajeev Saggar, Paresh C. Giri, Chunqin Deng, Dana Johnson, Mary K. McCloy, Lloyd Liang, Faisal Shaikh, Jason Hong, Richard N. Channick, Shelley S. Shapiro, Joseph P. Lynch, John A. Belperio, Samuel S. Weigt, Allison L. Ramsey, David J. Ross, David M. Sayah, Michael Y. Shino, Ariss Derhovanessian, Alexander E. Sherman, Rajan Saggar

المصدر: Pulmonary Circulation, Vol 11 (2021)

مصطلحات موضوعية: Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the respiratory system, RC705-779

الوصف: The association of autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis remains unclear. We report cases of severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg and right ventricular dysfunction) and extensive pulmonary fibrosis after pulmonary arterial hypertension-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Of 286 screened patients, 55 demonstrated severe pulmonary hypertension and extensive pulmonary fibrosis and were treated with parenteral prostacyclin therapy. The (+)AI subgroup (n = 34), when compared to the (–)AI subgroup (n = 21), was more likely to be female (77% versus 19%) and younger (58.7 ± 12.1 versus 66.0 ± 10.7 years), and revealed lower forced vital capacity (absolute) (1.9 ± 0.7 versus 2.9 ± 1.1 L), higher D L CO (% predicted) (31.1 ± 15.2 versus 23.2 ± 8.0), and increased unadjusted transplant-free survival (1 year (84.6 ± 6.3% versus 45 ± 11.1%)), 3 years (71 ± 8.2% versus 28.6 ± 11.9%), and 5 years (47.6 ± 9.6% versus 6.4 ± 8.2%); (p = 0.01)). Transplant-free survival was unchanged after adjusting for age and gender. The pulmonary hemodynamic profiles improved after parenteral prostacyclin therapy, independent of AI status. The baseline variables associated with mortality included age at pulmonary hypertension diagnosis (heart rate (HR) 1.23 (confidence interval (CI) 1.03–1.47); p = 0.02) and presence of AI (HR 0.26 (confidence interval (CI) 0.10–0.70); p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-8940Test

الوصول الحر: https://doaj.org/article/de848169b58d43ad9c6dc063d0502e7cTest

المؤلفون: Michael C. Garcia, Vijaya Surampudi, Zhaoping Li, Rajan Saggar, Sapna Shah

المصدر: Respiratory Medicine Case Reports, Vol 31, Iss , Pp 101193- (2020)

مصطلحات موضوعية: Lung transplantation, Obesity, Weight loss, Survival, Diseases of the respiratory system, RC705-779

الوصف: A 47-year-old male with morbid obesity and progressive pulmonary fibrosis was admitted to the intensive care unit (ICU) with worsening hypoxia and nocturnal ventilator dependence. Due to a significant oxygen requirement, the patient could only safely remain in an acute care setting. Unfortunately, he was not eligible for lung transplantation due to having obesity, a relative contraindication to lung transplantation due to potential for post transplantation complications and increased mortality. Therefore, we treated the patient with a modified very low calorie diet (MVLCD) to achieve weight loss. He had successful, sustained weight loss over a period of seven weeks and reached a target weight that made him eligible for transplantation. He subsequently underwent successful bilateral lung transplantation. The patient had improved metabolic parameters and no side effects attributable to the reduced calorie diet. This report shows that in patients with end stage lung disease and a poor prognosis without transplantation, inpatient weight loss is safe and may allow for potentially lifesaving lung transplantation.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S221300712030407XTest; https://doaj.org/toc/2213-0071Test

الوصول الحر: https://doaj.org/article/7449ea34d2e04bf389ab1fa2c714af71Test

المؤلفون: Gregoire Ruffenach, Soban Umar, Mylene Vaillancourt, Jason Hong, Nancy Cao, Shervin Sarji, Shayan Moazeni, Christine M Cunningham, Abbas Ardehali, Srinivasa T Reddy, Rajan Saggar, Gregory Fishbein, Mansoureh Eghbali

المصدر: EMBO Molecular Medicine, Vol 11, Iss 9, Pp n/a-n/a (2019)

مصطلحات موضوعية: non‐fibrotic area, prolactin‐induced protein, Slug, vascular remodeling, Medicine (General), R5-920, Genetics, QH426-470

الوصف: Abstract Pulmonary hypertension secondary to pulmonary fibrosis (PF‐PH) is one of the most common causes of PH, and there is no approved therapy. The molecular signature of PF‐PH and underlying mechanism of why pulmonary hypertension (PH) develops in PF patients remains understudied and poorly understood. We observed significantly increased vascular wall thickness in both fibrotic and non‐fibrotic areas of PF‐PH patient lungs compared to PF patients. The increased vascular wall thickness in PF‐PH patients is concomitant with a significantly increased expression of the transcription factor Slug within the macrophages and its target prolactin‐induced protein (PIP), an extracellular matrix protein that induces pulmonary arterial smooth muscle cell proliferation. We developed a novel translational rat model of combined PF‐PH that is reproducible and shares similar histological features (fibrosis, pulmonary vascular remodeling) and molecular features (Slug and PIP upregulation) with human PF‐PH. We found Slug inhibition decreases PH severity in our animal model of PF‐PH. Our study highlights the role of Slug/PIP axis in PF‐PH.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1757-4676Test; https://doaj.org/toc/1757-4684Test

الوصول الحر: https://doaj.org/article/e06b37c3ad3342498cbb6d5a007c42dbTest