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Sunder T, Thangaraj PR, Kuppusamy MK. Venous thromboembolism following lung transplantation. World J Transplant 2025; 15:99241. [DOI: 10.5500/wjt.v15.i2.99241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/12/2024] [Accepted: 11/14/2024] [Indexed: 02/21/2025] Open
Abstract
Lung transplantation (LT) is currently a surgical therapy option for end-stage lung disease. Venous thromboembolism (VTE), which can occur after LT, is associated with significant morbidity and mortality. Because of improved outcomes, increasing numbers of patients are receiving LT as treatment. Patients on the waitlist for LT tend to be older with weakness and frailty in addition to pulmonary symptoms. These factors contribute to a heightened risk of postoperative VTE. Furthermore, patients who clinically deteriorate while on the waitlist may require extra corporeal membrane oxygenation as a bridge to LT. Bleeding and thromboembolism are common in these patients. Pulmonary embolism (PE) in a freshly transplanted lung can have significant effects leading to morbidity and mortality. PE typically leads to impairment of gas exchange and right ventricular strain. In LT, PE can affect healing of bronchial anastomosis and may even contribute to the development of chronic allograft lung dysfunction. This article discussed the incidence, clinical features and diagnosis of VTE after LT. Furthermore, the treatment modalities, complications, and outcomes of VTE were reviewed.
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Affiliation(s)
- Thirugnanasambandan Sunder
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
| | - Paul Ramesh Thangaraj
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
| | - Madhan Kumar Kuppusamy
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
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Mohammad M, Kristensen AW, Hartmann JP, Wareham NE, Buttar SN, Greve AM, Lund TK, Jensen K, Schultz HHL, Perch M, Berg RMG, Mortensen J. Survival in Patients With Evidence of Pulmonary Thromboembolism on Ventilation-Perfusion SPECT 12 Weeks After Double Lung Transplantation: A Retrospective Cohort Study. Clin Transplant 2025; 39:e70103. [PMID: 39927856 PMCID: PMC11809467 DOI: 10.1111/ctr.70103] [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: 09/29/2024] [Revised: 01/06/2025] [Accepted: 01/22/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Patients who have undergone double lung transplantation (DLTx) are at increased risk of pulmonary thromboembolism (PTE). Although the presence of clinically overt PTE can adversely affect short-term mortality, the prognostic impact of asymptomatic (silent) PTE detected by routine imaging after DLTx is unclear. This study aimed to determine whether PTE identified by routine ventilation-perfusion single-photon emission computed tomography (V̇-Q̇ SPECT) 12 weeks post-DLTx is associated with subsequent all-cause and graft-related mortality. METHODS Single-center retrospective cohort study evaluating 130 DLTx recipients who underwent routine V̇-Q̇ SPECT imaging 12 weeks posttransplant between 2012 and 2017. V̇-Q̇ SPECT scans were assessed for perfusion and ventilation defects indicative of PTE. The association between PTE and mortality outcomes was analyzed using multivariable Cox regression, Kaplan-Meier survival curves, and cumulative incidence functions. RESULTS PTE was identified in 24.6% (n = 32) of the patients 12 weeks post-DLTx. After 3 months of follow-up, there was no detectable difference in lung function between patients with and without PTE. Moreover, the presence of PTE was not associated with increased hazard ratios for all-cause mortality (HR = 0.72; 95% CI: 0.37-1.41; p = 0.34) or graft-specific mortality (HR = 0.95; 95% CI: 0.42-2.16; p = 0.91). CONCLUSIONS PTE is a frequent finding on routine V̇-Q̇ SPECT 12 weeks post-DLTx that does not inform risk of all-cause or graft-related mortality. These findings suggest that an incidentally detected PTE in asymptomatic patients may not necessitate changes in clinical management for asymptomatic DLTx patients.
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Affiliation(s)
- Milan Mohammad
- Centre for Physical Activity ResearchCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
- Department of Biomedical Sciences, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
| | - Anna W. Kristensen
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
- Department of Obstetrics and GynecologyCopenhagen University HospitalCopenhagenDenmark
| | - Jacob P. Hartmann
- Centre for Physical Activity ResearchCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
- Department of Biomedical Sciences, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
| | - Neval E. Wareham
- Centre of Excellence for Health, Immunity, and Infections (CHIP)Copenhagen University HospitalRigshospitaletCopenhagenDenmark
| | - Sana N. Buttar
- Department of Cardiothoracic SurgeryCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
- Department of Clinical Medicine, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
| | - Anders M. Greve
- Department of Clinical BiochemistryCopenhagen University Hospital RigshospitaletCopenhagenDenmark
| | - Thomas K. Lund
- Department of Cardiology, Section for Lung TransplantationRigshospitalet, University Hospital of CopenhagenCopenhagenDenmark
| | - Kristine Jensen
- Department of Cardiology, Section for Lung TransplantationRigshospitalet, University Hospital of CopenhagenCopenhagenDenmark
| | - Hans H. L. Schultz
- Department of Cardiology, Section for Lung TransplantationRigshospitalet, University Hospital of CopenhagenCopenhagenDenmark
| | - Michael Perch
- Department of Cardiology, Section for Lung TransplantationRigshospitalet, University Hospital of CopenhagenCopenhagenDenmark
| | - Ronan M. G. Berg
- Centre for Physical Activity ResearchCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
- Department of Biomedical Sciences, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
- Neurovascular Research Laboratory, Faculty of Life Sciences and EducationUniversity of South WalesPontypriddUK
| | - Jann Mortensen
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital – RigshospitaletCopenhagenDenmark
- Department of Cardiology, Section for Lung TransplantationRigshospitalet, University Hospital of CopenhagenCopenhagenDenmark
- Department of MedicineThe National HospitalTorshavnFaroe Islands
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Blanco I, Torres-Castro R, Barberà JA. Pulmonary vascular disease in chronic lung diseases: cause or comorbidity? Curr Opin Pulm Med 2024; 30:437-443. [PMID: 38958570 DOI: 10.1097/mcp.0000000000001091] [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: 07/04/2024]
Abstract
PURPOSE OF REVIEW To provide timely and relevant insights into the complex relationship between pulmonary vascular disease (PVD) and chronic lung disease (CLD), focusing on the causative and consequential dynamics between these conditions. RECENT FINDINGS There are shared pathogenic mechanisms between pulmonary arterial hypertension (PAH) and group 3 pulmonary hypertension, including altered expression of mediators and growth factors implicated in both conditions. Factors such as hypoxia, hypoxemia, and hypercapnia also contribute to pulmonary vascular remodelling and endothelial dysfunction. However, the role of hypoxia as the sole driver of pulmonary hypertension in CLD is being reconsidered, particularly in chronic obstructive pulmonary disease (COPD), with evidence suggesting a potential role for cigarette smoke products in initiating pulmonary vascular impairment. On the other hand, interstitial lung disease (ILD) encompasses a group of heterogeneous lung disorders characterized by inflammation and fibrosis of the interstitium, leading to impaired gas exchange and progressive respiratory decline, which could also play a role as a cause of pulmonary hypertension. SUMMARY Understanding the intricate interplay between the pulmonary vascular compartment and the parenchymal and airway compartments in respiratory disease is crucial for developing effective diagnostic and therapeutic strategies for patients with PVD and CLD, with implications for both clinical practice and research.
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Affiliation(s)
- Isabel Blanco
- Department of Pulmonary Medicine, Hospital Clínic, University of Barcelona
- Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES); Madrid, Spain
| | - Rodrigo Torres-Castro
- Department of Pulmonary Medicine, Hospital Clínic, University of Barcelona
- Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona
- Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Joan Albert Barberà
- Department of Pulmonary Medicine, Hospital Clínic, University of Barcelona
- Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES); Madrid, Spain
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Mohammadi D, Keshavamurthy S. Pulmonary Embolism Following Lung Transplantation: Prevention and Management. Int J Angiol 2024; 33:123-127. [PMID: 38846988 PMCID: PMC11152625 DOI: 10.1055/s-0044-1786859] [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: 06/09/2024] Open
Abstract
Thromboembolic events are the third leading cardiovascular diagnosis following stroke and myocardial infarction. In the United States, 300,000 to 600,000 people per year are diagnosed with venous thromboembolism, either deep venous thrombosis or pulmonary embolism (PE). Of those patients, thousands die from PE despite heightened vigilance and improved therapies. Lung transplant recipients are at increased risk of developing PE due to multiple risk factors unique to this population. Additionally, the transplant recipients are more susceptible to morbid complications from PE. As a result, prevention, timely recognition, and intervention of PE in the lung transplant population are of the utmost importance.
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Affiliation(s)
- Daniel Mohammadi
- Department of Cardiothoracic Surgery, University of Kentucky, Lexington, Kentucky
| | - Suresh Keshavamurthy
- Department of Cardiovascular and Thoracic Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas
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Shlobin OA, Shen E, Wort SJ, Piccari L, Scandurra JA, Hassoun PM, Nikkho SM, Nathan SD. Pulmonary hypertension in the setting of interstitial lung disease: Approach to management and treatment. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative-Group 3 Pulmonary Hypertension. Pulm Circ 2024; 14:e12310. [PMID: 38205098 PMCID: PMC10777777 DOI: 10.1002/pul2.12310] [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: 04/20/2023] [Revised: 10/09/2023] [Accepted: 11/01/2023] [Indexed: 01/12/2024] Open
Abstract
Pulmonary hypertension (PH) due to interstitial lung disease (ILD), a commonly encountered complication of fibrotic ILDs, is associated with significant morbidity and mortality. Until recently, the studies of pulmonary vasodilator therapy in PH-ILD have been largely disappointing, with some even demonstrating the potential for harm. This paper is part of a series of Consensus Statements from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative for Group 3 Pulmonary Hypertension, with prior publications covering pathogenesis, prevalence, clinical features, phenotyping, clinical trials, and impact of PH-ILD. It offers a comprehensive review of and a holistic approach to treatment of PH-ILD, including the management of underlying interstitial lung diseases, importance of treating the comorbidities, emphasis on importance of exercise and palliation of dyspnea, and review of the most up-to-date guidelines for referral for potential lung transplant work up. It also summarizes the prior, ongoing, and possibly future studies in treatment of the vascular derangement of this morbid condition.
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Affiliation(s)
- Oksana A. Shlobin
- Advanced Lung Disease and Transplant ProgramInova Health SystemFalls ChurchVirginiaUSA
| | - Eric Shen
- United Therapeutics CorporationResearch Triangle ParkNorth CarolinaUSA
| | - Stephen J. Wort
- National Heart and Lung InstituteImperial College LondonLondonUK
| | - Lucilla Piccari
- Department of Pulmonary MedicineHospital del MarBarcelonaSpain
| | | | - Paul M. Hassoun
- Department of Medicine, Division of Pulmonary and Critical Care MedicineJohns Hopkins UniversityBaltimoreMarylandUSA
| | | | - Steven D. Nathan
- Advanced Lung Disease and Transplant ProgramInova Health SystemFalls ChurchVirginiaUSA
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Marshall S, Tsveybel K, Boukedes S, Chepuri R, Coppolino A, El-Chemaly S, Hartigan P, Kennedy J, Keshk M, Klibaner-Schiff E, Lee S, Mallidi H, Sharma N, Thaniyavarn T, Young J, Townsend K, Goldberg H. Limited Effect of Prevention Strategies on Incidence of Clinically Detectable Venous Thromboembolism After Lung Transplantation. Transplant Proc 2023; 55:2191-2196. [PMID: 37802745 DOI: 10.1016/j.transproceed.2023.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/02/2023] [Accepted: 06/30/2023] [Indexed: 10/08/2023]
Abstract
BACKGROUND Thromboembolic complications are common post-lung transplant, leading to significant morbidity. We instituted multiple interventions because of an observed 36.8% incidence of venous thromboembolism (VTE) (Incidence rate (IR) 5.74/1000 pt days) in our recipients. METHODS Our initiative commenced January 2015 with enoxaparin initiation within 6-8 hours of intensive care unit arrival and continuation for 4-6 weeks. We evaluated the IR of VTE in lung transplant recipients within 90 days of transplant. In 2017, the protocol was modified to extend the time to initiation of prophylaxis to within 72 hours of ICU arrival. In 2019, we further amended our intraoperative vascular access strategy. RESULTS Eighteen of 26 lung transplant recipients (LTR) met inclusion criteria in the 2015 cohort. Six of 18 (33.3%) developed VTE, 50% of which were upper extremity (UE), line associated. Fifty two of 75 LTR were eligible for enoxaparin prophylaxis in the 2017 cohort. Fifteen of 52 subjects (28.8%) developed VTE, 77.8% of which were UE and line associated. Despite improved adherence in 2017, there was little change in VTE IR (3.90/1000 pt days compared with 3.85/1000 pt days). Twenty six of 43 LTR met protocol inclusion criteria in the 2019 cohort. Ten subjects (38.5%) developed VTE, 67% of which were UE and line associated (IR 5.18/1000 pt days). CONCLUSION Our prospective study found that LTR remain at high risk for VTE despite aggressive prophylaxis with 4-6 weeks of enoxaparin and adjustment of vascular access approach. Alternative interventions should be investigated to minimize VTE development in this vulnerable population.
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Affiliation(s)
- Shirley Marshall
- Lung Transplant Program, Brigham & Women's Hospital, Boston, Massachusetts
| | - Karen Tsveybel
- Lung Transplant Program, Brigham & Women's Hospital, Boston, Massachusetts
| | - Steve Boukedes
- Lung Transplant Program, Brigham & Women's Hospital, Boston, Massachusetts
| | - Rasika Chepuri
- Division of Pulmonary and Critical Care, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Antonio Coppolino
- Division of Thoracic Surgery, Brigham & Women's Hospital, Boston, Massachusetts
| | - Souheil El-Chemaly
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Philip Hartigan
- Department of Anesthesia, Brigham and Women's Hospital, Boston, Massachusetts
| | - John Kennedy
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Mohamed Keshk
- Division of Thoracic Surgery, Brigham & Women's Hospital, Boston, Massachusetts
| | | | - Stefi Lee
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Division of Pulmonary and Critical Care, Veterans Affairs Boston Healthcare System, Boston, Massachusetts
| | - Hari Mallidi
- Division of Thoracic Surgery, Brigham & Women's Hospital, Boston, Massachusetts
| | - Nirmal Sharma
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Division of Pulmonary and Critical Care, Veterans Affairs Boston Healthcare System, Boston, Massachusetts
| | - Tany Thaniyavarn
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Division of Pulmonary and Critical Care, Veterans Affairs Boston Healthcare System, Boston, Massachusetts
| | - John Young
- Division of Thoracic Surgery, Brigham & Women's Hospital, Boston, Massachusetts; Division of Thoracic Surgery, Veterans Affairs Boston Health care System, Boston, Massachusetts
| | - Keri Townsend
- Lung Transplant Program, Brigham & Women's Hospital, Boston, Massachusetts
| | - Hilary Goldberg
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
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Altun I, Zhao Y, Basnet S, Raymond A, Fang A, Nezami N. The Role of Mechanical Thrombectomy for Acute Massive Pulmonary Embolism in a Patient With Unilateral Lung Transplant and Atrial Septal Defect. J Endovasc Ther 2023:15266028231201357. [PMID: 37776207 DOI: 10.1177/15266028231201357] [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: 10/02/2023]
Abstract
PURPOSE The risk of thromboembolic disease is high in patients with lung transplantation and is associated with significant morbidity and mortality with single healthy transplanted lung. We present a case involving successful endovascular management of life-threatening acute massive pulmonary embolism (PE) in a patient with single lung transplant and atrial septal defect (ASD). CASE REPORT A 65-year-old man with a history of interstitial lung disease status post single left orthotopic lung transplant in 2012 presented with acute massive PE and clot burden in the pulmonary arteries of the transplanted left lung. Severe right heart dysfunction, hemodynamic instability, and requirement for vasopressors persisted post systemic thrombolytic therapy. As a result, the patient underwent successful endovascular mechanical thrombectomy with immediate improvement in oxygen saturation and hemodynamic status. The procedure was performed without adverse outcomes or paradoxical embolization despite the presence of ASD. The right heart dysfunction resolved, the patient was extubated the next day, and was discharged to home 2 days post procedure. CONCLUSIONS Endovascular mechanical thrombectomy was safely used to treat acute massive PE in a single transplanted lung in the presence of ASD. CLINICAL IMPACT Endovascular mechanical thrombectomy could be safely utilized to treat patients with lung transplant and acute massive or submassive pulmonary embolism. However, safely of mechanical thrombectomy should be determined in case-based scenarios and based on time interval from transplantation to when the thrombectomy is required.
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Affiliation(s)
- Izzet Altun
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Yuanlong Zhao
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Suresh Basnet
- Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Aislynn Raymond
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Adam Fang
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA
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Piccari L, Allwood B, Antoniou K, Chung JH, Hassoun PM, Nikkho SM, Saggar R, Shlobin OA, Vitulo P, Nathan SD, Wort SJ. Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative - Group 3 Pulmonary Hypertension. Pulm Circ 2023; 13:e12213. [PMID: 37025209 PMCID: PMC10071306 DOI: 10.1002/pul2.12213] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 03/03/2023] [Accepted: 03/21/2023] [Indexed: 04/08/2023] Open
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.
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Affiliation(s)
- Lucilla Piccari
- Department of Pulmonary Medicine Hospital del Mar Barcelona Spain
| | - Brian Allwood
- Department of Medicine, Division of Pulmonology Stellenbosch University & Tygerberg Hospital Cape Town South Africa
| | - Katerina Antoniou
- Department of Thoracic Medicine University of Crete School of Medicine Heraklion Crete Greece
| | - Jonathan H Chung
- Department of Radiology The University of Chicago Medicine Chicago Illinois USA
| | - Paul M Hassoun
- Department of Medicine, Division of Pulmonary and Critical Care Medicine Johns Hopkins University Baltimore Maryland USA
| | | | - Rajan Saggar
- Lung & Heart-Lung Transplant and Pulmonary Hypertension Programs University of California Los Angeles David Geffen School of Medicine Los Angeles California USA
| | - Oksana A Shlobin
- Advanced Lung Disease and Transplant Program, Inova Health System Falls Church Virginia USA
| | - Patrizio Vitulo
- Department of Pulmonary Medicine IRCCS Mediterranean Institute for Transplantation and Advanced Specialized Therapies Palermo Sicilia Italy
| | - Steven D Nathan
- Advanced Lung Disease and Transplant Program, Inova Health System Falls Church Virginia USA
| | - Stephen John Wort
- National Pulmonary Hypertension Service at the Royal Brompton Hospital London UK
- National Heart and Lung Institute, Imperial College London UK
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Mohanka M, Banga A. Alterations in Pulmonary Physiology with Lung Transplantation. Compr Physiol 2023; 13:4269-4293. [PMID: 36715279 DOI: 10.1002/cphy.c220008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Lung transplant is a treatment option for patients with end-stage lung diseases; however, survival outcomes continue to be inferior when compared to other solid organs. We review the several anatomic and physiologic changes that result from lung transplantation surgery, and their role in the pathophysiology of common complications encountered by lung recipients. The loss of bronchial circulation into the allograft after transplant surgery results in ischemia-related changes in the bronchial artery territory of the allograft. We discuss the role of bronchopulmonary anastomosis in blood circulation in the allograft posttransplant. We review commonly encountered complications related to loss of bronchial circulation such as allograft airway ischemia, necrosis, anastomotic dehiscence, mucociliary dysfunction, and bronchial stenosis. Loss of dual circulation to the lung also increases the risk of pulmonary infarction with acute pulmonary embolism. The loss of lymphatic drainage during transplant surgery also impairs the management of allograft interstitial fluid, resulting in pulmonary edema and early pleural effusion. We discuss the role of lymphatic drainage in primary graft dysfunction. Besides, we review the association of late posttransplant pleural effusion with complications such as acute rejection. We then review the impact of loss of afferent and efferent innervation from the allograft on control of breathing, as well as lung protective reflexes. We conclude with discussion about pulmonary function testing, allograft monitoring with spirometry, and classification of chronic lung allograft dysfunction phenotypes based on total lung capacity measurements. We also review factors limiting physical exercise capacity after lung transplantation, especially impairment of muscle metabolism. © 2023 American Physiological Society. Compr Physiol 13:4269-4293, 2023.
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Affiliation(s)
- Manish Mohanka
- Pulmonary and Critical Care Medicine, University of Texas Southwestern, Dallas, Texas, USA
| | - Amit Banga
- Pulmonary and Critical Care Medicine, Stanford University School of Medicine, Stanford, California, USA
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10
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Is there a procoagulant state long-term after lung transplantation? A prospective study. Respir Med 2021; 188:106584. [PMID: 34560353 DOI: 10.1016/j.rmed.2021.106584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 08/18/2021] [Accepted: 08/22/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Venous thromboembolism (VTE) is a major complication after lung transplantation (LT). However, its pathophysiology remains unknown, and coagulation profiles have yet to be described. OBJECTIVE The aim of this study was to longitudinally assess coagulation status after LT. METHODS We performed a prospective study and described the coagulation profiles of 48 patients at 5 different time-points: before LT and at 24-72 h, 2 weeks, 4 months, and 1 year after LT. RESULTS At baseline, almost all analyzed coagulation factors were within the normal range, except for FVIII, which was above the normal range. Von Willebrand factor (vWF) and FVIII were increased after LT and remained high at 1 year after transplantation. The cumulative incidence of VTE was 22.9%. Patients who developed VTE had higher FVIII activity 2 weeks after LT. CONCLUSIONS This is the first study to describe coagulation profiles up to 1 year after LT. We show that most markers of a procoagulant state normalize at 2 weeks after LT, but that values of FVIII and vWF remain abnormal at 1 year. This problem has received little attention in the literature. Larger studies are necessary to confirm the results and to design appropriate prophylactic strategies.
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11
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Luppi F, Kalluri M, Faverio P, Kreuter M, Ferrara G. Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management. Respir Res 2021; 22:109. [PMID: 33865386 PMCID: PMC8052779 DOI: 10.1186/s12931-021-01711-1] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 04/11/2021] [Indexed: 02/07/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with an estimated median survival time of 3–5 years after diagnosis. This condition occurs primarily in elderly subjects, and epidemiological studies suggest that the main risk factors, ageing and exposure to cigarette smoke, are associated with both pulmonary and extrapulmonary comorbidities (defined as the occurrence of two or more disorders in a single individual). Ageing and senescence, through interactions with environmental factors, may contribute to the pathogenesis of IPF by various mechanisms, causing lung epithelium damage and increasing the resistance of myofibroblasts to apoptosis, eventually resulting in extracellular matrix accumulation and pulmonary fibrosis. As a paradigm, syndromes featuring short telomeres represent archetypal premature ageing syndromes and are often associated with pulmonary fibrosis. The pathophysiological features induced by ageing and senescence in patients with IPF may translate to pulmonary and extrapulmonary features, including emphysema, pulmonary hypertension, lung cancer, coronary artery disease, gastro-oesophageal reflux, diabetes mellitus and many other chronic diseases, which may lead to substantial negative consequences in terms of various outcome parameters in IPF. Therefore, the careful diagnosis and treatment of comorbidities may represent an outstanding chance to improve quality of life and survival, and it is necessary to contemplate all possible management options for IPF, including early identification and treatment of comorbidities.
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Affiliation(s)
- Fabrizio Luppi
- Respiratory Unit, University of Milano Bicocca, S. Gerardo Hospital, ASST Monza, Monza, Italy
| | - Meena Kalluri
- Division of Pulmonary Medicine, Department of Medicine, University of Alberta, 3-134 Clinical Sciences Building, 11304 83 Ave., Edmonton, AB, T6G 2G3, Canada
| | - Paola Faverio
- Respiratory Unit, University of Milano Bicocca, S. Gerardo Hospital, ASST Monza, Monza, Italy
| | - Michael Kreuter
- Centre for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, University of Heidelberg, German Center for Lung Research, ThoraxklinikHeidelberg, Germany
| | - Giovanni Ferrara
- Sensory Motor Adaptive Rehabilitation Technology (SMART) Network, University of Alberta, Edmonton, AB, Canada. .,Division of Pulmonary Medicine, Department of Medicine, University of Alberta, 3-134 Clinical Sciences Building, 11304 83 Ave., Edmonton, AB, T6G 2G3, Canada.
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12
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Ribeiro Neto ML, Budev M, Culver DA, Lane CR, Gomes M, Wang XF, Rocha PN, Olman MA. Venous Thromboembolism After Adult Lung Transplantation: A Frequent Event Associated With Lower Survival. Transplantation 2018; 102:681-687. [PMID: 29019812 DOI: 10.1097/tp.0000000000001977] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The incidence of venous thromboembolism (VTE) after lung transplantation (LTX) varies significantly across studies. Two studies have suggested that these thrombotic events are associated with a lower posttransplant survival. Herein, we sought to determine the incidence, predictors, and impact of VTE on survival after LTX at a quaternary referral center. METHODS This was a large cohort study of LTX recipients. Key outcome parameters were time to VTE after transplant and survival. Deep vein thrombosis (DVT) diagnosis required a positive ultrasound. Pulmonary embolism diagnosis required either a positive chest computed tomography angiogram or a high-probability ventilation/perfusion scan. RESULTS The overall incidence of VTE among 701 LTX recipients was 43.8%, of which 97.7% were DVT episodes, of which 71.3% were in the upper extremities. Predictors of VTE were prior history of DVT (hazard ratio [HR], 2.82; 95% confidence interval [CI], 1.49-5.37), days in intensive care (HR, 1.01; 95% CI, 1.01-1.02), and the use of extracorporeal membrane oxygenation (HR, 2.22; 95% CI, 1.43-3.45). Importantly, VTE predicted a lower posttransplant survival (HR, 1.70; 95% CI, 1.28-2.26), when occurring within or after the first 30 days. The location of the DVT, either upper extremity or below the knee, also predicted a poor survival. CONCLUSIONS VTE was frequent in LTX recipients and predicted a poor survival even when located in the upper extremities or below the knee. These data suggest that aggressive VTE screening/treatment protocols be implemented in post-LTX population.
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Affiliation(s)
- Manuel L Ribeiro Neto
- Respiratory Institute, Cleveland Clinic, Cleveland, OH.,Health Sciences Postgraduate Program, Federal University of Bahia, Ondina, Salvador, Bahia, Brazil
| | - Marie Budev
- Respiratory Institute, Cleveland Clinic, Cleveland, OH
| | - Daniel A Culver
- Respiratory Institute, Cleveland Clinic, Cleveland, OH.,Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | | | - Marcelo Gomes
- Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH
| | - Xiao-Feng Wang
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Paulo Novis Rocha
- Health Sciences Postgraduate Program, Federal University of Bahia, Ondina, Salvador, Bahia, Brazil
| | - Mitchell A Olman
- Respiratory Institute, Cleveland Clinic, Cleveland, OH.,Lerner Research Institute, Cleveland Clinic, Cleveland, OH
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Pinho DF, Banga A, Torres F, Mathews D. Ventilation perfusion pulmonary scintigraphy in the evaluation of pre-and post-lung transplant patients. Transplant Rev (Orlando) 2018; 33:107-114. [PMID: 30415913 DOI: 10.1016/j.trre.2018.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/04/2018] [Accepted: 10/20/2018] [Indexed: 12/18/2022]
Abstract
Lung transplantation is an established treatment for patients with a variety of advanced lung diseases. Imaging studies play a valuable role not only in evaluation of patients prior to lung transplantation, but also in the follow up of patients after transplantation for detection of complications. After lung transplantation, complications can occur as a result of surgical procedure, pulmonary embolism and ultimately chronic lung allograft dysfunction. Lung scintigraphy, which includes physiologic assessment of lung ventilation and perfusion by imaging, has become an important procedure in the evaluation of these patients, assuming a complementary role to high resolution anatomic imaging (computed tomography [CT]), as well as spirometry. The purpose of this atlas article is to demonstrate the uses of ventilation perfusion scintigraphy in the pre-transplantation setting for surgical planning and in the evaluation of complications post-lung transplantation based upon experience at our institution.
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Affiliation(s)
- Daniella F Pinho
- Department of Radiology, The University of Texas Southwestern Medical Center, United States.
| | - Amit Banga
- Lung Transplant Program, Division of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Texas Southwestern Medical Center, United States
| | - Fernando Torres
- Lung Transplant Program, Division of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Texas Southwestern Medical Center, United States
| | - Dana Mathews
- Department of Radiology, The University of Texas Southwestern Medical Center, United States
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14
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Lichvar AB, Moore CA, Ensor CR, McDyer JF, Teuteberg JJ, Shullo MA. Evaluation of Direct Oral Anticoagulation Therapy in Heart and Lung Transplant Recipients. Prog Transplant 2018; 26:263-9. [PMID: 27597772 DOI: 10.1177/1526924816661951] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
CONTEXT Anticoagulation therapy is common in thoracic transplant recipients. Direct oral anticoagulants (DOACs) are alternatives to warfarin therapy, but characterization of their use in solid organ transplant is absent. OBJECTIVE The primary objective of this study was to describe a thoracic transplant patient population initiated on DOAC therapy. Secondary objectives were to assess adverse reactions, venous thromboembolism (VTE) recurrence, and drug-drug interactions during DOAC therapy. STUDY DESIGN Single-center retrospective cohort study. SETTING A tertiary care medical center including inpatient hospitalization and outpatient transplant clinic visits. PATIENTS Thoracic transplant recipients who were initiated on DOACs between May 1, 2011, and March 1, 2015, at the University of Pittsburgh Medical Center were included. RESULTS A total of 37 patients were included in the analysis. A majority of the patients were lung transplant recipients (86.4%) with a median age of 60.7 years. Twenty-eight patients had a history of VTE. The primary indication for DOAC initiation was VTE (86.5%). Rivaroxaban (78.4%) was the most commonly utilized agent. Dose reductions for major drug interactions (37.8%), renal insufficiency (10.8%), or both (8.1%) occurred within the study. Two patients had breakthrough VTE during DOAC therapy. Eight bleeding events were reported in the cohort, one of which was considered a major bleed. There was no difference in the incidence of bleeding in patients with drug-drug interactions and without drug-drug interactions during DOAC therapy (26.0% vs 7.1%, P = .154). CONCLUSION Direct oral anticoagulant therapy was well tolerated by thoracic transplant recipients. Drug interactions and renal dose adjustments were common.
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Affiliation(s)
- Alicia B Lichvar
- Division of Transplantation, Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Cody A Moore
- University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA
| | - Christopher R Ensor
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - John F McDyer
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Jeffrey J Teuteberg
- School of Medicine, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Michael A Shullo
- School of Pharmacy, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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15
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Spagnolo P, Tzouvelekis A, Bonella F. The Management of Patients With Idiopathic Pulmonary Fibrosis. Front Med (Lausanne) 2018; 5:148. [PMID: 30013972 PMCID: PMC6036121 DOI: 10.3389/fmed.2018.00148] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 04/30/2018] [Indexed: 12/14/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF), the most common form of fibrosing idiopathic interstitial pneumonia, is an inexorably progressive disease with a 5-year survival of ~20%. In the last decade, our understanding of disease pathobiology has increased significantly and this has inevitably impacted on the approach to treatment. Indeed, the paradigm shift from a chronic inflammatory disorder to a primarily fibrotic one coupled with a more precise disease definition and redefined diagnostic criteria have resulted in a massive increase in the number of clinical trials evaluating novel candidate drugs. Most of these trials, however, have been negative, probably because of the multitude and redundancy of cell types, growth factors and profibrotic pathways involved in disease pathogenesis. As a consequence, until recently IPF has lacked effective therapies. Finally, in 2014, two large phase 3 clinical trials have provided robust evidence that pirfenidone, a compound with anti-fibrotic, anti-oxidant and anti-inflammatory properties, and nintedanib, a tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor receptors are able to slow down functional decline and disease progression with an acceptable safety profile. While this is a major achievement, neither pirfenidone nor nintedanib cures IPF and most patients continue to experience disease progression and/or exacerbation despite treatment. Therefore, in recent years increasingly more attention has been paid to preservation of quality of life and, in the advanced phase of the disease, palliation of symptoms. Lung transplantation, the only curative treatment, remains a viable option for only a minority of highly selected patients. The unmet medical need in IPF remains high, and more efficacious and better tolerated drugs are urgently needed. However, a truly effective therapeutic approach should also address quality of life and highly prevalent concomitant conditions and complications of IPF.
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Affiliation(s)
- Paolo Spagnolo
- Respiratory Disease Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
| | - Argyris Tzouvelekis
- Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece
| | - Francesco Bonella
- Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany
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16
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Kumar A, Kapnadak SG, Girgis RE, Raghu G. Lung transplantation in idiopathic pulmonary fibrosis. Expert Rev Respir Med 2018; 12:375-385. [DOI: 10.1080/17476348.2018.1462704] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Anupam Kumar
- Division of Pulmonary & Critical Care Medicine, Richard DeVos Heart & Lung Transplant Program, Spectrum Health-Michigan State University College of Human Medicine, Grand Rapids, MI, USA
| | - Siddhartha G. Kapnadak
- Division of Pulmonary and Critical Care Medicine, University of Washington Medical Center, Seattle, WA, USA
| | - Reda E. Girgis
- Medical Director, Lung Transplantation and Pulmonary Hypertension, Richard DeVos Heart & Lung Transplant Program, Spectrum Health- Michigan State University College of Human Medicine, Grand Rapids, MI, USA
| | - Ganesh Raghu
- Center for Interstitial Lung Diseases, Division of Pulmonary & Critical Care Medicine, University of Washington Medical Center, Seattle, WA, USA
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17
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Aboagye JK, Hayanga JW, Lau BD, Bush EL, Shaffer DL, Hobson DB, Kraus PS, Streiff MB, Haut ER, D’Cunha J. Venous Thromboembolism in Patients Hospitalized for Lung Transplantation. Ann Thorac Surg 2018; 105:1071-1076. [DOI: 10.1016/j.athoracsur.2017.10.041] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 09/05/2017] [Accepted: 10/11/2017] [Indexed: 12/01/2022]
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18
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Sáez-Giménez B, Berastegui C, Sintes H, Perez-Miranda J, Figueredo A, López Meseguer M, Monforte V, Bravo C, Santamaría A, Ramon MA, Gómez-Ollés S, Roman A. Prophylaxis with enoxaparin for prevention of venous thromboembolism after lung transplantation: a retrospective study. Transpl Int 2017; 30:1266-1274. [DOI: 10.1111/tri.13021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 04/24/2017] [Accepted: 07/31/2017] [Indexed: 01/25/2023]
Affiliation(s)
- Berta Sáez-Giménez
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Cristina Berastegui
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Helena Sintes
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Javier Perez-Miranda
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Ana Figueredo
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Manuel López Meseguer
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Víctor Monforte
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); Instituto de Salud Carlos III; Madrid Spain
| | - Carlos Bravo
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); Instituto de Salud Carlos III; Madrid Spain
| | - Amparo Santamaría
- Hemostasis and Thrombosis Unit; Department of Hematology; Hospital Universitari Vall d'Hebrón; Barcelona Spain
| | - Maria Antonia Ramon
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); Instituto de Salud Carlos III; Madrid Spain
| | - Susana Gómez-Ollés
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); Instituto de Salud Carlos III; Madrid Spain
| | - Antonio Roman
- Pulmonology Service, Lung Transplant Program; Hospital Universitari Vall d'Hebrón; Universitat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); Instituto de Salud Carlos III; Madrid Spain
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19
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Kristensen AW, Mortensen J, Berg RMG. Pulmonary thromboembolism as a complication of lung transplantation. Clin Transplant 2017; 31. [DOI: 10.1111/ctr.12922] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2017] [Indexed: 11/30/2022]
Affiliation(s)
- Anna Warncke Kristensen
- Department of Clinical Physiology, Nuclear Medicine & PET; University Hospital Rigshospitalet; Copenhagen Denmark
| | - Jann Mortensen
- Department of Clinical Physiology, Nuclear Medicine & PET; University Hospital Rigshospitalet; Copenhagen Denmark
| | - Ronan M. G. Berg
- Department of Clinical Physiology and Nuclear Medicine; Bispebjerg and Frederiksberg Hospitals; Copenhagen Denmark
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20
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Shlobin OA, Brown AW, Nathan SD. Pulmonary Hypertension in Diffuse Parenchymal Lung Diseases. Chest 2016; 151:204-214. [PMID: 27554299 DOI: 10.1016/j.chest.2016.08.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 07/29/2016] [Accepted: 08/05/2016] [Indexed: 10/21/2022] Open
Abstract
Pulmonary hypertension (PH) can be triggered by any number of disease processes that result in increased pulmonary vascular resistance. Although historically associated with idiopathic pulmonary arterial hypertension (PAH), most patients with PH do not have the idiopathic subtype, but rather PH associated with another underlying diagnosis, such as left heart or lung disease. The World Health Organization (WHO) classification of PH helps conceptualize the different categories based on presumed etiology. WHO group 3 is PH associated with lung disease. This review focuses on PH in diffuse parenchymal lung diseases (DPLDs), such as the idiopathic interstitial pneumonias and other more rare forms of DPLD. Although there are clear associations of PH with DPLD, the exact pathophysiologic mechanisms and full clinical significance remain uncertain. Treatment of PH related to DPLD remains investigational, but an area of great interest given the negative prognostic implications and the growing number of available pulmonary vasoactive agents.
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Affiliation(s)
- Oksana A Shlobin
- Advanced Lung Disease and Transplant Program, Inova Heart and Vascular Institute, Inova Fairfax Hospital, Falls Church, VA.
| | - A Whitney Brown
- Advanced Lung Disease and Transplant Program, Inova Heart and Vascular Institute, Inova Fairfax Hospital, Falls Church, VA
| | - Steven D Nathan
- Advanced Lung Disease and Transplant Program, Inova Heart and Vascular Institute, Inova Fairfax Hospital, Falls Church, VA
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21
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Barry AE, Chaney MA, Cartwright BL, Birch ML, Wall MH. CASE 3--2016: Cardiopulmonary Instability Following Single-Lung Transplant. J Cardiothorac Vasc Anesth 2015; 30:539-47. [PMID: 26748977 DOI: 10.1053/j.jvca.2014.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Indexed: 11/11/2022]
Affiliation(s)
- Aaron E Barry
- Departments of Anesthesia and Critical Care, University of Chicago, Chicago, IL
| | - Mark A Chaney
- Departments of Anesthesia and Critical Care, University of Chicago, Chicago, IL.
| | | | - Martin L Birch
- Anesthesiology, University of Minnesota, Minneapolis, MN
| | - Michael H Wall
- Anesthesiology, University of Minnesota, Minneapolis, MN
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22
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Brown AW, Kaya H, Nathan SD. Lung transplantation in IIP: A review. Respirology 2015; 21:1173-84. [PMID: 26635297 DOI: 10.1111/resp.12691] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Revised: 08/10/2015] [Accepted: 10/24/2015] [Indexed: 12/15/2022]
Abstract
The idiopathic interstitial pneumonias (IIP) encompass a large and diverse subtype of interstitial lung disease (ILD) with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) being the most common types. Although pharmacologic treatments are available for most types of IIP, many patients progress to advanced lung disease and require lung transplantation. Close monitoring with serial functional and radiographic tests for disease progression coupled with early referral for lung transplantation are of great importance in the management of patients with IIP. Both single and bilateral lung transplantation are acceptable procedures for IIP. Procedure selection is a complex decision influenced by multiple factors related to patient, donor and transplant centre. While single lung transplant may reduce waitlist time and mortality, the long-term outcomes after bilateral lung transplantation may be slightly superior. There are numerous complications following lung transplantation including primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, gastroesophageal reflux disease (GERD) and airway disease that limit post-transplant longevity. The median survival after lung transplantation is 4.7 years in patients with ILD, which is less than in patients with other underlying lung diseases. Although long-term survival is limited, this intervention still conveys a survival benefit and improved quality of life in suitable IIP patients with advanced lung disease and chronic hypoxemic respiratory failure.
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Affiliation(s)
- A Whitney Brown
- Advanced Lung Disease and Transplant Program, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Hatice Kaya
- Pulmonary Critical Care and Sleep Division, George Washington University, Washington, District of Columbia, USA
| | - Steven D Nathan
- Advanced Lung Disease and Transplant Program, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA.
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23
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Evans CF, Iacono AT, Sanchez PG, Goloubeva O, Kim J, Timofte I, Cheema FH, Pham SM, Griffith BP, Rajagopal K. Venous Thromboembolic Complications of Lung Transplantation: A Contemporary Single-Institution Review. Ann Thorac Surg 2015; 100:2033-9; discussion 2039-40. [DOI: 10.1016/j.athoracsur.2015.05.095] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 05/10/2015] [Accepted: 05/15/2015] [Indexed: 10/23/2022]
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24
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Farghaly S, El-Abdin AZ. Pulmonary fibrosis as a risk factor for thromboembolic disease. THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2015. [DOI: 10.4103/1687-8426.158056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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25
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Deep vein thrombosis and pulmonary embolism after solid organ transplantation: an unresolved problem. Transplant Rev (Orlando) 2015; 29:85-92. [DOI: 10.1016/j.trre.2014.12.005] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Revised: 12/11/2014] [Accepted: 12/12/2014] [Indexed: 01/15/2023]
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26
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Kistler KD, Nalysnyk L, Rotella P, Esser D. Lung transplantation in idiopathic pulmonary fibrosis: a systematic review of the literature. BMC Pulm Med 2014; 14:139. [PMID: 25127540 PMCID: PMC4151866 DOI: 10.1186/1471-2466-14-139] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 07/29/2014] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a distinct form of interstitial pneumonia with unknown origin and poor prognosis. Current pharmacologic treatments are limited and lung transplantation is a viable option for appropriate patients. The aim of this review was to summarize lung transplantation survival in IPF patients overall, between single (SLT) vs. bilateral lung transplantation (BLT), pre- and post Lung Allocation Score (LAS), and summarize wait-list survival. METHODS A systematic review of English-language studies published in Medline or Embase between 1990 and 2013 was performed. Eligible studies were those of observational design reporting survival post-lung transplantation or while on the wait list among IPF patients. RESULTS Median survival post-transplantation among IPF patients is estimated at 4.5 years. From ISHLT and OPTN data, one year survival ranged from 75% - 81%; 3-year: 59% - 64%; and 5-year: 47% - 53%. Post-transplant survival is lower for IPF vs. other underlying pre-transplant diagnoses. The proportion of IPF patients receiving BLT has steadily increased over the last decade and a half. Unadjusted analyses suggest improved long-term survival for BLT vs. SLT; after adjustment for patient characteristics, the differences tend to disappear. IPF patients account for the largest proportion of patients on the wait list and while wait list time has decreased, the number of transplants for IPF patients has increased over time. OPTN data show that wait list mortality is higher for IPF patients vs. other diagnoses. The proportion of IPF patients who died while awaiting transplantation ranged from 14% to 67%. While later transplant year was associated with increased survival, no significant differences were noted pre vs. post LAS implementation; however a high LAS vs low LAS was associated with decreased one-year survival. CONCLUSIONS IPF accounts for the largest proportion of patients awaiting lung transplants, and IPF is associated with higher wait-list and post-transplant mortality vs. other diagnoses. Improved BLT vs. SLT survival may be the result of selection bias. Survival pre- vs. post LAS appears to be similar except for IPF patients with high LAS, who have lower survival compared to pre-LAS. Data on post-transplant morbidity outcomes are sparse.
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27
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Telich-Tarriba JE, Anaya-Ayala JE, Davies MG, El-Sayed HF. Percutaneous mechanical thrombectomy for extensive acute lower-extremity deep venous thrombosis in a patient after double-lung transplantation. Ann Vasc Surg 2012; 26:573.e1-4. [PMID: 22321479 DOI: 10.1016/j.avsg.2011.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2011] [Revised: 09/22/2011] [Accepted: 10/06/2011] [Indexed: 10/14/2022]
Abstract
Venous thromboembolism, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), has been estimated to affect 25% of patients after major surgery; however, the literature on venous thromboembolism after thoracic transplantation and optimal approach remains limited. We report the status of a 67-year-old female who developed massive right lower-extremity DVT after double-lung transplantation. Because her surgery had taken place a week before this event, it was decided that pharmaco-thrombolysis was contraindicated due to the high risk of bleeding complications in a fresh double-lung transplant recipient. The patient was taken emergently to the operating room for percutaneous mechanical thrombectomy, which provided grade III (complete lysis) and restored venous patency in the affected extremity. This report highlights the successful use of purely percutaneous mechanical thrombectomy for acute DVT in a double-lung recipient, and also advocates inferior vena cava filter placement to prevent embolic events during the mechanical thrombectomy.
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Affiliation(s)
- Jose E Telich-Tarriba
- Department of Cardiovascular Surgery, Methodist DeBakey Heart and Vascular Center, The Methodist Hospital Research Institute, Houston, TX 77030, USA
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28
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Shlobin OA, Nathan SD. Pulmonary hypertension secondary to interstitial lung disease. Expert Rev Respir Med 2011; 5:179-89. [PMID: 21510729 DOI: 10.1586/ers.11.11] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Interstitial lung diseases (ILDs) may be complicated by the development of pulmonary hypertension (PH), which is associated with worse functional impairment and a poorer prognosis. This article reviews the current state of knowledge on the prevalence, pathogenesis, diagnosis and prognosis of ILD-related PH. Whether the treatment of ILD-related PH changes clinical outcomes is currently unknown, but the current studies are summarized and the authors' perspective is offered.
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Affiliation(s)
- Oksana A Shlobin
- Advanced Lung Disease and Transplant Program, Inova Heart and Vascular Institute, Falls Church, VA 22042, USA
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29
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Lloyd CR, Walsh SLF, Hansell DM. High-resolution CT of complications of idiopathic fibrotic lung disease. Br J Radiol 2011; 84:581-92. [PMID: 21697412 PMCID: PMC3473493 DOI: 10.1259/bjr/65090500] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) has a more variable clinical course than has been traditionally recognised. Many patients will remain stable over time while others experience relatively rapid deterioration. The prognosis and clinical course of patients with other fibrosing lung diseases is also variable. A number of conditions may complicate the clinical course of the idiopathic fibrosing lung diseases, which results in morbidity and mortality, but also represents potentially treatable causes of worsening symptoms. Infection and malignancy have a long-recognised association with IPF while other conditions, particularly pulmonary hypertension and acute exacerbation of IPF, are being increasingly recognised in this patient population. Many of these patients have serial high-resolution CT (HRCT) examinations that may demonstrate one or more of these supervening conditions. In this article we review the more common conditions that may complicate the course of idiopathic fibrosing lung disease with an emphasis on the HRCT appearance, which the reporting radiologist should be aware of.
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Affiliation(s)
- C R Lloyd
- Department of Radiology, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
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Miwa S, Shirai M, Kobayashi S, Kaida Y, Suda T, Hayakawa H, Chida K. Chronic pulmonary thromboembolism pathologically showing homogeneous cellular alveolitis. Intern Med 2011; 50:2195-200. [PMID: 21963740 DOI: 10.2169/internalmedicine.50.5410] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 60-year-old man was admitted to our hospital complaining of general malaise. Examination of arterial blood gases on room air revealed hypoxia. Pulmonary function test showed restrictive abnormality. Chest high-resolution CT showed diffuse mosaic attenuation without evident pulmonary artery abnormality on contrast chest CT. Based on these findings, interstitial pneumonia or chronic pulmonary thromboembolism was suspected. The findings of bronchoalveolar lavage revealed 4.4×10(5) cells/mL, including 89.6% macrophages, 9.4% lymphocytes, and 1.0% neutrophils. TBLB showed marked alveolitis. Moreover video-assisted thoracoscopic surgical biopsy was performed. Biopsies of the lung specimen showed focal infarct with surrounding mild mononuclear cell infiltrates (homogenous cellular alveolitis). (99m)Tc pulmonary perfusion and (81m)Kr ventilation scintigraphy showed V/Q mismatch. Furthermore, pulmonary angiography also revealed inadequate artery flow corresponding to the mismatch area of scintigraphy. Collagen vascular diseases and abnormality of coagulation factors were not detected. Multiple perfusion defects persisted for more than 6 months. Thus, finally the patient was diagnosed with chronic pulmonary thromboembolism, pathologically showing homogenous cellular alveolitis.
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Affiliation(s)
- Seiichi Miwa
- Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Japan.
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Singer JP, Huang MY, Hui C, Blanc PD, Boettger RF, Golden J, Watkins K, Hoopes C, Leard LE. Supratherapeutic anticoagulation from low-molecular-weight heparin in lung transplant recipients. J Heart Lung Transplant 2010; 29:1009-13. [PMID: 20627627 PMCID: PMC3045833 DOI: 10.1016/j.healun.2010.04.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2010] [Revised: 04/15/2010] [Accepted: 04/16/2010] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Venous thromboembolism (VTE) is common after lung transplantation. Enoxaparin is an approved therapy for VTE and anti-factor Xa level can be used to monitor enoxaparin activity. Some studies have demonstrated elevated anti-factor Xa levels are associated with an increased risk of hemorrhage. Having identified a high incidence of supratherapeutic anti-factor Xa levels in lung transplant recipients, we aimed to elucidate the relationship between enoxaparin dose and anti-factor Xa level in this patient population. METHODS We identified post-lung transplantation patients with VTE receiving therapeutic enoxaparin who had anti-factor Xa level measured. Standard enoxaparin dosing was defined as 0.9 to 1.1 mg/kg. After identifying a high incidence of supratherapeutic anti-factor Xa levels, we implemented "non-standard" dosing of 0.8 mg/kg. Multivariate linear regression analysis was used to examine the association between enoxaparin dose and anti-factor Xa level; age, body mass index (BMI) and creatinine clearance were included as covariates. RESULTS In the cohort, 18 patients received standard and 8 patients received non-standard enoxaparin dosing. Twelve of 18 patients (67%; 95% confidence interval [CI]: 43% to 91%) receiving standard dosing had supratherapeutic anti-factor Xa levels vs 0 of 8 patients (0%; 95% CI: 0% to 37%) receiving lower non-standard dosing (p = 0.002). Anti-factor Xa levels were significantly different between the two groups; the mean anti-factor Xa level was 1.3 IU/ml (95% CI: 1.06 to 1.53) in the standard group vs 0.79 IU/ml (95% CI: 0.67 to 0.91) in the non-standard group (p = 0.008). After controlling for covariates, for each 0.1-mg/kg increase in enoxaparin, the mean anti-factor Xa level increased by 0.18 IU/ml (95% CI: 0.05 to 0.31; p = 0.011; model r(2) = 0.53). CONCLUSIONS Standard dosing of enoxaparin in lung transplant recipients is associated with a high incidence of supratherapeutic anti-Xa levels. Further study will be required to correlate this finding with risk of hemorrhage.
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Affiliation(s)
- Jonathan P Singer
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
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Hennessy SA, Grogan EL, Harthun NL, Jones DR, Kozower BD, Ailawadi G, Lau CL. Transplant Pneumonectomy in a Patient With an Acutely Thrombosed Allograft. Ann Thorac Surg 2010; 89:975-7. [DOI: 10.1016/j.athoracsur.2009.07.085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2009] [Revised: 07/22/2009] [Accepted: 07/23/2009] [Indexed: 11/25/2022]
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Dumonceaux M, Knoop C, Rondelet B, Estenne M. Complications de la transplantation pulmonaire : complications péri-opératoires, rejet aigu et chronique. Rev Mal Respir 2009; 26:639-53. [DOI: 10.1016/s0761-8425(09)74694-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
Lung disease in advanced stages is often accompanied by multiple comorbidities. Often, these processes lead to significant morbidity and occasionally mortality. Symptoms of pulmonary comorbidities, including pulmonary embolus, pulmonary hypertension, sleep-disordered breathing, and lung malignancy, may be intertwined with symptoms of advancing lung disease. However, the occurrence of extrapulmonary processes, including depression, diabetes mellitus, osteoporosis, and gastroesophageal reflux disease, may be subtle. Clinicians caring for advanced lung disease should be aware of the many comorbid processes that may accompany advancing lung disease.
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Affiliation(s)
- Joel Anthony Nations
- Pulmonary and Critical Care Medicine, National Naval Medicine Center, Bethesda, MD, USA.
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Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The Association between Idiopathic Pulmonary Fibrosis and Vascular Disease. Am J Respir Crit Care Med 2008; 178:1257-61. [DOI: 10.1164/rccm.200805-725oc] [Citation(s) in RCA: 172] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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Nathan SD, Shlobin OA, Ahmad S, Barnett SD, Burton NA, Gladwin MT, Machado RF. Pulmonary hypertension in patients with bronchiolitis obliterans syndrome listed for retransplantation. Am J Transplant 2008; 8:1506-11. [PMID: 18510629 DOI: 10.1111/j.1600-6143.2008.02277.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Bronchiolitis Obliterans Syndrome (BOS) is a major cause of morbidity and mortality post-lung transplantation. Pulmonary hypertension (PH) may complicate the course of patients with advanced lung disease. We sought to characterize the prevalence of PH in patients with BOS. We performed a retrospective analysis of lung transplant recipients with BOS relisted for transplantation with the United Network for Organ Sharing (UNOS). Right heart catheterization (RHC) data were required for analysis. Eighty patients with BOS qualified for the analysis. PH was present in 32.5% of patients with an average mean pulmonary artery pressure (mPAP) of 32.3 mmHg (range: 26-63 mmHg). Of these, 42.3% had an elevated pulmonary capillary wedge pressure. There was no difference in PH prevalence between bilateral (26.5%) and single lung recipients (41.9%), nor did it differ by primary disease. There was no correlation between pulmonary function data and the presence or severity of PH. There was no difference in oxygen requirements or 6-min walk distance between patients with and without PH. This is the first report of PH in patients with BOS. Many of these cases occur in association with diastolic dysfunction. Although no impact on functional status or outcomes was discerned, further studies appear warranted.
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Affiliation(s)
- S D Nathan
- Inova Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA.
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Bobadilla JL, Love RB, Jankowska-Gan E, Xu Q, Haynes LD, Braun RK, Hayney MS, Munoz del Rio A, Meyer K, Greenspan DS, Torrealba J, Heidler KM, Cummings OW, Iwata T, Brand D, Presson R, Burlingham WJ, Wilkes DS. Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am J Respir Crit Care Med 2008; 177:660-8. [PMID: 18174545 DOI: 10.1164/rccm.200612-1901oc] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE The pathogenesis of primary graft dysfunction (PGD), a serious complication of lung transplantation, is poorly understood. Human studies and rodent models have shown that collagen type V (col[V]), stimulates IL-17-dependent cellular immunity after lung transplantation. OBJECTIVES To determine whether patients with end-stage lung disease develop pretransplant col(V)-specific cellular immunity, and if so, the impact of this response on PGD. METHODS Trans-vivo delayed-type hypersensitivity (TV-DTH) assays were used to evaluate memory T-cell responses to col(V) in 55 patients awaiting lung transplantation. Pa(O(2))/Fi(O(2)) index data were used to assess PGD. Univariate risk factor analysis was performed to identify variables associated with PGD. Rats immunized with col(V) or irrelevant antigen underwent lung isografting to determine if prior anti-col(V) immunity triggers PGD in the absence of alloreactivity. MEASUREMENTS AND MAIN RESULTS We found that 58.8% (10/17) of patients with idiopathic pulmonary fibrosis, and 15.8% (6/38) of patients without idiopathic pulmonary fibrosis tested while on the wait list for a lung transplant were col(V) DTH positive. Col(V) reactivity was CD4(+) T-cell and monocyte mediated, and dependent on IL-17, IL-1beta, and tumor necrosis factor (TNF)-alpha. Pa(O(2))/Fi(O(2)) indices were impaired significantly 6-72 hours after transplantation in col(V)-reactive versus nonreactive patients. Univariate risk factor analysis identified only preoperative TV-DTH to col(V) and ischemic time as predictors of PGD. Finally, in a rat lung isograft model, col(V) sensitization resulted in significantly lower Pa(O(2))/Fi(O(2)), increased local TNF-alpha and IL-1beta production, and a moderate-to-severe bronchiolitis/vasculitis when compared with control isografts. CONCLUSIONS The data suggest that activation of innate immunity by col(V)-specific Th-17 memory cells represents a novel pathway to PGD after lung transplantation.
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Affiliation(s)
- Joseph L Bobadilla
- Microbiology and Immunology, Director, Center for Immunobiology, Indiana University School of Medicine, Van Nuys Medical Sciences Building MS224, 635 Barnhill Drive, Indianapolis, IN 46202-5120, USA
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Yegen HA, Lederer DJ, Barr RG, Wilt JS, Fang Y, Bagiella E, D'Ovidio F, Okun JM, Sonett JR, Arcasoy SM, Kawut SM. Risk Factors for Venous Thromboembolism After Lung Transplantation. Chest 2007; 132:547-53. [PMID: 17573512 DOI: 10.1378/chest.07-0035] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND The risk factors for venous thromboembolism (VTE) following lung transplantation are not well established. We aimed to estimate the incidence of VTE and to identify the risk factors for VTE after lung transplantation. METHODS We performed a nested case-control study within the cohort of 121 patients who underwent lung transplantation at our center between August 2001 and July 2005. Control subjects were matched to case patients on the number of days from the time of transplant. Cox proportional hazards models were used to identify risk factors for VTE. RESULTS Twenty-four patients had deep vein thromboses, and 6 patients had pulmonary emboli (3 patients had both) [22% of the cohort]. In multivariate models, older age (p < 0.05), diabetes mellitus (p = 0.03), and pneumonia (p = 0.02) were associated with a higher rate of VTE. CONCLUSIONS VTE is a frequent complication of lung transplantation. Older age, diabetes, and pneumonia increase the rate of VTE. Future studies of intensive VTE prophylaxis may be warranted.
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Affiliation(s)
- Hilary A Yegen
- Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
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Kahan ES, Petersen G, Gaughan JP, Criner GJ. High Incidence of Venous Thromboembolic Events in Lung Transplant Recipients. J Heart Lung Transplant 2007; 26:339-44. [PMID: 17403474 DOI: 10.1016/j.healun.2007.01.009] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2006] [Revised: 12/20/2006] [Accepted: 01/07/2007] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Previous studies have reported a 12% incidence of venous thromboembolic events (VTEs) in lung transplant recipients (LTRs). Characterization of risk factors for VTEs in LTRs is lacking. We identified the incidence and risk factors associated with post-transplant VTEs. METHODS A retrospective review of 153 LTRs from 1994 to 2006 was performed. Patients were categorized by age, race, gender, weight, underlying diagnosis, procedure, ischemic time, length of stay (LOS), cardiopulmonary bypass (CPB), location and number of VTEs, mobility, immunosuppression, renal, hepatic, hematologic and coagulation profiles and nutritional status. RESULTS A single VTE occurred in 29% of LTRs within the study period. Fifty-eight percent had multiple VTEs and 7% had a radiologically confirmed pulmonary embolism. Median time from transplant to first VTE was 69 days. Sixty percent of VTEs occurred within 1 year, 20% of which occurred within the first month, 19% between 2 and 5 years, and 13% at beyond 5 years post-transplant. Seventy-six percent of VTEs occurred during hospitalization, 19% during outpatient status. Forty-eight percent were of the upper extremity and 47% were of the lower extremity. Sixty-one percent of LTRs were taking cyclosporine and 39% tacrolimus. VTE and non-VTE groups were similar in age, weight, body mass index (BMI), ischemic time, procedure or underlying diagnosis precipitating the need for transplant. Univariate analysis revealed LOS and CPB as significant predictors of a single VTE (p = 0.036, hazard ratio [HR] 1.006 and p = 0.045, HR 1.91, respectively). Multivariate analysis revealed only CPB as a significant predictor (p = 0.047, HR 1.929). CONCLUSIONS Analysis of a cohort of LTRs for a median period of 1.5 years revealed a VTE incidence much higher than previously reported, especially within the first month after transplantation.
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Affiliation(s)
- Erika S Kahan
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
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Nathan SD, Noble PW, Tuder RM. Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots. Am J Respir Crit Care Med 2007; 175:875-80. [PMID: 17255562 DOI: 10.1164/rccm.200608-1153cc] [Citation(s) in RCA: 152] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and a course that is unpredictable. Pulmonary hypertension may complicate the course of IPF and potentially impact prognosis. There are multiple factors that might influence the onset and severity of pulmonary hypertension in IPF. The relationship between the physiologic and pathobiologic manifestations of the progressive fibrotic process and interceding pulmonary hypertension has not been well defined. This article serves to explore these relationships and to hypothesize about the possible linkage between these entities. From a prognostic standpoint, recent evidence suggests this to be important to assess for pulmonary hypertension in patients with IPF. The appropriate triggers for evaluating for pulmonary hypertension and the best method of detection require further study. Despite the relative ease of noninvasive methods, such as echocardiography, right-heart catheterization remains the best diagnostic test. The appeal of pulmonary hypertension in IPF is that it may be an enticing therapeutic target in a disease that otherwise does not have any proven effective therapies. Which agent(s) might be useful and when they should be implemented mandate the appropriate studies being performed. Some of the data presented in this article have previously been reported in abstract form only.
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Affiliation(s)
- Steven D Nathan
- Medical Director, Advanced Lung Disease and Transplant Program, INOVA Heart & Vascular Institute, INOVA Fairfax Hospital, Falls Church, VA 22042, USA.
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Reed A, Snell GI, McLean C, Williams TJ. Outcomes of patients with interstitial lung disease referred for lung transplant assessment. Intern Med J 2006; 36:423-30. [PMID: 16780448 DOI: 10.1111/j.1445-5994.2006.01103.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Patients with interstitial lung disease (ILD) very frequently die before the opportunity to receive lung transplantation (LTx). This retrospective study describes the clinical course of 86 patients with ILD referred for LTx assessment between January 1999 and December 2002. AIMS (i) To describe the outcomes, (ii) to identify reasons of delay to transplantation, (iii) to describe the causes of death/complications and (iv) to assess the pathological diagnosis and concordance with explanted lung pathology. METHODS Data were collected from the case notes of all patients with ILD referred to the Alfred Hospital over a 4-year period. RESULTS Twenty women and 66 men, mean age of 55 +/- 8 years, were referred for LTx assessment. Forty-five patients were deemed not suitable for LTx and 41 were listed. Twenty-two patients underwent transplantation, 16 died on the waiting list and 7 are still on the waiting list. Complications were frequent (e.g. pulmonary embolism, malignancy and infection) and carried high mortality. Patients dying on the waiting list appeared generally to be in accelerated decline, dying shortly after listing, with no evidence in their lung function test assessment predicting them as a poor prognosis group. CONCLUSIONS Serious complications and death on the waiting list of patients with idiopathic pulmonary fibrosis are high, not apparently because of delayed referral but usually in patients undergoing very rapid decline.
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Affiliation(s)
- A Reed
- Department of Allergy, The Alfred Hospital and Monash University, Melbourne, Victoria, Australia
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Mal H. Que faire des formes graves de pneumopathies infiltrantes diffuses (exacerbations aiguës, insuffisance respiratoire chronique sévère) : place des nouveaux traitements, indications de transplantation. Rev Mal Respir 2006. [DOI: 10.1016/s0761-8425(06)71557-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Magro CM, Waldman WJ, Knight DA, Allen JN, Nadasdy T, Frambach GE, Ross P, Marsh CB. Idiopathic Pulmonary Fibrosis Related to Endothelial Injury and Antiendothelial Cell Antibodies. Hum Immunol 2006; 67:284-97. [PMID: 16720208 DOI: 10.1016/j.humimm.2006.02.026] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2005] [Indexed: 01/10/2023]
Abstract
Mechanisms underlying idiopathic pulmonary fibrosis are not well understood. This paper presents data supporting the hypothesis that microvascular endothelial cell injury and antiendothelial cell antibodies play roles in human idiopathic pulmonary fibrosis. Serologic and pathologic features of 40 patients diagnosed with idiopathic pulmonary fibrosis were evaluated. All patients had open lung biopsies indicating either usual or nonspecific interstitial pneumonitis. All biopsies had morphologic evidence of microvascular injury to the endothelium, and direct immunofluorescence testing revealed variable deposition of IgG, IgM, or IgA within septal microvasculature suggestive of humorally mediated microvascular injury. Ultrastructural studies revealed changes of endothelial cell injury and necrosis and evidence of repetitive episodes of microvascular injury characterized by basement membrane zone collagen deposition and lamellation. Serum samples demonstrated reactivity to multiple endothelial cell antigenic epitopes, and indirect immunofluorescent testing demonstrated a prominent pattern of fluorescence in pulmonary endothelial cell preparations. Serum samples were positive in 37/40 patients for antiphospholipid antibodies with one fourth having positive lupus anticoagulant tests accompanied by thrombotic episodes. In patients with idiopathic pulmonary fibrosis, Factor VIII levels and C-reactive protein levels were also elevated, supporting the presence of endothelial cell injury and inflammation. These data underscore a potential role for immune-based microvascular injury in the evolution of usual or nonspecific interstitial pneumonitis and indicate that those patients have evidence of microvascular injury and endothelial cell necrosis. The high prevalence of antiphospholipid antibodies in these patients may lead to an inherent thrombophilic tendency.
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Affiliation(s)
- Cynthia M Magro
- Department of Pathology, The Ohio State University, Columbus, OH, USA.
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Izbicki G, Bairey O, Shitrit D, Lahav J, Kramer MR. Increased Thromboembolic Events After Lung Transplantation. Chest 2006; 129:412-416. [PMID: 16478860 DOI: 10.1378/chest.129.2.412] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND Lung transplantation is a good therapeutic option for end-stage lung disease. Data on thromboembolic complications following lung transplantation are scarce. STUDY OBJECTIVES To evaluate the incidence of thromboembolic events following lung transplantation, and to determine their possible association with hypercoagulable state. DESIGN Retrospective study in a single, tertiary-care, university-affiliated referral center. SUBJECTS AND METHOD The records of 70 patients who underwent lung transplantation in our institution between September 1997 and September 2003 were reviewed for thromboembolic complications. Parameters pertaining to risk of thrombophilia were measured in the patients with thromboembolic complications. RESULTS Thromboembolic complications developed in 6 of the 70 patients (8.6%) at 4 to 24 months after transplantation: deep vein thrombosis (DVT) in 2 patients, pulmonary embolism (PE) in 1 patient, both DVT and PE in 1 patient, and retinal vein thrombosis in 2 patients. The fibrinogen level was elevated in all six patients, and factor VIII, IX, and/or XI levels were elevated in five patients. Heterozygosity for 5 10-methylene tetrahydrofolate reductase was documented in two patients, and mutation for factor II or factor V-Leiden mutation was found in one patient. Levels of protein C and protein S and activated protein C resistance were within normal range in all patients. Four patients had mildly elevated levels of at least one antiphospholipid antibody; none had a positive lupus anticoagulant test result. Overall, all patients demonstrated abnormalities on hypercoagulability tests. CONCLUSIONS Thromboembolic complications occur at a high rate (8.6%) in lung transplant recipients and are associated with abnormalities in hypercoagulability. The cause remains unclear. Our results should prompt a high index of suspicion for these potentially fatal complications, which would lead to early diagnosis and successful treatment.
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Affiliation(s)
- Gabriel Izbicki
- Pulmonary Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Osnat Bairey
- Pulmonology Institute, Hematology Institute, Hemostasis Laboratory, Rabin Medical Center, Petah Tiqva
| | - David Shitrit
- Pulmonology Institute, Hematology Institute, Hemostasis Laboratory, Rabin Medical Center, Petah Tiqva
| | - Judith Lahav
- Pulmonology Institute, Hematology Institute, Hemostasis Laboratory, Rabin Medical Center, Petah Tiqva
| | - Mordechai R Kramer
- Pulmonology Institute, Hematology Institute, Hemostasis Laboratory, Rabin Medical Center, Petah Tiqva.
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Abstract
PURPOSE OF REVIEW Interstitial lung disease includes a heterogeneous group of disorders that leads to respiratory insufficiency and death in a significant number of patients. Lung transplantation is a therapeutic option in select candidates. RECENT FINDINGS The indications, transplant procedure options, and outcomes continue to evolve. Various recipient comorbidities influence the choice of procedure in patients with interstitial lung disease. Single lung transplants are used as the procedure of choice and bilateral transplants are reserved for patients with suppurative lung disease and patients with pulmonary hypertension. Issues unique to patients with interstitial lung disease affect the morbidity, mortality and recurrence of the disease. SUMMARY Lung transplantation is an effective therapy for respiratory failure in interstitial lung disease with survival following transplant being similar to that achieved in transplant recipients with other diseases.
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Affiliation(s)
- Raed Alalawi
- Division of Pulmonary and Critical Care Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Mal H, Brugière O, Dauriat G, Groussard O, Valeyre D, Fournier M, Lesèche G. [Lung transplantation in patients with pulmonary fibrosis]. REVUE DE PNEUMOLOGIE CLINIQUE 2005; 61:232-8. [PMID: 16142197 DOI: 10.1016/s0761-8417(05)84816-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Lung transplantation has been developed over the last fifteen years as a therapeutic option for different forms of advanced-stage lung disease. Idiopathic pulmonary fibrosis is a good indication. For these patients, single lung transplantation is usually preferred, bilateral lung transplantation to a lesser extent. Survival is similar for these two types of transplantation. The post-transplantation survival in patients with pulmonary fibrosis is about 65-70% at one year and 40% at five years. This rate is lower than observed for COPD or cystic fibrosis. If there are no complications, the patient can recover nearly normal lifestyle. Among the different complications, reimplantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.
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Affiliation(s)
- Hervé Mal
- Service de Pneumologie et Réanimation Respiratoire, Hôpital Beaujon, AP-HP, 100, boulevard Général-Leclerc, 92110 Clichy.
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Abstract
Lung transplantation remains the only therapeutic option shown to improve survival for many end-stage interstitial lung diseases. Although idiopathic pulmonary fibrosis is the most common indication, transplantation has been performed for many other diseases. This article reviews the current indications and outcomes for the procedure and problems encountered in lung transplantation for interstitial lung diseases. The role of transplant for specific diseases also is discussed.
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Affiliation(s)
- Brandon S Lu
- Division of Pulmonary and Critical Care Medicine, Loyola University Medical Center, 2160 South 1st Avenue, Maywood, IL 60153, USA
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