Lung and Heart-Lung Transplantation PDF

Preface

Lung and Heart-Lung Transplantation provides a comprehensive and stateof- the-art review of clinical and investigative aspects of lung (and heart-lung) transplantation. In this book, international experts from diverse programs representing multiple countries (Australia, Belgium, Canada, Germany, United Kingdom, and United States) and disciplines (surgery, medicine, and immunology) have compiled a superb synthesis of a vast array of information gleaned over the past three decades. Since the first successful heart–lung transplant at Stanford University in 1981, more than 20,000 lung transplants and 3000 heart-lung transplants have been performed worldwide. Over the 25 years spanning the seminal transplant, extensive refinements in surgical techniques, advances in medical knowledge, availability of newer immunosuppressive regimens, and liberal use of antimicrobial prophylactic strategies led to improved prognosis. Unfortunately, despite improvements in survival, chronic allograft rejection remains a vexing and potentially lethal complication, affecting more than half of all lung transplant recipients during the course of the disease. Substantial insights into the pathogenesis of acute and chronic lung allograft rejection have been gleaned from animal models as well as research studies in human lung transplant recipients, but effective treatment for chronic allograft rejection is still lacking. However, a greater understanding of the mechanisms of allograft rejection may stimulate development of newer and more effective strategies to prevent and treat this complication.

This book provides a superlative review of past successes (and failures) associated with lung transplantation, but also provides insight into the latest advances and evolving concepts of lung transplantation. In Chapter 1, Dr. Rutherford and colleagues present a fascinating historical overview of lung transplants and heart-lung transplants, and review cumulative data from the International Registry on outcomes associated with these surgeries worldwide. In Chapter 2, Drs. Cobbold and Waldmann discuss the role of regulatory T cells and dendritic cells in transplantation (rejection and tolerance). In Chapter 3, Dr. Meyer expands on basic immune mechanisms that are operative in allogeneic recognition, rejection, and tolerance. These two basic science chapters provide a framework for understanding the pitfalls inherent in clinical lung transplantation and insights into future strategies to limit or prevent allograft rejection.

Chapters 4 through 9 delineate the indications for lung transplantation for specific disease states [e.g., chronic obstructive pulmonary disease, cystic fibrosis, pulmonary hypertension (primary and secondary forms), interstitial lung diseases, pulmonary Langerhans cell histiocytosis and lymphangioleiomyomatosis, and end-stage lung or pulmonary vascular/cardiac disorders in children]. Each of these chapters reviews the past and current results of lung transplantation in those specific patient cohorts, and also discusses available medical therapies (before or in lieu of lung transplantation) and factors unique to each disease that influence the decision to refer for lung transplantation. Specific parameters or criteria (e.g., physiologic, radiographic, clinical) that guide the decision to refer for lung transplantation are developed for each disease state. For example, in Chapter 4, Drs. Kotloff and Martinez provide an elegant and comprehensive review of both medical and surgical (i.e., lung volume reduction surgery and transplant) treatment options for chronic obstructive pulmonary disease. They discuss in depth various medical therapies (i.e., bronchodilators, corticosteroids, oxygen, pulmonary rehabilitation) and prognostic factors to take into account to assess the suitability of lung transplantation. The role of lung volume reduction surgery and selection criteria for this surgery are discussed in depth. In Chapter 5, Drs. Coakley and Yankaskas discuss complications commonly observed in cystic fibrosis (e.g., differing pharmacokinetics, intestinal dysmotility, and other gastrointestinal complications, diabetes mellitus, chronic sinusitis, and specific infectious complications with cystic fibrosis such as panresistant Pseudomonas aeruginosa, Burkholderia cepacea, Aspergillus, and atypical mycobacteria). In Chapter 6, Dr. Saggar and colleagues delineate the specific problems inherent with primary or secondary forms of pulmonary arterial hypertension (e.g., early pulmonary edema following transplantation and the impact of adverse right ventricular function) and controversies regarding single or bilateral lung transplantation for this disease. Chapters 7 and 8 review specific interstitial lung disorders including idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, connective tissue disease-associated pulmonary fibrosis, sarcoidosis, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis. For each of these disorders, medical therapies are discussed in detail and criteria are developed for lung transplant candidates. In Chapter 9, Drs. Mallory and Elidemir describe the experience of lung-transplant and heart-lung transplant pediatric patients with diverse end-stage pulmonary or pulmonary vascular/cardiac disorders. Limited availability of donor organs is a major limiting factor and is responsible for prolonged waiting times among patients listed for lung transplantation. Given the potential for death while awaiting lung transplantation, living lobar lung transplantation was adopted as an alternative to cadaveric lung transplantation and may be lifesaving in patients with terminal respiratory illnesses. In Chapter 10, Drs. Bowdish and Barr review the indications for living lobar lung transplantation, criteria for donor and recipient selection, technique, and outcomes of this operation. Given the shortage of donor organs, combined heart–lung transplantation, a technique utilized in the 1980s for end-stage pulmonary vascular disease (particularly for pulmonary arterial hypertension and complex congenital cardiac defects) has been utilized less often in recent years. In Chapter 11, Drs. Moffatt-Bruce and Reitz discuss the indications for heart-lung transplantation, outcomes, and specific complications associated with this operation and also review medical and surgical alternatives (e.g., atrial septostomy, pulmonary thromboendarterectomy, lung transplantation with repair of cardiac defects) that may obviate the need for heart-lung transplantation. The limited lung donor pool and prolonged waiting times for lung transplants have necessitated changes in strategies for organ procurement and allocation as well as improved lung preservation techniques. Chapters 12 through 14 discuss the systems of organ allocation in the United States, Europe, and Australia, including major and complex changes in organ allocation in the United States introduced in 2005. In Chapter 15, Drs. D'Ovidio and Keshavjee articulate novel techniques to enhance lung preservation and expand the donor pool. Chapter 16, by Drs. Schnickel and Ardehali, expands on this concept to advocate more liberal use of donor organs (including use of ‘‘nonstandard'' lungs). Immunosuppressive therapy is a double-edged sword, as excessive immunosuppression increases the risk for infectious and neoplastic complications while inadequate immunosuppression places the allograft(s) at risk. Chapters 17 and 18 discuss in detail the various immunosuppressive agents currently available, including corticosteroids, antimetabolites, cytotoxic agents, calcineurin inhibitors, and monoclonal or polyclonal antibodies directed against T cells, B cells, or specific receptors. The mechanisms of action, efficacy, monitoring strategies, and complications of each of these agents are discussed in detail. In Chapter 19, Dr. McCurry and colleagues review novel and future approaches to immunosuppression with a focus on inhaled cyclosporine and Campath-1H.

Potentially serious complications of lung transplantation include primary graft dysfunction, complications at the bronchial anastomotic site(s), infections, chronic and acute allograft rejection, cardiovascular and metabolic derangements, and neoplasia. In Chapter 20, Dr. Mulligan discusses primary graft dysfunction, risk factors, management, and outcomes associated with primary graft dysfunction. In Chapter 21, Drs. Angel and Susanto discuss complications that may arise at the bronchial anastomotic site and potential therapeutic interventions. Chapters 22 through 28 describe the myriad opportunistic infections that may complicate solid organ transplantation. In Chapter 22, Dr. Zamora discusses in detail the incidence and impact of viral infections on lung transplant recipients; their relationship to allograft rejection; and prophylactic, preemptive, and treatment strategies for a host of viral infections. He also discusses the emergence of novel and community-acquired viruses, resistant strains, and strategies for the recognition, prevention, and treatment of viral infections. The incidence, spectrum, diagnostic modalities, clinical impact, and treatment of fungal infections among solid organ transplant recipients are discussed in Chapters 23 through 25. In Chapter 23, Dr. Kubak provides an in-depth discussion of coccidiodomycosis; in Chapter 24, Dr. Kauffman discusses the endemic mycoses, histoplasmosis and blastomycosis, with emphasis on evolving newer therapies. In Chapter 25, Drs. Husain and Silveira emphasize that infections due to Aspergillus spp are common among lung transplant recipients (particularly at the bronchial anastomoses) compared to other solid organ transplant recipients and outline prophylactic and treatment strategies for this potentially lethal pathogen. They also discuss Cryptococcus, Fusarium, Zygomycetes, and dermatiaceous molds, many of which are resistant to many of the commonly utilized antifungal agents. Other opportunistic pathogens complicating solid organ transplant recipients are discussed in Chapter 26 (bacteria, Nocardia spp, and Pneumocystic jirovecii), Chapter 27 (Legionella spp), and Chapter 28 (nontuberculous mycobacteria and Mycobacterium tuberculosis).

Rejection of the allograft(s) remains the Achilles heel of lung transplantation and the major obstacle to long-term survival. Chapters 29 through 32 discuss in depth the epidemiology, pathogenesis, risk factors, and clinical features of acute rejection (Chapter 29), histopathological features of acute and chronic rejection as well as opportunistic infections (Chapter 30), and chronic rejection (Chapters 31 and 32). The basic immunological mechanism operative in chronic and acute allograft rejection (including roles of cytokines, chemokines, HLA matching, gastrointestinal reflux, etc.) are discussed in detail. The role of specific diagnostic or monitoring techniques (e.g., pulmonary function tests, bronchoscopy, imaging procedures, etc.) to identify complications of lung transplantation is reviewed in detail in Chapters 33 and 34. Monitoring of pulmonary physiology is an integral component of follow-up to assure adequate function of the lung allograft(s) and to identify complications that may develop (particularly episodes of rejection or infection). In Chapter 33, Dr. Estenne presents a comprehensive review of physiological responses (normal and abnormal) that may be observed in lung transplant recipients, including effects of lung denervation, sternotomy or thoracotomy, immunosuppressive medications, impaired mucociliary clearance, muscle weakness, and allograft rejection. He details physiological and imaging studies that may be useful to follow lung transplant recipients longitudinally. In Chapter 34, Drs. Suh, Myers, and Goldin elegantly describe the role of radiographic imaging to detect various complications (e.g., mechanical, traumatic, or ischemia-reperfusion injury; infections; acute or chronic rejection; pulmonary embolism; malignancy; drug-induced injury) at various time points following lung transplantation. Finally, Chapters 35 through 37 discuss late complications that may occur following lung transplantation. In Chapter 35, Drs. Patel, Kobashigawa, and Hamilton discuss cardiac, lipid, and atherosclerotic complications among lung transplant recipients. In Chapter 36, Dr. Maurer addresses osteoporosis and metabolic bone disease among lung transplant recipients. Finally, in Chapter 37 Dr. Weigt and colleagues discuss the spectrum of posttransplant lymphoproliferative disorders, including pathogenesis, risk factors, histopathological types, clinical features, diagnosis (including immunohistochemical stains) and treatment.

In summary, this book combines the insights and experience of the best international experts in lung transplantation and provides a global and state-of-the-art perspective of the current and future role of lung transplantation worldwide. The book will be of great interest not only to pulmonologists, transplant physicians, surgeons, nurses, and medical personnel with an interest in transplantation, but also to basic scientists with an interest in transplant immunology.