Lung Transplantation

This book provides a detailed account of the principles and practice of contemporary lung transplantation. An accomplished, international team of contributing authors have combined their expertise to provide the latest scientific developments and clinical knowledge based on their extensive experience. The book covers pulmonary vascular and parenchymal lung disease, which necessitate transplantation, together with all aspects of the multidisciplinary management of lung transplant patients. It concludes by looking at future developments in the treatment of advanced respiratory failure.

Lung transplantation has assumed an important role in the therapeutic approach to selected patients with advanced lung disease, but the procedure remains plagued by numerous problems that limit its widespread applicability and constrain its outcomes. Increasingly, the supply of suitable donor organs is insufficient to meet current demands. Immunosuppressive therapy is associated with myriad risks, most notably infection, renal failure, and malignant disorders. Despite current immunosuppressive strategies, rejection of allografts is common and frequently leads to irreversible organ dysfunction. As a consequence of these problems, lung transplantation remains limited in its ability to appreciably extend life; median survival is only five years. Judicious selection of candidates and vigilant care of recipients are essential to an optimal outcome, but the achievement of enduring results awaits further scientific and clinical advances. It is with this perspective that Lung Transplantation comprehensively reviews current clinical issues and casts an eye toward the future of the field. The first section consists of 10 chapters detailing the diseases for which transplantation is most commonly indicated. Four of these chapters are devoted to various aspects of pulmonary hypertension, a curious editorial choice, given that pulmonary vascular disease is the indication for less than 5 percent of transplantation procedures worldwide. In addition, the section has inconsistencies in the breadth of material covered. For example, the chapters on pulmonary hypertension focus exclusively on aspects of the disease itself, avoiding any discussion of issues related to transplantation, such as the controversy regarding the optimal surgical procedure. In contrast, the chapter on cystic fibrosis superficially reviews the molecular basis of the disease and recent advances in treatment, offering a discussion of lung transplantation that is at times specific to cystic fibrosis and at other times overly generic in scope. The chapters on emphysema and bronchiectasis are much better balanced in their coverage. The strength of this textbook lies in the second section, which contains well-written, comprehensive chapters on lung transplantation. Topics covered in this section relate broadly to patient selection, surgical techniques, and post-transplantation care. Chapters on mechanisms of graft injury and immunosuppressive agents provide a strong foundation of the immunologic principles that underlie clinical care. A chapter devoted to imaging and a chapter on transplant pathology offer, respectively, extensive radiographic and histopathological images of post-transplantation complications. Another highlight of this section is a discussion of the psychological aspects of chronic lung disease and lung transplantation, issues that have received far less attention than the physical health of patients but that are equally important to the quality of life. The final section of Lung Transplantation looks to the future, with chapters on tissue engineering, xenotransplantation, and the artificial lung. Notably absent is a discussion of expanding the donor pool through the use of organs from donors without a heartbeat. A detailed discussion of current research efforts to induce immunologic tolerance also would have fit nicely with the theme of the final section, since tolerance may be the holy grail that will permit achievement of long-term graft and patient survival. Despite these relatively minor criticisms, Lung Transplantation succeeds as a state-of-the-art review of an evolving field. The book is relevant not only to transplantation specialists but to all clinicians who care for patients with advanced lung disease. Comprehensive in scope, this textbook is nonetheless sufficiently succinct to permit it to be read cover to cover and sufficiently well written to motivate one to do so. Robert Kotloff, M.D.
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(Figure) In their excellent book, Inflammation and Cardiac Diseases, Feuerstein, Libby, and Mann focus first on vascular inflammation. Half of all patients who have myocardial infarctions have normal plasma lipid levels. Numerous clinical studies involving such patients have identified a set of inflammatory biologic markers that predict the risk of cardiovascular events. Many of these markers -- interleukin-6, fibrinogen, and C-reactive protein, to name a few -- are components of the acute-phase response, an innate, systemic inflammatory reaction. Why is an acute immune response chronically activated in patients with atherosclerosis? What is the role of acute-phase reactants in heart disease? Masterly chapters on interleukin-6 and C-reactive protein answer these questions. The editors then turn their attention to inflammation in the myocardium during ischemia, reperfusion, and heart failure. Our understanding of the pathogenesis of heart failure has evolved from hypervolemic models to hemodynamic and then neurohormonal ones. Basic-science and clinical researchers have discovered that inflammation and myocardial remodeling play a critical role in heart failure. Innate immunity is activated when neutrophils and monocytes migrate into the injured myocardium, damaging myocytes by releasing innate immune effectors such as complement and radicals, and stimulating inflammation by secreting proinflammatory cytokines, including interferon-(gamma), tumor necrosis factor (alpha) (TNF-(alpha)), and chemokines. In clearly focused sections of the book, the authors explore the roles of each of these innate immune signals in cardiac disease. Mann tells a fascinating story in his chapter on cytokines that illustrates the importance of understanding the nuances of specific inflammatory pathways in heart disease. TNF-(alpha) levels are elevated in patients with ischemic or idiopathic dilated cardiomyopathy. Early preclinical and clinical studies suggested that interfering with TNF-(alpha) synthesis was beneficial. However, two large, randomized clinical trials failed to show any benefit to using selective TNF-(alpha) antagonists. In fact, patients receiving anti-TNF-(alpha) drugs had a slightly increased risk of death or hospitalization. Clearly, key aspects of inflammation in cardiac disease are still not understood. Our knowledge of this subject is still evolving. Inflammation and Cardiac Diseases is an excellent summary of the ways in which innate immune pathways are activated in diseases of the heart. The book challenges us to identify the triggers of such immunity, to explore the role of innate immune signaling in cardiac disease, and to develop new types of immunomodulatory therapies. Charles J. Lowenstein, M.D.
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