Idiopathic Pulmonary Fibrosis PDF

PREFACE

Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is a devastating disease of unknown etiology, which progresses relentlessly to respiratory failure within 2 to 8 years of onset. IPF is associated with the histological pattern of usual interstitial pneumonia (UIP), and is the most common of the idiopathic interstitial pneumonias (IIPs), comprising 46–71% of IIPs. Unfortunately, despite exhaustive research efforts, the prognosis of IPF remains dismal, with 5-year mortality rates exceeding 70%. Historically, corticosteroids and immunosuppressive and cytotoxic agents have been the mainstay of therapy, but have not been proven to be effective. Within the past decade, key advances in the diagnosis of UIP include: 1) an enhanced ability to diagnose IPF/UIP by high-resolution thin-section computed tomographic (HRCT) scans and 2) the recognition that other types of IIPs—particularly nonspecific interstitial pneumonia (NSIP), respiratory bronchiolitis interstitial lung disease (RBILD), and desquamative interstitial pneumonia (DIP)—were often erroneously categorized as IPF/UIP in early publications, even though prognosis and responsiveness to therapy among these disorders are markedly different from those of UIP. More importantly, concepts of pathogenesis have evolved dramatically within the past decade. Early concepts of pathogenesis postulated that inflammatory cellular influx and release of cellular products (enzymes, oxygen radicals, cytokines, etc.), were pivotal to lung destruction and fibrosis. Unfortunately, therapies based on abrogating inflammation appear to be ineffectual. More recent studies suggest that inflammation plays at best a minor role, whereas epithelial cell injury, recruitment of fibroblasts (FBs) and myofibroblasts, and alterations in FB phenotype and activation state play cardinal roles in the pathogenesis of IPF.

In this book, internationally recognized clinicians, scientists, and investigators discuss the latest advances and concepts in the epidemiology, diagnosis, classification, and treatment of this frustrating and enigmatic disorder. The first several chapters examine several clinically relevant aspects of IPF including epidemiology (Drs. Coultas and Hubbard), genetics of IPF and its variants (Dr. Wahidi et al.), clinical features (Dr. King), histopathology (Dr. Travis), nonspecific interstitial pneumonia (Dr. Martinez et al.), physiological aberrations (Drs. Martinez and Lynch), radiological features including HRCT (Dr. Zisman et al.), the role of other imaging and radionuclide tests (Dr. Singh et al.), and bronchoalveolar lavage (Drs. Baughman and Costabel). Additionally, Dr. Wells et al. discuss pulmonary fibrosis among connectivetissue disorders, which shares many features with IPF but differs in histopathological features and prognosis.

Following these practical and state-of-the-art articles, the next large section of the volume focuses on putative biological and immunological mechanisms that may play key roles in the pathogenesis of IPF. Chapters are devoted to several possible contributory mechanisms that may be involved in lung injury or propagation of fibrosis including: cytokine phenotypes; chemokines; polymorphonuclear leukocytes; integrins; oxidants; coagulation pathways; arachidonic acid metabolites; matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs); extracellular matrix components; fibroblasts and myofibroblasts, fibroblast growth factors; type II alveolar epithelial cells; surfactant apoproteins, bronchiolar epithelium; and viruses.

In the final section, Dr. Westall et al. provide an overview of current treatment options for IPF including pharmacological therapy and lung transplantation. Given the limited efficacy of currently available therapies for IPF, Drs. Brown and Schwarz discuss the need to identify and develop novel treatment options based on the evolving understanding of the pathogenesis of this disorder. Hopefully, identification of effective antifibrotic therapies will improve the outcome of what currently is a frustrating and enigmatic disease. Finally, Dr. Crystal, whose seminal insights more than 25 years ago provided a template for future studies of IPF, concludes with an elegant chapter (with Drs. Heguy and Kaplan) detailing what is known about the genetics of IPF (including genetic polymorphisms that influence susceptibility to fibrosis), animal models, assessment of gene expression, and how such information may lead to novel treatment strategies based on more specific gene targets.

This volume is comprehensive and provides invaluable insights that are relevant not only to practicing clinicians but to educators, clinical investigators, and basic scientists. We believe this volume is the most comprehensive and scholarly publication devoted to IPF/UIP, and an important addition to the field.