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WEINBERGER, MD, MACP, FRCP Executive Vice President and Chief Executive Offcer Emeritus American College of Physicians Adjunct Professor of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania; Senior Lecturer on Medicine Harvard Medical School Boston, Massachusetts BARBARA A. COCKRILL, MD Harold Amos Associate Professor of Medicine Harvard Medical School Pulmonary Vascular Disease and Lung Centers Brigham and Women’s Hospital Boston, Massachusetts JESS MANDEL, MD, FACP Professor of Medicine University of California San Diego School of Medicine La Jolla, California 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 Principles of Pulmonary Medicine, Seventh Edition ISBN: 978-0-323-52371-4 Copyright © 2019 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this feld are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identifed, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2014, 2008, 2004, 1998, 1992, 1986 by Saunders, an imprint of Elsevier, Inc. ISBN: 978-0-323-52371-4 Library of Congress Cataloging-in-Publication Data Names: Weinberger, Steven E., author. | Cockrill, Barbara A., author. | Mandel, Jess, author. Title: Principles of pulmonary medicine / Steven E. Weinberger, Barbara A. Cockrill, Jess Mandel. Description: Seventh edition. | Philadelphia, PA : Elsevier, [2019] | Includes bibliographical references and index. Identifers: LCCN 2017029947 | ISBN 9780323523714 (pbk. : alk. paper) Subjects: | MESH: Lung Diseases | Respiration Disorders Classifcation: LCC RC756 | NLM WF 600 | DDC 616.2/4–dc23 LC record available at https://lccn.loc.gov/2017029947 Content Strategist: Robin Carter Senior Content Development Specialist: Marybeth Thiel Publishing Services Manager: Patricia Tannian Project Manager: Stephanie Turza Design Direction: Bridget Hoette Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1 To Janet, Eric, and Mark Steven E. Weinberger To my parents, Fred and Shirley Cockrill Barbara A. Cockrill To my parents, Martha and Gerald Mandel Jess Mandel This page intentionally left blank Introduction to the Seventh Edition Principles of Pulmonary Medicine was frst published in 1986 as a “concise, core reference [that] emphasizes pathophysiology and diagnosis as the basis for optimal management of respiratory disorders. Physiologic, radiologic, and pathologic features of diseases are correlated with clinical fndings providing an integrated, comprehensive approach.” Much has changed over seven editions of the book and the more than 30 years that have elapsed since the frst edition. Our understanding of many disease processes has improved, particularly at a molecular level; our diagnostic tests have become more sophisticated; and our therapeutic armamentarium has been expanded and improved. The single author of the frst four editions, Steven E. Weinberger, MD, MACP, FRCP, has been joined by two additional authors, Barbara A. Cockrill, MD, and Jess Mandel, MD, FACP, since the ffth edition; their knowledge, experience, and perspectives have clearly enhanced the quality of the book. Since the ffth edition, we have expanded the number of supplementary images and self-assessment questions accessible on the internet, recognizing the importance of learners being able to assess their knowledge and their understanding of concepts that can at times be daunting to grasp. At the same time, however, much remains unchanged since the frst edition. Although the primary audience has always been the medical student taking a respiratory pathophysiology course, the book has also been extensively used by residents and practicing physicians as well as by other healthcare professionals who care for patients with pulmonary disease. A persistent goal throughout all editions of the book has been to present physiologic concepts, pathogenetic and pathophysiologic mechanisms, and radiologic and pathologic correlates of disease in a clear fashion that can be easily understood even by the beginning student of pulmonary medicine. We have also continued to include margin notes throughout the text, which summarize the major points and concepts and allow the reader to quickly review the material. Finally, starting with the second edition, we have included three appendixes that provide simplifed methods for interpreting pulmonary function tests and arterial blood gases, while also presenting sample problems that test the reader’s ability to use respiratory equations, assess pulmonary function abnormalities, and interpret arterial blood gases. We have been most gratifed by the popularity of the textbook, which has been used extensively not only in the United States and Canada but also in other countries throughout the world. Various editions have been translated into Spanish, Portuguese, Italian, Japanese, Chinese, and Polish. Although there may be some differences in diagnostic and therapeutic approaches to pulmonary diseases in different countries, the conceptual underpinnings of physiology, pathophysiology, and disease mechanisms that we are trying to convey in a readable fashion are universal. viii n Principles of Pulmonary Medicine It has been a pleasure to work with the editorial staff at Elsevier in development of this edition, just as it has been for past editions. We particularly want to express our appreciation to Stephanie Turza, Marybeth Thiel, and Robin Carter, who have been most supportive throughout the development and production process. Finally, we are most grateful to our spouses and children for their support and understanding as we had to sacrifce time with them to prepare this new edition of the book. Steven E. Weinberger, MD, MACP, FRCP Barbara A. Cockrill, MD Jess Mandel, MD, FACP