Murray and Nadel’s TEXTBOOK OF RESPIRATORY MEDICINE Editors Robert J. Mason, MD Dean E. Schraufnagel, MD Cetalie & Marcel Weiss Chair in Pulmonary Medicine Professor of Medicine and Pathology Department of Medicine Department of Medicine National Jewish Health Section of Pulmonary, Critical Care, Sleep and Allergy Professor of Medicine University of Illinois at Chicago University of Colorado Denver Health Sciences Center Chicago, Illinois Denver, Colorado John F. Murray, MD, FRCP, DSc (Hon) V. Courtney Broaddus, MD Professor Emeritus Professor of Medicine Department of Medicine University of California, San Francisco University of California, San Francisco Chief, Division of Pulmonary and Critical Care San Francisco General Hospital Medicine San Francisco, California San Francisco General Hospital San Francisco, California Jay A. Nadel, MD, DSc (Hon), DLaw (Hon) Thomas R. Martin, MD Professor of Medicine and Physiology Professor of Medicine Division of Pulmonary and Critical Care University of Washington Cardiovascular Research Institute Investigator Chief of Medicine and Director University of California, San Francisco Primary and Specialty Medicine Service Line San Francisco, California Veterans Affairs Puget Sound Health Care System Seattle, Washington Talmadge E. King, Jr., MD Julius R. Krevans Distinguished Professorship in Internal Medicine Chair, Department of Medicine University of California, San Francisco San Francisco, California VOLUME I Murray and Nadel’s TEXTBOOK OF RESPIRATORY MEDICINE 5th Edition 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 MURRAY AND NADEL’S TEXTBOOK OF RESPIRATORY MEDICINE ISBN: 978-1-4160-4710-0 (2 Volume Set) Copyright © 2010 by Saunders, an imprint of Elsevier Inc. Part number: 9996080986 (Volume 1) Part number: 9996081044 (Volume 2) 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. Permissions may be sought directly from Elsevier’s Rights Department: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail: We dedicate this textbook to Dr. Julius H. Comroe, Jr., who was our mentor during the formative years of our professional development. Dr. Comroe was one of the truly great academicians of his generation. He was an investigator of exceptional merit, an educator whose infuence was worldwide, and a medical statesman of exemplary integrity and vision. In dedicating this book, we acknowledge especially Dr. Comroe’s scholarly contributions and his commitment to the importance of basic science in the solution of clinical problems. JFM JAN RJM VCB TRM TEK DES Contributors Lewis Adams, PhD Najib T. Ayas, MD, MPH Professor, Griffth School of Physiotherapy and Associate Professor of Medicine, Divisions of Exercise Science, Griffth University, Gold Coast Respiratory and Critical Care Medicine, University Campus, Queensland, Australia of British Columbia; Staff Physician, Intensive Care Dyspnea Unit, Providence Healthcare; Staff Physician, Vancouver General Hospital, Vancouver, British Columbia, Canada Anthony J. Alberg, PhD, MPH Respiratory System Mechanics and Energetics Associate Professor and Blatt Ness Chair, Division of Epidemiology and Biostatistics, Department of Medicine, and Associate Director for Cancer Ronald C. Balkissoon, MD Prevention and Control, Hollings Cancer Center, Associate Professor, Department of Medicine, National Medical University of South Carolina, Charleston, Jewish Health, Denver, Colorado South Carolina Disorders of the Upper Airways Epidemiology of Lung Cancer John R. Balmes, MD Division of Occupational and Environmental Medicine, Richard K. Albert, MD and Division of Pulmonary and Critical Care Professor of Medicine, University of Colorado Denver; Medicine, Department of Medicine, University Chief of Medicine, Denver Health; Adjunct Professor of California, San Francisco, San Francisco, of Engineering and Computer Science, University of California Denver, Denver, Colorado Indoor and Outdoor Air Pollution Preoperative Evaluation Srinivas R. Bapoje, MD, MPH Kurt H. Albertine, PhD Hospitalist, Department of Hospital Medicine, Denver Medical Gross Anatomy, Pediatric Fellowship Core Health Medical Center; Assistant Professor, Internal Curriculum, and Assistant Dean for Faculty Medicine, University of Colorado Denver School of Administration, University of Utah School of Medicine, Denver, Colorado Medicine, Salt Lake City, Utah; Editor-in-Chief, Preoperative Evaluation The Anatomical Record, American Association of Anatomists, Rockville, Maryland Joan Albert Barberà, MD Anatomy of the Lungs Senior Consultant Physician, Servei de Pneumologia, Institut del Tòrax, and Research Associate Director, Hospital Clínic, Barcelona, Spain Devanand Anantham, MRCP, MBBS, FCCP Pulmonary Complications of Abdominal Instructor in Medicine, Duke-National University of Disease Singapore Graduate Medical School; Consultant, Singapore General Hospital, Singapore, Peter J. Barnes, DM, DSc, FRCP, FMedSci, FRS Singapore Professor of Thoracic Medicine, Imperial College Ultrasonography London, London, United Kingdom Pharmacologic Principles Douglas Arenberg, MD Associate Professor of Medicine, Division of Pulmonary Fuad M. Baroody, MD and Critical Care, Department of Internal Medicine, Professor of Surgery and Pediatrics, and Director, University of Michigan Medical School, Ann Arbor, Pediatric Otolaryngology, University of Chicago, Michigan Chicago, Illinois Metastatic Malignant Tumors Disorders of the Upper Airways vii viii Contributors Margaret R. Becklake, MD Kevin K. Brown, MD Professor Emeritus of Medicine and of Epidemiology, Professor and Vice Chairman, Department of Medicine, Biostatistics and Occupational Health, McGill National Jewish Health; Professor of Medicine, University; Honorary Physician, McGill University University of Colorado Denver School of Medicine, Health Centre, Royal Victoria Hospital Pavilion, Denver, Colorado Montréal, Québec, Canada Pulmonary Vasculitis Pneumoconioses and Other Mineral Dust-Related Diseases Paul G. Brunetta, MD Tobacco Education Center, Mount Zion Medical Joshua O. Benditt, MD Center, University of California, San Francisco, San Professor of Medicine, University of Washington School Francisco, California of Medicine; Medical Director of Respiratory Care Smoking Hazards and Cessation Services, University of Washington Medical Center, Seattle, Washington Jacques Cadranel, MD, PhD The Respiratory System and Neuromuscular Department of Pneumology and Respiratory Intensive Diseases Care, Université de Médecine Pierre et Marie Curie; Tenon Hospital, Paris, France Neal L. Benowitz, MD Lymphoma, Lymphoproliferative Diseases, and Professor of Medicine and Bioengineering and Other Primary Malignant Tumors Therapeutic Sciences, and Chief, Division of Clinical Pharmacology and Experimental Therapeutics, David P. Carbone, MD, PhD University of California, San Francisco; Chief, Professor of Medicine and Cell Biology, and Director, Division of Clinical Pharmacology, San Francisco Experimental Therapeutics Program, Vanderbilt- General Hospital, San Francisco, California Ingram Cancer Center; Director, Thoracic Oncology Smoking Hazards and Cessation Center, Harold Moses Chair for Cancer Research, and Director, Specialized Program of Research Paul D. Blanc, MD, MSPH Excellence in Lung Cancer, Vanderbilt University Professor of Medicine, and Endowed Chair, School of Medicine, Nashville, Tennessee Occupational and Environmental Medicine, Biology of Non-Small Cell Lung Cancer University of California, San Francisco, San Francisco, California Bartolome R. Celli, MD Acute Pulmonary Responses to Toxic Exposures Professor of Medicine, Tufts University; Chief, Division of Pulmonary, Critical Care and Sleep Medicine, Richard C. Boucher, MD Caritas St. Elizabeth’s Medical Center, Boston, Professor of Medicine, University of North Carolina at Massachusetts Chapel Hill School of Medicine, Chapel Hill, North Pulmonary Rehabilitation Carolina Cystic Fibrosis Edward D. Chan, MD Associate Professor of Medicine, National Jewish Alfred A. Bove, MD, PhD Health, University of Colorado Denver Health Emeritus Professor of Medicine, Temple University Sciences Center, Denver, Colorado School of Medicine; Chief of Cardiology, Temple Bronchiectasis University Medical Center, Philadelphia, Pennsylvania Moira Chan-Yeung, MBBS, FRCP, FRCPC, FHKAM, Diving Medicine FHKCP Emeritus Professor of Medicine, Department of Elisabeth Brambilla, MD, PhD Medicine, Faculty of Medicine, University of British Department of Pathology, CHU Albert Michallon, and Columbia, Vancouver, British Columbia, Canada; Institut Albert Bonniot, Centre de Recherche, Professor of Medicine (Honorary), University of Université Joseph Fourier, Grenoble, France Hong Kong, Hong Kong, SAR, China Lymphoma, Lymphoproliferative Diseases, and Asthma in the Workplace and Occupational Other Primary Malignant Tumors Asthma V. Courtney Broaddus, MD Richard N. Channick, MD Professor of Medicine, University of California, San Director, Pulmonary Hypertension Program, Francisco; Chief, Division of Pulmonary and Critical Massachusetts General Hospital; Editor-in-Chief, Care Medicine, San Francisco General Hospital, San Advances in Pulmonary Hypertension, Boston, Francisco, California Massachusetts Pleural Effusion; Tumors of the Pleura Pulmonary Hypertension Contributors ix Jean Chastre, MD Robert L. Cowie, MD Service de Réanimation Médicale, Groupe Hospitalier Professor of Medicine and of Community Health Pitié-Salpêtrière, Paris, France Science, University of Calgary; Respirologist, and Ventilator-Associated Pneumonia Director, Tuberculosis Services, Alberta Health Services, Calgary, Alberta, Canada Kian Fan Chung, MD, DSc, FRCP Pneumoconioses and Other Mineral Dust-Related Professor of Respiratory Medicine, National Heart and Diseases Lung Institute, Imperial College London; Honorary Robert O. Crapo, MD, FCCP Consultant Physician, Royal Brompton Hospital, Professor, University of Utah; Director of Pulmonary London, United Kingdom Function Laboratory, LDS Hospital, Salt Lake City, Cough Utah Pulmonary Function Testing Maria Cirino-Marcano, MD Assistant Professor of Medicine, Division of Pulmonary Kristina Crothers, MD Medicine, Albert Einstein College of Medicine, Assistant Professor, Division of Pulmonary and Critical Montefore Medical Center, Bronx, New York Care Medicine, Department of Internal Medicine, Pulmonary Complications of Stem Cell and Solid University of Washington School of Medicine; Organ Transplantation Harborview Medical Center, Seattle, Washington Pulmonary Complications of Human R. Edward Coleman, MD Immunodefciency Virus Infection Professor of Radiology, Vice Chair, Department of Radiology, and Director, Division of Nuclear Charles L. Daley, MD Medicine, Duke University Medical Center, Durham, Head, Division of Mycobacterial and Respiratory North Carolina Infections, and Professor of Medicine, National Nuclear Medicine Techniques Jewish Health, Denver, Colorado Nontuberculous Mycobacterial Infections Harold R. Collard, MD Assistant Professor, Department of Medicine, and Scott F. Davies, MD Director, Interstitial Lung Disease Program, University of Minnesota Medical School; Chief, University of California, San Francisco, San Department of Medicine, and Faculty, Division of Francisco, California Pulmonary and Critical Care Medicine, Department Diffuse Alveolar Hemorrhage and Rare Infltrative of Medicine, Hennepin County Medical Center, Disorders of the Lung Minneapolis, Minnesota Fungal Infections Carlyne D. Cool, MD Teresa De Marco, MD, FACC Associate Clinical Professor, Department of Pathology, Professor of Medicine and Surgery, Director, Heart University of Colorado Denver School of Medicine, Failure and Pulmonary Hypertension Program, and Aurora; Associate Professor, National Jewish Health, Medical Director, Heart Transplantation Program, Denver, Colorado University of California, San Francisco, San General Features of Non-Neoplastic Respiratory Francisco, California Pathology; Pulmonary Vasculitis Cor Pulmonale Jean-François Cordier, MD Lorenzo Del Sorbo, MD Professor of Respiratory Medicine, Claude Bernard Assistant Professor, Dipartimento di Anestesiologia e University; Head, Department of Respiratory Rianimazione, Università di Torino, Ospedale S. Medicine, Louis Pradel Hospital, Lyon, France Giovanni Battista-Molinette, Torino, Italy Lymphoma, Lymphoproliferative Diseases, and Hypoxemic Respiratory Failure Other Primary Malignant Tumors; Eosinophilic Lung Diseases Gregory P. Downey, MD Professor of Medicine, University of Colorado Denver; Tamera J. Corte, MBBS, BSc(Med), FRACP Executive Vice President for Academic Affairs, and Clinical Research Fellow in Interstitial Lung Disease, Professor, Departments of Medicine, Pediatrics, and Royal Brompton Hospital, London, United Kingdom Integrated Immunology, National Jewish Health, The Lungs and Connective Tissue Diseases Denver, Colorado Injury and Repair of the Lung Vincent Cottin, MD, PhD Claude Bernard University; Department of Pulmonary Wonder Drake, MD Medicine, and Reference Center for Orphan Lung Assistant Professor of Medicine, Vanderbilt University Diseases, Louis Pradel Hospital, Lyon, France School of Medicine, Nashville, Tennessee Eosinophilic Lung Diseases Sarcoidosis x Contributors Roland M. du Bois, MA, MD, FRCP, FCCP Hans G. Folkesson, PhD Senior Research Investigator, Imperial College London, Professor of Physiology and Pharmacology, London, United Kingdom; Professor of Medicine, Northeastern Ohio Universities Colleges of Medicine National Jewish Health, Denver, Colorado and Pharmacy, Rootstown, Ohio The Lungs and Connective Tissue Diseases Alveolar and Distal Airway Epithelial Fluid Transport James Duffn, MA, PhD Professor Emeritus, Departments of Physiology and Rodney J. Folz, MD, PhD Anaesthesia, University of Toronto, Toronto, University of Louisville School of Medicine; Professor Ontario, Canada of Medicine and Biochemistry and Molecular Hypoventilation and Hyperventilation Biology, and Chief, Division of Pulmonary, Critical Syndromes Care and Sleep Disorders Medicine, University of Louisville, Louisville, Kentucky Richard M. Effros, MD Pulmonary Complications of Stem Cell and Solid Clinical Professor of Medicine and Attending Physician, Organ Transplantation Harbor-UCLA Medical Center, Torrance, California; Emeritus Professor of Medicine, Medical College of Andrew P. Fontenot, MD Wisconsin, Milwaukee, Wisconsin; Attending Henry N. Claman Associate Professor of Medicine, Physician, Rancho Los Amigos Medical Center, University of Colorado Denver, Denver, Downey, California Colorado Acid-Base Balance Adaptive Immunity Mark D. Eisner, MD, MPH Joe G. N. Garcia, MD Division of Occupational and Environmental Medicine, Lowell T. Coggeshall Professor of Medicine, Section of and Division of Pulmonary and Critical Care Pulmonary and Critical Care Medicine, Department Medicine, Department of Medicine, University of Medicine, University of Chicago Pritzker School of California, San Francisco, San Francisco, of Medicine, Chicago, Illinois California Pulmonary Circulation and Regulation of Fluid Indoor and Outdoor Air Pollution Balance Brett M. Elicker, MD Assistant Professor of Clinical Radiology, University Gerald F. Gebhart, PhD of California, San Francisco, San Francisco, Professor, and Director, Center for Pain Research, California University of Pittsburgh School of Medicine, Radiographic Techniques Pittsburgh, Pennsylvania Chest Pain Armin Ernst, MD Interventional Pulmonology, Beth Israel Deaconess Thomas J. Giordano, MD, PhD Medical Center, Harvard Medical School, Boston, Professor, Department of Pathology and Internal Massachusetts Medicine, University of Michigan Health System, Ann Ultrasonography Arbor, Michigan Benign Lung Tumors Peter F. Fedullo, MD Professor of Medicine, and Director, Medical Intensive Nicolas Girard, MD Care Unit, University of California, San Diego, San Pilot Unit for Rare Malignant Thoracic Tumors, Diego, California Department of Respiratory Medicine, Reference Pulmonary Thromboembolism Center for Orphan Pulmonary Diseases, Louis Pradel Hospital, Lyon, France; Human Oncology and Matthew J. Fenton, PhD Pathogenesis Program, Memorial Sloan-Kettering Chief, Asthma, Allergy and Infammation Branch, Cancer Center, New York, New York Division of Allergy, Immunology and Lymphoma, Lymphoproliferative Diseases, and Transplantation, National Institute of Allergy and Other Primary Malignant Tumors Infectious Diseases, National Institutes of Health, Bethesda, Maryland Mark T. Gladwin, MD Innate Immunity in the Lungs Pulmonary, Allergy and Critical Care Medicine, Daniel Fertel, MD and Hemostasis and Vascular Biology Research Fellow, Division of Pulmonary, Allergy and Critical Institute, University of Pittsburgh, Pittsburgh, Care Medicine, Duke University Medical Center, Pennsylvania Durham, North Carolina Pulmonary Complications of Hematologic Asthma Disease