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Fishman’sPulmonary Diseasesand DisordersVolume 1

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Notice

Medicine is an ever-changing science. As new research andclinical experience broaden our knowledge, changes in treat-ment and drug therapy are required. The authors and thepublisher of this work have checked with sources believedto be reliable in their efforts to provide information that iscomplete and generally in accord with the standards acceptedat the time of publication. However, in view of the possibil-ity of human error or changes in medical sciences, neitherthe authors nor the publisher nor any other party who hasbeen involved in the preparation or publication of this workwarrants that the information contained herein is in everyrespect accurate or complete, and they disclaim all responsi-

bility for any errors or omissions or for the results obtainedfrom use of the information contained in this work. Readersare encouraged to confirm the information contained hereinwith other sources. For example and in particular, readers areadvised to check the product information sheet included inthe package of each drug they plan to administer to be certainthat the information contained in this work is accurate andthat changes have not been made in the recommended doseor in the contraindications for administration. This recom-mendation is of particular importance in connection withnew or infrequently used drugs.

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Fishman’s PulmonaryDiseases and DisordersFourth Edition

Volume 1

Editor-in-Chief

Alfred P. Fishman, MDWilliam Maul Measey Professor of MedicineUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Co-Editors

Jack A. Elias, MDWaldemar Von Zedtwitz Professor of MedicineChair, Department of Internal MedicineYale University School of MedicineNew Haven, Connecticut

Jay A. Fishman, MDAssociate Professor of MedicineHarvard Medical SchoolDirector, Transplant Infectious Disease and

Compromised Host ProgramMassachusetts General HospitalAssociate Director, MGH Transplantation CenterBoston, Massachusetts

Michael A. Grippi, MDVice Chairman, Department of MedicinePulmonary, Allergy, and Critical Care DivisionUniversity of Pennsylvania Health SystemChief of Medicine, Philadelphia VA Medical CenterPhiladelphia, Pennsylvania

Robert M. Senior, MDDorothy R. and Hubert C. Moog Professor of

Pulmonary Diseases in MedicineProfessor of Cell Biology & PhysiologyWashington University School of MedicineSt. Louis, Missouri

Allan I. Pack, MB, ChB, PhDProfessor of MedicineChief, Division of Sleep Medicine/Department

of MedicineDirector, Center for Sleep and Respiratory

NeurobiologyUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

New York Chicago San Francisco Lisbon London Madrid Mexico City MilanNew Delhi San Juan Seoul Singapore Sydney Toronto

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Fishman’s Pulmonary Diseases and Disorders, Fourth Edition

Copyright C© 2008, 1998, 1988, 1980 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the China.

Except as permitted under the United States Copyright Act of 1976, no part of this publication may be

reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior

written permission of the publisher.

1 2 3 4 5 6 7 8 9 0 CTP/CTP 0 9 8 7

ISBN 978-0-07-145739-2 (set)

MHID 0-0714-5739-9 (set)

ISBN 978-0-07-148899-0 (volume 1)

MHID 0-0714-8899-5 (volume 1)

ISBN 978-0-07-148900-3 (volume 2)

MHID 0-0714-8900-2 (volume 2)

This book was set in Minion by Aptara.

The production supervisor was Sherri Souffrance.

The designer was Alan Barnett.

The index was prepared by Coughlin Indexing Services.

China Printing & Translation Services, Ltd., was printer and binder.

Library of Congress Cataloging-in-Publication Data

Fishman’s pulmonary diseases and disorders / editor-in-chief, Alfred P. Fishman; section editors,

Jack A. Elias…[et al.]. – 4th ed.

p. ; cm

Includes bibliographical references and index.

ISBN-13: 978-0-07-145739-2 (hardback : set)

ISBN-10: 0-07-145739-9 (hardback : set)

1. Lungs—Diseases. I. Fishman, Alfred P. II. Elias, Jack A. III. Title: Pulmonary diseases and disorders.

[DNLM: 1. Lung Diseases. WF 600 F537 2007]

RC756.P826 2007

616.2′4—dc22

2006047332

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To Linda, Hannah; Mark, Martha, Eric; Sarah; Jay, Gayle, Aaron, and Brian

Alfred P. Fishman, MD

To Sandy, Lauren, Alma, and Gabby

Jack A. Elias, MD

To Barbara, Kristen, and Amy

Michael A. Grippi, MD

To Aaron, Brian, and Gayle

Jay A. Fishman, MD

To Martha, Jerry Flance, and Jack Pierce

Robert M. Senior, MD

To Fran, Alison, Angela, Andrew, and Allan Jr.

Allan I. Pack, MB, ChB, PhD

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Contents

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xiii

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxix

Volume 1

PART I PERSPECTIVES .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1. Milestones in the History of Pulmonary Medicine . . . .3Alfred P. Fishman

PART II SCIENTIFIC BASIS OF LUNG FUNCTION INHEALTH AND DISEASE .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Section One. Architecture for Normal LungFunction / 23

2. Functional Design of the Human Lung forGas Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23Matthias Ochs & Ewald R. Weibel

3. The Respiratory Muscles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71Marc Decramer

4. The Genetic, Molecular, and Cellular Basis ofLung Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .81Stijn DeLanghe, Pierre Del Moral, Denise Tefft,Saverio Bellusci, & David Warburton

5. Development and Growth of the Lung. . . . . . . . . . . . . . . .91Johannes C. Schittny & Peter H. Burri

6. Cellular and Molecular Mechanisms RegulatingAirway Smooth Muscle Physiology andPharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115Reynold A. Panettieri, Jr.

7. Pulmonary Surfactant System and AlveolarHomeostasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125Jeffrey A. Whitsett & Ann D. Horowitz

8. Transport Function of Airway Epithelia andSubmucosal Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .137Paul B. McCray, Jr. & Michael J. Welsh

Section Two. Physiological Principles of NormalLung Function / 147

9. Pulmonary Mechanics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .147Murray D. Altose

10. Control of Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161Neil S. Cherniack

11. Ventilation, Pulmonary Blood Flow, andVentilation-Perfusion Relationships . . . . . . . . . . . . . . . . . . 173Peter D. Wagner

12. Diffusion, Chemical Reactions, and DiffusingCapacity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191Robert A. Klocke

13. Blood-Gas Transport. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .201Michael P. Hlastala, Erik R. Swenson, &Robert A. Klocke

14. Acid-Base Balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .207Stanley Goldfarb & Kumar Sharma

Section Three. The Lungs in Different PhysiologicalStates / 223

15. Exercise, Integration, and Adaptation. . . . . . . . . . . . . . . .223Alfred P. Fishman

16. Breathing in Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233Brian J. Whipp & Susan A. Ward

17. The Lungs in Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253Daniel B. Rosenbluth & John Popovich, Jr.

18. Aging of the Respiratory System . . . . . . . . . . . . . . . . . . . . . .263Edward J. Campbell

Section Four. Lung Immunology / 279

19. Pulmonary Defense Mechanisms againstInfections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279Herbert Y. Reynolds & Jack A. Elias

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20. Lymphocyte- and Macrophage-MediatedInflammation in the Lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291Frederic F. Little, Kevin C. Wilson, Jeffrey S. Berman,& David M. Center

21. Mast Cells and Eosinophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307Edward S. Schulman & Peter H. S. Sporn

22. Antibody-Mediated Lung Defenses andHumoral Immunodeficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . 321David N. Weissman, Kenneth S. Landreth,& Nevin W. Wilson

Section Five. Lung Injury and Repair / 335

23. Cytokines and Chemokines in Lung Inflammationand Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335Robert M. Strieter, John A. Belperio, & Michael P. Keane

24. Leukocyte Accumulation in Pulmonary Disease . . .347Nicholas W. Lukacs & Peter A. Ward

25. Oxidative and Nitrosative Lung Injury . . . . . . . . . . . . . . . 359John D. Lang, Jr., Ian C. Davis, Rakesh P. Patel,& Sadis Matalon

26. The Pathogenesis of Pulmonary Fibrosis . . . . . . . . . . . .371Moises Selman & Annie Pardo

PART III SYMPTOMS AND SIGNS OF RESPIRATORYDISEASE .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385

Section Six. Clinical Approach to the Patient / 387

27. Approach to the Patient with RespiratorySymptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387Darren B. Taichman & Alfred P. Fishman

28. Skin Disease in Patients with PulmonaryDisease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427Jeffrey P. Callen

29. Pulmonary-Systemic Interactions. . . . . . . . . . . . . . . . . . . . .443Alfred P. Fishman

Section Seven. Diagnostic Procedures / 455

30. Radiographic Evaluation of the Chest. . . . . . . . . . . . . . . .455Wallace T. Miller

31. Pulmonary Cytopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511Prabodh K. Gupta & Zubair W. Baloch

32. Interventional Radiology in the Thorax:Nonvascular and Vascular Applications . . . . . . . . . . . . . .533Aalpen A. Patel & Scott O. Trerotola

33. Scintigraphic Evaluation of Pulmonary Disease . . . 547Abass Alavi, Daniel F. Worsley, & Ghassan El-Haddad

34. Pulmonary Function Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . 567Michael A. Grippi & Gregory Tino

35. Principles and Applications of CardiopulmonaryExercise Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .611Karl T. Weber & Ahmad Munir

36. Bronchoscopy, Transthoracic Needle Aspiration,and Related Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 629Anil Vachani, Luis Seijo, Michael Unger,& Daniel Sterman

37. Thoracoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649Larry R. Kaiser

38. Perioperative Respiratory Considerations. . . . . . . . . . .663Horace M. DeLisser & Michael A. Grippi

39. Evaluation of Impairment and Disability Due toLung Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 677Paul E. Epstein

PART IV OBSTRUCTIVE LUNG DISEASES.. . . . . . . . . . . . . .691

Section Eight. Chronic Obstructive PulmonaryDisease / 693

40. Pathologic Features of Chronic ObstructivePulmonary Disease: Diagnostic Criteria andDifferential Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .693Joanne L. Wright & Andrew Churg

41. Chronic Obstructive Pulmonary Disease:Epidemiology, Pathophysiology, andPathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 707Robert M. Senior & Jeffrey J. Atkinson

42. Chronic Obstructive Pulmonary Disease:Clinical Course and Management . . . . . . . . . . . . . . . . . . . . 729Robert A. Wise

43. Cigarette Smoking and Disease . . . . . . . . . . . . . . . . . . . . . . . 747Stephen I. Rennard, Lisa M. Hepp, & David M.Daughton

44. Rehabilitation in Chronic Obstructive PulmonaryDisease and Other Respiratory Disorders . . . . . . . . . . . 763Andrew L. Ries

Section Nine. Asthma / 773

45. The Biology of Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773Sameer K. Mathur & William W. Busse

46. Asthma: Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787Andrea J. Apter & Scott T. Weiss

47. Aspirin- and Exercise-Induced Asthma . . . . . . . . . . . . . .799Gregory P. Geba

48. Asthma: Clinical Presentation andManagement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .815Rodolfo M. Pascual, JeRay J. Johnson,& Stephen P. Peters

49. Allergic Bronchopulmonary Aspergillosis(Mycosis) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 837Geoffrey Chupp & Carolyn L. Rochester

Section Ten. Other Obstructive Disorders / 845

50. Upper Airway Obstruction in Adults . . . . . . . . . . . . . . . . . 845Sidney S. Braman & Muhanned A. Abu-Hijleh

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51. Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 863Judith Voynow & Thomas F. Scanlin

52. Bronchiolitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 887Talmadge E. King, Jr. & Brent W. Kinder

53. Bullous Disease of the Lung . . . . . . . . . . . . . . . . . . . . . . . . . . . .913David M. F. Murphy & Alfred P. Fishman

PART V OCCUPATIONAL AND ENVIRONMENTALDISORDERS.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .931

Section Eleven. Occupational Disorders / 933

54. Occupational Lung Disorders: General Principlesand Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 933Mridu Gulati & Carrie A. Redlich

55. Asbestos-Related Lung Disease . . . . . . . . . . . . . . . . . . . . . . .943William N. Rom

56. Chronic Beryllium Disease and Hard-MetalLung Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .959Mary Elizabeth Kreider & Milton D. Rossman

57. Coal Workers’ Lung Diseases and Silicosis . . . . . . . . . . 967Edward L. Petsonk & John E. Parker

58. Occupational Asthma, Byssinosis, and IndustrialBronchitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981J. Allen D. Cooper, Jr.

59. Acute and Chronic Responses to ToxicInhalations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 993Robert P. Dickson & David A. Schwartz

Section Twelve. Environmental Disorders / 1009

60. Indoor and Outdoor Air Pollution . . . . . . . . . . . . . . . . . . .1009Jonathan M. Samet & Mark J. Utell

61. High-Altitude Physiology and ClinicalDisorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1037Sukhamay Lahiri, Santhosh M. Baby, & CamilloDiGiulio

62. Diving Injuries and Air Embolism . . . . . . . . . . . . . . . . . . . 1045James M. Clark

63. Thermal Lung Injury and Acute SmokeInhalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1053Daniel L. Traber & Perenlei Enkhbaatar

PART VI DRUG-INDUCED LUNG DISEASES .. . . . . . . . . 1065

64. Pulmonary Toxicity Associated withChemotherapeutic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 1067Lynn T. Tanoue & John R. McArdle

65. Drug-Induced Lung Disease Due toNonchemotherapeutic Agents . . . . . . . . . . . . . . . . . . . . . . 1087Hilary C. Cain

PART VII INTERSTITIAL AND INFLAMMATORYLUNG DISEASES .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1103

Section Thirteen. Immunologic and InterstitialDiseases / 1105

66. Interstitial Lung Disease: A Clinical Overview andGeneral Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1105Michael A. Nead & David G. Morris

67. Systemic Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1125David R. Moller

68. Idiopathic Pulmonary Fibrosis . . . . . . . . . . . . . . . . . . . . . . . 1143Eric B. Meltzer & Paul W. Noble

69. Hypersensitivity Pneumonitis . . . . . . . . . . . . . . . . . . . . . . . .1161Richard I. Enelow

70. Radiation Pneumonitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1173Kenneth B. Roberts & Sara Rockwell

71. Pulmonary Manifestations of the CollagenVascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1193Gregory P. Cosgrove & Marvin I. Schwarz

72. The Eosinophilic Pneumonias . . . . . . . . . . . . . . . . . . . . . . . .1213Kristina Crothers & Carolyn L. Rochester

Section Fourteen. Depositional and InfiltrativeDisorders / 1233

73. Depositional Diseases of the Lungs. . . . . . . . . . . . . . . . .1233Robert J. Homer

74. Pulmonary Langerhan’s-Cell Histiocytosis. . . . . . . . .1245Talmadge E. King, Jr.

75. Pulmonary Lymphangioleiomyomatosis . . . . . . . . . . 1255Talmadge E. King, Jr.

76. The Lungs in Patients with Inborn Errors ofMetabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1265Masazuni Adachi & Francis A. Caccavo

PART VIII ALVEOLAR DISEASES .. . . . . . . . . . . . . . . . . . . . . . . 1279

77. Alveolar Hemorrhage Syndromes . . . . . . . . . . . . . . . . . . 1281Joseph P. Lynch, III & James W. Leatherman

78. Mechanisms of Aspiration Disorders . . . . . . . . . . . . . . . 1299Richard D. Zorowitz

79. Pulmonary Alveolar Proteinosis . . . . . . . . . . . . . . . . . . . . . 1313Bruce C. Trapnell & Jonathan Puchalski

Appendixes

Appendix A: Normal Values: Typical Values fora 20-Year-Old Seated Man . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1323

Appendix B: Terms and Symbols in RespiratoryPhysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1325

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I-1

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Contents

Volume 2

PART IX DISORDERS OF THE PULMONARYCIRCULATION... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1329

80. The Pulmonary Circulation . . . . . . . . . . . . . . . . . . . . . . . . . . . 1331Alfred P. Fishman

81. Pulmonary Hypertension and Cor Pulmonale . . . . 1359Darren B. Taichman & Alfred P. Fishman

82. Pulmonary Thromboembolic Disease . . . . . . . . . . . . . .1423Gordon L. Yung & Peter F. Fedullo

83. Pulmonary Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1449Ulrich Specks

84. Pulmonary Arteriovenous Malformations . . . . . . . . . 1467Daniel M. Goodenberger

PART X DISORDERS OF THE PLEURAL SPACE .. . . . . 1485

85. Non-Malignant Pleural Effusions . . . . . . . . . . . . . . . . . . . . 1487Martin L. Mayse

86. Malignant Pleural Effusions. . . . . . . . . . . . . . . . . . . . . . . . . . .1505Steven A. Sahn

87. Pneumothorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1517Deborah J. Levine, Edward Y. Sako, & Jay Peters

88. Malignant Mesothelioma and Other PrimaryPleural Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1535Daniel H. Sterman, Leslie A. Litzky, & Steven M. Albelda

PART XI DISEASES OF THE MEDIASTINUM ... . . . . . . . 1553

89. Nonneoplastic Disorders of theMediastinum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1555Cameron D. Wright

90. Congenital Cysts of the Mediastinum:Bronchopulmonary Foregut Anomalies . . . . . . . . . . . 1571Neel R. Sodha & Malcolm M. DeCamp, Jr.

91. Acquired Lesions of the Mediastinum: Benignand Malignant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1583John R. Roberts & Larry R. Kaiser

PART XII DISORDERS OF THE CHEST WALL,DIAPHRAGM, AND SPINE .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1615

92. Nonmuscular Diseases of the Chest Wall . . . . . . . . . . 1617George E. Tzelepis & F. Dennis McCool

93. Effects of Neuromuscular Diseases onVentilation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1635Gerard Joseph Criner & Nathaniel Marchetti

94. Management of Neuromuscular RespiratoryMuscle Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1667John R. Bach

PART XIII SLEEP AND SLEEP DISORDERS .. . . . . . . . . . . 1677

95. The Stages of Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1679Adrian R. Morrison

96. Changes in the Cardiorespiratory SystemDuring Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1689Allan I. Pack

97. Sleep Apnea Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1697N. P. Patel & R. J. Schwab

98. Differential Diagnosis and Evaluation ofSleepiness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1727Charles F. P. George & Meir H. Kryger

PART XIV SURGICAL ASPECTS OF PULMONARYMEDICINE .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1737

99. Perioperative Care of the Patient UndergoingLung Resection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1739Robert J. Cerfolio

100. Thoracic Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1757Larry R. Kaiser & Francis W. DiPierro

101. Lung Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1769John C. Wain

PART XV NEOPLASMS OF THE LUNGS.. . . . . . . . . . . . . . .1799

Section Fifteen. Cancer of the Lungs / 1801

102. Genetic and Molecular Changes of HumanLung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1801Jeffrey A. Kern & Geoffrey McLennan

103. The Solitary Pulmonary Nodule: A SystematicApproach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1815David Ost & Alan M. Fein

104. The Pathology of Non–Small Cell LungCarcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1831Leslie A. Litzky

105. Part I: Treatment of Non–Small-Cell Lung Cancer:Surgical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1851Larry R. Kaiser

105. Part II: Treatment of Non-Small-Cell LungCancer: Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1867Ranee Mehra & Joseph Treat

105. Part III: Treatment of Non–Small-Cell LungCancer: Radiation Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . .1883Mitchell Machtay

106. Small Cell Lung Cancer: Diagnosis, Treatment,and Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1899Kevin Palka & David H. Johnson

107. Primary Lung Tumors Other Than BronchogenicCarcinoma: Benign and Malignant . . . . . . . . . . . . . . . . . .1917Reshma Biniwale & Steven M. Keller

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108. Extrapulmonary Syndromes Associated with LungTumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1929Bruce E. Johnson & John P. Chute

109. Pulmonary Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1941Richard S. Lazzaro & Joseph LoCicero, III

Section Sixteen. Lymphoproliferative Disorders / 1947

110. Lymphoproliferative and Hematologic DiseasesInvolving the Lung and Pleura. . . . . . . . . . . . . . . . . . . . . . .1947Douglas B. Flieder

PART XVI INFECTIOUS DISEASES OF THELUNGS .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1967

Section Seventeen. General Concepts / 1969

111. Pulmonary Clearance of Infectious Agents . . . . . . . 1969Galen B. Toews

112. Approach to the Patient with PulmonaryInfection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1981Jay A. Fishman

113. The Radiology of Pulmonary Infection . . . . . . . . . . . . . 2017Reginald E. Greene

114. The Pathology of Pulmonary Infection. . . . . . . . . . . . .2031Richard Kradin

115. Principles of Antibiotic Use and the Selection ofEmpiric Therapy for Pneumonia . . . . . . . . . . . . . . . . . . . . .2051Michael S. Niederman

116. Vaccination against Pulmonary Infections . . . . . . . . 2065Michael S. Simberkoff

117. Microbial Virulence Factors in PulmonaryInfections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2077Gregory Priebe & Gerald B. Pier

Section Eighteen. Common Syndromes in PulmonaryInfectious Diseases / 2085

118. Infections of the Upper Respiratory Tract . . . . . . . . . 2085Marlene L. Durand

119. Acute Bronchitis and Community-AcquiredPneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2097Thomas J. Marrie

120. Acute Exacerbations of Chronic ObstructivePulmonary Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2115Fernando J. Martinez & Jeffrey L. Curtis

121. Pneumonia in Childhood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2125Mark S. Pasternack

122. Aspiration, Empyema, Lung Abscesses, andAnaerobic Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2141Jay A. Fishman

123. Mediastinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2161Mark E. Rupp & Mary L. Ricardo-Dukelow

124. Microbiology and Infection in Cystic Fibrosis . . . . .2173Scott H. Donaldson & Richard C. Boucher

125. Bronchiectasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2183Alan F. Barker & Sheela Y. Ahmed

Section Nineteen. Pulmonary Infections in SpecialHosts / 2193

126. Pneumonia in Surgery and Trauma . . . . . . . . . . . . . . . . .2193Judith Hellman & Luca Bigatello

127. Pulmonary Infection in ImmunocompromisedHosts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2203Jay A. Fishman

128. Human Immunodeficiency Virus and PulmonaryInfections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2241John J.W. Fangman & Paul E. Sax

Section Twenty. Major Pathogens in PulmonaryInfections / 2265

129. Pneumonia Caused by Gram-Positive Bacteria. . .2265Thomas A. Cumbo & Timothy F. Murphy

130. Nosocomial Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2273Jay A. Fishman

131. Aspergillus, Candida, and Other OpportunisticMold Infections of the Lung . . . . . . . . . . . . . . . . . . . . . . . . . . 2291Georgios Chamilos & Dimitrios P. Kontoyiannis

132. Cryptococcosis and the Endemic Mycoses . . . . . . . .2327L. Joseph Wheat, Mitchell Goldman, & Kenneth Knox

133. Pneumocystis Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2351Jay A. Fishman

134. Viral Infections of the Lung and RespiratoryTract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2373John Treanor

135. Protozoan Infections of the Thorax . . . . . . . . . . . . . . . . .2397Louise C. Ivers & Edward T. Ryan

136. Helminthic Diseases of the Lungs . . . . . . . . . . . . . . . . . . .2413Jay A. Fishman

137. Zoonotic and Other Unusual BacterialPneumonias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2427Arnold N. Weinberg & Camille Nelson Kotton

Section Twenty-One. Mycobacterial Infections / 2447

138. The Epidemiology, Prevention, and Control ofTuberculosis in the United States . . . . . . . . . . . . . . . . . . . 2447Philip A. LoBue, Michael F. Iademarco,& Kenneth G. Castro

139. The Microbiology, Virulence, and Immunology ofMycobacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2459Jennifer A. Philips & Eric J. Rubin

140. Clinical Presentation and Treatment ofTuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2467Mary Elizabeth Kreider & Milton D. Rossman

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141. Mycobacterial Infections and HIV Infection . . . . . . .2487Petros C. Karakousis & Richard E. Chaisson

142. Diseases due to Non-TuberculousMycobacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2499Jay A. Fishman

PART XVII ACUTE RESPIRATORY FAILURE .. . . . . . . . . . 2507

Section Twenty-Two. Lung Failure / 2509

143. Respiratory Failure: An Overview . . . . . . . . . . . . . . . . . . . .2509Michael A. Grippi

144. Acute Respiratory Distress Syndrome:Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2523Michael A. Matthay

145. Acute Lung Injury and the Acute RespiratoryDistress Syndrome: Clinical Features,Management, and Outcomes . . . . . . . . . . . . . . . . . . . . . . . .2535Jason D. Christie & Paul N. Lanken

146. Sepsis, Systemic Inflammatory ResponseSyndrome, and Multiple Organ DysfunctionSyndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2561Stuart F. Sidlow & Clifford S. Deutschman

147. Acute Respiratory Failure in the SurgicalPatient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2573Robert M. Kotloff

Section Twenty-Three. Respiratory PumpFailure / 2591

148. Pump Failure: The Pathogenesis of HypercapnicRespiratory Failure in Patients with Lung andChest Wall Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2591Steven G. Kelsen & Nathaniel Marchetti

Section Twenty-Four. Management and TherapeuticInterventions / 2613

149. Oxygen Therapy and Pulmonary OxygenToxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2613Michael F. Beers

150. Pulmonary Pharmacotherapy. . . . . . . . . . . . . . . . . . . . . . . .2631Karen J. Tietze & Scott Manaker

151. Intubation and Upper Airway Management . . . . . .2645C. William Hanson III & Erica R. Thaler

152. Hemodynamic and Respiratory Monitoring inAcute Respiratory Failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2659Barry D. Fuchs & Patrick Neligan

153. Principles of Mechanical Ventilation. . . . . . . . . . . . . . . .2675Martin J. Tobin

154. Nutrition in Acute Respiratory Failure . . . . . . . . . . . . . .2691Lisa M. Bellini

155. Treatment of Agitation in the IntensiveCare Unit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2701John P. Kress & Jesse B. Hall

156. Decision Making in the Intensive Care Unit . . . . . . .2713Bruno DiGiovine & Mark A. Kelley

157. Ethics in the Intensive Care Unit. . . . . . . . . . . . . . . . . . . . .2721Paul L. Lanken

Appendixes

Appendix A: Normal Values: Typical Values fora 20-Year-Old Seated Man . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2735

Appendix B: Terms and Symbols in RespiratoryPhysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2737

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I-1

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Contributors

Muhanned A. Abu-Hijleh, MD, FCCPDirector, Interventional Pulmonology and Special

Procedures UnitClinical Assistant Professor of MedicineRhode Island Hospital/Brown Medical SchoolDivision of Pulmonary, Sleep, and Critical Care MedicineProvidence, Rhode Island

Masazuni Adachi, MD, ScDProfessor of PathologyState University of New YorkDownstate Medical CenterConsultantDepartment of LaboratoriesIsaac Albert Research InstituteKingsbrook Jewish Medical CenterBrooklyn, New York

Sheela Y. Ahmed, MDFellow, Division of Pulmonary and Critical Care MedicineOregon Health and Sciences UniversityPortland, Oregon

Abass Alavi, MDProfessor of Radiology and Director of Research EducationDivision of Nuclear MedicineHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Steven M. Albelda, MDWilliam Maul Measey Professor of MedicinePulmonary, Allergy, and Critical Care DivisionUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Murray D. Altose, MDProfessor of MedicineCase Western Reserve University School of MedicineChief of StaffCleveland VA Medical CenterCleveland, Ohio

Andrea J. Apter, MD, MScAssociate Professor of MedicineUniversity of PennsylvaniaSection of Allergy and ImmunologyDivision of Pulmonary Allergy Critical Care MedicineUniversity of Pennsylvania Health SystemPhiladelphia, Pennsylvania

Jeffrey J. Atkinson, MDAssistant ProfessorDivision of Pulmonary and Critical CareWashington University School of MedicineSt. Louis, Missouri

Santhosh M. Baby, PhDPostdoctoral Research FellowDepartment of Physiology and Pennsylvania Muscle InstituteUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

John R. Bach, MDProfessor of Physical Medicine and RehabilitationProfessor of NeurosciencesVice ChairmanDepartment of Physical Medicine and RehabilitationUMDNJ-New Jersey Medical SchoolNewark, New Jersey

Zubair W. Baloch, MD, PhDAssociate Professor Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicineStaff PathologistHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Alan F. Barker, MDProfessor of MedicineDivision of Pulmonary and Critical Care MedicineOregon Health and Sciences UniversityPortland, Oregon

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Contributors

Michael F. Beers, MDAssociate Professor of MedicinePulmonary and Critical Care DivisionDepartment of MedicineUniversity of Pennsylvania School of

MedicinePhiladelphia, Pennsylvania

Lisa M. Bellini, MDAssociate Professor of MedicineUniversity of Pennsylvania School of


Saverio Bellusci, PhDThe Developmental Biology ProgramSaban Research InstituteChildren’s Hospital of Los AngelesUniversity of Southern California Keck School of

Medicine and School of DentistryLos Angeles, California

John A. Belperio, MDAssistant Professor of MedicineDivision of Pulmonary and Critical Care

MedicineDavid Geffen School of Medicine at UCLALos Angeles, California

Jeffrey S. Berman, MDProfessor of MedicineBoston University School of MedicineChief, Pulmonary Medicine and Associate

Chief, Medical ServiceBoston Veterans Administration Health CareBoston, Massachusetts

Luca Bigatello, MDDepartment of Anesthesia and Critical CareMassachusetts General HospitalDepartment of AnesthesiaHarvard Medical SchoolBoston, Massachusetts

Reshma Biniwale, MDCardiothoracic Surgery FellowDepartment of Cardiothoracic SurgeryMontefiore Medical CenterBronx, New York

Richard C. Boucher, MDKenan Professor of MedicineDirector, Cystic Fibrosis/Pulmonary Research and

Treatment CenterUniversity of North CarolinaChapel Hill, North Carolina

Sidney S. Braman, MD, FCCPDirector, Division of PulmonaryPulmonary, Sleep, and Critical Care MedicineProfessor of MedicineRhode Island Hospital/Brown Medical SchoolProvidence, Rhode Island

Peter H. Burri, MDInstitute of AnatomyUniversity of BernBern, Switzerland

William W. Busse, MDProfessor and Chair of MedicineUniversity of Wisconsin Medical SchoolMadison, Wisconsin

Francis A. Caccavo, MSChief of the Core LaboratoryKingsbrook Jewish Medical CenterBrooklyn, New York

Hilary C. Cain, MDAssistant ProfessorDepartment of Internal MedicineSection of Pulmonary and Critical Care MedicineYale University School of MedicineNew Haven, Connecticut

Jeffrey P. Callen, MDProfessor of Medicine (Dermatology)Chief, Division of DermatologyUniversity of LouisvilleLouisville, Kentucky

Edward J. Campbell, MB, BS, FRACP, PhDDepartment of Internal MedicineUniversity of Utah Health CareSalt Lake City, Utah

Kenneth G. Castro, MDCenters for Disease Control and PreventionDivision of Tuberculosis EliminationAtlanta, Georgia

David M. Center, MDChief, Pulmonary, Allergy, and Critical Care MedicineGordon and Ruth Snider Professor of Pulmonary MedicineProfessor of Medicine and BiochemistryBoston University School of MedicineBoston, Massachusetts

Robert J. Cerfolio, MD, FACS, FCCPProfessor of SurgeryDepartment of General SurgeryDivision of Cardiothoracic SurgeryChief of Section of Thoracic SurgeryUniversity of AlabamaBirmingham, Alabama

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Contributors

Richard E. Chaisson, MDProfessor of MedicineEpidemiology and International HealthJohns Hopkins University School of MedicineBaltimore, Maryland

Georgios Chamilos, MDPostdoctoral Research FellowDepartment of Infectious DiseasesInfection Control and Employee HealthThe University of Texas M. D. Anderson Cancer

CenterHouston, Texas

Neil S. Cherniack, MDCase Western Reserve UniversityCleveland, OhioNew Jersey School of MedicineUniversity of Medicine and DentistryNewark, New Jersey

Jason D. Christie, MD, MSCEAssistant Professor of MedicineDivision of PulmonaryPulmonary, Allergy and Critical Care Medicine

Department of MedicineAssistant Professor of EpidemiologyDepartment of Biostatistics and EpidemiologySenior FellowCenter of Epidemiology and BiostatisticsUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Geoffrey Chupp, MDAssociate Professor of MedicineDirector, Yale Center for Asthma and Airways DiseaseDivision of Pulmonary and Critical Care MedicineYale School of MedicineNew Haven, Connecticut

Andrew Churg, MD, PhDProfessor, Department of PathologyUniversity of British ColumbiaVancouver, British Columbia, Canada

John P. Chute, MDAssociate Professor of MedicineAssistant Professor of Pharmacology and Cancer

BiologyDivision of Cellular TherapyDuke University Medical CenterDurham, North Carolina

James M. Clark, MDInstitute for Environmental MedicineUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

J. Allen D. Cooper, Jr., MDUniversity of Alabama HospitalBirmingham, Alabama

Gregory P. Cosgrove, MDAssistant Professor and Assistant DirectorInterstitial Lung Disease ProgramNational Jewish Medical and Research CenterUniversity of Colorado Health Sciences CenterDenver, Colorado

Gerard J. Criner, MDProfessor of MedicineChair, Division of Pulmonary and Critical Care

MedicineTemple University School of MedicinePhiladelphia, Pennsylvania

Kristina Crothers, MDAssistant Professor of MedicineSection of Pulmonary and Critical CareDepartment of Internal MedicineYale University School of MedicineNew Haven, Connecticut

Thomas A. Cumbo, MDClinical Associate Professor of MedicineUniversity at BuffaloState University of New YorkBuffalo, New York

Jeffrey L. Curtis, MDProfessorDepartment of Internal MedicineUniversity of Michigan Medical SchoolAnn Arbor, Michigan

David M. DaughtonUniversity of Nebraska Medical CenterOhama, Nebraska

Ian C. Davis, DVM, PhDAssistant ProfessorDepartment of AnesthesiologyUniversity of Alabama at BirminghamBirmingham, Alabama

Malcolm M. DeCamp, Jr., MDChief, Division of Cardiothoracic SurgeryBeth Israel Deaconess Medical CenterBoston, Massachusetts

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xvi

Contributors

Marc DecramerRespiratory Division University HospitalKatholieke Universiteit LeuvenAfdeling PneumologieLeuven, Belgium

Stijn DeLanghe, PhDThe Developmental Biology ProgramSaban Research InstituteChildren’s Hospital Los AngelesUniversity of Southern California Keck School of


Pierre Del MoralThe Developmental Biology ProgramSaban Research InstituteChildren’s Hospital Los AngelesUniversity of Southern California Keck School of


Horace M. DeLisser, MDPulmonary, Allergy, and Critical Care DivisionHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Clifford S. Deutschman, MS, MD, FCCMProfessor of Anesthesiology and Critical Care

and SurgeryUniversity of Pennsylvania School of


Robert P. Dickson, MDDepartment of MedicineUniversity of WashingtonSeattle, Washington

Camillo DiGiulio, MDProfessorDepartment of Biomedical SciencesG. d’Annunzio UniversityChieti-Pescara, Italy

Francis W. DiPierro, MDEastern Maine Medical CenterBangor, Maine

Scott H. Donaldson, MDAssistant Professor of MedicineUniversity of North CarolinaChapel Hill, North Carolina

Marlene L. Durand, MDAssistant ProfessorHarvard Medical SchoolDirector, Infectious Disease ServiceMassachusetts Eye and Ear InfirmaryAssociate PhysicianMassachusetts General HospitalBoston, Massachusetts

Ghassan El-Haddad, MDDepartment of Nuclear OncologyDivision of Nuclear MedicineHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Jack A. Elias, MDWaldemar Von Zedtwitz Professor of

MedicineChair, Department of Internal MedicineYale University School of MedicineNew Haven, Connecticut

Richard I. Enelow, MDAssociate Professor of MedicineYale University School of MedicineNew Haven, ConnecticutVA Connecticut Health Care SystemWest Haven, Connecticut

Perenlei Enkhbaatar, MD, PhDAssistant ProfessorThe University of Texas Medical BranchGalveston, Texas

Paul E. Epstein, MDClinical Professor of MedicineUniversity of PennsylvaniaPhiladelphia, Pennsylvania

John J. W. Fangman, MDAssistant Professor of MedicineDivision of Infectious DiseaseMedical College of WisconsinMilwaukee, Wisconsin

Peter F. Fedullo, MDDirectorMedical Intensive Care UnitProfessor of Clinical MedicineUniversity of CaliforniaSan Diego, California

Alan M. Fein, MDProHealth Care AssociatesLake Success, New York

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Contributors

Steven H. Feinsilver, MDAssociate Professor of Medicine (Clinical)New York University School of MedicineNew York, New YorkDirectorPulmonary and Sleep MedicineCardiovascular Medical AssociatesGarden City, New York

Alfred P. Fishman, MDWilliam Maul Measey Professor of MedicineUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Jay A. Fishman, MDAssociate Professor of MedicineHarvard Medical SchoolDirectorTransplant Infectious Disease and Compromised

Host ProgramMassachusetts General HospitalAssociate DirectorMGH Transplantation CenterBoston, Massachusetts

Douglas B. Flieder, MDDepartment of PathologyFox Chase Cancer CenterPhiladelphia, Pennsylvania

Barry D. Fuchs, MDPulmonary, Allergy, and Critical Care DivisionHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Gregory P. Geba, MDAssistant Professor of Pulmonary MedicineDepartment of Internal MedicineYale UniversityNew Haven, Connecticut

Charles F. P. George, MD, FRCPC, FCCP, DABSMProfessor of MedicineUniversity of Western OntarioDirectorSleep Medicine Clinic and LaboratoryLondon Health Sciences CentreLondon, Ontario, Canada

Stanley Goldfarb, MDAssociate DeanClinical EducationUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Mitchell Goldman, MDAssociate Professor of MedicineIndiana University School of MedicineIndianapolis, Indiana

Daniel M. Goodenberger, MDProfessor and ChairDepartment of Internal MedicineUniversity of Nevada School of MedicineLas Vegas, Nevada

Reginald E. Greene, MDRadiology DivisionMassachusetts General HospitalBoston, Massachusetts

Michael A. Grippi, MDVice Chairman, Department of MedicinePulmonary, Allergy, and Critical Care DivisionUniversity of Pennsylvania Health SystemChief of Medicine, Philadelphia VA Medical CenterPhiladelphia, Pennsylvania

Mridu Gulati, MD, MPHAssistant Professor of MedicinePulmonary and Critical Care MedicineOccupational and Environmental MedicineDepartment of MedicineYale University School of MedicineNew Haven, Connecticut

Prabodh K. Gupta, MB, MDProfessor Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicineDirector Cytopathology and CytometryHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Jesse B. Hall, MDProfessor of MedicineDepartment of MedicineSection of Pulmonary and Critical CareUniversity of ChicagoChicago, Illinois

C. William Hanson III, MDProfessor of Anesthesiology and Critical CareSurgery and Internal MedicineUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Judith Hellman, MDDepartment of Anesthesia and Critical CareMassachusetts General HospitalCharlestown, Massachusetts

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Contributors

Lisa M. HeppUniversity of Nebraska Medical CenterOmaha, Nebraska

Michael P. Hlastala, PhDProfessor of Physiology and Biophysics and

MedicineUniversity of WashingtonSeattle, Washington

Robert J. Homer, MD, PhDAssociate Professor of PathologyDepartment of PathologyYale University School of MedicineDirector of Anatomic PathologyVA Connecticut Healthcare SystemNew Haven, Connecticut

Michael F. Iademarco, MD, MPHCenters for Disease Control and PreventionDivision of Tuberculosis EliminationAtlanta, Georgia

Louise C. Ivers, MD, MPH, DTM&HPartners In HealthHarvard Medical SchoolDivision of Infectious DiseasesMassachusetts General HospitalBoston, Massachusetts

Bruce E. Johnson, MDAssociate Professor of MedicineHarvard Medical SchoolBoston, Massachusetts

David H. Johnson, MDCornelius A. Craig Professor of MedicineDirectorDivision of Hematology and OncologyVanderbilt-Ingram Cancer CenterNashville, Tennessee

JeRay J. Johnson, MDFellow in Pulmonary and Critical Care MedicineSection on Pulmonary, Critical CareCare, Allergy and Immunologic DiseasesDepartment of Internal MedicineWake Forest University School of MedicineWinston-Salem, North Carolina

Larry R. Kaiser, MDJohn Rhea Barton Professor and ChairmanDepartment of SurgeryUniversity of PennsylvaniaPhiladelphia, Pennsylvania

Petros C. Karakousis, MDAssistant ProfessorCenter for Tuberculosis ResearchJohns Hopkins University School of MedicineBaltimore, Maryland

Michael P. Keane, MDDepartment of MedicineDivision of Pulmonary and Critical Care MedicineUCLALos Angeles, California

Steven M. Keller, MDDepartment of Cardiothoracic SurgeryMontefiore Medical CenterBronx, New York

Mark A. Kelley, MDExecutive Vice PresidentHenry Ford Health SystemDetroit, Michigan

Steven G. Kelsen, MDDivision of Pulmonary MedicineTemple University HospitalPhiladelphia, Pennsylvania

Jeffrey A. Kern, MDProfessor, Case Western Reserve UniversityDivision Chief, Pulmonology/Critical Care and

Sleep MedicineUniversity HospitalsCleveland, Ohio

Brent W. Kinder, MDPulmonary FellowDepartment of MedicineUniversity of CaliforniaSan Francisco, California

Talmadge E. King, Jr., MDThe Constance B. Wofsy Distinguished Professor

and Vice-ChairmanDepartment of MedicineUniversity of CaliforniaSan FranciscoChief, Medical ServicesSan Francisco General HospitalSan Francisco, California

Robert A. Klocke, MDProfessor Emeritus of Medicine and Physiology nd BiophysicsUniversity of BuffaloErie County Medical CenterBuffalo, New York

Kenneth Knox, MDRichard L. Roudebush Veterans’ Administration HospitalIndianapolis, Indiana

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xix

Contributors

Dimitrios P. Kontoyiannis, MD, ScD,FACP, FIDSA

Associate Professor of MedicineDirector of Clinical MycologyDepartment of Infectious DiseasesInfection Control and Employee HealthThe University of Texas M. D. Anderson Cancer

CenterHouston, Texas

Robert M. Kotloff, MDProfessor of MedicinePulmonary, Allergy, and Critical Care DivisionDepartment of MedicineUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Camille Nelson Kotton, MDInfectious Diseases UnitMassachusetts General HospitalBoston, Massachusetts

Richard Kradin, MDAssociate ProfessorHarvard Medical SchoolDirector of Infectious Disease PathologyDepartment of Pathology and the Pulmonary and

Critical Care UnitMassachusetts General HospitalBoston, Massachusetts

Mary Elizabeth Kreider, MDPulmonary and Critical Care SectionHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

John P. Kress, MDAssistant Professor of MedicineDepartment of MedicineSection of Pulmonary and Critical CareUniversity of ChicagoChicago, Illinois

Meir H. Kryger, MD, FRCPCSleep Disorders CenterSt. Boniface General HospitalSection of Respiratory DiseasesUniversity of Manitoba, WinnipegManitoba, Canada

Sukhamay Lahiri, D Phil (Oxon),D Phil (Cal)

ProfessorDepartment of PhysiologyUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Kenneth S. Landreth, PhDProfessor of MicrobiologyImmunology and Cell BiologyWest Virginia University School of MedicineMorgantown, West Virginia

John D. Lang, Jr., MDAssociate ProfessorDepartment of AnesthesiologyUniversity of Alabama at BirminghamBirmingham, Alabama

Paul N. Lanken, MDProfessor of MedicineDivision of PulmonaryAllergy and Critical Care MedicineDepartment of MedicineProfessor of Medical EthicsDepartment of Medical EthicsSenior Fellow, Center for BioethicsUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Richard S. Lazzaro, MDAttending SurgeonMaimonides Medical CenterBrooklyn, New York

James W. Leatherman, MDHennepin Faculty AssociatesHennepin County Medical CenterMinneapolis, Minnesota

Deborah J. Levine, MDAssistant ProfessorDivision of Pulmonary DiseaseDepartment of MedicineThe University of Texas Health Science CenterSan Antonio, Texas

Frederic F. Little, MDAssistant Professor of MedicineBoston University School of MedicineBoston, Massachusetts

Leslie A. Litzky, MDAssociate ProfessorDepartment of Pathology and Laboratory MedicineDirectorSection of Medical PathologyUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Philip A. LoBue, MDCenters for Disease Control and PreventionDivision of Tuberculosis EliminationAtlanta, Georgia

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Contributors

Joseph LoCicero, III, MDDirector Surgical Oncology Maimonides Cancer

CenterBrooklyn, New York

Nicholas W. Lukacs, PhDDepartment of PathologyUniversity of Michigan Medical SchoolAnn Arbor, Michigan

Joseph P. Lynch III, MDProfessor of Clinical MedicineAssociate Chief, Division of Pulmonary,

Critical Care Medicine, and HospitalistsDavid Geffen School of Medicine at UCLALos Angeles, California

Mitchell Machtay, MDWalter J. Curran Associate Professor and

Vice ChairDepartment of Radiation OncologyJefferson Medical CollegePhiladelphia, Pennsylvania

Scott Manaker, MD, PhDAssociate Professor of MedicinePulmonary, Allergy and Critical Care

DivisionUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Nathaniel Marchetti, DOAssistant Professor of MedicineDivision of Pulmonary and Critical Care

MedicineTemple University School of MedicinePhiladelphia, Pennsylvania

Thomas J. Marrie, MDDeanFaculty of Medicine and DentistryWalter C. Mackenzie Health Sciences

CenterEdmonton, Alberta, Canada

Fernando J. Martinez, MD, MSProfessor of Internal MedicineUniversity of Michigan Medical SchoolAnn Arbor, Michigan

Sadis Matalon, PhDProfessorDepartment of AnesthesiologyUniversity of Alabama at BirminghamBirmingham, Alabama

Sameer K. Mathur, MD, PhDClinical InstructorUniversity of Wisconsin Medical SchoolMadison, Wisconsin

Michael A. Matthay, MDProfessorMedicine and AnesthesiaSenior AssociateCardiovascular Research InstituteAssociate DirectorIntensive Care UnitUniversity of CaliforniaSan Francisco, California

Martin L. Mayse, MDAssistant Professor of Medicine and SurgeryDirector, Interventional PulmonologyWashington UniversitySt. Louis, Missouri

John R. McArdle, MDAssistant Professor of MedicinePulmonary and Critical Care SectionYale University School of MedicineNew Haven, Connecticut

F. Dennis McCool, MDProfessor of MedicineBrown University Medical SchoolChief, Pulmonary Critical Care MedicineMemorial Hospital of Rhode IslandPawtucket, Rhode Island

Paul B. McCray, Jr., MDProfessorDepartment of PediatricsRoy J. and Lucille A. Carver College of MedicineUniversity of IowaIowa City, Iowa

Geoffrey McLennan, MD, PhDProfessor, Pulmonary, Critical Care, and

Occupational MedicineUniversity of IowaIowa City, Iowa

Ranee Mehra, MDAssociate MemberFox Chase Cancer CenterPhiladelphia, Pennsylvania

Eric B. Meltzer, MDFellowDepartment of MedicineDivision of Pulmonary, Allergy, and Critical CareDuke University Medical CenterDurham, North Carolina

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Contributors

Wallace T. Miller, MDEmeritus ProfessorDepartment of RadiologyUniversity of Pennsylvania School of MedicineUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

David R. Moller, MDAssociate Professor of MedicineJohns Hopkins University School of MedicineBaltimore, Maryland

David G. Morris, MDAssistant Professor of MedicineDirectorInterstitial Lung Diseases ProgramYale University School of MedicineDivision of Pulmonary and Critical Care

MedicineYale-New Haven HospitalNew Haven, Connecticut

Adrian R. Morrison, DVM, PhDProfessorLaboratory for Study of the Brain in SleepDepartment of Animal BiologySchool of Veterinary MedicineUniversity of PennsylvaniaPhiladelphia, Pennsylvania

Ahmad MunirAssistant Professor of MedicineUniversity of Tennessee Health Science CenterMemphis, Tennessee

David M. F. Murphy, MDDeborah Heart and Lung CenterBrowns Mills, New Jersey

Timothy F. Murphy, MDUB Distinguished Professor of MedicineChief, Division of Infectious DiseasesUniversity at BuffaloState University of New YorkBuffalo, New York

Michael A. Nead, MD, PhDSenior Instructor in MedicinePulmonary and Critical CareDepartment of Internal MedicineUniversity of Rochester Medical CenterStrong Memorial Hospital and Highland HospitalDepartment of Pulmonary and Critical CareRochester, New York

Patrick Neligan, MDDepartment of AnesthesiaHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Michael S. Niederman, MDProfessor and Vice-ChairmanDepartment of MedicineSUNY at Stony BrookStony Brook, New YorkChairmanDepartment of MedicineWinthrop-University HospitalMineola, New York

Paul W. Noble, MDProfessor of Medicine and Division ChiefDepartment of Pulmonary, Allergy, and Critical

Care MedicineDuke University School of MedicineDurham, North Carolina

Matthias Ochs, MDLecturerExperimental Morphology UnitInstitute of AnatomyUniversity of BerneBerne, Switzerland

David Ost, MDDepartment of Cardiothoracic SurgeryDivision of Thoracic SurgeryNew York UniversityNew York, New York

Allan I. Pack, MB, ChB, PhDProfessor of MedicineChief, Division of Sleep Medicine/Department of MedicineDirectorCenter for Sleep and Respiratory NeurobiologyUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Kevin Palka, MDInstructor in MedicineDivision of Hematology and OncologyVanderbilt-Ingram Cancer CenterNashville, Tennessee

Reynold A. Panettieri, Jr., MDPulmonary, Allergy and Critical Care DivisionUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Annie Pardo, PhDFacultad de CienciasUniversidad Nacional Autonoma de MexicoCiudad Universitaria, Mexico

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Contributors

John E. Parker, MDProfessor and Section ChiefSection of Pulmonary and Critical Care MedicineRobert C. Byrd Health Sciences CenterWest Virginia University School of MedicineMorgantown, West Virginia

Rodolfo M. Pascual, MDAssistant Professor of MedicineSection on PulmonaryCritical Care, Allergy and Immunologic DiseasesDepartment of Internal MedicineWake Forest University School of MedicineWinston-Salem, North Carolina

Mark S. Pasternack, MDAssociate Professor of PediatricsDivision of Infectious DiseasesMassachusetts General HospitalBoston, Massachusetts

Aalpen A. Patel, MDAssistant Professor of Radiology and SurgeryDepartment of RadiologyInterventional RadiologyUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Nirav P. Patel, MDDivision of Sleep MedicineUniversity of PennsylvaniaPhiladelphia, Pennsylvania

Rakesh P. Patel, PhDAssistant ProfessorDepartment of PathologyUniversity of Alabama at BirminghamBirmingham, Alabama

Jay Peters, MDDivision Chief and Fellowship DirectorDivision of Pulmonary Disease/Critical CareProfessor, Department of MedicineThe University of Texas Health Science CenterSan Antonio, Texas

Stephen P. Peters, MD, PhD, FACP, FCCP,FAAAAI, FCPP

Professor of Medicine and PediatricsDirector of ResearchSection on Pulmonary, Critical CareAllergy and Immunologic DiseasesTraining Program Director, Allergy and ImmunologyDepartment of Internal Medicine and Center for Human

GenomicsWake Forest University School of MedicineWinston-Salem, North Carolina

Edward L. Petsonk, MDAdjunct ProfessorSection of Pulmonary and Critical Care MedicineRobert C. Byrd Health Sciences CenterWest Virginia University School of MedicineSenior Medical OfficerDivision of Respiratory Disease StudiesNational Institute for Occupational Safety and HealthMorgantown, West Virginia

Jennifer A. Philips, MD, PhDAssociate PhysicianDepartment of MedicineDivision of Infectious DiseasesBrigham and Women’s HospitalBoston, Massachusetts

Gerald B. Pier, PhDProfessor of Medicine (Microbiology and Molecular

Genetics)Harvard Medical SchoolChanning LaboratoryDepartment of MedicineBrigham and Women’s HospitalBoston, Massachusetts

John Popovich, Jr., MD, MACPChairDepartment of Internal MedicineHenry Ford HospitalDetroit, Michigan

Gregory Priebe, MDAssistant Professor of Anaesthesia (Pediatrics)Harvard Medical SchoolChanning LaboratoryDepartment of MedicineBrigham and Women’s HospitalDepartments of Anesthesiology (Critical Care) and Medicine

(Infectious Diseases)Children’s HospitalBoston, Massachusetts

Jonathan Puchalski, MDFellow in Pulmonary MedicineDivision of Pediatric Pulmonary MedicineCincinnati Children’s HospitalDivision of Pulmonary and Critical Care MedicineUniversity of Cincinnati College of MedicineCincinnati, Ohio

Carrie A. Redlich, MD, MPHProfessor of MedicinePulmonary and Critical Care MedicineOccupational and Environmental MedicineDepartment of MedicineYale University School of MedicineNew Haven, Connecticut

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Contributors

Steven I. Rennard, MDPulmonary and Critical Care MedicineUniversity of Nebraska Medical CenterOmaha, Nebraska

Herbert Y. Reynolds, MDProfessor of Medicine EmeritusThe Pennsylvania State University College of Medicine

and Milton S. Hershey Medical CenterHershey, PennsylvaniaAdjunct Professor of MedicineUniformed Services University of the Health

SciencesBethesda, Maryland

Mary L. Ricardo-Dukelow, MDClinical InstructorDepartment of Internal MedicineUniversity of Nebraska Medical CenterOmaha, Nebraska

Andrew L. Ries, MD, MPHAssociate Dean for Academic AffairsProfessor of Medicine and Family and Preventive

MedicineUniversity of CaliforniaSan DiegoMedical DirectorPulmonary Rehabilitation ProgramUniversity of CaliforniaSan Diego Medical Center

John R. Roberts, MD, MBAThe Surgical Clinic, PLLCNashville, Tennessee

Kenneth B. Roberts, MDAssociate Professor of Therapeutic RadiologyYale University School of MedicineAttending PhysicianYale-New Haven HospitalNew Haven, Connecticut

Carolyn L. Rochester, MDAssociate Professor of MedicineSection of Pulmonary and Critical CareDepartment of Internal MedicineYale University School of MedicineNew Haven, Connecticut

Sara Rockwell, PhDProfessorDepartment of Therapeutic RadiologyYale University School of MedicineNew Haven, Connecticut

William N. Rom, MD, MPHSol and Judith Bergstein Professor of Medicine and Professor

of Environmental MedicineDepartments of Medicine (Pulmonary Disease) and

Environmental MedicineNew York University Medical CenterNew York, New York

Daniel B. Rosenbluth, MDAssociate Professor of MedicineDivision of Pulmonary and Critical Care MedicineWashington University School of MedicineSt. Louis, Missouri

Milton D. Rossman, MDPulmonary and Critical Care SectionHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Eric J. Rubin, MD, PhDAssociate Professor of Immunology and Infectious

DiseasesHarvard School of Public HealthBoston, Massachusetts

Mark E. Rupp, MDProfessorDepartment of Internal MedicineUniversity of Nebraska Medical CenterNebraska Medical CenterOmaha, Nebraska

Edward T. Ryan, MDAssistant Professor of MedicineHarvard Medical SchoolAssistant Professor of Immunology and Infectious

DiseasesHarvard School of Public HealthDirectorTropical and Geographic Medicine CenterMassachusetts General HospitalBoston, Massachusetts

Steven A. Sahn, MDProfessor of Medicine and DirectorDivision of Pulmonary, Critical Care

Allergy and Sleep MedicineMedical University of South CarolinaCharleston, South Carolina

Edward Y. Sako, MD, PhDProfessorDepartment of SurgeryThe University of Texas Health Science CenterSan Antonio, Texas

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Contributors

Jonathan M. Samet, MD, MSProfessor and ChairmanDepartment of EpidemiologyDirectorInstitute for Global Tobacco ControlJacob I and Irene B. Fabrikant Professor in Health

Risk and SocietyJohns Hopkins Bloomberg School of Public HealthBaltimore, Maryland

Paul E. Sax, MDAssociate Professor of MedicineHarvard Medical SchoolClinical DirectorDivision of Infectious Diseases and HIV ProgramBrigham and Women’s HospitalBoston, Massachusetts

Thomas F. Scanlin, MDProfessor of PediatricsUniversity of Medicine & Dentistry of New JerseyChief, Division of Pulmonary Medicine and Cystic

Fibrosis CenterBristol-Myers Squibb Children’s Hospital at Robert Wood

Johnson University HospitalNew Brunswick, New Jersey

Johannes C. Schittny, PhDInstitute of AnatomyUniversity of BernBern, Switzerland

Edward S. Schulman, MDProfessor of MedicineDirectorDivision of Pulmonary and Critical Care MedicineDrexel University College of MedicinePhiladelphia, Pennsylvania

Richard J. Schwab, MDUniversity of Pennsylvania Medical CenterPulmonary, Allergy and Critical Care DivisionPhiladelphia, Pennsylvania

David A. Schwartz, MDDirectorNational Institute of Environmental Health SciencesResearch Triangle ParkNorth Carolina

Marvin I. Schwarz, MDThe James C. Campbell Professor of Pulmonary MedicineDirectorPulmonary Sciences and Critical Care Medicine

FellowshipUniversity of Colorado Health Sciences CenterDenver, Colorado

Luis M. Seijo, MDAssociate Clinical ProfessorResidency Program DirectorPulmonary DivisionClınica Universitaria de NavarraPamplona, Spain

Moises Selman, MDInstituto Nacional de Enfermedades RespiratoriasMexico

Robert M. Senior, MDDorothy R. and Hubert C. Moog Professor of Pulmonary

Diseases in MedicineProfessor of Cell Biology & PhysiologyWashington University School of MedicineSt. Louis, Missouri

Kumar Sharma, MD, FAHAProfessor of MedicineDirector Center for Diabetic Kidney DiseaseThomas Jefferson UniversityDepartment of MedicineDivision of NephrologyPhiladelphia, Pennsylvania

Stuart F. Sidlow, MDAssistant Professor in Anesthesiology and Critical CareUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Michael S. Simberkoff, MDChief of StaffVA New York Harbor Healthcare SystemProfessor of MedicineNew York University School of MedicineNew York, New York

Neel R. Sodha, MDDepartment of SurgeryDivision of Cardiothoracic SurgeryBeth Israel Deaconess Medical Center and Harvard

Medical SchoolBoston, Massachusetts

Ulrich Specks, MDProfessor of MedicineMayo Clinic College of MedicineDivision of Pulmonary and Critical Care MedicineMayo ClinicRochester, Minnesota

Peter H. S. Sporn, MDProfessor of MedicineDivision of Pulmonary and Critical Care MedicineFeinberg School of MedicineNorthwestern UniversityChicago, Illinois

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Contributors

Daniel H. Sterman, MDAssociate Professor of MedicineAssociate Professor of Medicine in SurgeryDirector of Interventional PulmonologyClinical DirectorThoracic Oncology Gene Therapy ProgramPulmonary, Allergy and Critical Care DivisionUniversity of Pennsylvania Medical CenterPhiladelphia, Pennsylvania

Robert M. Strieter, MDProfessor and ChiefDivision of Pulmonary and Critical Care MedicineVice Chair of the Department of MedicineProfessor of Pathology and PediatricsDavid Geffen School of Medicine at UCLALos Angeles, California

Erik R. Swenson, MDProfessor of Medicine and Physiology and

BiophysicsUniversity of WashingtonSeattle, Washington

Darren B. Taichman, MD, PhDAssistant Professor of MedicineDirector, Medical Intensive Care UnitPenn-Presbyterian Medical CenterAssociate DirectorPulmonary Vascular Disease ProgramHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Lynn T. Tanoue, MDAssociate Professor of MedicinePulmonary and Critical Care Section Yale University

School of MedicineNew Haven, Connecticut

Denise Tefft, PhDDevelopmental Biology ProgramSaban Research InstituteChildren’s Hospital Los AngelesUniversity of Southern California Keck School of


Erica R. Thaler, MDAssociate Professor of OtorhinolaryngologyUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Karen J. Tietze, PharmDProfessor of Clinical PharmacyUniversity of the SciencesPhiladelphia, Pennsylvania

Gregory Tino, MDPulmonary, Allergy, and Critical Care DivisionHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Martin J. Tobin, MDDivision of Pulmonary and Critical Care

MedicineEdward Hines Jr Veterans Affairs Hospital

and Stritch School of MedicineLoyola University of ChicagoHines, Illinois

Galen B. Toews, MDAssociate Dean for Research and Graduate

StudiesMedical SchoolProfessor of Internal MedicineChief, Division of Pulmonary and Critical Care

MedicineThe University of Michigan Health SystemAnn Arbor, Michigan

Daniel L. Traber, PhDProfessorThe University of Texas Medical BranchGalveston, Texas

Bruce C. Trapnell, MDDirectorRare Lung Diseases ConsortiumProfessorDepartments of Medicine and PediatricsUniversity of Cincinnati College of Medicine

Cincinnati Children’s Research FoundationCincinnati, Ohio

John Treanor, MDProfessor of MedicineInfectious Diseases UnitUniversity of Rochester Medical CenterRochester, New York

Joseph Treat, MDAttending PhysicianDepartment of Medical OncologyFox Chase Cancer CenterPhiladelphia, Pennsylvania

Scott O. Trerotola, MDProfessor of Radiology and SurgeryDepartment of RadiologyInterventional RadiologyUniversity of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

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Contributors

George E. Tzelepis, MDAssociate Professor of MedicineUniversity of Athens Medical SchoolChief, Pulmonary ServicesLaiko University HospitalAthens, Greece

Michael Unger, MD, FACP, FCCPDirectorPulmonary Cancer Detection and Prevention

ProgramDirectorPulmonary Endoscopy and High-Risk Lung Cancer

ProgramFox Chase Cancer CenterPhiladelphia, Pennsylvania

Mark J. Utell, MDProfessor of Medicine and of Environmental

MedicineDirectorOccupational Medicine Program and Associate

Chair of Environmental MedicineDirectorPulmonary UnitUniversity of Rochester Medical CenterRochester, New York

Anil Vachani, MDAssistant ProfessorDepartment of MedicineDivision of Pulmonary, Allergy and Critical CareUniversity of PennsylvaniaPhiladelphia, Pennsylvania

Judith A. Voynow, MDAssociate Professor of PediatricsDuke University Medical CenterDurham, North Carolina

Peter D. Wagner, MDDepartment of MedicineUniversity of California San DiegoLa Jolla, California

John C. Wain, MDDivision of Thoracic SurgeryMassachusetts General Hospital and Harvard

Medical SchoolBoston, Massachusetts

David Warburton, DSc, MD, FRCPDevelopmental Biology ProgramThe Saban Research InstituteChildren’s HospitalLos Angeles, California

Peter A. Ward, MDDepartment of PathologyUniversity of Michigan Medical SchoolAnn Arbor, Michigan

Susan A. Ward, DPhilInstitute of Membrane and Systems BiologyUniversity of Leeds, Leeds, UK

Karl T. Weber, MDDivision of CardiologyMemphis Medical CenterMemphis, Tennessee

Ewald R. Weibel, MD, DScProfessor EmeritusInstitute of AnatomyUniversity of BerneBerne, Switzerland

Arnold N. Weinberg, MDInfectious Diseases UnitMassachusetts General HospitalBoston, Massachusetts

Scott T. Weiss, MD, MScProfessor of MedicineHarvard Medical SchoolChanning LaboratoryDepartment of MedicineBrigham and Women’s HospitalBoston, Massachusetts

David N. Weissman, MDNational Institute for Occupational Safety and HealthCenters for Disease Control and PreventionMorgantown, West Virginia

Michael J. Welsh, MDProfessorHoward Hughes Medical InstituteDepartments of Internal Medicine and Physiology and

BiophysicsRoy J. and Lucille A. Carver College of MedicineUniversity of IowaIowa City, Iowa

L. Joseph Wheat, MDPresident and DirectorMiraVista DiagnosticsIndianapolis, Indiana

Brian J. Whipp, PhD, DScInstitute of Membrane and Systems BiologyFaculty of Biological SciencesUniversity of LeedsLeeds, United Kingdom

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Contributors

Jeffrey A. Whitsett, MDChief, Section of NeonatologyPerinatal and Pulmonary BiologyDepartment of PediatricsCincinnati Children’s Hospital Medical Center and the

University of Cincinnati College of MedicineCincinnati, Ohio

Kevin C. Wilson, MDAssistant Professor of MedicineBoston University School of MedicineBoston, MassachusettsDeputy EditorPulmonary, Critical Care, and Sleep MedicineUpToDateWaltham, Massachusetts

Nevin W. Wilson, MD, FAAP, FAAAIProfessor and Chair, Department of PediatricsUniversity of Nevada School of MedicineReno, Nevada

Robert A. Wise, MDProfessor of MedicinePulmonary and Critical Care MedicineJohns Hopkins University School of MedicineBaltimore, Maryland

Daniel F. Worsley, MDAssistant ProfessorUniversity of British ColumbiaChief, Division of Nuclear MedicineVancouver General HospitalVancouver, British Columbia, Canada

Cameron D. Wright, MDAssociate Professor of SurgeryHarvard Medical SchoolAssociate Division ChiefDepartment of Thoracic SurgeryMassachusetts General HospitalBoston, Massachusetts

Joanne L. Wright, MD, FRCP(C)Department of PathologyUniversity of British ColumbiaVancouver, British Columbia, Canada

Gordon L. Yung, MB, BSDirectorAdvance Lung Disease ProgramAssociate Clinical Professor of

MedicineUniversity of CaliforniaSan Diego, California

Richard D. Zorowitz, MDAssociate ProfessorDepartment of Physical Medicine and

RehabilitationUniversity of Pennsylvania School of

MedicineMedical DirectorPiersol Rehabilitation UnitHospital of the University of

PennsylvaniaPhiladelphia, Pennsylvania

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Preface

This book is now in its fourth edition. The first edition ap-peared in print in 1980. Each edition since then has pro-vided a contemporary update of the growth of understand-ing of pulmonary disease and of the management of its clin-ical manifestations. Advances have been made in leaps andbounds. A 2006 review (Lopez et al.) summarized the im-pressive progress made in three key subsets of pulmonarymedicine, chronic obstructive pulmonary disease (COPD),asthma, and critical care medicine.

COPD affords a practical illustration of the growth inunderstanding of a prevalent disease. The designation COPD,originally adopted as a convenient term for communicationabout the spectrum of chronic bronchitis and emphysema,now covers a wide range of clinical entities, ranging frompredominant inflammation of the airways to disruption andover-expansion of the pulmonary paremchyma in emphy-sema.

COPD is the fourth leading cause of chronic morbidityand mortality in the United States. More than 12 millionpeople have COPD and an additional 12 million do not knowthat they have the disease. Of all the leading killers, COPDis the only disease with mortality rates that are on the rise.World Health Organization projections indicate COPD willbecome the third leading cause of mortality worldwide by2020.

Smoking is a predominant etiologic factor for COPD.However, as many as one of six people with COPD have neversmoked. It is also understood that not all who smoke pay theprice in terms of lung disease. The rates among women havedramatically increased since World War II. Vulnerability toharmful effects of smoking is believed to be rooted, at leastin part, in genetic predisposition. This likelihood is currentlyunder active investigation.

One particular limitation of the term “COPD” was re-cently highlighted by the advent of lung volume reductionsurgery (LVRS) for the treatment of emphysema. It was clearfrom the outset that not all patients with emphysema are suit-able candidates for LVRS. A major step toward the identifica-tion of those patients with emphysema who can be expectedto benefit from the procedure was taken by the National Em-

physema Treatment Trial (NETT). This trial, unique in its co-sponsorship by three federal agencies—The National Heart,Lung & Blood Institute (NHLBI), The Health Care FinanceAgency (HCFA) and the Agency for Health Care Policy andResearch (AHCPR), began by excluding those patients withemphysema who were not likely to benefit from LVRS. Theseproved to be patients with a low FEV in conjunction witheither homogeneous emphysema or a very low diffusing ca-pacity for carbon monoxide (DLCO). In patients who provedto be eligible for LVRS, NETT took into account the risksposed by the surgical procedure and the fact that it affords noguarantee of successful outcome.

A second major study addressed the global impact ofCOPD. It has been estimated that in the United States al-most 12 million people have COPD Smoking has long beenknown to be the predominant cause of COPD, but attempts atpromoting widespread smoking cessation have largely beenineffective. Currently, COPD is being attacked on a variety ofresearch fronts. Among these is the link between COPD andlung cancer. Other research is directed at clarifying the role ofinflammation in the pathogenesis of COPD and trials of ther-apeutic interventions to minimize the ravages of the disease.Among the on-going trials are investigations which seek todetermine the therapeutic effectiveness of novel agents, suchas the phosphodiesterase inhibitors (PDE4 inhibitors). Othertrials, using monoclonal antibodies seek to modify the inflam-matory component of COPD. The global impact of COPDcontinues to provide impetus to the search for mechanismsthat can be attacked therapeutically.

Looking back, the growth of pulmonary medicine hasbeen punctuated and accelerated by certain iconic break-throughs. Diagnostic radiology was revolutionized in theearly 1990’s by the introduction of spiral-computed tomog-raphy (CAT scan), which afforded a novel way to imagethe lung. Since then, improvements in the technology ofthe apparatus have enhanced its value as a diagnostic toolwhile enabling smaller doses of radiation to be delivered tothe patients. Because of its ease of use and its availability,the use of the CAT scan has become widespread. In addi-tion, continuing refinements hold promise of enhancing the

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visualization of the microarchitecture of the lungs in healthand disease.

Technological advances have played a key role in af-fording insights not only into the microarchitecture of thelungs but also into their physiological functions. Recent ad-vances hold promise of even more to come. For example, theadvent of virtual bronchoscopy has brought with it the like-lihood of access to information about the bronchial tree andits surrounding structures without subjecting the patient tothe stress of direct bronchoscopy. Moreover, the meaning of“virtual” continues to enlarge. Originally, the term referredto two-dimensional representations of the bronchial tree ob-tained by x-ray computed tomography (CT). Currently, theterm also applies to more detailed images and less-intrusivemethods obtained by such techniques as ultrasound or mag-netic resonance imaging (MRI).

The newer imaging techniques not only afford staticrepresentations of the details of the airways and pulmonaryparenchyma but also hold promise for functional studies,e.g., dynamic studies of pulmonary mechanics. Such studieswould deal not only with the mechanics of the entire lung butalso with the mechanics of regions of the lung. The increasein resolution on the one hand, and in the ease of acquisitionof data on the other, has also enabled application of non-invasive imaging to the exploration of such functions of thelungs as ventilation-perfusion relationships.

Pulmonary medicine continues to be on the march. Inrecent years, the inclusion of sleep-disordered breathing haswidened the scope of pulmonary medicine. National meet-ings devoted to pulmonary medicine attract ever-increasingaudiences. This edition of “Pulmonary Diseases and Disor-ders” deals with the current understanding of lung diseasesand the management of these diseases. Even a cursory com-parison of this edition with previous editions reveals thatconsiderable progress has been made in recent years. Despitethis impressive progress, it is clear that much remains to bedone. Patients and pulmonologists can look forward to fur-ther developments in the years ahead.

The experience and knowledge of each of the editorshave been directed at ensuring that the specialized, as wellas the general, aspects of pulmonary medicine have been ex-pertly covered and well presented. Although the book is a col-lective arbeit, discussion and debate among the editors andauthors have led to a collaborative and comprehensive work,integrated by a meeting of the minds and the sharing of theexperiences. By the process of peer review, the book aspiresto provide a readable and balanced coverage of what is latestand most meaningful in pulmonary diseases and disorders.

I have already indicated how much this book owes tothe experts who comprise the editorial board. The editors, inturn, would have little to work with were it not for the splendidchapters contributed by the individual authors. And, in thisedition, we also were aided by several medical fellows. Myspecial thanks to Charles De La Cruz, Colin Gillespie, HowardHuang, Josh Kayser, Bianca Monteiro, Stephen Ryan, and RaelSundy for their assistance. The editors also benefited greatlyfrom close collaboration with the publisher whose personnel

have listened carefully and implemented with patience andunderstanding.

I owe a great deal to those close to home. Betsy AnnBozzarello, a collaborator for more than 20 years, managed tofree time for me to devote to the book while she catalyzed andorchestrated the efforts of others. My family has providedthe encouragement and peace of mind that such an effortinevitably calls for. My wife, Linda, has been unwavering inher tolerance and support. My daughter, Hannah, who is inher junior year at the University of Michigan and is trying herown hand at writing, is impressed by the enormity of the un-dertaking but remains optimistic about the outcome of sucha venture. My sons, Mark and Jay, authors and editors in theirown rights, share my conviction that this book is a worthwhileundertaking. Their spouses, Gayle and Martha, the formera nurse and the latter a pediatric pulmonologist, have alsobeen supportive. I am greatly indebted to all of the above.

Alfred P. Fishman

SUGGESTED READING

Fabbi L.: Global impact of chronic disease. Focus on COPD.J COPD Management 7:4–23, 2006.

Lopez AD, Shibuya K, et al.: Chronic obstructive pulmonarydisease: current burden and future projections. Eur RespirJ 27:397–412, 2006.

Minino AM, Heron M, et al.: Deaths: Final data for 2004.Health e-stats. National Center for Health Statistics, 2007.

Pauwels RA, Buist AS, Calverly PAM, Jenkins CR, Hurd SS,et al.: NHBI/WHO Workshop summary. Global strategyfor the diagnosis, management and prevention of chronicobstructive pulmonary disease. Am J Respir Crit Care Med163:1256–1276, 2001.

Rabe KF: Guidelines for chronic obstructive pulmonary dis-ease treatment and issues of implementation. Proc AmThorac Soc 3:641–644, 2006.

Sin DD, Anthonisen NR, et al.: Mortality in COPD: role ofcomorbidities. Eur Respir J 28:1245–1257, 2006.

Zielinski J, Badnarek M, et al.: Increasing COPD awareness.Eur Respir J 27:833–852, 2006.

ACKNOWLEDGMENT

The editors wish to acknowledge the contributions made bythe authors to the previous edition, whose work forms partof the chapters in this edition but who are not authoringcurrent chapters.

Alfred P. Fishman, MDJack A. Elias, MD

Jay A. Fishman, MDMichael A. Grippi, MDRobert M. Senior, MD

Allaan I. Pack, MB, ChB, PhD

fishman’s pulmonary diseases and disorders pcx/scf p2: pcx mhbd084-fm mhbd084-fishman december 19,...

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