Bronchial AsthmaMechanisms and TherapeuticsEdited byEarle B.Weiss, M.D.and Maurice S. Segal, M.D.

5

N

i

4- .

I

i

J

BronchialAsthma

Edited by

Mechanisms andTherapeutics

Earle B. Weiss, M.D .Director, Department of Respiratory Diseases,The St. Vincent Hospital ;Associate Professor of 1bIedicine,L !*,,IN ersit.y of >V'Tassachusett Medical School ;°Associate Affiliate Professor of T .ife Sciences,Worcester Polytechnic Institute, IN"orcester

Maurice S. Segal, M .D.Emeritus Professor of Medicine .Tufts T iiiversity School of -Medicine,Director. F ounda tion for Research inBronchial Asthma and Related Diseases, Boston

Little, Brown and CompanyBoston

COpIRIGIIr q%~ 1976 IT Lrc -rr.l •: . Bi

N \gin Co rr,\,vINC.)

FIRST .vol rION

_ALT. IIIGIITS RESERVED . NU F'AR' OF TIFFS ROOK \IAY BE

1TEPRODTIClrD TN ANY 11)1UI OR 141' ANY ELECTRONIC OR

AIECII:ANLC •1 , MEANS . INCLUDING 1NFORALVIION STORAGE

AND RI:TRIEVA] . SYSTEMS, R'ICICOT :T PERMISSION IN

WRITING PROAL I'll L" I'U .RIISIIER . EXCEPT III A ITLViF.WL:R

\VIIO MAY QUO TI: BRIEF PASSAGES IN A BE-VT 1 -11l-

LII3R .rRV oP (,C)NGRli55 (~ :\'I'.\LOG ( .A1rD No, 75-25161

ISBN 0 316 92586 0

PItINTED IN -1. 111: LTNITI:I, STATES OP AMRItIC .A

F

Foci oun wivi-:s, Vicky and Sylvia

Dum spiro, spcro. 1-I =bile I breathe. I hope .

Sonne 1200 years have elapsed since Hippoc-rates used the word asthma to describe itsepisodic shorts Less of breath. Since this early-observation, much. of the causaLiort of as tlinrahas beep unraveled and it] its wake :irrationalremedies have been abandoned . Time hasr- ielded considerable, if not immense . technological advances encompassing basic and ap-plied disciplines and . hence. a large spectrumof therapeutic modalities . The availability- ofthese modalities, ill turn, has increased thedemands upon the pllvsiciazi for precision illdiagnosis and treatment, a principle whicthguided the formulation for this book . We be-liere that a sound acquisition . Of f •undametttalsis a prerequisite to a rational therapeutic ap-proach, asci have therefore devoted a portionof the book to mcchanisms and the balance tothereperrlics .From its simpler origins, astlnla has now

become a model of the complex iitterrelatiott-ships of biochemical. and. biophysical plic-noniena affecting the integrated structures ofthe anrway-s and the gas exchange processes,with the inciting pathophyslological . mccli-attislrms finally- expressed as clinical sighs andsvnnptoms. Our knowledge has culminated inthe application of a variety of rational meas-tires and modalities aimed at preventing,ameliorating, or reversing these interrelatedevents. However, the implications of this dis-order are becoming so immense, it is doubtfulthat ally oine investigator or physician canmaster the technical background needed toassimilate the disparate disciplines encorrl-passiug this subject . It may also be impos-sible for one book. to solve this dilemma, butwe have attempted to organize in cute volume

Iii

Preface

the essential fill ndamentals as rre perceivet hens .

To achieve our goal . we have endeavoredto itrtegrate a cooperative effort of collaboratorr. clearly- mindful that this approach iss ubject . t o certain limitations . Although thehook is directed toward the Specialist . internn-rst. or advanced student . effort has been bladeto provide the introduction and preparationfor any in [crested reader with the usual medi-cal background . Because each subject repre-sents the professional attitude and experi-ences (f.' the contributing author, we have.permitted each chapter to retain its respec-tive flavor, opinions 'even divergent) . andapproach, yet topically integrated into thewhole as a balanced . accurate pr•eselltatiortof the current status of asthma . W e hope thestudent of this subject will find, therefore, asufficient. breadth and depth of knowledge inthis work, as is our -intent. In this rapidlyevolving discipline, iii rvhiich there is an ever-increasillg reliance upont factual data. Weenlist : apologize for rcrtaiii emissions or lim -tations in subject platter, which is of neces-sity constrained by lrraxnan and technical fac-tors ; rve ciicourage Ow.' readers to c:olnlnuni-cate with us their comments and suggestlulls .

Above all. the physician tending the pa-tient with bronchial asthma must be a hru-manist.ic scientist. mindful not only of factualdetails but also of the total needs of the pa-tient throughout all phases of this frigliteln-ing acid potentially life- threatening disorder .Tt: is our intent 'that these pages will provideguidance to a rational. lmdersLa .u.ding andsnottagement of a process uinpredictable in itscourse and often all too difficult to control .

The ltnmerous cmrrtributillg authors have0111' sincere gratitude for their patience, ami-

I

viii. Preface

able cooperation, and expert contributions ; aseditors we have gained much from the di-verse and distinguished faculty whichbrought this hoot: to fruition . We note withregret the passing of two authors since theinception of ourr endeavor . Dr. Milton Rosezr-hlat t and Dr. Raymond Havez . INTe remainthankful to all those unnamed persons whohave ably assisted the respective authors inthis effort and are particularly indebted toour own secretarial staff . including NESSSophie Nikolow, for their timeless and de-voted efforts. Doctors Ralph Itendall,. Avi-rrash Patwardhan, and Datung Kung have

our gratitude for their invaluable criticismsand suggestions on various chapters, as dothe staff of Little, Brown and Company, inparticular Mrs . Aime 1\Ierian and Mrs . LinRichter, for their able guidance. The supportof the Foundation for Research in BronchialAsthma and Related Diseases :is also ac.knowl-ed ged .

Finally. we dedicate this volume to ourwives, Vicky and Sylvia . who should be wel-come to fired us at home now that the workis completed .

F. B . '\V.A1 . S . S .

tm

ix

Contents

Section 9 n'IEC-RA-NIS]VTS IN ASTIIIIA : IaiJN.UAMRN'I ALS of IMa i so?.o(. . THF.olii1-:s,

IMMEDIATEEHYPERSENS1'rIA'II'x .P 1AR1VTACOLOGICAL-\•IEI)IATORs Ba!'A-.ADRENEnc. IC .

THEORY A-ND BIOCFcADE . CIrOLINERGIC MECH ANISMS. ANI) I .A - ri AST 11M_ATIC RE AC. : TIONS

Preface

Contributing Authors

I Mechanisnns of Bronchial Asthma

Val

xv

Section 1 IIIsronicAL REVIEW_ I3rr•INITION, RE] .,vrroN 'Io CnnoNtcOBSID CTIVE PIJJ .nMONARY DISEASES,. EPIDEMIOLOGY, AaLND Gm ETIcs

1 • History of BronchiaL Asthma \EIL •IUN B . ROSENr3LATT D

? • Definition and Clinical Categorization J . G . SC :AIJI?IN(i 19

3. The Interrelationships of Asthma,Chronic Bronchitis, and Emphysema

CORDON L . S--', IDF:R 31

1 •. Fpidemiology. Prevalence, and Mortalityinn Asthma

~. The Genetic Basis for Atopic Al erg I I

Mani

r'RANK Tl . s1 LIL .L I).

PAUL I . . Iix, \CT nNn D:1VII) c . . MARSH

43

6. General Introduction . to Immunology GLEAT.n J . GLEIGH ANDTHO:~,MAS 13 . TOMASU, JR .

67

J. The Nonspecific Immune Responses JOSEPH A . BLLLANTI AINDDENNIS C= . N.LEHAN

89

8. Secretory Immune Systems .J 0SEPH A . BLLLA11 TI A-NDLAWRENCE D . 1•-- IIL`TEiI •: L •

100-

9. Pharmacodynamics and Mechanisms ofAsthma

W. E. BROCri.r .F:HI= RST 117

10 . The Regi-Adrenergic Theory' and Cyclic .AIMP-h-lediatedControl -Iechani,ms'inIITIxna11 Asthma

11 .

Allto0r,ll)ic Iiegl.llation andAir\vay Re pon ;IVeuess

12 . Biochenac•a 1 C:haracte-•ristics of1lnnledialte Ilyper~eltsiti.vity Reactions

1 i. I111nlunoglohu 1 -il _ l?

1 1 . (die iiical \'Iediaio :cs in Asthma

1 .3 . Thc- l'I'ostagl.-,mdins : BiochenliArv,l'athoplty~sialogy, and CiITlicel PILarniac.ologytll .''tst111na anrl. OiherlalngDisor(lers

Vi . '.1'lho Iii ins : Basic Clio)nisiry. BiologicalAc. lion, and Implication in Ilu1m(11 Astllnia

17. Nou.1imnediate Asthmatic; Raac.tiorls

18. Respiratory]\iechanics in A thln~z

19 . Spiroltletl ~-, Lung plumes, andDistrihi_(tion of Ventilation i,1 A.tithzna

20. \eI_llilatiol, •Perfusia11 and DiffusionDlsturhances 111 Ast'_Ix11a

21 . Pathophysiology of Gas Exchange aridArserial Blood Gas and p ff in Istlulia

?2. Circulator- Response in BronchialAstlnna

2:3. T.lze Pathology of Bronchial Astllnla

2d. The ivh .lst Cell

`2'3_ Bxonc.Itial Mucus : Pln-sic.al and

.'\IJ,D(itt 57.1 , NTTV.\11T ANDu1r .n.r{i .(a cc . r-'r~r7T:L

.1 . A . 1\-A)Lf :

1\T1( . :TI!,T:L I{ALINER AND

1 ; . 1 1: :1- -cI~- AF-S,Lz

ITANS 13ENNI(',I-x,s . GUNNA1 O . JOITANSSON, ANDIiEDVI' ; RALIR-T INDS'IRO\I

\T.\RTT1\ P- VALrN'rINE

JIRD _~AKILANO ANTI BOB-MT L. RODGERS

R. WW- . nnLr:Fna1LyEn ANDITOWA1IT) .1 . Sc ;ilt~ART7

.T . P1,11-YS

Section. 3 RR. ; xnAronv PiIYSIOI,oGy : BLOOD (TAS, _P11, AND CT.RCVLAT-011Y AND

CAl{n1&c FACTORS IN AS7.'IiIYI :\

N . R . -',1C r'ADDInN . JR .

r . B. AJ(: I'ADD?N, -1B ., ANDR.OLAND H . mc;RAlx. JR .

JOHN 13 . 'WEST

I-i . N . V. PALATER AND

STEPHEN INT. AYREs

Section ,4 PATHOLOGY OF AS'J'IIMA : hk:FL:;tiSE l~'IECIIANiS?4IS AND P 1'ERiNIF V':'AT .

A` I'il RI\

J. A. HAY ES

1JAVIJ LAC:i NOFF

T. ITAVER AT\Y) P. ROUSSELL

xi Contents

II Diagnostics and Therapeutics

26. The Deposition of Aerosol Particles in

PAUL GROSSthe Respiratory Tract : The FactorsGoverning Their Distribution and Their

423

433

439

457

Clearance from the Lungs

27. Pulmonary Distribution and Clearance

RUY V. LOUREN~Oof Particles in Disease

28. Lung Defense in Asthma

GERALD S. DAVIS AND GARETH M . GREEN

29. Experimental Asthma in Man and

AREND BOUHUYSin Animals

Section 5 ETIOLOGICAL AND ENVIRONMENTAL CONSIDERATIONS IN ASTHMA :UPPER RESPIRATORY TRACT, WEATHER, INDUSTRIAL PROBLEMS, EXERCISE-INDUCEDASTHMA, HOUSE DUST AND MOLDS, ASTHMA IN THE TROPICS, AND THE ROLE OFMARIHUANA

30. Etiological Factors in Asthma : Allergens , PAUL P. VAN ARSDEL, JR .and Other Provoking Factors

473

31 . Allergic Rhinitis

JOHN T. CONNELL 481

32. The Upper Respiratory Passages (Nose,

WERNER D. cHASINThroat, and Sinuses) in Bronchial Asthma

491

33. Environmental Influences in Asthma

MANUEL LOPEZ, FREDRICK WESSELS,AND JOHN E. SALVAGGIO

503

34, Industrial Diseases with Asthma

RAYMOND L. H . MURPHY, JR . 517

35 . Exercise-Induced Asthma

R. MICHAEL SLY 537

36. House Dust and Mites in Bronchial

KJELL AASAsthma

547

37. Mold Fungi and Bronchial Asthma

A. W. FRANKLAND 557

38. Tropical Considerations and Pulmonary

SUDHAKAR RAMCHANDRA KAMATManifestations in Helminth Infestation

565

39. Marihuana and Respiratory Function

JERROLD C. BERNSTEIN 585

Section 6 DIAGNOSTIC CONSIDERATIONS : PRINCIPLES OF APPROACH, RADIOGRAPHY,SKIN TESTS, BRONCHIAL PROVOCATION, SIGNIFICANCE OF THE EOSINOPHIL,SPUTUM, AND DIFFERENTIAL DIAGNOSIS

40. Principles of Diagnosis and Treatment ROBERT P. MC COMBS 597

41 . Radiographic Findings in Asthma MURRAY L. JANOWER 603

xii Contents

42. Diagnostic Tests and HyposensitizationTherapy in Asthma

43. Bronchial Provocation Tests

44. The Eosinophil in Allergy and Asthma

45 . Sputum in Bronchial Asthma

46. Differential Diagnosis of Asthma

Section 7 TREATMENT, REHABILITATION, COMPLICATIONS, AND MORTALITY

IN ASTHMA

47 . Therapeutic Schedules in Asthma

48 . Bronchodilator and Antiasthmatic Drugs

49. Bronchodilator Adrenergic Therapy

50. Recent Work on Selective

;iBeta-Adrenoceptor Stimulants

51 . Theophylline

52. Pituitary-Adrenal Function :Considerations in Asthma

53. Treatment Schedules with Steroids

54. Corticosteroid Resistance in BronchialAsthma

55. Problems of Hydration, Expectorants,Antihistamines, and Sedatives in Asthma

56. Disodium Cromoglycate (CromolynSodium) in Bronchial Asthma

57. The Status of Immunotherapy inAsthma

58. Concepts of Immunological Interventionin the Treatment of Asthma

59. Infection in Asthma and AntibioticTherapy

60. Status Asthmaticus

RICHARD F. LOCKEY ANDSAMUEL C. BUKANTZ

SHELDON L. SPECTOR ANDRICHARD S. FARR

RICHARD W. HONSINGER, JR .

MAURICIO J . DULFANO ANDARNULFO RODRIGUEZ-CORNEJO

KENNETH F. MACDONNELL

FRANCIS C. LOWELL

DOMINGO M . AVIADO AND HARRY

HAROLD A. LYONS

ROY T. BRITTAIN AND DAVID JACK

M. HENRY WILLIAMS, JR ., ANDCHANG SUP SHIM

JAMES C. MELBY

JOSE S. BOCLES

JAMES S . G. COX

RICHARD R. ROSENTHAL ANDLAWRENCE M. LICHTENSTEIN

ALFRED D. STEINBERG ANDCHARLES H . KIRKPATRICK

RICHARD H . MEADE III

EARLE B. WEISS

613

639

xiii Contents

61 . Ventilatory Care of Status Asthmaticus

62. Bronchial Asthma in Children

63. Intractable Asthma in Children

64. Pregnancy and Asthma

65 . Helium-Oxygen Therapy in BronchialAsthma

66. Preoperative and PostoperativeConsiderations in Patients with BronchialAsthma

67. Anesthetic Considerations

68. The Role of Surgery in the Managementof Chronic Bronchial Asthma

69. Hypnosis in Bronchial Asthma

70. Psychosomatic Aspects of BronchialAsthma

71 . The Application of RehabilitationMedicine to Bronchial Asthma

72. Complications in the Course of BronchialAsthma

73. Death in Bronchial Asthma

Index

THOMAS L. PETTY 915

SHELDON C. SIEGEL, ROGER M. KATZ,

927AND GARY S. RACHELEFSKY

M . MURRAY PESHKIN

957

SHELDON MINTZ

971

ALVAN L. BARACH AND

983MAURICE S. SEGAL

MYRON STEIN AND

991MOHAMED I. ABDEL-RASSOUL

SYBIL W. WOO, INDER V. MALHOTRA,

999AND JOHN HEDLEY-WHYTE

SERGE J . DOS, MYRON J. JACOBSON,

1007AND HARRY S . SOROFF

G. P. MAHER-LOUGHNAN

1041

PETER H. KNAPP,

1055ALEKSANDER A. MATHE, ANDLOUIS VACHON

ALBERT HAAS, REGINA CASTILLO,

1081AND FELICIA LUSTIG

THOMAS A. SULLIVAN AND

1107KAYE H. KILBURN

MAURICE S. SEGAL

1121

1143

Mohamed I. Abdel-Rassoul, M .D .CHAPTER 66

Kjell Aas, M.D .CHAPTER 36

K. Frank Austen, M.D .CHAPTER 12

Domingo M. Aviado, M.D .CHAPTER 48

Stephen M . Ayres, M .D .CHAPTER 22

Hedvig Bahr-Lindstrom, Ph .D .CHAPTER 13

Alvan L. Barach, M.D .CHAPTER 65

Joseph A . Bellanti, M.D .CHAPTERS 7 AND 8

Hans Bennich, M.D .CHAPTER 13

Jerrold G. Bernstein, M.D .CHAPTER 39

xv

Contributing Authors

Pulmonary Fellow, University of California,Los Angeles, School of Medicine

Associate Professor of Medicine, PediatricDepartment and Pediatric Research Institute,University of Oslo, Oslo, Norway

Theodore B . Bayles Professor of Medicine,Harvard Medical School ; Physician-in-Chief,Robert Breck Brigham Hospital, Boston

Professor of Pharmacology, University ofPennsylvania School of Medicine, Phila-delphia

Professor and Chairman, Department of In-ternal Medicine, Saint Louis UniversitySchool of Medicine ; Physician-in-Chief, Uni-versity Hospitals, Saint Louis, Missouri

Research Assistant, Institute of Chemistry I,Karolinska Institute, Stockholm, Sweden

Consultant in Medicine, The PresbyterianHospital, New York

Professor of Medicine and Microbiology,Georgetown University School of Medicine ;Director, Pediatric Virology, GeorgetownUniversity Medical Center, Washington,D.C .

Associate Professor, Institute for MolecularBiology, Aarhus University, Aarhus, Den-mark

Assistant Clinical Professor of Psychiatry,Harvard Medical School; Associate MedicalDirector, Human Resource Institute of Bos-ton (Brookline) ; Assistant Psychiatrist, Mas-sachusetts General Hospital, Boston

xvi Contributing Authors

Paul L. Black, B .A .CHAPTER 5

Jose S. Bocles, M .D .CHAPTER 55

Arend Bouhuys, M.D .CHAPTER 29

Roy T. Brittain, Ph.D .CHAPTER 50

Walter E . Brocklehurst, Ph .D .CHAPTER 9

Stuart M. Brooks, M .D .CHAPTER 54

Samuel C. Bukantz, M.D .CHAPTER 42

Regina Castillo, M .D .CHAPTER 71

Werner D. Chasin, M.D .CHAPTER 32

John T. Connell, M.D .CHAPTER 31

James S. G. Cox, Ph.D .CHAPTER 56

Gerald S. Davis, M .D .CHAPTER 28

Postgraduate Research Student, Clinical Im-munology Division, The Johns Hopkins Uni-versity School of Medicine, Baltimore

Associate Professor of Medicine, Universityof Miami School of Medicine ; AttendingPhysician, Jackson Memorial Hospital, Mi-ami, Florida

Professor of Medicine and Epidemiology,Yale University School of Medicine, and Di-rector, Yale University Lung Research Cen-ter; Attending Physician, Yale-New HavenHospital, New Haven, Connecticut

Director of Biology, Allen & Hanburys Re-search Limited, Ware, Hertfordshire, Eng-land

Honorary Lecturer, University College, Lon-don ; Research Advisor, Lilly Research Cen-ter, Ltd., Windlesham, England

Associate Professor of Medicine and Environ-mental Health, and Chief, Clinical StudiesDivision, Department of EnvironmentalHealth, University of Cincinnati College ofMedicine, Cincinnati, Ohio

Professor, Department of Internal Medicine,University of South Florida College of Medi-cine ; Chief, Allergy Section, Medical Serv-ice, Veterans Administration Hospital, Tampa

Associate Physician of Chest Rehabilitation,Institute for Rehabilitation Medicine, NewYork University School of Medicine

Chairman, Otolaryngology Division, TuftsUniversity School of Medicine ; Otolaryn-gologist-in-Chief, New England Medical Cen-ter Hospital, Boston

Director; Nasal Disease Study Center, andAttending Physician, Allergy Unit, St . Vin-cent's Hospital, New York

Director of Research and Development, Fi-sons Ltd., Pharmaceutical Division, Lough-borough, Leicestershire, England

Assistant Professor, Department of Medicine,The University of Vermont College of Medi-cine, Burlington

xvii Contributing Authors

Serge J. Dos, M .D .CHAPTER 68

Mauricio J . Dulfano, M .D .CHAPTER 45

Richard S. Farr, M.D .CHAPTER 43

Charles W. Fishel, Ph .D .CHAPTER 10

D. C. Flenley, Ph.D ., M.B.Ed .CHAPTER 21

A. W. Frankland, M.D .CHAPTER 37

Lawrence D . Frenkel, M .D .CHAPTER 8

Gerald J. Gleich, M.D .CHAPTER 6

Gareth M. Green, M .D .CHAPTER 28

Paul Gross, M.D .CHAPTER 26

Assistant Professor of Surgery and AssistantProfessor of Clinical Physiology, State Uni-versity of New York at Stony Brook HealthSciences Center School of Medicine ; StaffSurgeon, Veterans Administration Hospital,Northport, New York

Associate Professor of Medicine, State Uni-versity of New York Downstate Medical Cen-ter College of Medicine, Brooklyn ; Chief,Respiratory Care Center and Sputum Labora-tory, Veterans Administration Hospital,Brooklyn

Professor of Medicine, The University ofColorado School of Medicine ; Head, Depart-ment of Medicine and Section of Allergy andClinical Immunology, National Jewish Hos-pital and Research Center, Denver

Professor and Chairman, Medical Microbiol-ogy Department, University of South FloridaCollege of Medicine, Tampa

Senior Lecturer, University of Edinburgh ;Honorary Consultant Physician, The RoyalInfirmary, Edinburgh, Scotland

Director, Allergy Department, St . Mary'sHospital, London, England

Assistant Professor of Pediatrics, GeorgetownUniversity School of Medicine ; AttendingPediatrician, Georgetown University Hospi-tal, Washington, D .C .

Associate Professor of Medicine, Immunol-ogy, and Microbiology, Mayo Medical School ;Consultant, Departments of Microbiology,Medicine, and Immunology, Mayo Clinicand Mayo Foundation, Rochester, Minnesota

Professor of Medicine, and Director, Pulmo-nary Unit, Department of Medicine, TheUniversity of Vermont College of Medicine,Burlington

Distinguished Research Professor of Pathol-ogy, Medical University of South CarolinaCollege of Medicine, Charleston ; Director ofResearch Laboratory, Industrial Health Foun-dation, Pittsburgh, Pennsylvania

xvui Contributing Authors

Albert Haas, M.D .CHAPTER 71

+R. Havez, M.D .CHAPTER 25

J. A . Hayes, M.D ., M .R.C.Path .CHAPTER 23

John Hedley-Whyte, M .D .CHAPTER 67

Richard W. Honsinger, Jr., M.D .CHAPTER 44

Roland H. Ingram, Jr., M.D .CHAPTER 19

David Jack, Ph .D., F.R.I.C .CHAPTER 30

Myron J. Jacobson, M.D ., F.A.C.S .CHAPTER 68

Murray L. Janower, M.D .CHAPTER 41

S. Gunnar 0. Johansson, M .D .CHAPTER 13

Michael Kaliner, ivi.D .CHAPTER 12

t Deceased.

Professor of Experimental RehabilitationMedicine, Institute for Rehabilitation Medi-cine, New York University School of Medi-cine ; Director, Chest Rehabilitation, BellevueHospital, New York

Professor of Biochemistry, Faculte de Mede-cine de Lille, Lille, France

Associate Professor of Pathology, BostonUniversity School of Medicine; AssociatePathologist, Boston City Hospital

Professor of Anaesthesia, Harvard MedicalSchool ; Anaesthetist-in-Chief, Beth IsraelHospital, Boston

Clinical Associate, Department of Medicine,The University of New Mexico School ofMedicine, Albuquerque ; Attending Staff, LosAlamos Medical Center, Los Alamos, NewMexico

Associate Professor of Medicine, HarvardMedical School ; Director, Pulmonary Dis-ease Division, Peter Bent Brigham Hospital,Boston

Managing Director, Allen & Hanburys Re-search Limited, Ware, Hertfordshire, Eng-land

Associate Professor of Surgery, State Uni-versity of New York at Stony Brook HealthSciences Center School of Medicine ; StaffSurgeon, Veterans Administration Hospital,Northport, New York

Associate Professor of Radiology, Universityof Massachusetts Medical School ; Physician-in-Chief, Department of Radiology, The St .Vincent Hospital, Worcester

Assistant Professor in Clinical Immunology,The Blood Center, University Hospital, Upp-sala, Sweden

Senior Investigator, National Institute of Al-lergy and Infectious Diseases, National Insti-tutes of Health, Bethesda, Maryland

xix Contributing Authors

Sudhakar R . Kamat, M.B.B .S .,F.R.C.B . (U.K .)CHAPTER 38

Roger M. Katz, M.D .CHAPTER 62

Robert W. Kellermeyer, M.D .CHAPTER 16

Kaye H. Kilburn, M.D .CHAPTER 72

Charles H . Kirkpatrick, M .D .CHAPTER 58

Dennis G. Kleban, M.D .CHAPTER 7

Peter H. Knapp, M.D .CHAPTER 70

David Lagunoff, M .D .CHAPTER 24

David P. Lauler, M .D .CHAPTER 53

Lawrence M . Lichtenstein, M.D ., Ph.D .CHAPTER 57

Richard F. Lockey, M .D .CHAPTER 42

Senior Clinical Research Officer in ChestMedicine, Seth G . S. Medical College ; Assist-ant Physician, K. E. M. Hospital, Parel, Bom-bay, India

Clinical Assistant Professor of Pediatrics,University of California, Los Angeles, Schoolof Medicine ; Allergy Medical Clinic, Inc .,Los Angeles

Professor of Medicine, Case Western ReserveUniversity School of Medicine ; AssociatePhysician in Medicine, University Hospitalsof Cleveland, Cleveland, Ohio

Professor of Medicine and Associate Profes-sor of Anatomy, University of Missouri Med-ical School ; Director, Pulmonary Disease,Veterans Administration Hospital, Columbia,Missouri

Head, Clinical Allergy and HypersensitivitySection, National Institute of Allergy and In-fectious Diseases, National Institutes ofHealth, Bethesda, Maryland

Clinical Instructor, Department of Pediatrics,Georgetown University School of Medicine ;IiTstructor, Pediatric Allergy and Immunol-ogy; Georgetown University Medical Center,Washington, D .C .

Professor and Associate Chairman, Divisionof Psychiatry, Boston University School ofMedicine; Psychiatrist, University Hospital,Boston

Professor of Pathology, The University ofWashington School of Medicine, Seattle

Adjunct Assistant Clinical Professor of Med-icine, Cornell University Medical College,New York

Associate Professor of Medicine, The JohnsHopkins University School of Medicine ; At-tending Physician, The Good Samaritan Hos-pital, Baltimore

Assistant Professor, Department of InternalMedicine, University of South Florida Col-lege of Medicine ; Assistant Chief, AllergySection Medical Service, Veterans Adminis-tration Hospital, Tampa

xx Contributing Authors

Manuel Lopez, M.D .

Assistant Professor of Medicine, Tulane Uni-CHAPTER 33

versity School of Medicine, New Orleans,Louisiana

Buy V. Lourenco, M .D .

Professor of Medicine, University of IllinoisCHAPTER 27 Abraham Lincoln School of Medicine ; At-

tending Physician and Director, PulmonarySection, University of Illinois Hospital,Chicago

Francis C . Lowell, M.D .

Associate Professor of Medicine, HarvardCHAPTER 47

Medical School ; Chief, Allergy Unit, Massa-chusetts General Hospital, Boston

Felicia Lustig, Ph .D .

Assistant Professor of Rehabilitation Medi-CHAPTER 71

cine, Institute for Rehabilitation Medicine,New York University School of Medicine,New York

Harold A. Lyons, M.D .

Professor of Medicine, State University ofCHAPTER 49

New York Downstate Medical Center Collegeof Medicine, Brooklyn ; Director, PulmonaryDivision and Pulmonary Laboratory, KingsCounty Hospital Center, Brooklyn

Kenneth F. MacDonnell, M.D .

Associate Professor of Medicine, Tufts Uni-CHAPTER 46

versity School of Medicine ; Director, Pul-monary and Respiratory Units, St. Eliza-beth's Hospital, Boston

G. P . Maher-Loughnan, D.M. (Oxon), B .Ch .

Consultant Physician, Colindale Hospital,CHAPTER 69

London, England

Inder V. Malhotra, M.D .

Assistant Professor of Anaesthesia, HarvardCHAPTER 67

Medical School, Boston

David G. Marsh, Ph.D .

Associate Professor of Medicine and Micro-CHAPTER 5 biology, The Johns Hopkins University

School of Medicine ; Research Immunologist,O'Neill Laboratories, The Good SamaritanHospital, Baltimore

Aleksander A. Mathe, M .D .

Associate Professor of Psychiatry and Phar-CHAPTER 70

macology, and Director, Laboratory of Bio-genic Amines and Allergy, Boston UniversitySchool of Medicine, Boston

Robert P. McCombs, M.D .

Professor of Medicine, Tufts UniversityCHAPTER 40

School of Medicine ; Chief, Allergy Clinic,New England Medical Center Hospital,Boston

E. R. McFadden, Jr., M.D .

Associate Professor of Medicine, HarvardCHAPTERS 18 AND 19

Medical School; Director, Pulmonary Func-tion Laboratory, Peter Bent Brigham Hos-pital, Boston

xxi Contributing Authors

Richard H. Meade III, M .D .

Associate Professor of Medicine, Tufts Uni-CHAPTER 59

versity School of Medicine ; Senior Physician,Department of Medicine, New England Med-ical Center Hospital, Boston

James C. Melby, M.D .

Professor of Medicine, Boston UniversityCHAPTER 52

School of Medicine ; Head, Section of Endo-crinology and Metabolism, Boston UniversityMedical Center, Boston

Sheldon Mintz, M.D., F.R.C.P. (C)

Assistant Professor, University of TorontoCHAPTER 64

Faculty of Medicine ; Staff Physician, Tri-hospital Respiratory Service, Toronto, On-tario, Canada

Raymond L. H. Murphy, Jr ., M.D .

Assistant Clinical Professor of OccupationalCHAPTER 34

Medicine, Harvard School of Public Health,Boston; Director, Pulmonary Services, Lem-uel Shattuck Hospital, Jamaica Plain, Mas-sachusetts

Jay A. Nadel, M.D .

Professor of Medicine and Radiology, andCHAPTER 11

Staff Member, Cardiovascular Research Insti-tute, University of California, San Francisco,School of Medicine

Jiro Nakano, M.D ., Ph.D .

Professor of Pharmacology and AssociateCHAPTER 15

Professor of Medicine, University of Okla-homa College of Medicine, Oklahoma City

K. N. V. Palmer, M.D .

Reader in Medicine, University of Aberdeen ;CHAPTER 21

Honorary Consultant Physician, AberdeenRoyal Infirmary, Aberdeen, Scotland

J. Pepys, M .D .

Professor of Clinical Immunology, Cardio-CHAPTER 17

thoracic Institute, British Postgraduate Med-ical Federation, University of London andBrompton Hospital, London, England

M. Murray Peshkin, M.D .

Emeritus Clinical Professor of PediatricsCHAPTER 63 (Allergy), Mount Sinai School of Medicine

of The City University of New York ; Con-sulting Allergist, Mount Sinai Hospital, NewYork

Thomas L. Petty, M.D .

Associate Professor of Medicine, and Head,CHAPTER 61

Division of Pulmonary Medicine, Universityof Colorado School of Medicine, Denver

Gary S. Rachelefsky, M .D .

Clinical Assistant Professor of Pediatrics,CHAPTER 62

University of California, Los Angeles, Schoolof Medicine; Allergy Medical Clinic, Inc .,Los Angeles

xxii Contributing Authors

Robert L . Rodgers, M .S .CHAPTER 15

Arnulfo Rodriguez-Cornejo, M .D .CHAPTER 45

+Milton B . Rosenblatt, M.D .CHAPTER 1

Richard R. Rosenthal, M.D .CHAPTER 57

Philippe Roussel, M.D .CHAPTER 25

Harry Salem, Ph.D .CHAPTER 48

John E. Salvaggio, M .D .CHAPTER 33

J. G. Scadding, M .D .CHAPTER 2

Howard J. Schwartz, M.D .CHAPTER 16

Maurice S . Segal, M.D .CHAPTERS 65 AND 73

Chang Sup Shim, M .D .CHAPTER 51

1- Deceased .

Department of Pharmacology, University ofOklahoma College of Medicine, OklahomaCity

Fellow in Chest Diseases, Veterans Admin-istration Hospital, Brooklyn, New York

Clinical Associate Professor of Medicine, NewYork Medical College ; Attending Physician,Doctors and Metropolitan Hospital, NewYork

Instructor in Medicine, The Johns HopkinsUniversity School of Medicine, Baltimore

Professor of Biochemistry, Unite des Pro-teines, Institut National de la Santa et de laRecherche Medicale, Faculte de Medecine deLille, Lille, France

Associate Professor of Pharmacology, Uni-versity of Pennsylvania School of Medicine,Philadelphia ; Director of Pharmacology,Cooper Laboratories, Inc ., Cedar Knolls, NewJersey

Henderson Professor of Medicine, TulaneUniversity School of Medicine, New Orleans ;Visiting Physician, Charity Hospital, NewOrleans, Louisiana

Emeritus Professor of Medicine, Universityof London; Honorary Consulting Physician,Brompton Hospital, London, England

Assistant Professor of Medicine, Case West-ern Reserve University School of Medicine ;,Associate Physician, University Hospitals,Cleveland, Ohio

Emeritus Professor of Medicine and Consult-ant, Continuing Education, Tufts UniversitySchool of Medicine ; Director, Foundation forResearch in Bronchial Asthma and RelatedDiseases, Boston

Assistant Professor of Medicine, Albert Ein-stein College of Medicine of Yeshiva Univer-sity ; Attending Physician, Bronx MunicipalHospital Center, Bronx, New York

xxiii Contributing Authors

Sheldon C . Siegel, M .D .

Clinical Professor of Pediatrics, University ofCHAPTER 62

California, Los Angeles, School of Medicine ;Allergy Medical Clinic, Inc ., Los Angeles

R. Michael Sly, M.D .

Associate Professor of Pediatrics and DirectorCHAPTER 35 of Pediatric Allergy and Immunology, Loui-

siana State University School of Medicine;Visiting Physician, Department of Pediatrics,Louisiana State University Division, CharityHospital of Louisiana at New Orleans

Gordon L. Snider, M.D .

Professor of Medicine and Head, PulmonaryCHAPTER 3 Medicine Section, Boston University School of

Medicine; Chief, Pulmonary Medicine Sec-tions, Veterans Administration Hospital andUniversity Hospital, Boston

Harry S. Soroff, M.D ., F.A.C.S .

Professor and Chairman, Department of Sur-CHAPTER 68 gery, State University of New York at Stony

Brook Health Sciences Center School of Medi-cine ; Surgical Service, Veterans Administra-tion Hospital, Northport, New York

Sheldon Spector, M .D .

Associate Professor of Medicine, The Univer-CHAPTER 43

sity of Colorado School of Medicine ; Head,Clinical Section of Allergy, Clinical Immu-nology, and Chest Diseases, National JewishHospital and Research Center, Denver

Frank F. Speizer, M .D .

Assistant Professor in Medicine, HarvardCHAPTER 4

Medical School ; Chief, Division of ClinicalEpidemiology, Channing Laboratory, BostonCity Hospital, Boston

Myron Stein, M.D .

Professor of Medicine, University of Cali-CHAPTER 66

fornia, Los Angeles, School of Medicine ; Di-rector, Pulmonary Division, Cedars-SinaiMedical Center, Los Angeles

Alfred D. Steinberg, M .D .

Senior Investigator, Arthritis and Rheuma-CHAPTER 58

tism Branch, National Institute of Arthritisand Metabolic Diseases, National Institutesof Health, Bethesda, Maryland

Thomas A. Sullivan, M .D .

Knoxville Pulmonary Group, Knoxville, Ten-CHAPTER 72

nessee

Andor Szentivanyi, M.D .

Chairman, Department of Pharmacology,CHAPTER 10

and Professor of Pharmacology and InternalMedicine, University of South Florida Col-lege of Medicine, Tampa

George W. Thorn, M.D .

Emeritus Hersey Professor of the Theory andCHAPTER 53

Practice of Physic, Harvard Medical School ;Emeritus Physician-in-Chief, Peter Bent Brig-ham Hospital, Boston

xxiv Contributing Authors

Thomas B. Tomasi, Jr ., M.D., Ph.D .

Professor of Immunology and Medicine,CHAPTER 6

Mayo Medical School ; Chairman, Depart-ment of Immunology, Mayo Clinic and MayoFoundation, Rochester, Minnesota

Louis Vachon, M.D .

Associate Professor of Psychiatry, BostonCHAPTER 70

University School of Medicine; Psychiatrist,University Hospital, Boston

Martin D. Valentine, M.D .

Assistant Professor of Medicine, The JohnsCHAPTER 14 Hopkins University School of Medicine ;

Physician, Division of Allergy and Hyper-sensitivity, The Good Samaritan Hospital,Baltimore

Paul P. Van Arsdel, Jr ., M.D .

Professor of Medicine and Head, Division ofCHAPTER 30

Allergy, The University of WashingtonSchool of Medicine ; Attending Physician,University Hospital, Seattle

Earle B. Weiss, M.D .

Director, Department of Respiratory Diseases,CHAPTER 60 The St. Vincent Hospital ; Associate Professor

of Medicine, University of MassachusettsMedical School ; Associate Affiliate Professorof Life Sciences, Worcester Polytechnic In-stitute, Worcester

Emile E. Werk, M.D .

Professor of Medicine and Chief, UniversityCHAPTER 54 Medical Service, University of North Caro-

lina College of Medicine; Chief, MedicalServices, New Hanover Memorial Hospital,Wilmington, North Carolina

Fredrick Wessels, M.D .

Former Clinical Research Fellow in AllergyCHAPTER 33

and Immunology, Tulane University Schoolof Medicine; Allergy and Immunology As-sociation, Ltd ., Phoenix, Arizona

John B. West, M.D., Ph.D .

Professor of Medicine, University of Cali-CHAPTER 20

fornia, San Diego, School of Medicine, LaJolla ; Attending Physician, University Hos-pital, San Diego

M. Henry Williams, Jr., M.D .

Professor of Medicine, Albert Einstein Col-CHAPTER 51 lege of Medicine of Yeshiva University ; Di-

rector, Chest Service, Department of Medi-cine, Bronx Municipal Hospital Center,Bronx, New York

Sybil W. Woo, M.D .

Associate Professor of Anaesthesia, The Uni-CHAPTER 67

versity of Connecticut Health Center, Hart-ford