Jay A. NadelI. Leonard Bernstein and David I. Bernstein and Moira Chan-Yeung and Jean-Luc MaloJack Pepys and I. Leonard BernsteinMargaret R. Becklake and Jean-Luc Malo and Moira Chan-YeungAnthony J. Newman-Taylor and Berran YucesoyPiero Maestrelli and Leonardo M. Fabbri and Cristina E. MappVictor J. Johnson and Michael I. LusterDavid I. Bernstein and Paloma Campo and Xaver BaurCatherine Lemiere and Raymond E. Biagini and C. Raymond ZeissP. Sherwood Burge and Gianna Moscato and Anthony Johnson and Moira Chan-YeungOlivier Vandenplas and Andre Cartier and Jean-Luc MaloMark Nieuwenhuijsen and Xaver Baur and Dick HeederikMark C. Swanson and Dick HeederikJacques Lesage and Guy PerraultI. Leonard Bernstein and Helena Keskinen and Paul D. Blanc and Moira Chan-Yeung and Jean-Luc MaloGary M. Liss and Henrik Nordman and Susan M. Tarlo and David I. BernsteinJonathan A. Bernstein and Katherine SarloDick Heederik and Anthony J. Newman-TaylorSusan Gordon and Robert K. Bush and Anthony J. Newman-TaylorOlivier Vandenplas and Donald Beezhold and Susan M. TarloSantiago Quirce and David I. Bernstein and Jean-Luc MaloAdam V. Wisnewski and Carrie A. Redlich and Cristina E. Mapp and David I. BernsteinMoira Chan-Yeung and Jean-Luc MaloI. Leonard Bernstein and Rolf MergetJean-Luc Malo and Hae-Sim Park and I. Leonard BernsteinDenyse Gautrin and I. Leonard Bernstein and Stuart M. Brooks and Paul K. HennebergerGregory R. Wagner and Paul K. HennebergerMoira Chan-Yeung and I. Leonard Bernstein and Susanna Von Essen and Jaspal Singh and David A. SchwartzEva Hnizdo and Susan M. Kennedy and Paul D. Blanc and Kjell Toren and I. Leonard Bernstein and Moira Chan-YeungYvon Cormier and Mark SchuylerDick Menzies and Kathleen KreissDavid C. Christiani and Jean-Luc Malo and Andrea SiracusaC. G. Toby Mathias and Boris D. Lushniak

Preface	p. iii
Contributors	p. xvii
Introduction	p. xxiii
Part I General Considerations
1 Definition and Classification of Asthma in the Workplace	p. 1
Introduction	p. 1
Classification of Asthma in the Workplace	p. 1
Definitions	p. 2
Nosological Working Definitions for Diagnostic and Epidemiological Purposes	p. 5
Conclusion	p. 7
References	p. 7
2 Historical Aspects of Occupational Asthma	p. 9
Introduction	p. 9
Current Status of OA	p. 21
Actions of Regulatory Bodies	p. 22
Key Advances from 1993 to 2005	p. 23
Future Research Trends	p. 27
References	p. 28
3 Epidemiological Approaches in Occupational Asthma	p. 37
Introduction-The Role of Epidemiology	p. 37
Methodological Issues	p. 39
Distribution and Determinants of OA	p. 58
Natural History	p. 68
Screening and Surveillance	p. 73
Uses, Usefulness, and Applications	p. 74
Research Needs	p. 75
Summary	p. 77
References	p. 77
4 Genetics and Occupational Asthma	p. 87
Introduction	p. 87
The Importance of Well-Defined Phenotypes in Genetic Studies	p. 88
Genetic Basis of Asthma	p. 88
Molecular Genetics	p. 90
Association Studies in Complex Diseases	p. 94
Future Directions	p. 103
References	p. 104
5 Pathophysiology	p. 109
Introduction	p. 109
Pathophysiological Mechanisms Common to Non-OA and OA	p. 110
Mechanisms of OA	p. 112
Pathologic Features of OA	p. 121
Conclusions	p. 129
Directions for Future Research	p. 129
References	p. 130
6 Animal Models of Occupational Asthma: Tools for Understanding Disease Pathogenesis	p. 141
Introduction	p. 141
Occupational Asthma Produced by Low-Molecular-Weight Chemical Haptens	p. 141
Occupational Asthma to High-Molecular-Weight Protein Allergens	p. 151
Summary and Future Directions	p. 153
References	p. 153
Part II Assessment and Management
7 Clinical Assessment and Management of Occupational Asthma	p. 161
Introduction	p. 161
The Occupational History	p. 162
Immunologic Assessment	p. 164
Evaluation of OA with Lung Function Studies	p. 166
Noninvasive Markers of Airways Inflammation	p. 168
Differential Diagnosis	p. 169
General Approach to the Clinical Assessment of OA	p. 169
Rational Approach for Diagnosing OA	p. 170
Clinical Management	p. 172
Directions of Future Research	p. 175
References	p. 175
8 Immunological and Inflammatory Assessments	p. 179
Introduction	p. 179
Immunological Assessment by Skin Tests	p. 180
Immunological Assessment by Serological Assays	p. 180
Noninvasive Assessment of Airway Inflammation	p. 187
Discussion of Illustrative Case History	p. 190
Directions of Future Research	p. 191
References	p. 191
9 Physiological Assessment: Serial Measurements of Lung Function and Bronchial Responsiveness	p. 199
Introduction	p. 199
Diurnal Variation in Airways Caliber	p. 199
Before and After Shift Measurements	p. 201
Longitudinal Measurements of Lung Function	p. 201
Serial Measurements of Peak Expiratory Flow	p. 201
Serial Measurements of Nonallergic Bronchial Responsiveness	p. 215
Summary	p. 219
Directions for Future Research	p. 220
References	p. 220
10 Occupational Challenge Tests	p. 227
Introduction-Historical Background	p. 227
Purpose and Justification for the Tests	p. 228
Performing the Test	p. 229
Duration and Schedule of Exposure and Monitoring Spirometry	p. 233
Methodology	p. 233
Patterns of Reaction	p. 239
Pitfalls	p. 243
OCT in the Case of Alveolitis	p. 245
OCT with Occupational Agents as a Research Tool	p. 246
Conclusion and Research Needs	p. 246
References	p. 246
11 Environmental Monitoring: General Considerations, Exposure-Response Relationships, and Risk Assessment	p. 253
Introduction-Monitoring General Considerations	p. 253
Exposure-Response Relationships	p. 260
Risk Assessment	p. 269
References	p. 270
12 Quantification of Bio-Active Protein Aerosols	p. 275
Introduction	p. 275
Exposure Assessment in the Evaluation of OA	p. 276
Purpose of Air Sampling	p. 276
Protocols for Monitoring Occupational Exposure	p. 277
Immunoassays	p. 282
Measurements to Control Exposure to Occupational Allergens	p. 287
Conclusions	p. 293
Directions of Future Research	p. 293
References	p. 293
13 Environmental Monitoring of Chemical Agents	p. 297
Introduction	p. 297
Monitoring Methods	p. 298
Exposure Evaluation Strategy as Related to OA	p. 305
Examples of Evaluation of Exposure to Specific Sensitizing Agents	p. 306
Conclusion and Research Needs	p. 313
References	p. 314
14 Medicolegal Aspects, Compensation Aspects, and Evaluation of Impairment/Disability	p. 319
Introduction-Background	p. 319
Current State of the Compensation System for Asthma in the United States	p. 321
Medicolegal Definitions of OA	p. 323
Outcomes of Workers Compensated for Work-Related Asthma	p. 327
The International Perspective	p. 328
Assessment of Impairment/Disability	p. 335
Recommendations for the Future	p. 346
Summary	p. 347
References	p. 347
15 Prevention and Surveillance	p. 353
Introduction-Prevention	p. 353
Primary Prevention	p. 354
Secondary Prevention	p. 357
Tertiary Prevention	p. 362
Public Health Surveillance	p. 363
Conclusions	p. 369
References	p. 369
Part III Specific Agents Causing Occupational Asthma with a Latency Period
16 Enzymes	p. 377
Introduction	p. 377
Prevalence and Risk Factors	p. 378
Immunopathogenesis	p. 379
Specific Causes of Enzyme-Induced OA	p. 380
Evaluation and Treatment	p. 386
Management	p. 387
Immunosurveillance	p. 387
Directions of Future Research	p. 388
Conclusions	p. 389
References	p. 389
17 Occupational Asthma in the Baking Industry	p. 393
Introduction	p. 393
Allergens: Nature and Sources	p. 394
Measurement of Dust Exposure and Airborne Allergens	p. 398
Epidemiology	p. 400
Diagnosis	p. 404
Management	p. 406
Prevention	p. 406
Summary	p. 408
References	p. 408
18 Laboratory Animal, Insect, Fish, and Shellfish Allergy	p. 415
Introduction	p. 415
Animals	p. 415
Insects	p. 424
Fishes and Shellfishes	p. 427
Research Needs	p. 428
References	p. 428
19 Latex Allergy	p. 437
Introduction	p. 437
Natural Rubber Latex	p. 437
Pathogenesis	p. 439
Epidemiology	p. 442
Clinical Manifestations	p. 444
Diagnostic Procedures	p. 446
Management and Outcome	p. 448
Prevention	p. 449
Conclusion, Research Needs, and Perspectives	p. 451
References	p. 452
20 High-Molecular-Weight Protein Agents	p. 463
Introduction	p. 463
Animal-Derived Allergens	p. 463
Mold	p. 465
Plants	p. 466
Flowers	p. 467
Greenhouse Workers	p. 469
Vegetable Gums	p. 470
Other Allergens	p. 471
Perspectives and Research Needs	p. 472
References	p. 472
21 Polyisocyanates and Their Prepolymers	p. 481
Introduction	p. 481
Background	p. 483
Clinical Manifestations of Polyisocyanate Hypersensitivity	p. 484
Epidemiology	p. 485
Uptake, Distribution, and Excretion of Polyisocyanates	p. 486
Pathogenesis: Airway Inflammation and Cellular Responses	p. 486
Genetics	p. 488
Toxicity of Isocyanates	p. 488
Animal Studies	p. 489
Diagnosis	p. 491
Laboratory Testing	p. 491
Bronchoprovocation Testing	p. 492
Industrial Hygiene	p. 493
Surveillance and Prevention	p. 494
Treatment	p. 494
Future Directions in Research	p. 495
References	p. 495
22 Western Red Cedar (Thuja plicata) and Other Wood Dusts	p. 505
Introduction	p. 505
Occupational Asthma Due to WRC (Thuja plicata)	p. 506
Occupational Asthma Due to Other Wood Dusts	p. 514
Occupational Asthma Due to Other Agents Present in Wood Dust	p. 515
Chronic Bronchitis with and Without Airflow Obstruction	p. 515
Hypersensitivity Pneumonitis Associated with Wood Dust Exposure	p. 519
Organic Dust Toxic Syndrome	p. 520
Research Needs	p. 520
Summary	p. 520
References	p. 520
23 Metals	p. 525
Introduction	p. 525
General Properties of Metals	p. 525
Differential Diagnosis of Metal-Induced Asthma	p. 526
Occupational Exposure Variables	p. 527
Classification	p. 527
First Series of Transitional Metals	p. 529
Second Series of Transitional Metals	p. 534
Third Series of Transitional Metals	p. 535
Group III Metal Series	p. 544
Indeterminate Metals	p. 546
Directions for Future Research	p. 547
Conclusion	p. 547
References	p. 548
24 Other Chemical Substances Causing Occupational Asthma	p. 555
Introduction	p. 555
Azobisformamide or Azodicarbonamide	p. 556
Amines	p. 556
Colophony and Fluxes	p. 558
Formaldehyde	p. 560
Chloramine T and Other Biocides	p. 561
Hairdressing Chemicals	p. 562
Diazonium Salts and Reactive Dyes	p. 562
Pharmaceutical Products	p. 563
Polyvinylchloride and Adhesives	p. 564
Acrylates	p. 565
Acid Anhydrides	p. 565
Others	p. 566
Structure-Activity Relationships of Respiratory Sensitization Potential	p. 567
Multiple Chemical Sensitivity Syndrome	p. 568
Conclusion and Research Needs	p. 569
References	p. 569
Part IV Specific Disease Entities and Variants
25 Reactive Airways Dysfunction Syndrome and Irritant-Induced Asthma	p. 581
Introduction	p. 581
Clinical Description of the Syndrome	p. 582
Other Case and Series Reports of RADS	p. 583
Presence or Absence of RADS After High-Level Irritant Exposures During Disasters	p. 586
Pathology	p. 592
Hypothesis of Pathogenetic Mechanisms	p. 595
Diagnosis of RADS	p. 599
Comparison Between RADS and Other Forms of OA	p. 603
Epidemiologic Studies	p. 604
Other Forms of IIA or Possible Variants of RADS	p. 607
Prognosis	p. 616
Management	p. 617
Conclusions	p. 618
Directions of Future Research	p. 619
References	p. 619
26 Asthma Exacerbated at Work	p. 631
Introduction	p. 631
Definitions of WEA	p. 632
Frequency of WEA	p. 632
Excess Frequency of WEA	p. 634
Distinctive Features of Adults with WEA	p. 635
Clinical Approach to a Patient with WEA	p. 636
Challenges in Studying WEA	p. 637
Classification of WEA	p. 638
Conclusions	p. 638
Directions of Future Research	p. 639
References	p. 639
27 Acute Airway Diseases Due to Organic Dust Exposure	p. 641
Introduction	p. 641
Cotton and Other Textile Dusts	p. 642
Grain Dust	p. 654
Exposure in Swine Confinement Barns	p. 663
Endotoxin and Airway Disease Caused by Organic Dust Exposure	p. 666
Summary	p. 670
Directions for Future Research	p. 670
References	p. 671
28 Chronic Airway Disease Due to Occupational Exposure	p. 683
Introduction	p. 683
Exposure to Mineral Dust	p. 685
Exposure to Organic Dusts	p. 691
Exposure to Irritant Gases and Fumes	p. 694
Exposure to Toxic Agents That Cause Bronchitis and Bronchiolitis Obliterans (BO)	p. 696
Defining the Problem of COPD from an Epidemiological Perspective	p. 698
Contribution of Occupation to the Burden of COPD	p. 700
Overall Summary	p. 701
Directions for Future Research	p. 702
References	p. 702
29 Hypersensitivity Pneumonitis and Organic Dust Toxic Syndromes	p. 713
Introduction-Hypersensitivity Pneumonitis	p. 713
Organic Dust Toxic Syndrome	p. 726
Overall Summary	p. 727
Directions for Future Research	p. 728
References	p. 728
30 Building-Related Illnesses	p. 737
Introduction	p. 737
Definitions	p. 738
Specific BRI	p. 739
Nonspecific BRI	p. 745
Synthesis of Evidence Regarding Nonspecific BRI	p. 765
Approach to the Patient	p. 766
Conclusions	p. 772
Research Priorities	p. 773
References	p. 774
31 Upper Airways Involvement	p. 785
Introduction-Definition	p. 785
Exposures	p. 786
Clinical Features	p. 786
Assessment of Nasal Responses	p. 787
Biochemical Markers of Inflammatory and Immune Responses	p. 788
Pathogenesis	p. 790
Occurrence and Determinants	p. 791
Natural History	p. 791
Management	p. 792
Future Research	p. 792
References	p. 793
32 Occupational Urticaria	p. 797
Introduction	p. 797
Classifications of Urticaria	p. 798
Epidemiology	p. 798
Contact Urticaria	p. 804
Airborne Exposure Urticaria	p. 811
Physical Urticarias	p. 811
Diagnosis of Work-Related Urticaria	p. 813
Treatment	p. 816
References	p. 817
Appendix Jean-Luc Malo and Moira Chan-Yeung	p. 825
Index	p. 867