Asthma prevention

I. EPIDEMIOLOGY OF ASTHMA 1 1. Epidemiology of Asthma 3 Malcolm R. Sears I. Introduction 3 II. Definition and Diagnosis of Asthma 3 III. Airway Hyperresponsiveness as an Epidemiological Tool 5 IV. Atopy as an Epidemiological Tool 6 V. Recent Trends in Asthma Epidemiology 6 VI. Epidemiological Trends in Asthma Mortality 8 VII. Incidence and Prevalence in Children 8 VIII. Epidemiology of Adult Asthma 13 IX. Epidemiological Perspective on Prevention of Asthma 14 References 14 2. The Natural History of Wheezing in Children 21 Fernando D. Martinez I. Introduction 21 II. Incidence 22 III. Severity and Long-Term Prognosis of Early Wheezing Episodes 22 IV. Late Onset Wheezers 24 V. Bronchial Hyperresponsiveness (BHR) and Lung Function in Early Wheezing Phenotypes 25 VI. Predicting Early Asthma 27 VII. Early Development of T Helper-2 (Th2) Responses 28 VIII. Conclusions 30 References 30 xii Busse and Lemanske 3. Emerging Patterns of Asthma Worldwide 33 Erika von Mutius I. Introduction 33 II. Worldwide Distribution of Wheeze and Asthma 34 III. Contrasting Results from Developing and Developed Countries 36 IV. East–West Gradient across Europe 38 V. Differences in Rural and Urban Populations 41 References 43 4. Later Life Onset of Asthma 47 Chakradhar Kotaru and Richard J. Martin I. Introduction 47 II. Definition 48 III. Epidemiology 48 IV. Genotypic Associations with Adult Onset Asthma 52 V. Phenotypic Features of Later Onset Asthma 54 VI. Epidemiologic Associations 58 VII. Treatment and Prognosis 62 VIII. Conclusions 62 References 63 II. IMMUNOLOGY IN THE EARLY DEVELOPMENT OF ASTHMA 71 5. Ontogeny of the Immune Response 73 P.G. Holt and J. Rowe I. Introduction 73 II. Ontogeny of Fetal Immune System 73 III. Early Postnatal Development of Immune System 75 IV. Early-Life Immunity to Infectious Agents and Vaccines 80 V. Vaccination and Atopic Phenotype 82 VI. Postnatal Development of Immune Function and Susceptibility to Allergic Disease 83 References 85 6. Inflammatory Features of Childhood Asthma 99 Marzena Krawiec and Theresa Guilbert I. Introduction 99 II. Pathophysiology of Airway Inflammation in Children 100 Contents xiii III. Evaluation of Inflammation in Children 107 IV. Conclusion 122 References 122 III. RISK FACTORS IN THE DEVELOPMENT OF ASTHMA 133 7. Physiology 135 Alexander Mِller and Peter N. Le Souëf I. Introduction 135 II. Plethysmographic Measurements of Lung Volume and Airway Resistance 136 III. Tidal Breath Analysis for Infant Pulmonary Function Testing 138 IV. Tidal Forced Expirations 139 V. Raised Volume Rapid Thoraco-Abdominal Compression (RVRTC) 140 VI. Measurement of Functional Residual Capacity by Gas Dilution 141 VII. Measurement of Airway Mechanics Using Forced Oscillation 142 VIII. Assessment of Airway Responsiveness 144 IX. Factors Affecting Physiology in Infants and Children 144 X. Early Physiological Factors as Predictors of Future Physiological Function and Asthma 149 XI. Summary 151 References 152 8. Genetic Factors 161 Sabine Hoffjan and Carole Ober I. Introduction 161 II. Laboratory Techniques and Study Designs 163 III. Genome-Wide Screens 167 IV. Candidate Gene Studies 173 V. Conclusion 195 References 195 9. Birth Order 221 Tricia McKeever, Richard Hubbard, Sarah Lewis, and John Britton I. Introduction 221 II. Hay Fever, Eczema, and Allergic Sensitization in Relation to Birth Order 222 III. Asthma and Birth Order 223 xiv Busse and Lemanske IV. Infections 226 V. Immune System 228 VI. Day Care 228 VII. Multiple Births 228 VIII. Is the Birth Order Effect Already Present at Birth? 232 IX. Birth Order and Other Diseases 232 X. Summary 233 References 233 10. Infections: Causative 239 G. Daniel Brooks and Robert F. Lemanske, Jr. I. Introduction 239 II. Asthma Inception 239 III. Strategies for Preventing RSV 245 IV. Asthma Exacerbations 248 IV. Preventive Strategies 252 V. Conclusions 254 References 254 11. Allergens 263 Elizabeth A. Erwin, Judith A. Woodfolk, Peter W. Heymann, and Thomas A.E. Platts-Mills I. Introduction 263 II. Dust Mites 264 III. Animal Dander Allergens 267 IV. Allergens Derived from Fungi 270 V. Cockroach Exposure 272 VI. Relationship of Specific IgE Antibody Responses and Total IgE in Asthma Patients 274 VII. Conclusions 275 References 277 12. Asthma and Nonrespiratory Infections 283 Paolo Maria Matricardi I. Odd Influence on Asthma of Certain Nonrespiratory Infections (NRIs) 283 II. Testing Hygiene Hypothesis in Europe 284 III. Testing Hygiene Hypothesis in United States 285 IV. Does the Hygiene Hypothesis Explain Inner City Asthma? 287 V. Protection Provided by Nonrespiratory Infections 290 VI. Ability of HAV to Protect against Asthma 291 VII. Bacteria: Do Exogenous Endotoxins Protect from Asthma? 292 Contents xv VIII. Bacteria: Gut Microflora and Allergy 293 IX. Parasites and Asthma 295 X. The Role of NRIs in Preventing and Treating Asthma 296 XI. Conclusions 297 References 297 13. Antibiotics as Risk Factors in the Development of Asthma 303 Bengt Bjِrkstén I. Introduction 303 II. Epidemiological Studies 304 III. Aspects of Microbial Ecology 308 IV. Concluding Remarks 310 References 310 14. The Atopic March 313 U. Wahn, R. Nickel, S. Lau, C. Grüber, and S. Illi I. Introduction and Definition 313 II. Assessment of Determinants 314 III. Natural History of Atopic Manifestations 315 IV. Hereditary Factors 319 V. Nongenetic Factors 320 VI. Issues Related to Prevention 325 VII. Conclusion 327 References 327 15. Stress and Asthma 333 Rosalind J. Wright I. Introduction 333 II. Life Stress Model 334 III. Asthma Paradigm: Link to Stress 335 IV. Psychological Stress and Endocrine System 335 V. Stress and Autonomic Control of Airways 337 VI. Stress and Immune Function 339 VII. Stress and Infection 340 VIII. Stress and Glucocorticoid Resistance 341 IX. Psychological Stress and Oxidative Stress 342 X. Genetics 345 XI. Epidemiological Evidence 345 XII. Socioeconomic Status (SES) and Asthma Disparities 346 XIII. Summary 349 Acknowledgment 349 References 349 xvi Busse and Lemanske 16. Infant Feeding Practices and Prevention of Asthma 359 Anne L. Wright I. Introduction 359 II. Background 360 III. Possible Explanations for Conflicting Observations 364 IV. Implications for Prevention 367 V. Conclusions 368 References 369 IV. TREATMENT 375 17. Asthma in the Inner City 377 Kristin M. Burkart, Megan T. Sandel, and George T. O’Connor I. Excess Burden of Asthma in the Inner City 377 II. Causes of Excess Burdens of Asthma in Inner Cities 380 III. Asthma Prevention Strategies for Inner Cities 396 IV. Summary 401 References 401 18. Therapeutic Approaches to Childhood Asthma 419 Stanley J. Szefler I. Introduction 419 II. Managing Asthma in Children 420 III. Managing Asthma in Young Children 425 IV. When to Initiate Long-Term Controller Therapy in Children 428 V. Evolution of Asthma Therapy and Potential for Future Developments 429 VI. Conclusions 435 Acknowledgment 436 References 436 19. Allergen Avoidance 441 Jacqueline Pongracic I. Introduction 441 II. Principles of Allergen Avoidance 441 III. Environmental Control and Primary Prevention 452 IV. Summary 452 References 453 Contents xvii 20. Immunotherapy and Asthma 465 Moisés A. Calderَn-Zapata and Stephen R. Durham I. Introduction 465 II. Mechanisms of Immunotherapy 466 III. Efficacy and Safety of Specific Immunotherapy 470 IV. Long-Term Benefits Following Discontinuation of Immunotherapy 474 V. Immunotherapy and Progression of Rhinitis to Asthma 475 VI. Immunotherapy and Onset of New Allergic Sensitivities 476 VII. Allergen Immunotherapy: Future Strategies 476 VIII. Conclusions 477 References 478 21. Anti-Cytokine Therapy 483 Larry Borish I. Introduction 483 II. Mechanisms of Cytokine Inhibition 484 III. Inhibitors of Cytokines Associated with Innate Immunity 486 IV. Immune Deviation: Stimulation of Th1-Like Responses 489 V. Inhibition of Th2 Cytokines 492 VI. Anti-Inflammatory Cytokines 497 VII. Summary 499 References 499 22. IgE and Anti-IgE Therapy in Allergic Asthma and Rhinitis 505 E.M. Salagean, P.H. Howarth, and S.T. Holgate I. Introduction 505 II. Serum IgE and Epidemiology 507 III. IgE structure, Synthesis and Cell Interactions 509 IV. Anti-IgE and Its Development as Therapy 513 V. Therapeutic Potential of Omalizumab 518 VI. Other Approaches to Neutralizing IgE 535 VII. Conclusions 536 References 537 23. DNA Vaccination for Asthma 547 David H. Broide I. Introduction 547 II. Immunostimulatory DNA 548 xviii Busse and Lemanske III. Conjugation of CpG DNA and Protein Antigen 562 IV. Allergen Gene Vaccines and Asthma 564 V. Conclusion 564 Acknowledgment 565 References 565 24. DNA Vaccination for Asthma and Atopic Disorders 571 Kunihiko Kitagaki and Joel N. Kline I. Introduction 571 II. Epidemiology of Asthma: Are Microbial Infections Naturally Protective? 571 III. Pathogenesis of Asthma: Imbalance of Th1 and Th2? 572 IV. Immunostimulatory DNA; What is CpG? 573 V. Signal Transduction of CpG DNA: TLR-9 574 VI. CpG DNA Induces Th1-Type Immune Responses 574 VII. CpG-ODN in Prevention of Asthma 575 VIII. CpG-ODNs in Immunotherapy of Established Asthma 579 IX. Future Directions 582 Acknowledgment 583 References 583 25. Future Therapies 591 Jeffrey Stokes, Christopher Clark, and Thomas B. Casale I. Introduction 591 II. Immune-Modifying Therapies 592 III. Environmentally Based Therapies 602 IV. Conclusion 607 References 607 26. Regulation of IgE Synthesis 615 Lisa Cameron and Donata Vercelli I. Introduction 615 II. Induction of IgE Synthesis: Intercellular Interactions 615 III. Induction of IgE Synthesis: Molecular Events 620 IV. Modulating IgE Synthesis: Bench to Bedside 626 V. Conclusions 627 References 628 Index 637