Nutritional strategies for allergy prevention, diagnosis and treatment, with a specific focus on egg

337 Pages·2015·8.08 MB·English

by  Merryn J Netting

NUTRITIONAL STRATEGIES
FOR ALLERGY PREVENTION,
DIAGNOSIS A ND
TREATMENT, WITH A
SPECIFIC FOCU S ON EG G
ALLERGY
A thesis submitted for the degree of Doctor of Philosophy
Merryn J Netting
BSc BND Adv APD
Discipline of Paediatrics
School of Medicine
Faculty of Health Sciences
The University of Adelaide
Adelaide, South Australia, Australia
November 2015

iii
TABLE OF CONTENTS
PAGE
LIST OF TABLES ix
LIST OF FIGURES xi
ABSTRACT xiii
DECLARATION xv
ACKNOWLEDGEMENTS xvii
LIST OF ABBREVIATIONS xix
CONTEXTUAL STATEMENT 1
CHAPTER 1
5
INFLUENCE OF MATERNAL DIET DURING PREGNANCY AND
LACTATION ON DEVELOPMENT OF ATOPY
STATEMENT OF AUTHORSHIP 7
PAPER: ‘DOES MATERNAL DIET DURING PREGNANCY AND
9
LACTATION AFFECT OUTCOMES IN OFFSPRING?’
CHAPTER 2
27
HEN’S EGG ALLERGY AND ALLERGENICITY: A REVIEW OF THE
LITERATURE
2.1 INTRODUCTION 29
2.2 HEN’S EGG ALLERGY 31
2.3 CAN EGG ALLERGY BE PREVENTED? 34
2.3.1 EGG AVOIDANCE DURING PREGNANCY AND LACTATION 34
2.3.2 TIMING OF INTRODUCTION OF EGG INTO A CHILD’S DIET 35
2.4 HEN’S EGG ALLERGENS 37
EGG IN FOOD AND THE EFFECT OF FOOD PROCESSING ON
2.4.1 38
THE ALLERGENICITY OF EGG PROTEINS
CROSS REACTIVITY BETWEEN BIRD EGG, AND POULTRY
2.4.2 40
MEAT
2.5 DIAGNOSING EGG ALLERGY 41
SKIN PRICK AND EGG SPECIFIC SERUM IgE TESTING TO
2.5.1 43
PREDICT EGG ALLERGY
Overview of the Included Studies 44
iv
TABLE OF CONTENTS (CONT)
PAGE
Clinical History and Age of the Children Investigated 44
Type of Oral Food Challenge to Egg 44
Allergens Used as Skin Prick Test Reagents or for Serum Specific
46
IgE Levels
Statistical Methodology 46
Prediction of Egg Allergy in Children from an Unselected Population 57
Prediction of Egg Allergy in Children in Populations Referred for
57
Assessment of Suspected Allergy
Prediction of Tolerance to Egg in Children with Existing Egg Allergy 59
Predicting Tolerance to Baked Egg 60
Implications for Predictive Testing for Egg Allergy 61
2.5.2 ORAL FOOD CHALLENGES TO DIAGNOSE EGG ALLERGY 63
Type of Egg Used for Oral Food Challenges 64
Dosing 71
Time Between Doses 71
Post Challenge Observation 71
Summary of Results – Egg Oral Food Challenge Protocols 72
TRADITIONAL AND EMERGING APPROACHES TO DIETARY
2.6 75
MANAGEMENT OF EGG ALLERGY
DIETARY MANAGEMENT OF BREAST FED BABIES WITH EGG
2.6.1 75
ALLERGY
2.6.2 THE EGG FREE DIET 75
2.6.3 THE BAKED EGG CONTAINING DIET 75
2.6.4 SPECIFIC ORAL IMMUNOTHERAPY TO TREAT EGG ALLERGY 76
2.7 SUMMARY AND CONCLUSION 78
v
TABLE OF CONTENTS (CONT)
PAGE
CHAPTER 3
79
ALLERGENICITY OF PASTEURIZED WHOLE RAW HEN’S EGG
COMPARED WITH FRESH WHOLE RAW HEN’S EGG
STATEMENT OF AUTHORSHIP 81
PAPER: ‘ALLERGENICITY OF PASTEURIZED WHOLE RAW HEN’S
85
EGG COMPARED WITH FRESH WHOLE RAW HEN’S EGG’
CHAPTER 4
91
PREDICTING BAKED EGG TOLERANCE IN EGG ALLERGIC
CHILDREN
STATEMENT OF AUTHORSHIP 93
SUBMITTED PAPER: ‘PREDICTING BAKED EGG TOLERANCE IN
97
EGG ALLERGIC CHILDREN’
CHAPTER 5
121
HEATED ALLERGENS AND INDUCTION OF TOLERANCE IN FOOD
ALLERGIC CHILDREN
STATEMENT OF AUTHORSHIP 123
PAPER: ‘HEATED ALLERGENS AND INDUCTION OF
127
TOLERANCE IN FOOD ALLERGIC CHILDREN’
CHAPTER 6
147
RANDOMISED CONTROLLED TRIAL OF A BAKED EGG
INTERVENTION IN YOUNG EGG ALLERGIC CHILDREN
STATEMENT OF AUTHORSHIP 149
SUBMITTED PAPER: ‘RANDOMISED CONTROLLED TRIAL OF A
BAKED EGG INTERVENTION IN YOUNG EGG ALLERGIC 153
CHILDREN’
CHAPTER 7
183
DISCUSSION, CONCLUSION AND DIRECTIONS FOR FUTURE
RESEARCH
7.1 MAJOR FINDINGS REPORTED IN THIS THESIS 185
7.2 DISCUSSION 185
7.2.1 HETEROGENEITY AND HARMONISATION 186
7.2.2 BAKED EGG IN THE DIETS OF EGG ALLERGIC CHILDREN 188
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TABLE OF CONTENTS (CONT)
PAGE
7.3 IMPLICATONS FOR CLINICAL PRACTISE 192
7.4 OTHER RESEARCH QUESTIONS RAISED BY THIS THESIS 193
Maternal and Infant Diet During Early Life and Atopy
193
Development
Management of Infant Food Allergies by Manipulation of the
193
Maternal Diet During Lactation
Clinical Relevance of Egg Yolk Allergens and Potential For Baked
193
Egg Yolk Specific Oral Tolerance Induction
Clinical Algorithms to Predict Tolerance To Baked Egg 194
7.5 CONCLUDING REMARKS 194
CHAPTER 8
195
BIBLIOGRAPHY
APPENDICES
APPENDIX 1 215
CONFERENCE PRESENTATIONS AND ACCEPTED ABSTRACTS
SUPPORTING THIS THESIS
APPENDIX 2 217
E-TABLES FROM CHAPTER 1 PAPER: ‘DOES MATERNAL DIET
DURING PREGNANCY AND LACTATION AFFECT OUTCOMES IN
OFFSPRING?’
APPENDIX 3 259
SEARCH TERMS USED FOR SYSTEMATIC REVIEWS IN CHAPTER 2
APPENDIX 4 261
RANDOMISED CONTROLLED TRIAL (CAKE STUDY) PROTOCOL
APPENDIX 5 283
RANDOMISED CONTROLLED TRIAL (CAKE STUDY)
INFORMATION SHEET
APPENDIX 6 289
RANDOMISED CONTROLLED TRIAL (CAKE STUDY) CONSENT
FORM
vii
TABLE OF CONTENTS (CONT)
PAGE
APPENDIX 7 293
MATERIALS AND METHODS
MATERIALS 293
Buffers and Solutions Used for Western Blotting and Flow
298
Cytometric Analysis
METHODS 301
Preparation and Determination of Protein Content of Egg Samples 301
Pasteurised Raw Whole Egg Powder 301
Fresh Egg 301
InVitro Digestion Of Egg Protein 302
Sodium Dodecyl Sulphate Polyacrylamide (SDS-PAGE) Gel
303
Electrophoresis Of Egg Proteins
Pooled Sera For Use In Immunoblotting 303
Western Blot Analysis of Egg Proteins Using Pooled Sera from Egg
304
Allergic Children
Peripheral Blood Sample Collection 304
Isolation and Cryopreservation of Peripheral Blood Mononuclear Cells 305
Thawing of Cryogenically Stored PBMCS 305
Peripheral Blood Mononuclear Cell Culture And Antigenic Stimulation 306
Immunophenotyping of Peripheral Blood Mononuclear Cells 306
Determination of Cytokine Concentration in Supernatant After Culture 309
of PBMCS with Egg Allergens
Serum Specific IgE and IgG4 levels 310
310
Statistical Analysis
APPENDIX 8 311
Product Specifications for the CAKE Study 311
Materials 313
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ix
LIST OF TABLES
PAGE
CHAPTER 1
Table 1 Characteristics of Included Studies 12
Table 2 Risk for bias for Intervention Studies 15
Table 3 Summary of Dietary Associations by Outcome 19
CHAPTER 2
Table 2.1 Characteristics of Major Egg Proteins and Allergens 39
Table 2.2 Characteristics of Studies Using Skin Prick Testing or
45
Specific IgE Levels to Predict Egg Allergy
Table 2.3 Use of Skin Prick Testing to Predict Tolerance to Egg 48
Table 2.4 Use of Specific IgE Testing to Predict Tolerance to Egg 53
Table 2.5 The Form of Egg, Dose and Dosing Regime Used for Oral
65
Food Challenges in Egg Allergy Research
Table 2.6 Different Forms of Egg Used for Oral Food Challenges 70
Table 2.7 Standard Egg Oral Food Challenge Protocols 74
CHAPTER 4
Table 1 Reported Egg Allergen SPT and Specific IgE Decision
100
Points for Baked Egg Oral Food Challenges.
Table 2 Outcome of Baked Egg Oral Food Challenges. 105
Table 3 Characteristics of Study Participants. 106
Table 4 Summary of Skin Prick Test, Specific IgE, IgG4 Results,
IgE/IgG4 Ratios and Outcome of Baked Egg Oral Food 107
Challenge
Table 5 Capacity of Skin Prick Test and Specific IgE to Common
109
Egg Allergens to Predict Allergy to Baked Egg.
E-Table 1 Clinical History of Children with Anaphylaxis to Baked Egg
116
Oral Food Challenge.
x
LIST OF TABLES (CONT)
PAGE
CHAPTER 5
Table 1 Summary of Key Egg-Specific Oral Immunotherapy Trials 131
Table 2 Summary of Key Cow’s Milk-Specific Oral Immunotherapy
133
Trials
CHAPTER 6
Table 1 Demographic and Clinical Characteristics of Children at
162
Study Entry
Table 2 Skin Prick Test, Specific IgE, IgG4 Results and IgE/IgG4
Ratios in Baked Egg and Control Groups at Baseline and at 165
the End of the Intervention.
Appendix 2 Intervention Products 175
E-Table 1 CD4/CD8 Profiles 180
APPENDIX 2
E-Table 1 Maternal Diet and Eczema in Children 220
E-Table 2 Maternal Diet and Asthma in Children 228
E-Table 3 Maternal Diet and Wheeze in Children 234
E-Table 4 Maternal Diet and Hay Fever or Rhinitis in Children 239
E-Table 5 Maternal Diet and Sensitization in Children 241
APPENDIX 7
Table 1 Reagents Used for Tissue Culture 294
Table 2 Reagents Used for Western Blotting 295
Table 3 Reagents and Kits Used for Flow Cytometric Analysis 296
Table 4 Antibodies Used for Flow Cytometric Analysis 297
APPENDIX 8
Table 1 Ingredients Used for Intervention Products 314
Table 2 Summary of Product Development and Final Products for
317
CAKE Study