Exploring the prevalence, natural history and adverse events related to tree nut allergy

244 Pages·2017·10.2 MB·English

Exploring the prevalence,
natural history and adverse
events related to tree nut
allergy
Vicki Leanne McWilliam
ORCID Identifier: 0000-0002-5000-2181
Department of Paediatrics
Faculty of Medicine, Dentistry and Health Sciences
University of Melbourne
Submitted in total fulfilment of the requirements of the degree of
Doctor of Philosophy
November 2018

Abstract
Exploring the prevalence, natural history and adverse events
related to tree nut allergy.
Vicki McWilliam
Peanut and tree nut allergies are the most commonly reported trigger of food induced
anaphylaxis and fatalities. Whilst most childhood allergies are outgrown by school age, peanut
and tree nut allergy resolution has been reported to be as low as 10%. Despite the potential
severity and lifelong nature of both peanut and tree nut allergy much of the literature to date
has focused on peanut allergy epidemiology, and tree nut allergy prevalence, natural history
while adverse events have been under studied. There is very limited data on the prevalence of
allergies to the individual tree nuts nor the factors related to development of tree nut allergy.
Therefore, this thesis explores several key areas regarding tree nut allergy including the
prevalence, elements of the natural history and development of tree nut allergy, as well as the
frequency of adverse food reactions to tree nuts. This PhD has utilised data from the
population-based HealthNuts and SchoolNuts studies and the Royal Children’s Hospital allergy
clinic populations all based in Melbourne, Australia.
In a systematic review I published, I found limited tree nut allergy prevalence estimates based
on challenge-confirmed outcomes with current estimates less than 2%, while probable tree
nut allergy prevalence ranged from 0.05 to 4.9%. Prevalence of individual tree nut allergies
varied significantly by region with hazelnut the most common tree nut allergy in Europe,
walnut and cashew in the USA and Brazil nut, almond and walnut most commonly reported in
the UK. There was no challenge-confirmed Australian tree nut allergy data.
Among 6 year old children in the HealthNuts study, 3.3% had challenge confirmed tree nut
allergy and 2.6% of 10 to 14 year olds self-reported one or more tree nut allergies in the
SchoolNuts study. Cashew was the most common tree nut allergy both at 6 and 10 to 14 years
of age.
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Among those with peanut or egg allergy at 12 months of age in the HealthNuts study,
sensitisation rates to tree nut were as high as 48%, with 39% of those tree nut sensitised at 12
months tree nut allergic at 6 years of age.
Confirming other reports of adverse food reactions, the work conducted as part of this PhD has
found peanut and tree nut the most common triggers of adverse food reactions in the past
year for children aged 10 to 14 years, with cashew the most common individual tree nut
trigger reported.
Finally, a cashew SPT wheal size of 10mm was found to have 95% PPV to challenge confirmed
cashew allergy using the population based HealthNuts and SchoolNuts cohorts.
In summary, the results presented in this thesis have reported the first challenge confirmed
tree nut allergy prevalence rates in Australia and have highlighted one of the highest reported
tree nut allergy rates in the world to date, with cashew the most common tree nut allergy.
With up to half of those with food allergies already sensitised to tree nuts as early as one year
of age, improved methods for identifying and targeting children at highest risk of tree nut
allergy along with development of early prevention strategies are desperately needed, with
cashew allergy a priority tree nut in Australia.
Declaration
This is to certify that:
i. This thesis comprises only my original work towards the Doctor of Philosophy and
includes nothing, which is the outcome of work done in collaboration except where
specifically indicated in the text.
ii. This thesis has not been previously submitted, in part or whole, to any university of
institution for any degree, diploma, or other qualification.
iii. The thesis is less than 100,000 words in length, exclusive of tables, figures,
bibliographies and appendices.
Signed:
Date:
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Preface
This thesis is based primarily on data collected by the HealthNuts and SchoolNuts studies. The
HealthNuts study was developed and conducted by Professor Katie Allen (Principal
Investigator) in collaboration with Professor Shyamali Dharmage, Associate Professor Lyle
Gurrin, Dr. Nicholas Osborne, Professor Melissa Wake, Professor Mimi Tang, Professor Anne-
Louise Ponsonby, Dr Melanie Matheson, Dr Adrian Lowe and Dr David Hill. Waves 1, 2 and 3 of
the HealthNuts study, including recruitment, clinical assessment and some data cleaning was
completed by the HealthNuts study team and past PhD students prior to the commencement
of this PhD. I contributed to data entry and data cleaning of wave 3 data as well as all of the
data analysis that was included in this thesis.
The SchoolNuts study was also developed and conducted by Professor Katie Allen (Principal
Investigator) in collaboration with Professor Shyamali Dharmage, Associate Professor Lyle
Gurrin, Professor Susan Sawyer, Professor George Patton, Professor Jo Douglass, Associate
Professor Peter Vuillermin and Dr Jennifer Koplin. I participated in some of the recruitment
school visits, data entry and cleaning and the data analysis included in this thesis.
This thesis contains four publications of which I am primary author, conducted the data
analysis, wrote the first draft of the manuscript, responded to peer review and contributed
more than 50% of the work.
The systematic review of tree nut allergy prevalence, presented in Chapter 4, was planned
together with Katie Allen, Shyamali Dharmage, and Jennifer Koplin. Caroline Lodge and
Shyamali Dharmage provided methodological and statistical support for the analysis of the
data. All named co-authors contributed to interpretation of the results and provided
intellectual input on drafts of the manuscript and response to peer review.
The publication on self-reported adverse food reactions and anaphylaxis, presented in Chapter
5, was planned together with Katie Allen, Jennifer Koplin and the SchoolNuts Investigators.
Shyamali Dharmage and Jennifer Koplin provided statistical support for the analysis of the
data. All named co-authors contributed to interpretation of the results and provided
intellectual input on drafts of the manuscript and response to peer review.
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The publication on the prevalence and development of tree nut allergy, presented in Chapter
6, was planned together with Katie Allen and Jennifer Koplin. Jennifer Koplin, Shyamali
Dharmage and Ann-Louise Ponsonby provided statistical support for the analysis of the data.
All named co-authors contributed to interpretation of the results and provided intellectual
input on drafts of the manuscript and response to peer review.
The final publication on cashew oral food challenge outcomes and positive predictive values
for cashew SPT, presented in Chapter 7, was planned together with Katie Allen, Jennifer Koplin
and Rachel Peters. Data from HealthNuts and SchoolNuts was combined with data from two
allergy clinics -The Royal Children's Hospital and Melbourne Allergy and Children's Centre
(MACCS). Use of the RCH data required an ethics application which was prepared by myself
with input from all named authors. All RCH and MACCS data was collected and analysed by
myself. Lyle Gurrin and Rachel Peters provided statistical support for the analysis of the data.
All named co-authors contributed to interpretation of the results and provided intellectual
input on drafts of the manuscript which has recently been submitted for publication.
My PhD was funded by a scholarship from the Centre for Food and Allergy Research (CFAR) a
National Health and Medical Research funded Centre for Excellence. I also received a Royal
Children's Hospital travelling scholarship to present my research at an international
conference.
Over the course of my PhD I have been involved in ten additional papers as a co-author. I have
also participated in two Centre for Food and Allergy Research Summits and been involved in
the write up and publication of proceedings. Details of all co-authored manuscripts published
over the course of my PhD are listed under the other co-authored publications in the
Publications and Presentations section. Finally, I acted as a peer reviewer for several journals
including Clinical and Experimental Allergy, Paediatric Allergy and Immunology and the Journal
of Nutrition and Dietetics.
Acknowledgements
My PhD journey has been a long one intertwined with my ongoing clinical work as a food
allergy dietitian and all the personal roles we collect along the way (wife, Mum, friend, sister,
daughter etc, etc). I have been privileged to have an extremely experienced group of PhD
supervisors and I would like to take this opportunity to thank, Professor Katie Allen, Dr Jennifer
Koplin, Professor Mimi Tang, Professor Shyamali Dharmage and Dr Kirsten Perrett for their
guidance and support over the past 5 years. Their collective experience in food allergy,
epidemiology, statistics and conducting and publishing research has provided me with an
amazing foundation on many aspects of research. I would particularly like to thank my primary
supervisor Katie as without her initial support and encouragement that I could work a PhD into
my life this would not have started. She is one inspirational person with extensive expertise
and an enviable drive and passion for clinical allergy and research. I would also like to thank
Jennifer Koplin who has walked me through all aspects of statistical analysis and scientific
writing her advice, guidance and patience are an asset to the research group and were
invaluable throughout my PhD. I would like to thank Shyamali for the scientific rigour she has
taught me regarding the application of epidemiological concepts and publishing research and
Mimi for her clinical and research expertise. I would also like to thank Harriet Hiscock for her
guidance and support as Advisory panel chair and my colleague and fellow dietitian Heather
Gilbertson as an advisory panel member.
I would like to thank the study participants and families of the HealthNuts and SchoolNuts
studies for their time and participation and the various funding bodies that made these studies
possible: the Australian National Health and Medical Research Council, the Ilhan Food Allergy
Foundation, the Centre for Food and Allergy Research, The University of Melbourne and the
Murdoch Children’s Research Institute. I would also like to formally acknowledge and thank
the NHMRC funded Centre for Food and Allergy research for my PhD scholarship funding and
scientific oversight of my PhD.
I also thank the Gastro and Food Allergy Research group members at the Murdoch Children’s
Research Institute not only for your commitment and dedication to your work but for
embracing and supporting me as a PhD student within your group.
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Similarly my colleagues in the departments of Allergy & Immunology and Nutrition & Food
Services at the Royal Children’s Hospital who have either directly participated in my research,
co-authored papers or just kept checking in on how things were tracking.
Finally and most significantly I would also like to thank my family, my husband Steve and my
children Tom and April. I know it has been hard when I have been working long hours on
something or was away at conferences but your patience and love has been noted and so
appreciated. I am blessed with a great family and awesome friends who may not have got this
but they have come along for the ride and supported me all the way.