Risk Factors and Treatment of Paediatric Chronic Diseases Type 1 diabetes, Asthma and Allergy ...

236 Pages·2016·2.09 MB·English

Risk Factors and Treatment of Paediatric Chronic Diseases
Type 1 diabetes, Asthma and Allergy
Fariba Ahmadizar
The work presented in this thesis was performed at:
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for
Pharmaceutical Sciences (UIPS). Faculty of Science, Utrecht University, Utrecht, the
Netherlands
Cover design: Persoonlijkproefschrift.nl, Matthijs Ariëns
Layout: Persoonlijkproefschrift.nl, Juliet Campfens
Printing: Ipskamp Printing
ISBN: 978-94-028-0360-0
Fariba Ahmadizar
Risk factors and treatment of pediatric chronic diseases
Type 1 diabetes, asthma and allergy
Copyright: 2016 Fariba Ahmadizar
For articles published or accepted for publication, the copyright has been transferred to
the respective publisher. No part of this book may be reproduced, stored in the retrieval
system, or transmitted in any form or by any means, without prior permission of the au-
thor, or when appropriate, the publisher of the manuscript.
Risk Factors and Treatment of Paediatric Chronic Diseases
Type 1 diabetes, Asthma and Allergy
Risicofactoren en Behandeling van Pediatrische Chronische Ziekten
Type 1 diabetes, Astma en Allergie
(met een samenvatting in het Nederlands)
Proefschrift
ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de
rector magnificus, prof.dr. G.J. van der Zwaan, ingevolge het besluit van het
college voor promoties in het openbaar te verdedigen op maandag 24 oktober
2016 des middags te 2.30 uur
Fariba Ahmadizar
geboren op 26 maart 1973
te Baneh, Iran
Promotoren:
Prof. dr. A. de Boer
Prof. dr. A.H. Maitland-van der Zee
This thesis was partly accomplished with financial support from Iranian Ministry Of Health.
Printing of this thesis was kindly supported by Stichting KNMP Fondsen, Dutch Heart
Foundation, and Stichting Astma Bestrijding and Infection & Immunity.
“The sun will shine tomorrow”
TABLE OF CONTENTS
CHAPTER 1 GENERAL INTRODUCTION 9
CHAPTER 2 TRENDS IN COMORBIDITIES RELATED TO
TYPE 1 DIABETES IN CHILDREN 19
CHAPTER 2.1 Cardiovascular medication use and cardiovascular disease
in children and adolescents with type 1 diabetes: a popula-
tion-based cohort study 21
CHAPTER 2.2 Time trends in the prevalence of cardiovascular risk factors,
diseases and medication use in children and adolescents
with type 1 diabetes: a CPRD study 39
CHAPTER 2.3 Asthma related medication use and exacerbations in children
and adolescents with type 1 diabetes 63
CHAPTER 3 RISK FACTORS ASSOCIATED WITH ASTHMA
AND ALLERGY IN CHILDREN 81
CHAPTER 3.1 Genetic variation and the association with asthma and lung
function in children: results of the WHISTLER cohort study 83
CHAPTER 3.2 Early life antibiotic use and the risk of asthma and asthma
exacerbations in children 105
CHAPTER 3.3 Early life antibiotic exposure increases the risk of developing
allergic symptoms later in life: A meta-analysis 119
CHAPTER 3.4 Breast-feeding is associated with a decreased risk of asthma
exacerbations later in life 151
CHAPTER 3.5 Childhood obesity in relation to poor asthma control and ex-
acerbations- A meta-analysis 157
CHAPTER 4 GENERAL DISCUSSION 187
CHAPTER 5 APPENDICES 201
CHAPTER 5.1 English summary 203
CHAPTER 5.2 Samenvatting 209
CHAPTER 5.3 Acknowledgments 217
CHAPTER 5.4 List of co-authors 223
CHAPTER 5.5 List of publications 229
CHAPTER 5.6 About the author 233

Chapter 1 General introduction
Chapter 1
A chronic disease is defined as any physical, emotional, or mental condition that prolongs
for at least three months, affects a child’s normal activities and requires frequent hospi-
talizations1,2. One out of four children in the United States suffers from a chronic disease
which accounts for 15-18 million children younger than 17 years of age3,4. The impact of
chronic diseases on patients, their families, and societies is tremendous. They adversely
affect quality of life and increase the rate of comorbidities and mortality5-7. In the last de-
cades major progress in diagnosis and treatment of pediatric chronic disorders has been
realized. Improved screening and diagnostic tests leading to early detection, proper diag-
nosis based on updated guidelines, and improved drug therapy have led to that chronic
illnesses can now be effectively treated. High rate of children with chronic diseases that
survive childhood is a consequence of progress in clinical care1,2.
TYPE 1 DIABETES (T1DM) IN CHILDREN
Trend in epidemiology of T1DM
T1DM is one of the most common autoimmune disorders, with a worldwide estimated
prevalence rate of 497,000/1.9 billion children aged 1-14 years in 20138 . The incidence
rate of T1DM in children is increasing especially in those younger than 15 years of age.
Although there are geographic differences in reported trends (Table 1), the increasing
trend is estimated as being around 3% annually since the 1980s8,9.
Table 1. Top ten countries for number of children with T1DM (<15 years) in 2015; Source: IDF Diabetes Atlas. 2015
Rank Country/territory Number of children with T1DM
1 United States 84,100
2 India 70,200
3 Brazil 30,900
4 China 30,500
5 United Kingdom 19,800
6 Russian Federation 18,500
7 Saudi Arabia 16,200
8 Germany 15,800
9 Nigeria 14,400
10 Mexico 13,500
Abbreviation: T1DM: type 1 diabetes mellitus
Risk factors related to T1DM
Susceptibility of T1DM results from interactions between genetic disease susceptibility
and environmental factors as diabetogenic triggers or potentiators of beta-cell destruc-
tion10,11. HLA class II genes on chromosome 6 are the most important genes for T1DM;
accounting for nearly 50% of the genetic contribution to the disease12,13.
10