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Environmental determinants of health:
Asthma and allergy in children – causes and
prevention priorities
Anna Sidorchuk
MD, PhD, Research Scientist
Karolinska Institutet, Department of Public Health Sciences
Division of Social Medicine
E-mail: [email protected]
Outlines of the lecture

Public Health general issues – an overview

Step I: Define the health problem
 Asthma and allergy in children – clinical overview
 Can asthma and allergic diseases be considered a major public health problem in children
worldwide?
 Can asthma and allergic diseases be considered a major public health problem in children in
Sweden?

Step II: Identify the risk factors associated with the problem





Genes or environment? Who is the one to blame?
Prenatal risk factors
Childhood risk factors
Examples of the epidemiological studies
Step III: Develop and test community-level interventions
 Example of the Public Health Action
2
Environment
Public economic
strategies
Traffic
Agriculture
& food
Education
Sex &
life together
Leisure &
culture
Social-insurance
Eating habits
§
Illicit drugs
Social
network
Housing
Employment
?
Alcohol
Tobacco
Work
environment

Physical
activity
Age, sex,
heredity
Social
support
Contact
children
and adults
Social
assistance
Sleep
habits
Health-&
medical care
Haglund, Svanström, KI, revision, Beth Hammarström
3
How Public Health works: Steps to make
Public health’s approach to health problems in a community has been
described as a five-step process:
 (1) Define the health problem
 (2) Identify the risk factors associated with the problem
 (3) Develop and test community-level interventions to control or prevent
the cause of the problem
 (4) Implement interventions to improve the health of the population
 (5) Monitor those interventions to assess their effectiveness
4
What is a public health problem?
 Needs to affect more than 1% of the defined population
 Should be associated with serious consequences for;
 Health
 Economy
 The social life
 Contribute to inequalities in health
 Should be possible to prevent
Adopted from the “Health in Sweden: The National Public Health Report 2005”, The National Board of Health and
welfare/Centre for Epidemiology (Scand J Public Health Suppl. 2006;67:11-265).
5
Step I: Define the health problem
Adopted from the “Health in Sweden: The National Public Health Report 2005”, The National Board of Health and
welfare/Centre for Epidemiology (Scand J Public Health Suppl. 2006;67:11-265).
6
Historical background
The term "allergy" from the
Greek allos ('other') and ergon
('work') was introduced in
1906 in Munchener
Medizinische Wochenschrift
by Clemens von Pirquet, who
recognized that in both
protective immunity and
hypersensitivity reactions, an
external agent had induced
some form of “changed or
altered reactivity”
Asthma in children – clinical overview
 Asthma is a chronic lung condition characterized by reversible
narrowing and excessive mucus production of the airways
 This manifests as wheezing, coughing and breathlessness
 Asthma is an important health cause of school absenteeism
 The majority of children have well-controlled asthma; however,
under-recognition and inappropriate management may lead to
considerable ill-health
 For some children, exercise-induced asthma, night-time cough and
sleep disturbance interfere with physical and educational activities
thereby reducing their quality of life
Eczema in children – clinical overview
 Eczema (atopic dermatitis) is a chronic inflammatory condition of the
skin, which is common amongst school children and manifests with
itching and excoriation
 Eczema exacerbations may be provoked by allergens. Food allergens
(e.g. egg) may cause acute eczema after inadvertent ingestion
 Inhalant allergens (e.g. house-dust mite, cat dander) as well as
staphylococcal skin infection may also contribute to poor eczema
control
 Management of eczema is based on hydrating topical treatment
topical anti-inflammatory treatment and avoidance of specific and
nonspecific provocation factors
Allergic Rhinitis in children – clinical
overview
 Rhinitis is defined as an inflammation of the lining of the nose and is
characterized by nasal symptoms including rhinorrhoea (nasal
secretions), sneezing, nasal blockage and/or itching of the nose
 Allergic rhinitis is the most common form of noninfectious rhinitis and
is usually associated with an IgE-mediated immune response against
allergens e.g. grass pollen, house-dust mite or pets
 It is often associated with eye symptoms (rhinoconjunctivitis) that
may be the dominant problem
 Rhinitis is the most prevalent chronic allergic disease in children
 The presence of allergic rhinitis commonly exacerbates asthma,
increasing the risk of asthma attacks, emergency visits and
hospitalizations for asthma
Food allergy in children – clinical
overview
 Food allergy is common amongst school children, with an estimated
overall prevalence of 4–7%
 The symptoms in a child with food allergy can affect many organ
systems and may include hives or swelling (facial angioedema),
vomiting, abdominal pain, and diarrhoea, hoarseness or voice
changes, wheezing, dyspnoea and sneezing and/or cardiovascular
problems as dizziness or loss of consciousness
 Cow’s milk, hen’s egg, peanuts, tree nuts, wheat, soy, fish and
crustaceans are the most common foods causing allergic reactions
 Cow’s milk, egg allergy and wheat allergy may resolve by school age.
When persistent, they may cause severe reactions as seen with
peanut and tree nuts
Childhood asthma and allergy – public health problem
 Asthma and allergic disorders (in total) affect approx. one
of four schoolchildren worldwide
 It reduces quality of life and may impair school
performance
 There is a risk of severe reactions and, in rare cases, death
 Allergy is a multi-system disorder, and children often have
several co-existing diseases, i.e. allergic rhinitis, asthma,
eczema and food allergy
Childhood asthma and allergy – public health problem
 By the end of 20th century, descriptive data on asthma
and allergic diseases indicated a substantial and persistent
increase in prevalence
 The increase appeared particularly strong in industrialized
countries, especially among children
 There is an increase in the prevalence of allergic disease
from south-eastern Europe where it is relatively low (e.g.
in Albania) to the northwest (e.g. the United Kingdom).
Scandinavia has a middle position between these two
extremes
Childhood asthma and allergy – public health problem
 In parallel with this increase the possibilities of treating
allergic disorders have improved appreciably
 The development of steroid preparations for inhalation in
the treatment of asthma, and the development of
effective anti-histamine preparations for the treatment of
allergic rhinitis have been particularly important
Childhood asthma and allergy – public health problem
 The existence of allergic disorders was originally described
among economically privileged people in England during
the nineteenth century
 Certain allergic problems are still more prevalent among
higher social groups than at other levels of society
 Studies have also shown that asthma disease more
frequently causes severe symptoms and hospitalization
among children in exposed social circumstances than
among other children
Prevalence of asthma symptoms in 6-7 yr old children (ISAAC Phase III)
40
Co st
a
Rica
35
Prevalence (%)
30
25
Braz
il
20
Japa
n
15
10
5
Nige
ri
a
Germ Po land
Malt
a
an y
Uk ra
i
ne
Po rt
Ru ss
ugal
ia
Iran
Esto
n ia
Sing Sweden
Be lg
ap or
S
p ain
ium
e
India
Italy
Au st
Geo
ri a
Lith u
r
g
ia
ania
Indo
nes i
a
0
Au stUK
ralia
Ca na
da
Modified:
Asher MI. Lancet 2006,
V. 368:733-43
Childhood asthma and allergy – major
public health problem in Sweden
 Allergic disorders are the most common longterm health
problems among children in Sweden
 In The Children’s Environmental Health Survey 2003, 26%
of parents of 4-year-old children and 28% of parents of
12-year-old children stated that their children had some
kind of allergy disease
 Patient and causes-of-death statistics sow that asthma
have also objectively become more common among
young Swedes during the past 30 years
Childhood asthma and allergy – major
public health problem in Sweden
 The prevalence of allergic disorders varies geographically.
Asthma and allergic rhinitis are, with some exceptions,
most common in northern Sweden, where the rate of
increase has also been highest
 Mortality from allergic disorders has declined during the
past few decades thanks to improved medical treatment
 However, the number of serious allergic reactions
(anaphylactic shock) leading to hospitalization increased
threefold between 1987 and 2002
Childhood asthma and allergy – major
public health problem in Sweden
 Allergic rhinitis is more common among upper whitecollar workers than among unskilled blue-collar workers in
Sweden, while asthma is more common among the latter
 Both asthma and allergic rhinitis have increased more
rapidly among unskilled blue-collar workers during the
past few decades
Childhood asthma and allergy – major
public health problem in Sweden
 There are considerable differences between groups of
differing ethnic origins and different life styles in Sweden
 Children growing up in anthroposophical homes, for
example, ran only half the risk of developing an atopic
disorder. The same was true for children and adults of
Turkish origin
 Children and adults with Chilean origin, on the other
hand, run a twofold risk of being afflicted by atopic
asthma, and also a clearly increased risk of allergic rhinitis
and atopic eczema
Proportion of self-reported allergic disorders among boys and
girls aged 4 and 12 years, respectively, according to Children’s
Environmental Health Survey 2003, Sweden
From Hjern A, Scand J Public Health, 2006;67:125-31
Step II: Identify the risk factors
associated with the problem
Determinants of childhood allergy / asthma
Respiratory infections
Male sex
Micro-biological exposure
Allergens
Heredity +
Air pollution
ETS
”Western life style”
Certain viruses
Heredity -
Certain gut flora
Urban environment
High risk
Adopted and modified from the presentation by Prof. Göran Pershagen, 2009
Diet / breast feeding
Rural environment
Presence of older
siblings
Low risk
Genetic factors? Environmental factors?
Gene-by-environment interaction?
 Six gene variants has recently been found that can explain
nearly 40 percent of all cases of asthma in children
Moffatt M.F., Gut I.G., Demenais F. et. al. A large-scale, consortium-based genomewide association study of asthma NEJM, 2010
Gene
Locus
Predicted primary function
Suggested role in
asthma
Publication
ADAM33
20p13
Metalloproteinase
Airway remodelling
Van Eerdewegh et al. Nature 2002
PHF11
13q14
Zinc finger transcription factor
Immunoregulation
Zhang et al. Nature Genetics 2003
DPP10,
DRPR3
2q14
Dipeptidyl peptidase
Cytokine processing
Allen et al. Nature Genetics 2003
GPRA /
NPSR1
7p14
G-protein coupled receptor
Immunoregulation, neural
regulation
Laitinen et al. Science 2004
HLA-G
6p21
Human leukocyte antigen
Antigen presenting,
Immunoregulation
Nicolae et al. 2005 American Journal of
Human Genetics
CYFIP2
5q33
Cytoplasmic protein interaction
T cells
Noguchi et al. AJRCCM 2005
ORMDL3
17q21
Transmembrane protein anchored in the
ER
Unknown
Moffatt et al. Nature 2007
Adopted from the presentation by Prof. Göran Pershagen, 2009
Genetic factors? Environmental factors?
Gene-by-environment interaction?
 The substantial and rapid increases in the incidence of
asthma over the past few decades and the geographic
variation in both base prevalence rates and the magnitude
of the increases support the thesis that environmental
changes play a large role in the current asthma epidemic
Genetic factors? Environmental factors?
Gene-by-environment interaction?
 Although genetic predisposition is clearly evident, geneby-environment interaction probably explains much of the
international variation in prevalence rates for allergy and
asthma
Genetic factors? Environmental factors?
Gene-by-environment interaction?
 Environmental factors such as infections and exposure to
endotoxins may be protective or may act as risk factors,
depending in part on the timing of exposure in infancy
and childhood
 In recent years many of the environmental factors
previously indicated as risk and protective factors for
atopic diseases have been re-evaluated
Prenatal risk factors for asthma and allergy
Indoor environmental risk factors - Prenatal tobacco smoke
 Tobacco smoke is a complex mixture of more than 4800 different
compounds: known carcinogens and mutagens, or possess cytotoxic
and irritant properties. Tobacco smoke constituents include polycyclic
aromatic hydrocarbons and N-nitrosamines, free radicals, aromatic
amines, aldehydes, and metals such as nickel, chromium, and cadmium
 Prenatal maternal smoking has been consistently associated with early
childhood wheezing, and there is a dose–response relation between
exposure and decreased airway caliber in early life
 Prenatal maternal smoking is also associated with increased risks of
food allergy. This effect is increased when combined with postnatal
smoke exposure
Prenatal risk factors for asthma and allergy
Diet and nutrition
 Higher intake of fish or fish oil during pregnancy is associated with
lower risk of atopic disease (specifically eczema and atopic wheeze)
up to age 6 years
 Higher prenatal vitamin E and zinc levels have been associated with
lower risk of development of wheeze up to age 5
Childhood risk factors for asthma and allergy
Environmental tobacco smoke (ETS)
 Studies on the effects of parental smoking on childhood asthma show
that involuntary smoking, particularly maternal smoking, is an
independent risk factor for childhood allergic diseases, especially
occurring in first years of life
 Children raised in smoker homes have a higher incidence of
respiratory infections, recurrent wheezing, bronchitis, nocturnal
cough, and asthma
 It is difficult to distinguish the independent contributions of prenatal
and postnatal maternal smoking
Childhood risk factors for asthma and allergy
Housing conditions
 The role of indoor moulds or dampness for respiratory functioning
has recently been highlighted. It has been shown that signs of
dampness in the home are associated with respiratory symptoms and
asthma
 Factors related to renovation activities in the living area of the child,
such as painting, installation of certain interior materials, etc., have
been related to development of allergic diseases, particularly
respiratory allergy. This may indicate a negative influence by certain
chemical emissions on development of childhood asthma and allergic
diseases, but the role of specific compounds has not been elucidated
Childhood risk factors for asthma and allergy
Breastfeeding
 Exclusive breastfeeding for at least 3 months is associated with lower
rates of asthma between 2 and 5 years of age, with the greatest
effect occurring among those with a parental history of atopy
Childhood risk factors for asthma and allergy
Contact with furred animals
 Children susceptible to furred-animal allergy therefore develop their
allergy irrespective of whether they have animals in the home
 These factors affect chiefly the severity of their disease among people
with allergic disorders but that they play no significant part in the
development of the disease
Childhood risk factors for asthma and allergy
Outdoor risk factor – traffic-related air pollution
 Has an adverse effect on respiratory health of children, particularly
with respect to changes in lung function
 Positively associated with sensitization to polen and other outdoor
allergens
 There are associations between exposure to traffic-related air
pollution and exacerbation of asthma and asthmatic symptoms
Adopted from the presentation by Prof. Göran Pershagen, 2009
Childhood risk factors for asthma and allergy
Family structure and day-care attendance
 Family size and the number and order of siblings may affect the risk
of development of asthma
 Later-born children in large families would be expected to be at lower
risk of asthma than first-born children, because of exposure to their
older siblings’ infections
 Some studies on allergy showed that although large family size (more
than 4 children) is associated with a decreased risk of asthma, birth
order is not involved
 Early admission to day-care center may prevent development of
asthma in late childhood due to an increase in the rate of crossinfection between children
Childhood risk factors for asthma and allergy
Farm-related exposures
Allergy in children of farmers in Austria, Germany and Switzerland
Exposure during
first year of life
Asthma
OR (95%CI)
Allergic rhinitis
OR (95%CI)
Sensitization
OR (95%CI)
Visit to stable
No milk from farm
0.51
(0.14 – 1.86)
0.25
(0.05 – 1.13)
0.56
(0.25 – 1.27)
No visit to stable
Milk from farm
0.48
(0.21 – 1.1)
0.24
(0.10 – 0.56)
0.43
(0.24 – 0.77)
Visit to stable
Milk from farm
0.14
(0.04 – 0.48)
0.20
(0.08 – 0.50)
0.32
(0.17 – 0.62)
From Riedler et al. 2001
Adopted from the presentation by Prof. Göran Pershagen, 2009
Childhood risk factors for asthma and allergy
Wood smoke
 Results appear inconclusive
 Thus, studies in rural areas showed that children in families using
wood for heating and cooking had significantly lower prevalence of
allergic rhinitis and atopy than children living in homes with other
heating systems
 However, it is possible that use of wood for heating was a proxy for
certain types of farming also involving exposures to protective factors
for allergy in children
 Children are more susceptible to wood smoke than adults and
exposure occurring early in life may result in decreased pulmonary
function and increased severity and frequency of wheezing
Childhood risk factors for asthma and allergy
Life-style factors
Anthroposophy
Rudolf Steiner
Steiner schools
Holistic medicine
Biodynamic diet
Restrictive use of: antibiotics
antipyretics
vaccinations
Adopted from the presentation by Prof. Göran Pershagen, 2009
Allergy in children
of Steiner schools and Public schools
35
30
Steiner schools
Public schools
25
20
%
15
10
5
0
Clinical
Skin prick test
IgE
From Alm et al. 1999
Adopted from the presentation by Prof. Göran Pershagen, 2009
Example of longitudinal study on allergy in
children
BAMSE
1994 1995 1996
75%
THE
BAMSE
BIRTH
COHORT
7,221 born
children
Non-responders
(25.5%)
1997
1998
1999
2000
2001
Exposure questionnaire
and dust 4,089 100%
1 year symptom
questionnaire 3,925 96%
2 year symptom
questionnaire 3,843 94%
4 year follow up
questionnaire
clin. examination
+ lung function
blood
3720
2966
91 %
80 %
2614
70 %
Example of cross-sectional study on
allergy in children
The International Study of Asthma and Allergies in Childhood (ISAAC) – the
largest worldwide multicentre cross-sectional study on protective and risk
factors related to asthma, rhinoconjunctivitis and eczema in children
 Two age groups of children: 6-7 years and 13-14 years
 56 countries
 156 participating centres (target sample size – 3,000 children per each age
group per centre)
Step III: Develop and test communitylevel interventions to control or
prevent the cause of the problem
Preventive efforts against environmental risk factors seek primarily to
improve the situation for children who have allergic disorders
But they cannot be expected to reduce the occurrence of these disorders
to any major extent
Public Health Action
(example from the Global Allergy and Asthma European Network (GA2LEN) Task Forse)
Action points for all children with allergic disease at school
 Schools should enquire about allergic disease at the registration of
new pupils, and parents should inform the school of any new allergy
diagnosis
 A written allergy management plan should be obtained from the
doctor, including allergens/triggers to avoid, medications and contact
information
 The allergic child should be readily identifiable to all school staff
 Reasonable measures should be instituted to ensure appropriate
allergen avoidance
From Muraro A, et al., Allergy, 2010;65:681-89
Public Health Action
(example from the Global Allergy and Asthma European Network (GA2LEN) Task Forse)
Action points for all children with allergic disease at school
 Tobacco smoking should be banned
 School staff should be educated in allergen avoidance and recognition
and emergency treatment of allergic reactions
 Relieving and emergency medication should be available at all times
 School staff should be indemnified against prosecution for the
consequences of administering emergency or relieving medication
 Ensure protective measures continue on school trips/holidays
From Muraro A, et al., Allergy, 2010;65:681-89
General conclusions
 Athma and allergy in children are major public health problems both
globally and in Sweden
 Interactions between environmental exposures and genetic factors
are important for induction asthma and allergy in children
 There is a substantial potential for prevention of allergy among
children by reducing smoking among women in childbearing ages
 Protective factors for asthma and allergy in children are associated
with farming and an anthroposophic life style
 Exposure to traffic related air pollution may affect respiratory
symptoms, lung function and sensitization in children
 Secondary and tertiary prevention do seem to be most effective