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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: Anna.Sidorchuk@ki.se
                           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


                                                           Agri-
                                                           culture
                                                           & food
                                                                                 Leisure &
                                                    Education                    culture
                                   Traffic


                                                         Sex &                                   Social-insurance
                                                         life together       Eating habits
                                                                                                     §
                                      Illicit drugs
                                                                                                          Social
             Housing                                Social                                                assistance
                                                                                        Physical
                                                    network
          Employ-
          ment       ?                                                                   activity

                         Alcohol
                                                              Age, sex,
                                                                                                 Sleep
                                                                  heredity                       habits
               Tobacco                                                              Contact
                                    Social                                          children
     Work                                                                           and adults               Health-&
                                    support
     environment                                                                                             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



                  30



                  25                                                                                                                Braz
 Prevalence (%)




                                                                                                                                         il

                                                                                                                               U
                                                                                                                           Au st K
                  20                                                                                                            ralia
                                                                                                        Japa
                                                                                                             n         Ca na
                                                                                                                            da

                  15                                                                       Germ Po land       Malt
                                                                                    Uk ra      an y                a
                                                                            Ru ss        ine         Po rt
                                                                                 ia                        ugal
                                                              Esto                        Iran
                                                                    n ia
                  10                        Be lg                          Sing Sweden
                                                 ium               Sp ai        ap or
                                    India                                n            e
                                                              Italy
                                                        Au st
                                      Lith u    Geo          ri a
                       Nige                 ania    rgia
                  5        ri   a
                           Indo                                                                                                Modified:
                               nes i                                                                                           Asher MI. Lancet 2006,
                                    a
                  0                                                                                                            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 white-
  collar 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                         Allergens                    Micro-biological exposure



                                                                                                        Certain viruses
Male sex                            Heredity +                               Heredity -



  ETS                            Air pollution                      Certain gut flora                 Diet / breast feeding


                                                                             Rural environment      Presence of older
”Western life style”        Urban environment
                                                                                                    siblings




             High risk                                                                        Low risk


 Adopted and modified from the presentation by Prof. Göran Pershagen, 2009
   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 genome-
  wide association study of asthma NEJM, 2010
                                                                         Suggested role in
    Gene           Locus          Predicted primary function                                                  Publication
                                                                             asthma



  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,
                    2q14                Dipeptidyl peptidase             Cytokine processing         Allen et al. Nature Genetics 2003
   DRPR3



   GPRA /                                                              Immunoregulation, neural
                    7p14             G-protein coupled receptor
                                                                             regulation
                                                                                                       Laitinen et al. Science 2004
   NPSR1



                                                                         Antigen presenting,      Nicolae et al. 2005 American Journal of
   HLA-G            6p21             Human leukocyte antigen
                                                                                                             Human Genetics
                                                                         Immunoregulation




   CYFIP2           5q33           Cytoplasmic protein interaction             T cells                Noguchi et al. AJRCCM 2005




                               Transmembrane protein anchored in the
  ORMDL3           17q21                      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, gene-
  by-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 cross-
  infection between children
             Childhood risk factors for asthma and allergy
                        Farm-related exposures

    Allergy in children of farmers in Austria, Germany and Switzerland

            Exposure during                            Asthma          Allergic rhinitis        Sensitization
            first year of life                         OR (95%CI)           OR (95%CI)          OR (95%CI)

            Visit to stable                            0.51                0.25                 0.56
            No milk from farm                          (0.14 – 1.86)       (0.05 – 1.13)        (0.25 – 1.27)

            No visit to stable                         0.48                0.24                 0.43
            Milk from farm                             (0.21 – 1.1)        (0.10 – 0.56)        (0.24 – 0.77)

            Visit to stable                            0.14                0.20                 0.32
            Milk from farm                             (0.04 – 0.48)       (0.08 – 0.50)        (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
                          25                            Public schools

                          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            1997      1998     1999        2000    2001


                  Exposure questionnaire
         75%      and dust 4,089 100%

THE
BAMSE
                           1 year symptom
BIRTH                      questionnaire 3,925 96%
COHORT
7,221 born
children
                                  2 year symptom
Non-responders                    questionnaire 3,843 94%
(25.5%)



                                                      4 year follow up
                                                      questionnaire        3720   91 %
                                                      clin. examination    2966   80 %
                                                      + lung function
                                                      blood                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 community-
   level 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

								
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