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

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Environment Public economic strategies Traffic Agri culture & food Education Leisure & culture Housing Employ ment Alcoho l Sex & life together Illicit drugs Social network Age, sex, heredity Work environment Tobacco Social support Eating habits Social-insurance § Social assistance Physical activity Contact children and adults Sleep habits Health-& medical care

 Haglund, Svanström, KI, revision, Beth Hammarström

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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

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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).

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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).

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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 exacerbations may be provoked by allergens. Food allergens (e.g. egg) may cause acute eczema after inadvertent ingestion  Eczema (atopic dermatitis) is a chronic inflammatory condition of the skin, which is common amongst school children and manifests with itching and excoriation 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%   Cow’s milk, hen’s egg, peanuts, tree nuts, wheat, soy, fish and crustaceans are the most common foods causing allergic reactions  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, 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 35 30

Costa R ica

25

Brazil

20

Japan

15 10 5

Nigeria India Indone sia Belgiu Lithuan ia m Estonia Italy Spain

0

Russia Ukrain Swede ore n Germa e Iran Poland Portug al Malta Canad a UK lia

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 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

Micro-biological exposure Respiratory infections Allergens Male sex Heredity + Air pollution ETS ”Western life style” Urban environment Certain viruses Heredity Certain gut flora Diet / breast feeding Rural environment Presence of older 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

Gene Locus Predicted primary function

ADAM33

20p13 Metalloproteinase Suggested role in asthma Airway remodelling Publication Van Eerdewegh et al. Nature 2002

PHF11

13q14 Zinc finger transcription factor

DPP10, DRPR3

2q14

GPRA / NPSR1

7p14

HLA-G

6p21 Dipeptidyl peptidase G-protein coupled receptor Human leukocyte antigen Immunoregulation Cytokine processing Zhang et al. Nature Genetics 2003 Allen et al. Nature Genetics 2003 Immunoregulation, neural regulation Antigen presenting, Immunoregulation Laitinen et al. Science 2004 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 Adopted from the presentation by Prof. Göran Pershagen, 2009 Unknown Moffatt et al. Nature 2007

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 first year of life Visit to stable No milk from farm No visit to stable Milk from farm Visit to stable Milk from farm Asthma OR (95%CI) 0.51

(0.14 – 1.86) 0.48

(0.21 – 1.1) 0.14

(0.04 – 0.48) Allergic rhinitis OR (95%CI) 0.25

(0.05 – 1.13) 0.24

(0.10 – 0.56) 0.20

(0.08 – 0.50) Sensitization OR (95%CI) 0.56

(0.25 – 1.27) 0.43

(0.24 – 0.77) 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

35 30 25 20

%

15 10 5 0

Allergy in children of Steiner schools and Public schools

Steiner schools Public schools 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

75%

THE BAMSE BIRTH COHORT 7,221 born children Non-responders (25.5%)

BAMSE

1994 1995 1996 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 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