Renata Melnikova, MD, PhD student

IS ESTONIA ENDANGERED BY EPIDEMIC OF ALLERGY?

Epidemiology•E

pidemiology is the study of • the distribution and determinants of health-related states or events (including disease), and • the application of this study to the control of diseases and other health problems

•Various methods can be used to carry out epidemiological investigations: • surveillance and descriptive studies can be used to study distribution• analytical studies are used to study determinants

http://www.who.int/topics/epidemiology/en/

Bousquet Bousquet et al.et al., , Allergy Allergy 20112011

The epidemics of allergyThe epidemics of allergy

Studies, study areas, study populationThe name of the study

Study period

Age (y.o.)

Nr of participants

Study area

ECRHS 1993 - 2014

25 – 65 2460 Tartu

FinEsS 1995 - 2000

15 - 16 17525 Narva, Tallinn, Saaremaa

ISAAC 1993 – 2002

6 - 14 13548 Tallinn

Riikjärv et al., 1995

1992 – 93 10 - 12 1519 Tallinn, Tartu

Vasar et al., 2011

2003 10 – 20 1561 Elva, Narva, Pärnu, Võru

Eriksson et al., 2004

1997 - 2000

1 - ? 156 Tallinn, Tartu

Voor T, PhD thesis

1997-2003 0 - 5

115Tartu

Julge et al., 2001 1993 - 99 273

Budarova Master’s thesis, 2009

2007 - 8 1 58 Tallinn

Main fields of study •S

ensitization•B

ronchial asthma •R

hinitis/ rhinoconjunctivitis/ rhinitis and/or conjunctivitis•A

topic Dermatitis•U

rticaria•G

astroenteritis•F

ood hypersensitivity•R

isk factors• Heredity• Gender• Environment and lifestyle• Microflora

Prevalence of sensitization in Estonia

Riikjärv et al., 1995

Riikjärv et al., 2000

Raukas-Kivioja et al., 2007

Jõgi et al., 1995

Study area Tartu Tallinn

Tallinn Saaremaa

Tallinn Tartu

Study period 1992 1997 1999 1997-98 1994 - 95

Age (y.o.) 10 - 12 10 15 - 64 20 - 44

D.pteronyssinus

2.9 %

6.1% *

4.4% 6.1% 6.6% 15.0%

D. farinae ---------

---------

4.0% 5.2% 6.0% ---------

Timothy 3.5 %

4.8% 4.8% 1.8% * 5.8% 8.3%

Birch 2.2% 2.6% 4.1% 2.5% * 6.6% 6.0%

Cat 3.8% 6.1% *

7.2% 3.4% * 7.4% 12.3%

Dog 1.4% 2.0% 4.7% * 3.8% * 8.9% 11.7%

Cockroach ---------

---------

--------- 9.7% * 15.5% mono-allergy 3%

---------

* p<0.001

Prevalence of sensitization in Estonia SPT vs RAST (adult studies)

Jõgi et al., 1995

Jõgi et al., 1998

Methods SPT sIgE

D. pteronyssinus 15.0% 9.7%

Cat 12.3% 4.8%

Dog 11.7% ---------

Timothy 8.3% 9.2%

Birch 6.0% 6.6%

Mugwort 10.0% ---------

Cladospoorum 4.3% 1.2%

Alternaria 5.3% ---------

Prevalence of sensitization in Estonia SPT vs RAST (school children studies)• 1992 – 93correlation between the two methods was not good

Riikjärv et al., 1995

• 2003 – 4correlation between SPT and RAST is better•positive SPT 18.2% •positive sIgE 20%

Julge et al., 2009

SPT pos SPT neg

sIgE pos 32 39 (55%)

sIgEneg 7 (18%) 702

Sensitization to inhalant allergens, birth cohort studies

Julge et.al, 2001 (children born in 1993/94)

Voor PhD thesis(children born in 1997/98)

Julge et.al, 2001 (children born in 1993/94)

Voor PhD thesis (children born in 1997/98)

SPT SPT sIgE sIgE

cat 0.5 y.o.

--------- 1.6%

1 y.o. 1.4% 1.0% 4.2% 6%

2 y.o. 4.1% 3.8% 11.8% 7%

5 y.o. 1.4% 1% 13.6% 5%

birch 0.5 y.o.

--------- --------- 0% ---------

1 y.o. --------- --------- 3.5% 4%

2 y.o. 0.5% 0% 3.5% 3%

5 y.o. 1.0% 1% 13.5% 7%

house dust mite

1 y.o. 1.8% --------- 2.1% ---------

2 y.o. 2.3% --------- 7.6% ---------

5 y.o. 1.4% --------- 19.4% ---------

Swedish

---------

1%

2.3%

8%

---------

---------

5.4%

16%

---------

---------

---------

Swedish

---------

0%

2%

7%

---------

1%

3%

14%

---------

---------

---------

Sensitization to food, birth cohort studies

Julge et.al, 2001 (children born in 1993/94)

Voor PhD thesis(children born in 1997/98)

Julge et.al, 2001 (children born in 1993/94)

Voor PhD thesis (children born in 1997/98)

milk SPT SPT sIgE sIgE

3 month old

--------- 0% --------- 9%

6 month old

1.7% 0% 12% 9%/

1 year old 0.9% 1% 20.7% 6%

2 year old 0% 0% 25.8% 10%

5 year old no data 0% 23.2 6%

egg white

3 month old

--------- 4,5% --------- 11%

6 month old

5.2% 6% 4.2% 15%

1 year old 4.1% 6.4% 5.6% 10%

2 year old 1.8% 3.8% 20.6% 18%

5 year old 0% 1% 23.2% 13%

Swedish

3%

6.8%

3.8%

2.3%

1%

9%

16.4%

19.3%

11.6%

8%

Swedish

8%

13%

7%

5%

9%

12%

13%

17%

14%

8%

Sensitization to foodschool children study (ISAAC)

•IgE antibodies against a panel of common food allergens (egg white, milk, soya bean, fish, wheat and peanut) • Positive 8% , i.e. 13 out of 163 children • 2 of 12 patients having positive IgE to tested food and

answered food questionnaire reported hypersensitivity to food

Sandin et al., 2005

SensitisationSummary

•Prevalence in different areas was unequal

•Prevalence of the sensitization in Estonia in 90th was lower than in countries with western type of life

•In small children prevalence of sensitization to foods with age decrease and vs to inhalation allergens increase

•Sensitization to food allergens• About ¼ of small children have antigens milk or egg white• Children could have sensitization to some other foods as well (soya,

nuts, fish, flour)

•Prevalence of sensitisation had an upward trend

•sIgE and SPT are not the same

Prevalence (%) of asthma symptomswheezing/ or whistling

Study prevalence Study period

Age (y.o.)

Study centres

Jõgi et al., 1996 26.5% 1993/94 20 - 44

Tartu

Meren et al., 2001

21.7% 1995/96 15 - 64

Narva, Saaremaa, Tallinn

Vasar et al., 2011

2.9% 2003 10 - 20

Elva, Narva, Pärnu, Võru

Annus et al., 2005

8.5% 1993/94 13– 14 Tallinn

9.2% 2001/2002

Riikjärv et al., 1995

7.0% 1992/93 10 - 12

Tallinn, Tartu

Annus et al., 2001

8.4% 1996/97 Tallinn

Annus et al., 2005

9.3% 1993/94 6 – 7 Tallinn

9.7% 2001/2002

Prevalence (%) of asthma symptoms and self-reported asthma, ECRHS study (20 – 44 y)

Burney et al., Eur Respir J, 1996

in Estonia

Summarized data of different international centres across the World

Min 25th centile Median

75th centile Max

Wheeze 26,8 4,1 14,9 20,7 25,2 32,0Wheeze with breathlessness

7,8 1,4 7,7 9,8 13,9 16,3

Wheeze without a cold

12,8 2,0 9,3 12,7 16,2 21,6

Waking with tightness in the chest

13,9 6,2 9,7 13,5 17,5 20,5

Waking with breathlessness

8,1 1,5 4,7 7,3 8,9 11,4

Waking with cough

42,6 6,0 25,6 27,9 29,5 42,6

Attack of asthma 1,8 1,3 2,6 3,1 4,5 9,7Treatment for asthma

0,6 0,6 2,4 3,5 5,0 9,8

The proportion of asthma and chronic bronchitis diagnosed among subjects with wheeze

Pallasaho et al., European Journal of Epidemiology, 2005

Prevalence of asthma in childredStudy Age

(y.o.)Prevalence

Study period

Julge et.al, 2001, Voor PhD thesis

0,5 0% 1994, 1997/98

Julge et.al, 2001 1 0,5% 1994/95

Voor PhD thesis 3% 1998/99

Julge et.al, 2001 2 2% 1995/96

Voor PhD thesis 6% 1999/2000

Julge et.al, 2001 5 6,5% 1999

Voor PhD thesis 7% 2002/2003

Annus et al., 2005 6 - 7 1.4% 1993/94

4.1% 2001/2002

Riikjärv et al., 1995 10 - 12 2.9% 1992/93

Annus et al., 2001 2.5% 1996/97

Annus et al., 2005 13 - 14 3.3% 1993/94

4.7% 2001/2002

Prevalence of asthma in adults

Study prevalence Study period

Age (y.o.)

Study centres

Jõgi et al., 1996 2% 1993/94 20 - 44

Tartu

Meren et al., 2001

2% 1995/96 15 - 64

Narva, Saaremaa, Tallinn 5 – 8% #

# asthma diagnosed after additional study

Asthma/ asthmatic symptoms and atopy

•Children studies:•≥1 SPT positive• 26% among wheezers (49 – 58% in Sweden) • 9% among nonwheezers (16-22% in Sweden)

Annus et al., 2001

•Adult studies:• The prevalence of atopy among asthmatic 15% (in Barcelona 78%, an average for countries participated in ECRHS 56%)

Sunyer et al., 2004

Bronchial asthmaSummary• Prevalence of wheezing in Estonia is high, but prevalence of more specific symptoms was near median when compared to other European data

Jõgi et al., 1996, Burney et al., 1996

•Prevalence of asthma in Estonia 2 – 5%

Jõgi et al., 1996

Meren et al., 2001

•Asthma could be underdiagnosed

Meren et al., 2005

•Prevalence of sensitisation among asthmatics is lower than in western Europe

Annus et al., 2001, Sunyer et al., 2004

• Prevalence of asthma has an upward trendAnnus

et al., 2005

RhinitisStudy Study

periodDefinition Age Prevalen

ce

Rhinitis (referred to the 12-month prevalence)

Jõgi et al., 1996 1993-94 Do you have any nasal allergies including hay fever?

20 - 44

17.8%

Annus et al., 2005

1993/94 Has your child had a problem with sneezing, or a runny, or blocked nose when he/she did not have a cold or flu?

6 – 7 11.6%

2001/2002 13.1%

Annus et al., 2001

1996/97 10 - 12

6.2%

Annus et al., 2005

1993/9413 -14

23.3%

2001/2002 24.5%

Rhinoconjunctivitis

Annus et al., 2005

1993/94 In the past 12 month, has this nose problem been accompanied by itchy-watery eyes?

6 – 7 3.9%

2001/2002 4.7%

Annus et al., 2001

1996/97 10 - 12

6.2%

Annus et al., 2005

1993/9413 -14

5.3%

2001/2002 7.3% *

Vasar et al., 2011

2003 Diagnosed by a doctor 10 – 20

4.9%

* p<0.001

Rhinitis or rhinoconjunctivitis diagnosed after clinical evaluation

Age 1993/94 born Tartu children (Julge et.al, 2001)

1997/98 born Tartu children (Voor PhD thesis)

Relevant study conducted in Sweden,1996/2000 born children (Voor PhD thesis)

3 month --------- 0% 0%

6 month 0% 0% 0%

1 year 0% 0% 0%

2 years 1% 1% 0%

5 years old

5.5% 6% 14% *

* p<0.001

Time trends

Jõgi et al, Allergy 1996

1970-751970-75 1960-651960-65 1950-551950-55

Reported nasal allergies

Reported asthma relatedsymptoms

Annus et al., Pediatr Allergy Immunol 2005

Time trends

Atopic dermatitisStudy Prevalence Study

periodAge Definition

Annus et al., 2005

12% 1993 – 94 6 – 7 Flexural rush = Has your child had an itchy rash, that coming and going for at least 6 month, at any time in the past 12 month, affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes?

13.5% * 2001 – 2002

Annus et al., 2001

6.2% 1996 - 97 10 - 12

Annus et al., 2005

7.7% 1993 -/9413 -14

9.4% * 2001 – 2002

Julge et.al, 2001

4 – 15% 1993 – 1999 0 - 5

Diagnosed after clinical examination

Voor PhD thesis

2 – 8% 1997 - 2003

Vasar et al., 2011

8.3% 2003 10 - 20

* p<0.001

Atopic dermatitisAge 1993/94 born

Tartu children (Julge et.al, 2001)

1997/98 born Tartu children (Voor PhD thesis)

2007/2008 born Tallinn children (Budarova Master’s thesis, 2009)

3 month 4%

6 month 4 % 5%

1 year 10.5 % 7% 30%

2 years 15% 12%

5 years old 10% 8%

Risk factors of allergic diseases•h

eredity •g

ender•e

nvironment and the way of life:–hygiene hypothesis (intestinal microflora, antibiotics, infections, number of siblings, pet ownering)–diet (breastfeeding, fish intake), obesity–pollution (air pollution, smoking and environmental tobacco exposure)

Annus T., PhD thesis, 2005Bousquet et al., Allergy 2011

Risk factorsHeredity

•a significant factor for asthma and sensibilization (but not to mite and symptoms associated with it)

Jõgi et al., 1998

•family history of asthma was a risk factor for asthma (OR 4.3)

Meren et al., Respir Med 2001

•a risk factor for allergic disorders in the offspring• in particular for the same condition• the greatest risk with maternal asthma influence on asthma in girls (OR

9.9, 95% CI 4.1 – 23.8)

Annus PhD thesis

Sensitization and gender•w

as not associated with sensitization at 2 yVasar et. al., 2000

•sensitization was more common in boys (20% vs 10%)

Braback et al., 1995

•male sex was an independent risk factor for atopy (OR for positive IgE to cat 2.9, CI95% 1.1 – 7.5)

Jõgi et al., 1998

•men were significantly more sensitized to the storage mites compared with women (for Acarus siro 10.3% vs

5.0%, and Lepidoglyphus destructor 10.3% vs 5.3%) Raukas-Kivioja et al. 2003

Asthma/asthmatic symptoms and gender

•was not associated with atopic symptoms at 2 y

Vasar et. al., 2000

•Female sex was a risk factor for symptoms common in asthma, but not for diagnosed asthma

Meren et al., 2001•F

emale sex was a risk factor for nocturnal cough both in Tartu and Uppsala and for nocturnal chest tightness and nocturnal breathlessness in Tartu

Jõgi et al., 1996•the risk of wheezing (lifetime and last year wheezing), if atopic higher in girls (OR 3.5, 95% CI 1.4±9.1) than in boys (OR 1.6, 95% CI 0.6±3.9)

Annus PhD thesis

Atopy and infections

Nonatopic

Atopic p value

Janson et al., 2007(ECRHS, Reykjavik, Tartu, Uppsala)

36.6% 24.8% <0.001

Julge et al., 2010 43% 46% 0,05

H. pylory

respiratory infection •the number of severe respiratory infection before 5 years of age was not associated with BHR in adult

Jõgi et. al., 2004•in the birth cohort study was shown no correlation between the numbers of episodes of infections and allergy

Voor et al., 2005

Allergy development and intestinal microflora

Björkstén et al., JACI 2001

The intestinal microflora in allergic Estonian and Swedish 2-year-old children

• Allergic

• Non-allergic

Estonian children

Swedish children

Björkstén et al., Clinical and Experimental Allergy 1999

Allergy and microflora changers in Estonia within the first ears of independence

•Estoniian children born 1993/94 vs 1996/97• the counts of gram-positive anaerobic cocci and bacteroides were decreased • the pattern of microbiota became the same as that was in Sweden

E. Sepp et al., Clinical and Experimental Allergy 2005

Allergy and antibiotics•T

he use of antibiotics during the first year of life increased the risk for positive SPT (OR=1.7, 95%CI 1.12 - 5) in Estonian, but not in the Swedish infants

•There was no correlation between the use of antibiotics during the second year of life and SPT and AD

Voor et al., Clin Exp Allergy 2005

•In 6-7 old children allergic rhinitis, current asthma, and wheezing were related to the use of antibiotics in the first year of life

Annus PhD thesis

Risk factors for sensitizationdomestic location before the age of 5 years

SPT positive Urban area

Suburban area

Rural Test for trend, p-value

At least 1/15 tested allergens

39,2% 36,0% 28,3% p = 0.02

Pollen 19,4% 17,0% 8,7% p = 0.003

Cat 9,9% 9,0% 3,3% p = 0.01

Dog 12,1% 9,0% 4,9% p = 0.01

Raukas-Kivioja et al., Clin Exp Allergy 2003

Pet at home•E

xposure to pets during childhood was significant for mite asthma in adults (OR 6.5, CI95% 1.33 – 31.7)

Jõgi et al., 1998

•Having animals at home before the age of five was a risk factor for a positive SPT against cat dander (OR 2.4) but not to any other allergen in adults

Raukas-Kivioja et al., 2003

•Pet ownership was not associated with either atopic symptoms or sensitization at 2 y

Vasar et. al., 2000

Breastfeeding•4

/5 children with positive SPT to cow‘s milk at 6 or 12 months of age had been exclusively breastfed for < 1 month

Julge et al., Acta Paediatr 1997

•Infants who had been exclusively breast fed for at least two months had lower values of IgE • at 6 months

Julge et al., 1997• at 2 years

Vasar et al., 2000•P

rotective effect of breastfeeding for at least 3 month was visible only in boys and only for bronchial asthma and rhinoconjunctivitis

Annus PhD Thesis 2005•u

ntil 6 months of age might be beneficial•b

reast milk feeding till 12 month of age associates with AD development (74% of children had AD)

Budarova Master’s thesis, 2009

RHINE childhood fish intake and adult asthma

Laerum et al., Clinical and Experimental Allergy 2007

anytime

Obesity and onset of asthma/ respiratory symptoms

Gunnbjornsdottir et al, Eur Respir J 200461

Traffic/air pollution•a

high level of exhaust particles outside home was not a risk factor respiratory symptoms specific to allergic disease

Orru et al., 2009

•Influence of frequent truck traffic was–not a risk factor for wheezing or current asthma–was a risk factor of allergic rhinitis

Annus PhD thesis , 2005

•Living in the polluted area (Narva/Tallinn vs Saaremaa) was associated with higher risk for: –mainly bronchitic symptoms

Meren et al., 2001–for sensitization

Raukas-Kivioja et al., 2007

Smoking and asthma•r

espiratory symptoms (wheezing, sputum production, and chronic productive cough) and smoking were strongly correlated

•most symptoms increased significantly with the numbers of cigarettes smoked per day

Meren et al., 2001, Pallasaho et al., 2005

•Current smoking associated with wheezing and all nocturnal symptoms (but not nocturnal chest tightness)

J6gi et al., 1996

•Smoking was significantly associated with BHR

Jõgi et al., 2004

•Subjects who quit smoking during follow-up had an increased remission rate of bronchial asthma

Holm et al., 2007

Smoking and asthma•a

strong dose-response relationship between ETS exposure and respiratory symptoms in adults

•outside the home more serious effects than ETS exposures at home

Larsson et al., Eur Respir J 2003

•maternal (but not paternal) smoking was a risk factor for coughing attacks

•a highly significant dose-response relationship was seen between maternal smoking and coughing attacks (in Poland and Estonia, but not in Sweden)

Braback et al., 1995

Smoking/ exposure to tobacco smoke and sensitization

•Exposure to tobacco smoke at home during infancy was associated with an increased risk for atopic sensitisation to animal dander in 10 – 12 y.o. children

•Current (when a child is 10-12y) parental smoking was not related to atopic sensitisation

Braback et al. 1995

•Parental smoking were not associated with either atopic symptoms or sensitization at 2 y

Vasar et al., 2000

•Maternal smoking during childhood was associated with a doubled risk for sensitization to mite

Jõgi et al., 1998

Summary IField of study number

of participants

age (y.o.)

area of study

sensitization

inhalant allergenes

3818 0.25–67

Narva, Saaremaa, Tallinn, Tartu

food allergenes 551 1 - ? Tallinn, Tartu

bronchial asthma

questionnaires 37001 0.25–64

Elva,Pärnu,Saaremaa,Tallinn,Tartu,Võru

clinical examination

1949 0.25–20

Elva, Pärnu,Tallinn,Tartu,Võru

rhinitis

questionnaires 37001 0.25–64

Elva,Pärnu,Saaremaa,Tallinn,Tartu,Võru

clinical examination

1949 0.25 - 20

Elva, Pärnu, Tallinn, Tartu, Võru

atopic dermatitis

questionnaires 15555 0.25–20

Elva, Pärnu, Tallinn,Tartu,Võru

clinical examination

2007 0.25 - 20

Elva,Pärnu,Tallinn,Tartu,Võru

food hypersensitivity

496 1 - ? Tallinn, Tartu

Summary II•T

he prevalence of asthma in Estonia could be underestimated•T

he prevalence of allergic diseases and sensitization has growing trends

•Risk factors that shown significance in Estonian studies• heredity• gender• environment and life style• hygiene hypothesis (intestinal microbiota, antibiotics, infections,

number of siblings)• dietary (breastfeeding, fish intake)• obesity• smoking and environmental tobacco exposure • allergen exposure