IS ESTONIA ENDANGERED BY EPIDEMIC OF ALLERGY? Renata Melnikova, MD, Ph. D student
Epidemiology • Epidemiology 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/
The epidemics of allergy Bousquet et al. , Allergy 2011
Studies, study areas, study population The name of the study Study period Age (y. o. ) Nr of Study area participants ECRHS 1993 - 2014 25 – 65 2460 Tartu Fin. Es. S 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, Ph. D thesis 1997 -2003 Julge et al. , 2001 1993 - 99 Budarova Master’s thesis, 2009 2007 - 8 0 -5 1 115 273 58 Tartu Tallinn
Main fields of study • Sensitization • Bronchial asthma • Rhinitis/ rhinoconjunctivitis/ rhinitis and/or conjunctivitis • Atopic Dermatitis • Urticaria • Gastroenteritis • Food hypersensitivity • Risk factors • • Heredity Gender Environment and lifestyle Microflora
Prevalence of sensitization in Estonia Riikjärv et al. , 1995 Study area Riikjärv et al. , 2000 Raukas-Kivioja et al. , 2007 Jõgi et al. , 1995 Tartu Tallinn Saaremaa Tartu Tallinn Study period 1992 1997 Age (y. o. ) 10 - 12 1999 10 Tallinn 1997 -98 15 - 64 1994 - 95 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% 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% ----- * p<0. 001 monoallergy 3%
Prevalence of sensitization in Estonia SPT vs RAST (adult studies) Jõgi et al. , 1995 Jõgi et al. , 1998 Methods SPT s. Ig. E 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 – 93 correlation between the two methods was not good SPT pos SPT neg s. Ig. E pos 32 39 (55%) s. Ig. Eneg 7 (18%) 702 Riikjärv et al. , 1995 • 2003 – 4 correlation between SPT and RAST is better • positive SPT 18. 2% • positive s. Ig. E 20% Julge et al. , 2009
Sensitization to inhalant allergens, birth cohort studies Julge et. al, 2001 Voor Ph. D thesis (children born in 1993/94) in 1997/98) SPT cat SPT 0. 5 y. o. ----- Swedish s. Ig. E ----- s. Ig. E Swedish ----- 1. 6% 1 y. o. 1. 4% 1. 0% 1% 4. 2% 6% 0% 2 y. o. 4. 1% 3. 8% 2. 3% 11. 8% 7% 2% 5 y. o. 1. 4% 1% 8% 13. 6% 5% 7% 0. 5 y. o. --------- 0% --------- 1 y. o. --------- 3. 5% 4% 1% 2 y. o. 0. 5% 0% 5. 4% 3. 5% 3% 3% 5 y. o. 1. 0% 1% 16% 13. 5% 7% 14% house 1 y. o. dust 2 y. o. mite 5 y. o. 1. 8% --------- 2. 1% --------- 2. 3% --------- 7. 6% --------- 1. 4% --------- 19. 4% --------- birch
Sensitization to food, birth cohort studies Julge et. al, 2001 Voor Ph. D thesis (children born in in 1993/94) in 1997/98) in 1993/94) 1997/98) milk SPT Swedish s. Ig. E Swedish 3 month old ----- 0% 3% ----- 9% 8% 6 month old 1. 7% 0% 6. 8% 12% 9%/ 13% 1 year old 0. 9% 1% 3. 8% 20. 7% 6% 7% 2 year old 0% 0% 2. 3% 25. 8% 10% 5% 5 year old no data 0% 1% 23. 2 6% 9% 3 month old ----- 4, 5% 9% ----- 11% 12% 6 month old 5. 2% 6% 16. 4% 4. 2% 15% 13% 1 year old 4. 1% 6. 4% 19. 3% 5. 6% 10% 17% 2 year old 1. 8% 3. 8% 11. 6% 20. 6% 18% 14% 5 year old 0% 1% 8% 23. 2% 13% 8% egg white
Sensitization to food school children study (ISAAC) • Ig. E 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 Ig. E to tested food answered food questionnaire reported hypersensitivity to food Sandin et al. , 2005
Sensitisation Summary • Prevalence in different areas was unequal • Prevalence of the sensitization in Estonia in 90 th 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 • s. Ig. E and SPT are not the same
Prevalence (%) of asthma symptoms wheezing/ 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 Annus et al. , 2005 9. 3% 1993/94 9. 7% 2001/2002 Tallinn 6– 7 Tallinn
Prevalence (%) of asthma symptoms and selfreported asthma, ECRHS study (20 – 44 y) Wheeze with breathlessness Wheeze without a cold Summarized data of different international centres across the World 25 th centile Median 75 th centile Max in Estonia Min 26, 8 4, 1 14, 9 20, 7 25, 2 32, 0 7, 8 1, 4 7, 7 9, 8 13, 9 16, 3 12, 8 2, 0 9, 3 12, 7 16, 2 21, 6 13, 9 Waking with tightness in the chest Waking with 8, 1 breathlessness 42, 6 Waking with cough 1, 8 Attack of asthma 6, 2 9, 7 13, 5 17, 5 20, 5 1, 5 4, 7 7, 3 8, 9 11, 4 6, 0 25, 6 27, 9 29, 5 42, 6 1, 3 2, 6 3, 1 4, 5 9, 7 Treatment for asthma 0, 6 2, 4 3, 5 5, 0 9, 8 0, 6 Burney et al. , Eur Respir J, 1996
The proportion of asthma and chronic bronchitis diagnosed among subjects with wheeze Pallasaho et al. , European Journal of Epidemiology, 2005
Prevalence of asthma in childred Study Age (y. o. ) Prevalence Study period Julge et. al, 2001, Voor Ph. D thesis 0, 5 1 0% 1994, 1997/98 0, 5% 1994/95 3% 1998/99 2% 1995/96 6% 1999/2000 6, 5% 1999 7% 2002/2003 1. 4% 1993/94 4. 1% 2001/2002 2. 9% 1992/93 2. 5% 1996/97 3. 3% 1993/94 4. 7% 2001/2002 Julge et. al, 2001 Voor Ph. D thesis Julge et. al, 2001 2 Voor Ph. D thesis Julge et. al, 2001 5 Voor Ph. D thesis Annus et al. , 2005 Riikjärv et al. , 1995 6 -7 10 - 12 Annus et al. , 2001 Annus et al. , 2005 13 - 14
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 asthma Summary • 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 trend Annus et al. , 2005
Rhinitis Study period Definition Age Prevalence Rhinitis (referred to the 12 -month prevalence) Jõgi et al. , 1996 1993 -94 Do you have any nasal 20 - 44 allergies including hay fever? 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? 11. 6% 2001/2002 Annus et al. , 2001 1996/97 Annus et al. , 2005 1993/94 6– 7 13. 1% 10 - 12 13 -14 2001/2002 6. 2% 23. 3% 24. 5% Rhinoconjunctivitis Annus et al. , 2005 1993/94 2001/2002 Annus et al. , 2001 1996/97 Annus et al. , 2005 In the past 12 month, has this nose problem been accompanied by itchywatery eyes? 1993/94 * p<0. 001 2003 Diagnosed by a doctor 3. 9% 4. 7% 10 - 12 13 -14 2001/2002 Vasar et al. , 2011 6– 7 10 – 20 6. 2% 5. 3% 7. 3% * 4. 9%
Rhinitis or rhinoconjunctivitis diagnosed after clinical evaluation Age 1993/94 born Tartu children (Julge et. al, 2001) 1997/98 born Tartu Relevant study children (Voor Ph. D conducted in Sweden, thesis) 1996/2000 born children (Voor Ph. D 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 Reported nasal allergies Reported asthma related symptoms 1970 -75 1960 -65 1950 -55 Jõgi et al, Allergy 1996
Time trends Annus et al. , Pediatr Allergy Immunol 2005
Atopic dermatitis Study Prevalence Study period Age Definition Annus et al. , 2005 12% 1993 – 94 6– 7 13. 5% * 2001 – 2002 Annus et al. , 2001 6. 2% 1996 - 97 Annus et al. , 2005 7. 7% 1993 -/94 9. 4% * 2001 – 2002 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? Julge et. al, 2001 4 – 15% 1993 – 1999 Voor Ph. D thesis 2 – 8% 1997 - 2003 Vasar et al. , 8. 3% 2011 * p<0. 001 2003 10 - 12 13 -14 0 -5 10 - 20 Diagnosed after clinical examination
Atopic dermatitis Age 1993/94 born Tartu children (Julge et. al, 2001) 3 month 1997/98 born Tartu children (Voor Ph. D thesis) 2007/2008 born Tallinn children (Budarova Master’s thesis, 2009) 4% 6 month 4% 5% 1 year 10. 5 % 7% 2 years 15% 12% 5 years old 10% 8% 30%
Risk factors of allergic diseases • heredity • gender • environment 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. , Ph. D thesis, 2005 Bousquet et al. , Allergy 2011
Risk factors Heredity • 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 Ph. D thesis
Sensitization and gender • was not associated with sensitization at 2 y Vasar 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 Ig. E to cat 2. 9, CI 95% 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 • Female 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 Ph. D thesis
Atopy and infections H. pylory 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 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 Estonian children • • Allergic Non-allergic 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 • The 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 Ph. D thesis
Risk factors for sensitization domestic 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 • Exposure to pets during childhood was significant for mite asthma in adults (OR 6. 5, CI 95% 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 Ig. E • at 6 months Julge et al. , 1997 • at 2 years Vasar et al. , 2000 • Protective effect of breastfeeding for at least 3 month was visible only in boys and only for bronchial asthma and rhinoconjunctivitis Annus Ph. D Thesis 2005 • until 6 months of age might be beneficial • breast 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 anytime Laerum et al. , Clinical and Experimental Allergy 2007
Obesity and onset of asthma/ respiratory symptoms 61 Gunnbjornsdottir et al, Eur Respir J 2004
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 Ph. D 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 • respiratory 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 nocturnal chest tightness) • Smoking was significantly associated with BHR J 6 gi et al. , 1996 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 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 -12 y) 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 I Field of study number of participants age (y. o. ) area of study 0. 25– 67 Narva, Saaremaa, Tallinn, Tartu 1 -? Tallinn, Tartu 0. 25– 64 Elva, Pärnu, Saaremaa, Tallinn, Tartu, Võru 0. 25– 20 Elva, Pärnu, Tallinn, Tartu, Võru 0. 25– 64 Elva, Pärnu, Saaremaa, Tallinn, Tartu, Võru sensitization inhalant allergenes 3818 food allergenes 551 bronchial asthma questionnaires 37001 clinical examination 1949 rhinitis questionnaires 37001 clinical examination 1949 0. 25 - 20 Elva, Pärnu, Tallinn, Tartu, Võru atopic dermatitis questionnaires 15555 clinical examination 2007 food hypersensitivity 496 0. 25– 20 Elva, Pärnu, Tallinn, Tartu, Võru 0. 25 - 20 Elva, Pärnu, Tallinn, Tartu, Võru 1 -? Tallinn, Tartu
Summary II • The prevalence of asthma in Estonia could be underestimated • The 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
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