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Dirceu Solé Full Professor Division of Allergy, Clinical Immunology and Rheumatology Departament of Pediatrics Federal University of São Paulo President of SLAAI and ASBAI

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Dirceu SoléFull Professor Division of Allergy, Clinical Immunology and Rheumatology

Departament of Pediatrics – Federal University of São PauloPresident of SLAAI and ASBAI

Asher et al – Lancet 2006;368:733-43

20 Countries & 11 Territories

Total population = 569 million

Urban areas = 389 million(10% without potable water)

ColonizationPortuguese = Brazil

Spanish = All the others

Mallol & Solé, 2009

*among current wheezers** without asthma among current wheezers

Severe wheeze**

Severe

wheeze*

Severe

wheeze

Asthma

ever

Wheezing

12 mo

N

18.941.111.293,851Latin America

16.538.59.4388,811Global total

Severe wheeze**

Severe

wheeze*

Severe

wheeze

Asthma

ever

Wheezing

12 mo

N

18.938.313.6165,917Latin America

20.043.312.6798,685Global total

6-7yr-old

13-14yr-old

Mallol, Solé and ISAAC Phase 3 colaborators – J Asthma, in press

Latin-America

Total

17.8

13.2

18.8

13.7

6.9

7.0

44,550

304,811

90.9

90.9

Centre N Year between P1 P3 Change/ Responsephases year rate (%)

Latin-America

Total

20.9

10.6

21.4

11.6

7.1

7.1

21,112

193,436

83.8

84.8

Centre N Year between P1 P3 Change/ Responsephases year rate (%)

Asher et al – Lancet 2006;368:733-43

Pearce et al – Thorax 2007;62:757-65

Mallol et al – J Asthma 2009, in press

Pearce et al – Thorax 2007;62:758-66

Mexically ValeyMonterrey

HabanaMerida

Ciudad de Mexico 1

Ciudad de Mexico 4Toluca

Cuernavaca

San Pedro SulaSan Salvador

BarranquillaCaracas

David Panama

Ciudad Victoria

Ciudad de Mexico 3

Villahermosa

Managua

Costa Rica

Cali

Quito

ManausRecife

Maceio

LimaFeira de Santana

Vitoria da ConquistaBrasilia

Belo Horizonte

Bogota

Guayaquil

Caruaru

Aracaju

Salvador

Santa Cruz

Calama

Sao Paulo SulSao Paulo West

SaltaAssuncion

ItajaiPasso Fundo

Santa MariaPorto Alegre

PaysanduRosario city

Montevideo

Nova Iguaçu

Santo Andre

Curitiba

Santa Maria rural

Cordoba

Santiago South

Neuquen

ChiloeValdivia

Punta Arenas

0 5 10 15 20 25 30

Mallol, Solé, and LA ISAAC Phase 3 colaborators – J Asthma 2009 - in press

N Rhinitis Rhinolast yr conjunctivitis

Strachan et al – Pediatr Allergy Immunol 1997;

Aït-Khaled et al – Allergy 2009;64:123-48

Solé et al –Pediatr Allergy Immunol 2009 Sep 24. [Epub ahead of print]

Latin-America

Total

15.5

13.6

18.5

15.1

6.9

7.0

44,550

304,811

90.9

90.9

Centre N Year between P1 P3 Change/ Responsephases year rate (%)

Latin-America

Total

9.1

7.0

12.1

8.3

7.1

7.1

21,112

193,436

83.8

84.8

Centre N Year between P1 P3 Change/ Responsephases year rate (%)

Bjorksten et al –Pediatr Allergy Immunol 2008;19:110-24

Solé et al - Pediatr Allergy Immunol 2009 Sep 24. [Epub ahead of print]

Bjorksten et al –Pediatr Allergy Immunol 2008;19:110-24

0 10 20 30 40 50 60

Punta ArenasChiloé

ValdíviaNeuquen

MontevideoSantiago-S

RosarioPaysanduCordoba

Porto AlegreSanta Maria

Santa Maria-RPasso Fundo

ItajaíCuritiba

AsuncionSalta

S AndréSão Paulo-WSão Paulo-S

N IguaçuCalama

B HorizonteSta CruzBrasília

V ConquistaSalvador

F SantanaLima

AracajuMaceióCaruaru

RecifeManus

GuayaquilQuito

CaliBogotá

PanamáCosta Rica

CaracasBarranquilla

ManaguaS Salvador

S Pedro SulaV Hermosa

CuernavacaToluca

C Mexico 4C Mexico 3C mexico 1

MeridaLa HabanaC Victoria

MonterreyMexically

Solé et al -Pediatr Allergy Immunol. 2009 Sep 24. [Epub ahead of print]

Williams et al – J Allergy Clin Immunol 1999;103:125-38

Williams et al – J Allergy Clin Immunol 2008;121:947-54

Solé et al – Pediatr Allergy Immunol 2009, in press

N Flexural Severeeczema eczema

Latin-America

Total

7.2

7.0

9.0

7.6

6.9

7.0

44,550

304,811

90.9

90.9

Centre N Year between P1 P3 Change/ Responsephases year rate (%)

Latin-America

Total

8.7

6.9

10.5

8.6

7.1

7.1

21,112

193,436

83.8

84.8

Centre N Year between P1 P3 Change/ Responsephases year rate (%)

Asher et al – Lancet 2006;368:733-43

Bjorksten et al –Pediatr Allergy Immunol 2008;19:110-24

Solé et al – Pediatr Allergy Immunol 2009, in press

LA centers

English speaking center

Williams et al – J Allergy Clin Immunol 2008;121:947-54

Mexically ValeyMonterrey

Ciudad VictoriaHabanaMerida

Ciudad de Mexico 1Ciudad de Mexico 3Ciudad de Mexico 4

TolucaCuernavaca

VillahermosaSan Pedro Sula

San SalvadorManagua

BarranquillaCaracas

Costa RicaDavid Panama

BogotaCali

QuitoGuayaquil

ManausRecife

CaruaruMaceioAracaju

LimaFeira de Santana

SalvadorVitoria da Conquista

BrasiliaSanta Cruz

Belo HorizonteCalama

Nova IguaçuSao Paulo Sul

Sao Paulo WestSanto Andre

SaltaAssuncion

CuritibaItajai

Passo FundoSanta Maria rural

Santa MariaPorto Alegre

CordobaPaysandu

Rosario citySantiago South

MontevideoNeuquen

ValdiviaChiloe

Punta Arenas

0 5 10 15 20 25 30

Solé et al – J Investig Allergol Immunol 2009, in press

Min (%) Max (%) Mean (%) Variation

Asthma6-7yr13-14 yr

Severe asthma6-7 y13-14 yr

Rhinoconjunctivitis6-7 yr13-14 yr

Severe rhinitis6-7 yr13-14yr

Flexural eczema6-7 yr13-14 yr

Severe eczema6-713-14 yr

3.63.9

0.90.6

5.57.2

0.30.3

3.22.9

0.30.1

37.630.8

11.85.9

21.245.1

4.04.9

25.030.2

2.74.2

17.315.5

3.92.6

13.518.9

1.81.5

11.39.5

1.51.3

10.08.0

13.010.0

4.06.0

13.016.0

8.010.0

9.042.0

Gross National Product

Infant mortality rate

% population with potable water service

% population with sewage disposal services

Annual deaths – kids under 5 yrs of age

due to intestinal infectious diseases

Annual incidence of tuberculosis

http://www.studentsoftheworld.info/infopays/rank/PNB2.html; http://hdr.undp.org/en/reports/global/hdr2007-2008

http://en.wikipedia.org/wiki/Water_and_sanitation_in_Latin_America; http://www.paho.org/English/SHA/coredata/

tabulator/newTabulator.htm; http://en.wikipedia.org/wiki/List_of_countries_by_infant_mortality_rate_(2005)

Anderson et al – Occup Environ Med published online 5 Nov 2009

Prevalence of symptoms (ISAAC Ph 1):asthma, rhinoconjunctivitis, eczema

Particulate matter <10mm (PM10) – city-level

Associations evaluated by binomial regression

Adjusted for Gross National Product per capita

Results compared with a meta-analysis ofpublished multi-centre studies

0 50 100 150PM10

-1

-2

-3

-4

-5

Lo

g o

f se

ve

re w

he

eze

Spearman r =0.36p<0.001

-1

-2

-3

-4

-5

Lo

g o

f se

ve

re w

he

eze

0 50 100 150PM10

Spearman r =0.39p<0.001

Anderson et al – Occup Environ Med published online 5 Nov 2009

Anderson et al – Occup Environ Med published online 5 Nov 2009

European countries

Non-European higher income countries

Non-European lower income countries

Subtotal

Overall

The reasons for the wide international variations in the prevalence of childhood

asthma, rhinoconjunctivitis and eczema are not understood.

One factor might be exposure to ambient particulate matter (PM) since this isassociated with a range of respiratory outcomes and associations have been

observed with proximity to traffic pollution.

In a study of over a million children from 105 cities in 51 countries, we found little or

no evidence of associations with modelled urban background PM10.

The results suggest that community levels of ambient PM are unlikely to explain

international variations in prevalence.

Fututre studies of differences in prevalence between communities will benefit fromimproved exposure assessment and control for confounding factors at individual level.

Anderson et al – Occup Environ Med published online 5 Nov 2009

In a study of over a million children from 105 cities in 51countries, we found little or no evidence of associationswith modelled urban background PM10.

The results suggest that community levels of ambient PM

are unlikely to explain international variations in prevalence.

Mexically ValeyMonterrey

HabanaMerida

Ciudad de Mexico 1

Ciudad de Mexico 4Toluca

Cuernavaca

San Pedro SulaSan Salvador

BarranquillaCaracas

David Panama

Ciudad Victoria

Ciudad de Mexico 3

Villahermosa

Managua

Costa Rica

Cali

Quito

ManausRecife

Maceio

LimaFeira de Santana

Vitoria da ConquistaBrasilia

Belo Horizonte

Bogota

Guayaquil

Caruaru

Aracaju

Salvador

Santa Cruz

Calama

Sao Paulo SulSao Paulo West

SaltaAssuncion

ItajaiPasso Fundo

Santa MariaPorto Alegre

PaysanduRosario city

Montevideo

Nova Iguaçu

Santo Andre

Curitiba

Santa Maria rural

Cordoba

Santiago South

Neuquen

ChiloeValdivia

Punta Arenas

0 5 10 15 20 25 300 1 2 3 4 5 6

Mallol, Solé, and LA ISAAC Phase 3 colaborators – J Asthma 2009 - in press

Solé et al -Pediatr Allergy Immunol. 2009 Sep 24. [Epub ahead of print]0 10 20 30 40 50 60

Punta ArenasChiloé

ValdíviaNeuquen

MontevideoSantiago-S

RosarioPaysanduCordoba

Porto AlegreSanta Maria

Santa Maria-RPasso Fundo

ItajaíCuritiba

AsuncionSalta

S AndréSão Paulo-WSão Paulo-S

N IguaçuCalama

B HorizonteSta CruzBrasília

V ConquistaSalvador

F SantanaLima

AracajuMaceióCaruaru

RecifeManus

GuayaquilQuito

CaliBogotá

PanamáCosta Rica

CaracasBarranquilla

ManaguaS Salvador

S Pedro SulaV Hermosa

CuernavacaToluca

C Mexico 4C Mexico 3C mexico 1

MeridaLa HabanaC Victoria

MonterreyMexically

0 10 20 30 40 50

Mexically ValeyMonterrey

Ciudad VictoriaHabanaMerida

Ciudad de Mexico 1Ciudad de Mexico 3Ciudad de Mexico 4

TolucaCuernavaca

VillahermosaSan Pedro Sula

San SalvadorManagua

BarranquillaCaracas

Costa RicaDavid Panama

BogotaCali

QuitoGuayaquil

ManausRecife

CaruaruMaceioAracaju

LimaFeira de Santana

SalvadorVitoria da Conquista

BrasiliaSanta Cruz

Belo HorizonteCalama

Nova IguaçuSao Paulo Sul

Sao Paulo WestSanto Andre

SaltaAssuncion

CuritibaItajai

Passo FundoSanta Maria rural

Santa MariaPorto Alegre

CordobaPaysandu

Rosario citySantiago South

MontevideoNeuquen

ValdiviaChiloe

Punta Arenas

0 5 10 15 20 25 300 5 10 15 20 25 30

Solé et al – J Investig Allergol Immunol 2009, in press

http://faostat.fao.org/site/502/DesktopDefault.aspx?PageID=502

TotalCalories/capita/day

Protein/capita/day (g)Fat/capita/day (g)

AnimalCalories/capita/day

Protein/capita/day (g)Fat/capita/day (g)

VegetalCalories/capita/day

Protein/capita/day (g)Fat/capita/day (g)

Foliaki et al – J Allergy Clin Immunol 2009;124:982-9

Antibiotic use early in life may increase risk of asthma

and allergic diseases?

Ecologic analysis: antibiotics sales vs prevalence of symptoms

(asthma, allergic rhinoconjunctivitis, and atopic eczema - ISAAC Ph3)

99 centres from 28 countries

Data obtained from: Institute for Medical Statistics (IMS),

Health Global Services, UK

Analysis adjusted for gross national product (GNP)

Thailand (76%)

Syrian Arabic Republic (70%)

Panama (69%)

New Zealand (63%)

Nigeria (62%)

Chile (62%)

Mexico (61%)

Iran (60%)

Canada (59%)

Portugal (58%)

Colombia (57%)

Hungary (56%)

Spain (54%)

Belgium (53%)

Barbados (53%)

Lithuania (49%)

Brazil (48%)

India (48%)

Estonia (36%)

Taiwan (23%)

Foliaki et al – J Allergy Clin Immunol 2009;124:982-9

LA country( ) % children useantibiotics

Africa

Asia-Pacific

Eastern Mediterranean

Indian Subcontinent

Latin America

North America

N/Eastern Europe

Oceania

Western Europe

1

4

4

11

6

2

3

4

12

890

10,092

8,237

27,020

12,703

2,656

6,540

9,206

26,309

0.81 (0.02-3.20)

1.79(1.42-2.26)

1.54(1.24-1.90)

1.52 (1.23-1.88)

1.96 (1.67-2.30)

1.75 (1.42-2.17)

1.72 (1.40-2.12)

1.81 (1.58-2.07)

1.57 (1.42-1.74)

2.06 (0.26-16.61)

1.94 (1.60-2.34)

1.52 (1.06-2.18)

1.34 (1.11-1.62)

1.62 (1.37-1.92)

1.22 (0.92-1.63)

1.87 (1.41-2.48)

1.64 (1.39-1.94)

1.47 (1.31-1.65)

1.25 (0.45-3.44)

1.42 (1.20-1.69)

1.22 (0.80-1.84)

1.33 (1.06-1.66)

1.65 (1.40-1.95)

1.56 (1.18-2.04)

1.47 (1.17-1.85)

1.43 (1.24-1.65)

1.34 (1.21-1.49)

Region Centers Children Asthma (wheeze) Rhinoconjunctivitis Eczema

OR (CI95%)*

Foliaki et al – J Allergy Clin Immunol 2009;124:982-9

* Multiple regression analysis including centers with at least 70% data available for all covariates. All children who had a missing value of any

of the covariates have been removed. Adjusted for sex, region of the world, language, GNI, maternal education, breast-feeding, current

paternal smoking, consumption of vegetables, consumption of pulses, consumpption of fruits, paracetamol use in the first year of life,

current paracetamol use, older siblings, and younger siblings

These findings are consistent with the

hypothesis that antibiotic use increases the risk of

asthma, rhinitis, or eczema. If there is a causal

association of antibiotic use with asthma risk, it does

not appear to explain the international differences in

asthma prevalence.

Beasley et al – Lancet 2008;372:1039-48

205,487 children (6-7 yrs old)

73 centers in 31 countries

Association of:

Paracetamol for fever (first year of life and nowadays)

with increased risk of asthma and allergic diseases

Beasley et al – Lancet 2008;372:1039-48

Beasley et al – Lancet 2008;372:1039-48

Use of paracetamol in the first year of life and

later childhood, is associated with risk of asthma,

rhinoconjunctivitis, and eczema at age 6 to 7 years.

We suggest that exposure to paracetamol might be

a risk for the development of these diseases in

childhood

Higher variability on prevalence of these diseases between countries and in centersfrom the same country of Latin America

Significant increase among both age groups during a 7-year interval (Phase I and III) in several centers

Mean increase of Asthma prevalence rates doubled those from developed countries

Confirms Phase I results: probably the

Hygiene Hypothesis is not applicable to Latin

America

Asthma is a heterogeneous disease and local

studies are mandatory

Asthma and allergic diseases in schoolchildren

continue to be a major health problem in Latin

America