Post on 30-Dec-2015
Asthma in Non-Asthma in Non-Affluent CommunitiesAffluent Communities
Renato T. SteinRenato T. Stein
Pontifícia Universidade Pontifícia Universidade Católica RSCatólica RS
Porto Alegre, BrazilPorto Alegre, Brazil
ISAAC Study. Lancet 1998; 351: 1225–32.
Worldwide Prevalence of Asthma Symptoms: ISAAC Phase I Data
Asthma PhenotypesAsthma Phenotypes
Stein R et al. Thorax 1997
Risk for Recurrent Wheeze in Risk for Recurrent Wheeze in Children Infected by RSV Early in Children Infected by RSV Early in LifeLife
Stein R et al, Lancet 1999
ISAAC Phase IIISAAC Phase II
Thirty study centers in 22 countries Thirty study centers in 22 countries Parental questionnaires (n=54,439)Parental questionnaires (n=54,439) Skin prick tests (n=31,759)Skin prick tests (n=31,759) Serum IgE levels (n=8,951)Serum IgE levels (n=8,951) Economic development assessed by Economic development assessed by
gross national income per capita gross national income per capita (GNI)(GNI)
Weinmayr G et al. AJRCCM 2007 (Atopic sensitisation and the international variation of asthma symptom prevalence in children)
West Sussex
Oestersund
Linkoeping
Valencia
Madrid
Cartagena
Almeria
Tromso
Hawkes Bay
Utrecht
Rome
Reykjavik
Thessaloniki
Athens
Munich
Dresden
Hong Kong
1 10
Ankara
Ramallah
Riga
Mumbai
Kintampo
Tbilisi
Tallinn
Pichincha
Guangzhou
Beijing
Uruguaiana
Tirana
Combined affluent
Combined non-affluent
Combined non-affluentwithout Guangzhou
58.9 [21.4;162.2]
0,6 12Odds ratio with 95%-confidence
OR for the association of current OR for the association of current wheeze with skin prick test wheeze with skin prick test reactivityreactivity
West Sussex
Östersund
Linköping
Tromso
Utrecht
Rome
Thessaloniki
Athens
Munich
Dresden
Valencia
Madrid
Almeria
Cartagena
1 10
Tbilisi
Mumbai
Tallinn
Tirana
Combined affluent
Combined non-affluent
0,6 12
OR for the association of OR for the association of current wheeze with allergen-current wheeze with allergen-specific IgE specific IgE ((0.35 kUA/L)0.35 kUA/L)
Odds ratio with 95%-confidence
ISAAC – Phase II Data, ISAAC – Phase II Data, BrazilBrazil Cross sectional Cross sectional
studystudy with with questionnairesquestionnaires, , skin testsskin tests, stool , stool examinations for examinations for parasitesparasites, BHR, BHR
Population Population n=1199 Age: 10.1 n=1199 Age: 10.1 ((++ 0.8) 0.8)
Non-atopic asthma is associated with helminth infections and bronchiolitis in poor children
Pereira M et al. ERJ June 2007
Brazil data: ISAAC-IIBrazil data: ISAAC-II
Wheeze past yr: 26%Wheeze past yr: 26% >4 asthma attacks: 6.5%>4 asthma attacks: 6.5% Asthma ever: 12.7%Asthma ever: 12.7% Positive skin tests: 13.3%Positive skin tests: 13.3% Atopic wheeze past yr: 5.4%Atopic wheeze past yr: 5.4% Non-atopic wheeze: 20.9%Non-atopic wheeze: 20.9%
ISAAC II - BrazilISAAC II - Brazil
Current asthma: 9.4% (Current asthma: 9.4% (29% 29% atopic)atopic)
Bronchiolitis <2y (E.R. or Bronchiolitis <2y (E.R. or hospitalized) 6.1%hospitalized) 6.1%
N=1011n (%)
495 (49.0)865 (88.6)93 (9.6)
852 (84.7)322 (31.9)195 (19.3)*730 (72.2)474 (46.9)956 (94.7)*
78 (7.7)58 (5.8)
273 (27.0)93 (9.2)
131 (13.0)63 (6.3)70 (6.9)
Male genderBirth weight ≥ 2500Born before termBreast feeding ≥ 6 monthsCurrent maternal smoking≥ 8y of maternal schooling≥ 1 SiblingHumid householdPoor neighborhoodMaternal asthmaPaternal asthmaWheeze past 12 monthsActive asthmaAtopyBronchiolitis < 2 y.o.Severe asthma (≥ 4 attacks)
Analysis for children w Analysis for children w questionnaires, SPTs, parasitology questionnaires, SPTs, parasitology teststests
Pereira M et al. ERJ 2007 (accepted for publication)
Risk factors for wheeze and Risk factors for wheeze and asthma Multivariate logistic asthma Multivariate logistic regressionregression
Wheeze in previous 12m OR (95% C.I.)
Active Asthma OR (95% C.I.)
Maternal Hx Asthma 3.1 (1.8-5.3)*** 5.6 (2.8-11.1)*** Paternal Hx Asthma 3.9 (2.1-7.3)*** 3.6 (1.6-7.9)*** Bronchiolitis < 2y 5.4 (2.9-9.9)*** 18.1 (9.1-36.0)*** Any positive skin test 2.7 (1.8-4.1)*** 6.3 (3.4-11.8)*** Humid household 1.5 (1.1-2.1)** 2.2 (1.3-3.8)** Maternal smoking 1.2 (0.9-1.7) 1.1 (0.6-2.0) Born before term 1.4 (0.8-2.3) 0.7 (0.3-1.8) Years of maternal schooling 0.98 (0.92-1.0) 0.9 (0.8-0.9)* ? 2 Siblings 1.1 (0.8-1.5) 0.5 (0.3-0.9)* Higher-load Ascaris (?100eggs/g)
1.8 (0.98-3.4) 2.4 (1.0-6.1)*
Pereira M et al. ERJ 2007 (accepted for publication)
Asthma PhenotypesAsthma Phenotypes
Stein R et al. Thorax 1997
Inflammatory characteristics in Inflammatory characteristics in asthmatic children: Induced asthmatic children: Induced SputumSputum
55 children55 children– Atopic asthma (AA): asthma ever Atopic asthma (AA): asthma ever
and wheeze in past year + SKand wheeze in past year + SK+ve+ve
– Non-atopic asthma (NAA): asthma Non-atopic asthma (NAA): asthma ever and wheeze in past year + SKever and wheeze in past year + SK-ve-ve
– Non-atopic no-asthma (NANA): no Non-atopic no-asthma (NANA): no asthma/no wheeze ever + SKasthma/no wheeze ever + SK-ve-ve
Drews A, et al 2007
IS Eosinophil IS Eosinophil concentration in asthma concentration in asthma phenotypesphenotypes
Media
n (
IQ)
Drews A, et al 2007
IS Eosinophil >3% in IS Eosinophil >3% in asthma phenotypesasthma phenotypes
Drews A, et al 2007
IS Neutrophil IS Neutrophil concentration in asthma concentration in asthma phenotypesphenotypes
Drews A, et al 2007
Non-atopic asthma may be the Non-atopic asthma may be the most common phenotype in Latin most common phenotype in Latin AmericaAmerica
Main risk factor for asthma at age Main risk factor for asthma at age 10y: “Bronchiolitis” (RSV & 10y: “Bronchiolitis” (RSV & Rhinovirus) early in life Rhinovirus) early in life – Mostly neutrophilic inflammationMostly neutrophilic inflammation
ConclusionsConclusions
Hypertonic Saline StudyHypertonic Saline Study
2000 children with ISAAC phase II 2000 children with ISAAC phase II questionaires answeredquestionaires answered
1199 skin prick tests AND stool samples 1199 skin prick tests AND stool samples colectedcolected
50 with positive current asthma history in the
past 12 months
50 with no historyof current asthma AND no history of asthma
ever
Bronchoprovocation Bronchoprovocation
4.5% Hypertonic saline4.5% Hypertonic saline PFTsPFTs
BHR positive: > 15% decline of FEV1BHR positive: > 15% decline of FEV1
MAIN RESULTSMAIN RESULTS
17 (17.5%) positive for BHR.17 (17.5%) positive for BHR.– 10 (20.4%) Current wheeze.10 (20.4%) Current wheeze.– 7 (14.6%) Control (non-wheeze).7 (14.6%) Control (non-wheeze).
OR (CI 95%) = 1.5 (0.5 – 4.3)OR (CI 95%) = 1.5 (0.5 – 4.3) nsns
RESULTSRESULTS
VariablesVariables n/Mn/M %% OR (CI95%)OR (CI95%)
Current Current asthmaasthma
nono 13/813/800
16.16.33
1.5 (0.4 – 5.6)1.5 (0.4 – 5.6)yesyes 4/174/17 23.23.
55
SPTSPT+ve+ve
nono 13/813/822
15.15.99
2.1 (0.5 – 7.8)2.1 (0.5 – 7.8)yesyes 4/144/14 28.28.
66
Parasitosis vs. BHRParasitosis vs. BHRn/Nn/N %% OR (IC95%)OR (IC95%)
Helminth Helminth infectioninfection
negneg 11/711/733
15.15.11
1.5 (0.4 – 5.0)1.5 (0.4 – 5.0)pospos 5/235/23 21.21.
77
High helminth High helminth loadload
negneg 12/812/877
13.13.88 5.0 (1.1 – 5.0 (1.1 –
21.3)21.3)pospos 4/94/9 44.44.
44
Giardia Giardia lamblia lamblia
infectioninfection
negneg 16/816/833
19.19.22 0.8 (0.7 – 0.9)0.8 (0.7 – 0.9)
pospos 0/130/13 00
8
6
4
2
OddsRatiosforAsthma
Number wLRI in first year
0 1 ≥2
non atopic @ 6yrs
atopic @ 6yrs
Synergistic interaction between atopy and wLRI in y1 for persistent asthma
Sly, P et al.
Age (months)
Interferongammaresponses(Th1)
0 24-48
Non-AtopicAsthmatic
Non-Asthmatic
Maturation of Immune Responses Maturation of Immune Responses in Infancyin Infancy
AtopicAsthmatic
Holt P, Sly P
IMMATURE IMMUNE SYSTEM Slow TH1
Th2-driven
Immunity
Allergen exposure
Airway Inflammatio
n
Altered Aw
FunctionASTHMA
LRTI/ Bronchiolit
is
Airway Inflammatio
n
Altered Aw
Function
Intensification & low clearance
ALLERGIC PATHWAY
NON-ATOPIC/VIRUS PATHWAY
Environment
Genetic Predisposition
Genetic Predisposition