UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL

LET 01425 (TURMA A) – SINTAXE DO TEXTO

PROFESSORA: MARIA JOSÉ BOCORNY FINATTO

FUNCIONAMENTO DA COESÃO ENTRE

PAPERS DE PEDIATRIA EM PORTUGUÊS E INGLÊS

ALANA ZANARDO MAZUR

ANA PAULA SCHIZZI PAZ

PORTO ALEGRE, 2007

 FUNCIONAMENTO DA COESÃO ENTRE
PAPERS DE PEDIATRIA EM PORTUGUÊS E INGLÊS

Alana Zanardo Mazur (alanazmazur@gmail.com)

Ana Paula Schizzi Paz (anapaulaspaz@yahoo.com.br)

RESUMO

O objetivo deste trabalho é fazer uma análise dos padrões de coesão que ocorrem em papers de
pediatria na área de doenças alérgicas em português e em inglês. Para a realização desta análise,
utilizamos um paper em português, publicado no Jornal de Pediatria, e outro em inglês, publicado na
Pediatrics. Por serem de áreas comuns, percebemos que ambos possuem mais semelhanças do que
diferenças nos padrões coesivos. O referencial teórico para a nossa pesquisa foi o livro A Coesão Textual,
de Ingedore Koch.

Palavras-chave: coesão referencial, coesão seqüencial, tema e rema

ABSTRACT

The aim of this paper is to make an analysis of cohesion patterns which occur in pediatrics
papers in the field of allergic diseases in Portuguese and English. In order to accomplish our research, we
used a paper in Portuguese, published in Jornal de Pediatria (Pediatrics Journal), and another in English,
which was published in Pediatrics. Due to their common fields, we realized that both have more
similarities than differences on their cohesive patterns. The theoretical reference for our research was the
book A Coesão Textual (The Text Cohesion), by Ingedore Koch.

Key-words: reference cohesion, sequential cohesion, theme and rheme

1. INTRODUÇÃO

Este artigo tem por objetivo comparar padrões de coesões referenciais e

seqüenciais em artigos da área de pediatria. Os textos utilizados foram escritos
originalmente em português e em inglês. Os mecanismos de coesão utilizados neste
trabalho visam a facilitar a compreensão dos padrões coesivos dos artigos. Os contrastes
e as semelhanças entre as duas línguas também serão analisados, assim como a
construção sintática e os padrões de tema e rema.

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 2. MATERIAIS E MÉTODOS

Utilizamos dois artigos para a execução deste trabalho. Os dois pertencem à área
de medicina pediátrica e tratam de assuntos relacionados a doenças alérgicas, tais como
asma e rinite alérgica. O primeiro deles foi escrito em português e tem o título
Prevalência de sintomas de asma, rinite e eczema atópico entre crianças e adolescentes
brasileiros identificados pelo International Study of Asthma and Allergies in Childhood
(ISAAC) - Fase 3, o qual foi publicado no Jornal de Pediatria, Volume 82, Nº5, em 26
de abril de 2006. Seus autores são Dirceu Sole, Gustavo F. Wandalsen, Inês Cristina
Camelo-Nunes e Charles K. Naspitz, todos da Universidade Federal de São Paulo e
integrantes do grupo brasileiro do ISAAC (International Study of Asthma and Allergies
in Childhood).
Já o segundo foi escrito em inglês e tem o título Sensitization to Common
Allergens and Its Association With Allergic Disorders at Age 4 Years: A Whole
Population Birth Cohort Study, publicado na Pediatrics (Official Journal of the
American Academy of Pediatrics), Volume 108, Nº 2, em dois de agosto de 2001. Este
artigo foi escrito por Syed Hasan Arshad, Syed Mohammed Tariq, Sharon Matthews e
Eluzai Hakim. Todos eles fazem parte do David Hide Asthma and Allergy Research
Centre, St. Mary's Hospital, Newport, Isle of Wight, no Reino Unido. Ambos os artigos
foram retirados dos seus respectivos sites oficiais.
Após a pesquisa realizada para encontrar estes papers, fizemos marcações de
coesão referencial, coesão seqüencial frástica e parafrástica e padrões de tema e rema.
Estes papers estão em anexo ao trabalho, e as marcações dos elementos de coesão
observados contêm legendas indicativas.

3. REFERENCIAL TEÓRICO

3.1 DESCRIÇÃO DOS DADOS

Utilizamos como base teórica para esta pesquisa o livro A Coesão Textual, de
Koch (2004). Esta obra forneceu as ferramentas necessárias para a análise dos papers
em português e em inglês, tais como a classificação da coesão em referencial e

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seqüencial. A partir do que é dito por Koch em relação à coesão referencial, vamos
analisar primeiramente o paper em português. Neste tipo de coesão, observamos a
presença de artigos definidos (a, as, o e os - p.4) e artigos indefinidos (uma – p.6 e um –
p.7). Em alguns momentos, os artigos indefinidos aparecem como uma forma de
anáfora (o clima é um fator importante – p.3). Há a presença de numerais (faixa etária
dos 6 aos 7 anos – p.6), pronomes possessivos (a sua prevalência – p.8) e pronomes
demonstrativos (Este acena para o calor... – p.8). Este pronome demonstrativo exerce
uma função localizadora. Encontramos também pronomes relativos (adolescentes que
habitavam a cidade de Cartagena – p.9) e advérbios pronominais (regiões onde o
estudo foi realizado – p.4). Também na página 4, observamos a presença de um
advérbio pronominal no seguinte trecho: a área geográfica em que o estudo seria
conduzido; em que poderia ser substituído por onde. Foram detectadas várias elipses ao
longo do texto, como, por exemplo, na página 3: Os valores mais altos (...) foram
observados (...) e os mais baixos (...). Há alguns casos de expressões sinônimas; os mais
evidentes são os casos de siglas. Exemplos: eczema atópico (EA) e adolescentes (AD),
ambos na página 3. Não houve ocorrência de catáforas.
Quanto à coesão seqüencial, temos dois tipos: a parafrástica e a frástica. Na
coesão parafrástica, encontramos algumas expressões anunciadores de paráfrases (ou
seja, locais com menores variações de temperatura – p.3 e Em outras palavras – p.7),
recorrência de termos (asma: 55 vezes, eczema: 49 vezes, prevalência: 49 vezes, rinite:
20 vezes), recorrência de estruturas (prevalência de sintomas de eczema – p.3,
prevalência de sintomas de asma, rinite e eczema – p. 4, prevalência de sintomas – p.7;
relação entre a prevalência de asma – p.3, relação significante entre – p.8, relação
significante e negativa entre – p.8) e recorrência de tempo e aspecto verbal,
predominando verbos no presente do indicativo (Tais dados colocam – p.8) pretérito
perfeito (também foi ampla – p.3), pretérito perfeito composto (mostrou ter havido –
p.3), pretérito imperfeito (adolescentes que habitavam – p. 9) e futuro do pretérito (Esse
fato poderia ser explicado – p.8). Além disso, foi encontrada uma grande ocorrência de
voz passiva. Exemplos: foi respondido pelos pais e foram transcritos manualmente,
ambos na página 6.
Encontramos alguns exemplos de coesão seqüencial frástica na parte de
justaposição. São eles: obedecendo, quando possível (...) - p. 6 e No presente estudo –
p. 8. Na parte de conexão, selecionamos os seguintes exemplos: Assim, quanto maior a

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temperatura média anual, maior a prevalência de diagnóstico médico de asma e
eczema e Além disso, não se documentou (...), ambos na página 8.
Na parte de progressão temática, encontramos alguns tipos ao longo do paper em
português. Um deles é a progressão temática com um tema constante, que ocorre no
primeiro parágrafo da introdução, tendo ISAAC como tema constante. Há também uma
progressão por desenvolvimento de um rema subdividido no sexto parágrafo da página
3. No último parágrafo da mesma página, encontramos uma progressão com salto
temático. Já no primeiro parágrafo da página 8, encontramos um caso de progressão
temática linear.
O paper em inglês, na parte de coesão referencial, contém um artigo definido,
(the – em todas as páginas) e artigos indefinidos (a e an – p.12). Há a presença de
numerais (The population-attributable risk of atopy for eczema was 32% (prevalence:
43%; OR: 3.86) – p.11), pronomes possessivos (the presence of typical rash and its
distribution – p.4) e pronomes demonstrativos (Although, in theory, it is possible that a
child may be sensitized solely to an uncommon allergen not included in the battery, this
would be a rare occurrence – p.12). Este pronome demonstrativo exerce uma função
localizadora. Em alguns momentos, this aparece como uma forma de anáfora (House
dust mite sensitization was found to be the most important risk for asthma, with an OR
of 8.07. This is consistent (…) – p.12). Encontramos também pronomes relativos
(except that they had a higher prevalence – p.12) e advérbios pronominais (where R is
the OR for the allergic disease… – p.5). Na página 13, observamos a presença de um
advérbio pronominal no seguinte trecho: Their analysis included studies in which atopy
(...); in which poderia ser substituído por where. Foram detectadas algumas elipses ao
longo do texto, como, por exemplo, na página 2: The highest independent risk for
rhinitis was sensitization to grass pollen, and for eczema, sensitization to peanut. Há
alguns casos de expressões sinônimas; os mais evidentes são os casos de allergic
disease/allergic disorder e skin-prick test/skin-prick testing/skin-prick tested. Não
houve ocorrência de catáforas.
Na coesão parafrástica, encontramos recorrência de termos (atopy: 54 vezes,
children: 76 vezes, prevalence: 29 vezes, risk factor: 14 vezes), recorrência de
estruturas (households with and without dogs, households without dog, households
with dog, households with cat ownership, todos na página 7) e recorrência de tempo e
aspecto verbal, predominando verbos no presente do indicativo (Our birth cohort study
describes the relationship of atopy to symptoms of allergic disease in early childhood –

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p.3), pretérito perfeito (The prevalence of atopy in asthmatic children was 44%. – p.2),
pretérito perfeito composto (a whole-population birth cohort was recruited – p.3) e
futuro do pretérito (Therefore, 46% cases of rhinitis could be attributable to atopy –
p.11). Assim como no paper em português, encontramos uma grande ocorrência de voz
passiva. Exemplos: Overall, 68.4% children who were sensitized to house dust mite had
asthma, eczema, and/or rhinitis, na página 7, e Male preponderance was observed with
most allergens, na página 9.
Encontramos alguns exemplos de coesão seqüencial frástica na parte de
justaposição. São eles: (...) confirming the atopic nature of eczema at this age - p. 9 e
This study was funded by (…) – p. 14. Na parte de conexão, selecionamos os seguintes
exemplos: Although it generally is agreed that (...), na página 13, e Some less common
inhalant allergens, such as tree pollen (…), na página 12.
Na parte de progressão temática, encontramos alguns tipos ao longo do paper em
inglês. Um deles é a progressão temática com um tema constante, que ocorre nas duas
primeiras linhas do primeiro parágrafo da página 3. Na mesma página, no último
parágrafo, há progressão temática linear. No primeiro parágrafo da página 4, há um caso
de progressão com tema derivado. Já no primeiro parágrafo da página 5, encontramos
um caso de progressão por desenvolvimento de um rema subdividido.

3.2 COESÃO EM CONTRASTE

Ao analisarmos os dois papers, notamos que ambos são objetivos, coerentes e

bem estruturados. Embora o paper em inglês apresente vários elementos de
encadeamento entre parágrafos, tivermos a impressão de que eles estão um pouco mais
presentes no paper em português. Na verdade, o paper em inglês apresenta, sim, um
encadeamento entre parágrafos, só que ele se torna mais visível ao longo da leitura,
através do acréscimo de novas informações (manutenção tema-rema), algo que também
ocorre no paper em português. Quanto ao encadeamento entre frases, percebemos que
os dois papers mantêm um equilíbrio, apresentando um perfil parecido. Talvez por
serem papers que pertençam à mesma especialidade da medicina e que foram
publicados em jornais de pediatria é que eles tenham mais semelhanças do que
diferenças, mesmo que cada um deles tenha sido escrito em línguas distintas.

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 Em linhas gerais, constatamos que o encadeamento das frases e parágrafos dos
dois artigos é bastante utilizado. Esta “costura” que eles apresentam deixou-os bastante
coesos e coerentes, pois eles não apenas retomam elementos, mas também trazem novas
informações ao longo das frases e parágrafos, algo que faz a leitura chegar a algum
lugar, ou seja, ela avança e não é sempre repetitiva. Apesar disso, é possível fazer
algumas modificações no que diz respeito às expressões referenciais ao longo dos
textos, como substituição, ou talvez omissão de algumas delas, cuidando para não
alterar o recurso estilístico utilizado nos textos.

4. SÍNTESE DAS OBSERVAÇÕES E ALGUMAS CONSIDERAÇÕES

Alguns aspectos que chamaram a nossa atenção durante a realização deste

trabalho foram as terminologias utilizadas em cada uma das línguas, assim como os
conectores. No paper em inglês, encontramos muitas ocorrências da expressão allergic
disease e allergic disorder sendo utilizadas como se fossem sinônimos. Sabemos que a
tradução de disease e disorder para o português pode se tornar um pouco problemática
em alguns casos. Nesta situação, optaríamos por doenças alérgicas, e não por distúrbios
alérgicos.
Notamos também uma grande incidência do termo prevalência nos dois papers,
mas a maior ocorrência foi no paper em português (49 vezes vs. 29 vezes no inglês).
Outro detalhe que chamou a nossa atenção foi a maior variedade de conectores no paper
em português. Um fato que corrobora esta constatação é que não encontramos nenhum
elemento indicador de paráfrase no paper em inglês, enquanto que no paper em língua
portuguesa isto ocorre em alguns momentos.

5. REFERÊNCIAS BIBLIOGRÁFICAS

1. KOCH, Ingedore Grunfeld Villaça. A Coesão Textual. São Paulo: Contexto,

2005.

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 6. ANEXOS

PAPER 1
Prevalência de sintomas de asma, rinite e eczema atópico entre crianças e
adolescentes brasileiros identificados pelo International Study of Asthma and
Allergies in Childhood (ISAAC) - Fase 3, escrito por Dirceu Sole, Gustavo F.
Wandalsen, Inês Cristina Camelo-Nunes e Charles K. Naspitz, todos da Universidade
Federal de São Paulo e integrantes do grupo brasileiro do ISAAC (International Study
of Asthma and Allergies in Childhood). Jornal de Pediatria, vol. 82, nº5, Porto Alegre,
abril 2006.
Disponível em:
http://www.jped.com.br/conteudo/06-82-05-341/port.asp?cod=1521
Acesso em: 05 de novembro de 2007.

PAPER 2

Sensitization to Common Allergens and Its Association With Allergic

Disorders at Age 4 Years: A Whole Population Birth Cohort Study, escrito por Syed
Hasan Arshad, Syed Mohammed Tariq, Sharon Matthews e Eluzai Hakim, todos do
David Hide Asthma and Allergy Research Centre, St. Mary's Hospital, Newport, Isle of
Wight, Reino Unido. Pediatrics (Official Journal of the American Academy of
Pediatrics), vol. 108, nº 2, agosto 2001.
Disponível em:
http://pediatrics.aappublications.org/cgi/content/full/108/2/e33
Acesso em: 05 de novembro de 2007.

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- Coesão Referencial

- Coesão Seqüencial Frástica

- Coesão Seqüencial Paráfrástica

- Progressão Temática (tema e rema)

PREVALÊNCIA DE SINTOMAS DE ASMA, RINITE E ECZEMA ATÓPICO ENTRE

CRIANÇAS E ADOLESCENTES BRASILEIROS IDENTIFICADOS PELO
INTERNATIONAL STUDY OF ASTHMA AND ALLERGIES IN CHILDHOOD
(ISAAC) - FASE 3

Prevalence of symptoms of asthma, rhinitis, and atopic eczema among

Brazilian children and adolescents identified by the International Study of
Asthma and Allergies in Childhood (ISAAC) - Phase 3

Dirceu Solé1, Gustavo F. Wandalsen2, Inês Cristina Camelo-Nunes3,

Charles K. Naspitz1, ISAAC – Grupo Brasileiro4

Resumo

Objetivo: Determinar a prevalência de sintomas relacionados à asma, rinite e eczema

atópico em escolares (EC) entre 6 e 7 anos e adolescentes (AD) entre 13 e 14 anos, residentes
1
Professor titular, Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM),
São Paulo, SP.
2
Mestre, Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), São Paulo,
SP.
3
Doutora, Pesquisadora Associada, Universidade Federal de São Paulo - Escola Paulista de Medicina
(UNIFESP-EPM), São Paulo, SP.
4
ISAAC – Grupo Brasileiro: Maria Socorro Cardoso (Manaus, Amazonas); Bruno A. Paes Barreto
(Belém, Pará); Vera Dantas (Natal, Rio Grande do Norte); Murilo Britto (Recife, Pernambuco);
Almerinda R. Silva, Emanuel Sarinho (Caruaru, Pernambuco); Francisco J. Passos Soares, Mércia
Lamenha Medeiros Santos (Maceió, Alagoas); Jackeline Motta, Ricardo Gurgel (Aracaju, Sergipe); Leda
Solano de Freitas (Feira de Santana, Salvador e Vitória da Conquista, Bahia); Wellington Borges
(Brasília, Distrito Federal); Paulo Augusto Camargos (Belo Horizonte, Minas Gerais); Fábio Kuschnir,
Antônio José Ledo Alves da Cunha (Nova Iguaçu, Rio de Janeiro); Antônio Carlos Pastorino (São Paulo -
Oeste, São Paulo); Karyn Chacon de Mello (São Paulo - Sul, São Paulo); Cassia Gonzalez, Neusa F
Wandalsen (Santo André, São Paulo); Carlos Riedi, Nelson A. Rosário Filho (Curitiba, Paraná); Cláudia
Benhardt (Itajaí, Santa Catarina); Arnaldo Porto (Passo Fundo, Rio Grande do Sul); Gilberto B. Fischer
(Porto Alegre, Rio Grande do Sul); Vitor E. Cassol (Santa Maria, Rio Grande do Sul).

Fonte financiadora: Schering-Plough imprimiu os questionários escritos.

Artigo submetido em 19.01.06, aceito em 26.04.06

Como citar este artigo: Solé D. Wandalsen GF, Camelo-Nunes IC, Naspitz CK: ISAAC – Grupo
Brasileiro. Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian children and
adolescents identified by the International Study of Asthma and Allergies in Childhood (ISAAC) – Phase
3. J Pediatr (Rio J). 2006;82:341-6.

9
em 20 cidades brasileiras, empregando o questionário escrito padronizado do ISAAC, e avaliar
a sua associação com a latitude, altitude e temperatura média anual dos centros de residência.
Métodos: Participaram do estudo EC e AD das cinco regiões do Brasil, totalizando
23.422 questionários ISAAC respondidos pelos pais de EC e 58.144 pelos próprios AD. Os
índices de latitude, altitude e temperatura média anual foram obtidos do Instituto Brasileiro
de Geografia e Estatística.
Resultados: As prevalências médias para os EC e AD, respectivamente, foram:
asma ativa, 24,3 e 19,0%; rinoconjuntivite, 12,6 e 14,6%; e eczema flexural, 8,2 e 5,0%.
Associação significante e negativa foi observada entre latitude e prevalência de asma
diagnosticada por médico para os EC, asma grave, asma diagnosticada por médico, eczema e
eczema flexural para os AD. Não houve associação com a altitude dos centros.
Conclusões: A prevalência de asma, rinite e eczema atópico no Brasil foi variável.
Valores mais altos, sobretudo de asma e eczema, foram observados nos centros localizados
mais próximos ao Equador.

J Pediatr (Rio J). 2006;82(5):341-6: Crianças, asma, eczema atópico, rinite,

rinoconjuntivite alérgica, prevalência, ISAAC, epidemiologia.

Abstract

Objective: To determine the prevalence of symptoms of asthma, rhinitis, and atopic

eczema among schoolchildren aged 6 to 7 years and adolescents aged 13 to 14 years in 20
Brazilian cities by using standardized ISAAC written questionnaire, and to assess the
association of this prevalence with latitude, altitude and average annual temperature of
collaborating centers.
Methods: Schoolchildren and adolescents from five Brazilian regions participated in
the study, totaling 23,422 ISAAC questionnaires answered by schoolchildren’s parents and
58,144 questionnaires answered by adolescents. The value for latitude, altitude and average
annual temperature were obtained from the Brazilian Institute of Geography and Statistics.
Results: The mean prevalence rates among schoolchildren and adolescents were
respectively 24.3 and 19.0% for active asthma, 12.6 and 14.6% for rhinoconjunctivitis; and 8.2
and 5.0% for atopic eczema. A significant negative association was observed between latitude
and physician-diagnosed asthma among schoolchildren, severe asthma, physician-diagnosed
asthma, eczema and atopic eczema among adolescents. No association with altitude was found.
Conclusions: The prevalence of asthma, rhinitis and atopic eczema in Brazil varies
considerably. Higher prevalence rates, especially of asthma and eczema, were found at centers
located closer to the equator.

J Pediatr (Rio J). 2006;82(5):341-6: Children, asthma, atopic eczema, rhinitis,

allergic rhinoconjunctivitis, prevalence, ISAAC, epidemiology.

Introdução

O International Study of Asthma and Allergies in Childhood (ISAAC) foi

um marco importante entre os estudos epidemiológicos sobre prevalência de asma e
doenças alérgicas em crianças e adolescentes. O ISAAC foi idealizado para avaliar a
prevalência de asma e doenças alérgicas em crianças em diferentes partes do mundo,
empregando método padronizado (questionário escrito auto-aplicável e/ou vídeo
questionário)1,2. O questionário escrito (QE) auto-aplicável do ISAAC foi o
instrumento mais empregado, por ser de fácil compreensão, baixo custo e independente
da aplicação por entrevistador treinado1,2.

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 A população-alvo deveria ser constituída por escolares (EC) dentro de
determinada área geográfica (centro do ISAAC) de duas faixas etárias: 13 a 14 anos e
6 a 7 anos. A participação de EC na faixa etária dos 6 aos 7 anos, embora
recomendada, não era compulsória.
A amostra em estudo deveria incluir todas as crianças da faixa etária em
estudo, de uma amostra randomizada de escolas.
Uma vez definida a área geográfica e as escolas a serem incluídas, cada
centro de investigação deveria selecionar, com base nos registros escolares,
adolescentes (AD) com idades entre 13 e 14 anos, os quais seriam convidados a
responder o QE. A seleção do grupo adicional de 6 a 7 anos seguiria os mesmos
critérios, e os pais dessas crianças seriam convidados a responder o QE.
Na primeira fase do ISAAC, foram entrevistados 463.801 AD (13 e 14 anos)
oriundos de 155 centros de 56 países (Europa, Ásia, África, Américas do Norte e Sul e
Oceania) bem como 257.800 EC (6 e 7 anos) de 91 centros de 38 países das mesmas
regiões, exceto a África2-5.
A análise dos resultados obtidos ao final da fase 1, referentes à asma,
mostrou ter havido ampla variação, nas duas faixas etárias, com relação à prevalência
de sibilos nos últimos 12 meses (asma ativa), variando de 4,1 a 32,1% para os EC e de
2,1 a 32,2% para os AD2,3. Os valores mais baixos foram documentados na República
da Geórgia e Estônia, e os mais elevados, na Austrália2,3. Em ambas as faixas
etárias, o Brasil ficou entre os países com maiores prevalências3,6.
Com relação à rinite, a variação na prevalência de sintomas relacionados
também foi ampla4. A prevalência de sintomas nasais na ausência de resfriados no
último ano variou de 1,5 a 41,8% entre os EC e de 3,2 a 66,6% entre os AD4. Já a
prevalência de sintomas nasais associados a sintomas oculares (rinoconjuntivite
alérgica) variou de 0,8 a 14,9% para os EC e de 1,4 a 39,7% para os AD4. De modo
geral, houve concordância entre as prevalências de asma e de rinite: centros com baixa
prevalência de asma (inferior a 5%: Indonésia, Albânia, Romênia, Geórgia e Grécia)
tiveram baixa prevalência de rinite, e aqueles com prevalência de asma muito elevada
(superior a 30%: Austrália, Nova Zelândia, e Reino Unido) também apresentaram alta
prevalência de rinite3,4.
Os resultados sobre eczema atópico (EA) foram os que apresentaram maior
amplitude de variação (até 60 vezes), oscilando entre 0,3 e 20,5%2,5. Os valores mais
altos (acima de 15%) foram observados em centros urbanos da África, Austrália,
Norte e Oeste da Europa, e os mais baixos (inferiores a 5%) na China, Leste Europeu e
Ásia Central2,5.
A partir da obtenção desses dados, vários outros estudos foram realizados
com o intuito de verificar a relação entre a prevalência de asma e das doenças
alérgicas e possíveis fatores de risco. A imunização de rotina7, as notificações de
tuberculose8,9 e o padrão alimentar10 foram alguns dos fatores estudados. Em
estudo recente, Weiland et al. avaliaram a possível relação entre latitude, umidade
relativa do ar e variação anual da temperatura dos centros participantes do ISAAC fase
1 e a prevalência de asma e de doenças alérgicas11. Verificaram relação negativa
entre esses parâmetros e a prevalência de sintomas de asma. Por outro lado, a
prevalência de sintomas de eczema relacionou-se positivamente com a latitude e
negativamente com a temperatura média ambiental, ou seja, locais com menores
variações de temperatura foram associados a maiores níveis de prevalência11. Em
conclusão, esses autores apontam que o clima é um fator importante e capaz de
interferir na prevalência de asma e EA11.

11
 Na América Latina, ao final da primeira fase do ISAAC, Mallol et al.
documentaram relação significante entre prevalência e gravidade da asma e a latitude
dos centros participantes avaliados12. Alguns desses centros eram brasileiros.
O número reduzido de centros brasileiros participantes da fase 1, aliado à
ausência de centros em algumas regiões do país, impediu a realização dessa
avaliação6,13,14. Este estudo teve por objetivo avaliar a relação entre prevalência de
sintomas de asma, rinite e eczema e a latitude dos diferentes centros brasileiros
participantes ou não do ISAAC fase 3.

Casuística e métodos

Vinte e um centros de 20 cidades brasileiras participaram deste estudo. Os

alunos avaliados foram selecionados conforme o preconizado pelo protocolo
ISAAC1,15. Em cada centro, uma vez estipulada a área geográfica em que o estudo
seria conduzido, solicitou-se à Secretaria Municipal de Educação a relação das
escolas nela localizadas. A seguir, procedeu-se sorteio (tabela de números aleatórios)
das que participariam do estudo. As cidades, estados e regiões onde o estudo foi
realizado foram os seguintes: Manaus, Amazonas, Norte (N); Belém, Pará, N; Natal,
Rio Grande do Norte, Nordeste (NE); Recife, Pernambuco, NE; Caruaru, Pernambuco,
NE; Maceió, Alagoas, NE; Aracaju, Sergipe, NE; Feira de Santana, Bahia, NE;
Salvador, Bahia, NE; Vitória da Conquista, Bahia, NE; Brasília, Distrito Federal,
Cento-Oeste (CO); Belo Horizonte, Minas Gerais, Sudeste (SE); Nova Iguaçu, Rio de
Janeiro, SE; São Paulo (Oeste e Sul), São Paulo, SE; Santo André, São Paulo, SE;
Curitiba, Paraná, Sul (S); Itajaí, Santa Catarina, S; Passo Fundo, Rio Grande do Sul,
S; Porto Alegre, Rio Grande do Sul, S; Santa Maria, Rio Grande do Sul, S. Parte
desses centros tiveram os dados aprovados pelo ISAAC International Data Center e
foram considerados como centros oficiais (Tabelas 1 e 2). O estudo foi aprovado pelos
respectivos comitês de ética, e todos assinaram o termo de consentimento livre e
esclarecido.

12
13
 Optaram por não avaliar a faixa etária dos 6 aos 7 anos (não compulsória) os
seguintes centros: Belém, Recife, Caruaru, Brasília, Belo Horizonte, Curitiba, Passo Fundo,
Porto Alegre e Santa Maria.
O estudo teve início em 2002 e foi concluído em 2003, conforme recomendação do
ISAAC, obedecendo, quando possível, o mesmo período de coleta dos dados em todos os
centros. Na Região Sul, onde as estações são mais bem definidas, foi realizado antes da
primavera, evitando-se assim possíveis influências sazonais.
Após a definição da amostra, em cada uma das cidades, o QE ISAAC, previamente
traduzido e validado (cultura brasileira)14,16,17, foi respondido pelos pais ou responsáveis
dos EC de 6 e 7 anos de idade (n = 23.422) e pelos próprios AD nas salas de aula (n =
58.144, 13-14 anos de idade). Os dados obtidos foram transcritos manualmente para banco
de dados fornecido pelos coordenadores gerais do protocolo ISAAC.
Do módulo asma, foram consideradas as questões sobre sintomas, gravidade e
diagnóstico médico de asma, a saber: sibilos nos últimos 12 meses (asma ativa); sibilos

14
intensos capazes de limitarem a fala nos últimos 12 meses (asma grave); asma alguma vez na
vida (asma diagnosticada)1,3.
Do módulo rinite, foram consideradas as questões referentes a sintomas de rinite,
rinoconjuntivite alérgica e de formas graves de rinite: espirros, coriza e obstrução nasal
alguma vez nos últimos 12 meses (rinite); problemas nasais associados a olhos com prurido e
lacrimejamento nos últimos 12 meses (rinoconjuntivite alérgica); problema nasal
interferindo com atividade diária (rinite grave)1,4.
Das questões sobre eczema, foram avaliadas as referentes a sintomas e gravidade:
rash cutâneo que aparece e desaparece nos últimos 12 meses (eczema); este mesmo rash
cutâneo em locais característicos (eczema flexural); rash cutâneo e pruriginoso que interfere
com o sono nos últimos 12 meses (eczema grave)1,5.
Os valores de latitude, altitude e temperatura média anual de cada um dos centros
participantes foram obtidos junto ao Instituto Brasileiro de Geografia e Estatística18.
Para análise dos dados, foram empregados testes não-paramétricos: coeficiente de
correlação de Spearman (RS) e o cálculo do intervalo de confiança de 95% (IC95%). Em
todos os testes, fixou-se em 5% o nível de rejeição para a hipótese de nulidade.

Resultados

Entre os EC, as prevalências médias foram: asma ativa, 24,3%, com valores mais
elevados em São Paulo - Oeste e Vitória da Conquista; asma grave, 6,1%, e os valores mais
elevados em São Paulo - Oeste e Natal; asma diagnosticada por médico, 10,3% (Manaus e
Natal); rinite, 25,7% (Bahia, Feira de Santana, Salvador e Vitória da Conquista);
rinoconjuntivite, 12,6% (Bahia); rinite grave, 17,1% (Bahia); eczema, 11,5% (Nova Iguaçu,
Natal e Aracaju); eczema flexural, 8,2% (Natal, Aracaju e Nova Iguaçu); e eczema grave,
5,0% (Natal e Aracaju) (Tabela 1).
Entre os AD, as prevalências médias foram: asma ativa, 19,0%, com valores mais
elevados em Salvador e Vitória da Conquista; asma grave, 4,7%, com valores mais elevados
em Vitória da Conquista e Aracaju; asma diagnosticada por médico, 13,6% (Belém, Porto
Alegre e Caruaru); rinite, 29,6% (Belém, Salvador e Vitória da Conquista); rinoconjuntivite
alérgica, 14,6% (Belém, Salvador e Vitória da Conquista); rinite grave, 17,4% (Bahia);
eczema, 8,9% (Belém, Aracaju e Salvador); eczema flexural, 5,0% (Aracaju, Vitória da
Conquista e Natal); e eczema grave, 4,4% (Bahia e Aracaju) (Tabela 2).
O estudo da associação entre a latitude dos centros e a prevalência de sintomas e
de gravidade de asma, rinite e EA mostrou significância estatística e negativa para asma
diagnosticada por médico (RS = -0,622; IC95% -0,885 a -0,056; p = 0,031) para os EC,
asma grave (RS = -0,565; IC95% -0,806 a -0,163; p = 0,008), asma diagnosticada por
médico (RS = -0,479; IC95% -0,761 a -0,046; p = 0,028), eczema (RS = -0,718; IC95% -
0,881 a -0,405; p = 0,0002) e eczema flexural (RS = -0,530; IC95% -0,788 a -0,115; p =
0,013) para os AD. Em outras palavras, quanto menor a latitude (maior a proximidade do
Equador), maior a prevalência de respostas afirmativas a essas questões.
Com relação à temperatura média anual, houve associação significante e positiva
com o diagnóstico de asma pelo médico (RS = 0,459; IC95% 0,02 a 0,749; p = 0,037), assim
como com eczema (RS = 0,541; IC95% 0,129 a 0,794; p = 0,011) entre os AD. Assim,
quanto maior a temperatura média anual, maior a prevalência de diagnóstico médico de
asma e eczema.

15
 Discussão

As taxas de prevalência de asma e doenças alérgicas mais elevadas foram

observadas nos centros das Regiões Norte e Nordeste, exceção feita à de asma, que também
foi observada na Região Sul. O aumento em três vezes do número de centros
participantes em relação ao ISAAC fase 1 6,13,14, a presença de centros das cinco
regiões do país e o nível elevado de retorno dos QE distribuídos2,3 permitem-nos aceitar
a amostra aqui avaliada como representativa do Brasil.
O ISAAC fase 1 na América Latina concentrou dados de 17 centros de nove países e
reuniu 36.264 EC e 52.549 AD. A prevalência de asma e sintomas relacionados mostrou-se
alta e variável, como a descrita para países industrializados ou regiões desenvolvidas do
mundo12. A prevalência de asma ativa variou entre 8,6 e 32,1% para os EC e entre 6,6 e
27,0% para os AD, e os níveis mais elevados de prevalência foram observados nos centros
próximos à linha do Equador. Além disso, não se documentou relação entre exposição à
poluição atmosférica, exposição precoce a infecções respiratórias e gastrointestinais e a
prevalência de asma12. Tais dados colocam em cheque a validade da hipótese da higiene
para a América Latina como um todo12.
Weiland et al. investigaram a relação entre o clima (latitude, amplitude de variação
anual da temperatura exterior (diferença entre a máxima anual e a mínima anual) e teor de
umidade intradomiciliar) e a prevalência de doenças atópicas utilizando os dados do ISAAC
fase 1 (146 centros). Em relação aos sintomas de asma, verificaram relação inversa entre
altitude, variação anual de temperatura e umidade relativa intradomiciliar11. A análise de
parte desses dados mostrou, para países do Oeste Europeu, ter havido aumento da
prevalência dos sintomas de asma em associação ao aumento da umidade anual
intradomiciliar estimada11. No presente estudo, verificamos relação significante e negativa
para asma diagnosticada por médico entre os EC e de asma diagnosticada por médico e de
asma grave entre os AD. Esse fato poderia ser explicado por diferenças na conduta e
denominação da doença ao longo do país. Entretanto, ao considerarmos a prevalência de
formas graves, verificamos o mesmo comportamento para os AD. Tal fato seguramente
reforça a maior prevalência da asma ao Norte do país. Esse dado é corroborado pela
relação significante e positiva observada entre temperatura média e prevalência de asma
diagnosticada.
Com relação à rinite e sintomas relacionados, não documentamos relação
significante entre a sua prevalência e as variáveis analisadas para as duas faixas etárias, à
semelhança de outros estudos11. Por outro lado, houve relação significante e negativa entre
a prevalência de eczema e de eczema flexural e a latitude dos centros. Valores mais altos
ocorreram ao Norte do país, assim como de eczema em locais com maiores temperaturas
médias. A exposição a temperaturas mais elevadas e constantes, o alto teor de umidade
ambiental, a maior exposição da pele pelo uso de roupas mais leves, aliados à maior
freqüência de afecções dermatológicas nessa região poderiam ser algumas das razões para
justificar o aumento de prevalência de eczema, denominação que pode albergar vários
quadros dermatológicos. Todavia, o mesmo comportamento observado com a prevalência
de eczema flexural, característico de EA, põe em questionamento o apontado
anteriormente. Este acena para o calor e a umidade como fatores de risco para EA.
Diferente do observado no presente estudo, Weiland et al. documentaram aumento da
prevalência de eczema e sintomas relacionados, em ambas as faixas etárias, com o aumento
da latitude e diminuição com o aumento da amplitude da temperatura média anual externa,
assim como com o aumento da umidade relativa intradomiciliar do ar11.

16
 Nnoruka et al., ao avaliarem crianças nigerianas com EA, identificaram intolerância
ao calor, transpiração excessiva e umidade intradomiciliar como fatores agravantes para o
EA19, à semelhança de outros20. Já Fernández-Mayoralas et al. documentaram influência
da poluição atmosférica sobre a prevalência de EA em adolescentes que habitavam a cidade
de Cartagena (Espanha)21. Os autores verificaram níveis elevados de prevalência de EA e
de formas graves entre os que estavam expostos a níveis mais elevados de poluição21. No
presente estudo, não observamos qualquer influência da poluição atmosférica sobre a
prevalência de EA, sobretudo se considerarmos os centros de São Paulo e Santo André, onde
são tradicionalmente documentados os maiores níveis de poluição atmosférica do país.
Em conclusão, com o aumento do número de centros participantes deste estudo no
Brasil, pudemos encontrar, à semelhança do observado na América Latina ao final da fase 1,
maior freqüência de diagnóstico médico de asma, para EC e AD, e formas mais graves de
asma, eczema e eczema flexural entre os AD habitantes de centros mais próximos à linha do
Equador. A identificação de fatores de risco aos quais os habitantes desses centros
possam estar expostos é passo fundamental para a possível elucidação da etiopatogenia da
asma e das doenças alérgicas nessas localidades.

Referências

1. Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, et al. International
study of asthma and allergies in childhood (ISAAC): rationale and methods. Eur Respir J.
1995;8: 483-91.
2. Worldwide variation in prevalence of symptoms of asthma, allergic
rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and
Allergies in Childhood (ISAAC) Steering Committee. Lancet. 1998;351:1225-32.
3. Worldwide variations in the prevalence of asthma symptoms: the International Study
of Asthma and Allergies in Childhood (ISAAC). Eur Respir J. 1998;12:315-35.
4. Strachan D, Sibbald B, Weiland S, Ait-Khaled N, Anabwani G, Anderson HR, et al.
Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children:
the International Study of Asthma and Allergies in Childhood (ISAAC). Pediatr Allergy
Immunol. 1997;8:161-76.
5. Williams H, Robertson C, Stewart A, Ait-Khaled N, Anabwani G, Anderson R, et al.
Worldwide variations in the prevalence of symptoms of atopic eczema in the International
Study of Asthma and Allergies in Childhood. J Allergy Clin Immunol. 1999;103:125-38.
6. Solé D, Yamada E, Vanna AT, Werneck G, Solano de Freitas L, Sologuren MJ, et al.
International Study of Asthma and Allergies in Childhood (ISAAC): prevalence of asthma
and asthma-related symptoms among Brazilian schoolchildren. J Invest Allergol Clin
Immunol. 2001;11:123-8.
7. Anderson HR, Poloniecki JD, Strachan DP, Beasley R, Bjorksten B, Asher MI, et al.
Immunization and symptoms of atopic disease in children: results from the International
Study of Asthma and Allergies in Childhood. Am J Public Health. 2001;91:1126-9.
8. von Mutius E, Pearce N, Beasley R, Cheng S, von Ehrenstein O, Bjorksten B, et al.
International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and
eczema. Thorax. 2000;55:449-53.
9. Shirtcliffe P, Weatherall M, Beasley R, International Study of Asthma and Allergies
in Childhood. An inverse correlation between estimated tuberculosis notification rates and
asthma symptoms. Respirology. 2002;7:153-5.
10. Ellwood P, Asher MI, Bjorksten B, Burr M, Pearce N, Robertson CF. Diet and
asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological

17
analysis of the International Study of Asthma and Allergies in Childhood (ISAAC) data.
ISAAC Phase One Study Group. Eur Respir J. 2001;17:436-43.
11. Weiland SK, Husing A, Strachan DP, Rzehak P, Pearce N, ISAAC Phase One Study
Group. Climate and the prevalence of symptoms of asthma, allergic rhinitis, and atopic
eczema in children. Occup Environ Med. 2004;61:609-15.
12. Mallol J, Solé D, Asher I, Clayton T, Stein R, Soto-Quiroz M. Prevalence of asthma
symptoms in Latin America: the International Study of Asthma and Allergies in Childhood
(ISAAC). Pediatr Pulmonol. 2000;30:439-44.
13. Solé D, Camelo-Nunes IC, Vanna AT, Yamada E, Werneck F, de Freitas LS, et al.
Prevalence of rhinitis and related-symptoms in schoolchildren from different cities in Brazil.
Allergol Immunopathol (Madr). 2004;32:7-12.
14. Yamada E, Vanna AT, Naspitz CK, Solé D. International Study of Asthma and
Allergies in Childhood (ISAAC): validation of the written questionnaire (eczema component)
and prevalence of atopic eczema among Brazilian children. J Invest Allergol Clin Immunol.
2002;12:34-41.
15. Ellwood P, Asher MI, Beasley R, Clayton TO, Stewartt AW, ISAAC Steering
Committee. The international study of asthma and allergies in childhood (ISAAC): phase
three rationale and methods. Int J Tuberc Lung Dis. 2005;9:10-6.
16. Solé D, Vanna AT, Yamada E, Rizzo MC, Naspitz CK. International Study of
Asthma and Allergies in Childhood (ISAAC) written questionnaire: validation of the asthma
component among Brazilian children. J Invest Allergol Clin Immunol. 1998;8:376-82.
17. Vanna AT, Yamada E, Arruda LK, Naspitz CK, Sole D. International Study of
Asthma and Allergies in Childhood: validation of the rhinitis symptom questionnaire and
prevalence of rhinitis in schoolchildren in São Paulo, Brazil. Pediatr Allergy Immunol.
2001;12:95-101.
18. Instituto Brasileiro de Geografia e Estatística [site na Internet].
http://www.ibge.gov.br/home/geociencias/geografia. Acesso: 20/09/2005.
19. Nnoruka EM. Current epidemiology of atopic dermatitis in south-eastern Nigeria.
Int J Dermatol. 2001;43:739-44.
20. McNally NJ, Williams HC, Phillips DR. Atopic eczema and the home environment.
Br J Dermatol. 2001;145:730-6.
21. Fernández-Mayoralas DM, Caballero JMM, Alvarez LGM. Prevalencia de la
dermatitis atópica en escolares de Cartagena y su relación con el sexo y la contaminación. An
Pediatr (Barc). 2004;60:555-60.

Correspondência:
Dirceu Solé
Rua Mirassol 236, 72, Vila Clementino
CEP 04044-010 - São Paulo, SP
E-mail: dirceus@ajato.com.br

18
- Coesão Referencial

- Coesão Seqüencial Frástica

- Coesão Seqüencial Paráfrástica

- Progressão Temática (tema e rema)

SENSITIZATION TO COMMON ALLERGENS AND ITS ASSOCIATION

WITH ALLERGIC DISORDERS AT AGE 4 YEARS:
A WHOLE POPULATION BIRTH COHORT STUDY
Syed Hasan Arshad, DM, MRCP, Syed Mohammed Tariq, MRCP, Sharon Matthews,
SRN, and Eluzai Hakim, MRCP

ABSTRACT

Background. Atopy is defined as the genetic propensity to develop

immunoglobulin E antibodies in response to exposure to allergens and assessed by skin
prick test responses to common allergens. Although it is generally agreed that atopy
is an important risk factor for allergic diseases such as asthma, rhinitis, and eczema,
the extent to which atopy accounts for these diseases is controversial.

Objective. We aim to describe the prevalence of sensitization to common

allergens and investigate the degree of association of atopy (as defined by positive skin
prick test to 1 or more common allergens) to asthma, rhinitis, and eczema in a birth
cohort at the age of 4 years.

Methods. A birth cohort of 1456 children was recruited over a 14-month

period (1989-1990). These children have been seen previously at 1 and 2 years of age.
At 4 years, 1218 children were reviewed and an interview was administered or postal
questionnaire was completed for the presence of allergic diseases (asthma, rhinitis, and
eczema). Additionally, in 981 children, skin prick tests with a battery of 12
common allergens were performed. Allergens were house dust mite
(Dermatophagoides pteronyssimus), grass pollen mix, cat, dog, Alternaria alternata,
Cladosporium herbarum, cow's milk, hen's egg, soya, cod, wheat, and peanut. A mean
wheal diameter of at least 3 mm greater than the negative control was taken as
positive. This analysis is confined to the 981 (67% of the original population) who also
had skin prick tests to the standard battery. X² tests were used to test the univariate
association between each allergic disease and positive skin test. Multiple logistic
regression analysis was performed to obtain the adjusted odds ratios (ORs) and 95%
confidence intervals (CIs) for the independent effect of sensitization to each allergen on
allergic disease, adjusting for the effect of sensitization to other allergens. To ascertain
how much of allergic disease is attributable to atopy, we estimated the population-
attributable risk. This was calculated with the formula: P(R - 1) where R is the OR for

19
the allergic disease under consideration and P is the proportion of atopy in children
with that disease.

Results. Children who were skin prick-tested at 4 years were similar in most
characteristics to the rest of the population, except that they had a higher prevalence of
allergic disease. Allergic disorders (asthma, rhinitis, and eczema) were present in
276 (28.1%) of 981. One hundred ninety-two (19.6%) children were atopic (positive
reaction to 1 or more allergens). Sensitization to inhalant allergens was relatively
common (19.2%) as compared with food allergens (3.5%). House dust mite (11.9%),
grass pollen (7.8%), and cat (5.8%) were the most common positive reactions. A test
to the 4 most common allergens (house dust mite, grass pollen, cat, and A
alternata) could detect 94% of the atopic children. Sensitization to the 4 most
common allergens was strongly associated with the presence of allergic disorders.
There was a graded effect with the potent allergens, such as house dust mite, having
the greatest impact. For example, 50% of children sensitized to house dust mite had
asthma as opposed to 44% sensitized to cat, 42% sensitized to grass pollen, and 32%
sensitized to A alternata. Overall, 68.4% of children sensitized to house dust mite had
asthma, eczema, and/or rhinitis. The respective figures for grass pollen, cat, and A
alternata were 64.9%, 66.7%, and 57.4%. The proportion of children sensitized to
cat was not higher in households with cat ownership (households with cats: 5.1%
[19/374]; households without cats: 6.2% [36/580]; not significant [NS]). Similarly, no
difference was seen in sensitization to dog in households with and without dogs
(households with dogs: 1.8% [5/282]; households without dogs: 2.8% [19/673]; NS).
Boys were atopic more often than girls at this age (male: 112 of 497 [22.5%] vs female:
80 of 484 [16.5%]; OR: 1.47, 95% CI: 1.07-2.02). Male preponderance was observed
with most allergens, but this was statistically significant only for house dust mite (male:
75/497 [15.1%] vs female: 42/484 [8.7%]; OR: 1.87; CI: 1.25-2.79) and grass pollen
(male: 51/497 [10.3%] vs female: 26/484 [5.4%]; OR: 2.01; CI: 1.23-3.29).
An independent effect of allergen sensitization on asthma was observed only
with house dust mite with an OR of 8.07 (CI: 4.60-14.14). The highest independent
risk for rhinitis was sensitization to grass pollen (OR: 5.02; CI: 2.21-11.41), and for
eczema, sensitization to peanut (OR: 4.65; CI: 1.02-21.34).
The majority of children (98/192) were sensitized to >1 allergen. A graded
effect was observed with the risk of allergic disease in the child increasing with the
number of positive skin prick test reactions. This effect was consistent throughout the
spectrum of allergic diseases (asthma, eczema, and rhinitis). Nearly 80% of the
children with positive skin test reactions to 4 or more allergens had asthma, eczema,
and/or rhinitis compared with 20%, if they were nonatopic.
The prevalence of atopy in asthmatic children was 44%. With an OR of
4.56, the population-attributable risk was calculated to be 35%. Fifty-five percent of
children with rhinitis were atopic, and the OR of rhinitis was 5.85. Therefore, 46% of
the cases of rhinitis could be attributable to atopy. The population-attributable risk
of atopy for eczema was 32% (the prevalence of atopy in children with eczema: 43%;
and the OR for the development of eczema: 3.86).

Conclusion. Atopy is closely associated with asthma, rhinitis, and eczema at 4

years of age, with a direct and linear relationship. However, the proportion of cases
of allergic disease attributable to atopy is <50%. We propose a model for the
development of allergic disorders, where 30% to 40% of cases of allergic disease

20
(asthma, eczema, and rhinitis) in early childhood are attributable to atopy and 60% to
70% of cases could be accounted for by organ-based and other factors.

Key words: atopy, allergic diseases, asthma, eczema, rhinitis, skin-prick test.

Asthma, rhinitis, and eczema often are termed allergic or atopic diseases.
These terms are used loosely and interchangeably. Allergy is defined as an
exaggerated (immune-mediated) response to various proteins (allergens). Atopy is
defined as the genetic propensity to develop immunoglobulin E (IgE) antibodies in
response to exposure to allergen and is assessed by positive skin-prick test responses,
which may contribute to the development of the clinical disorder (phenotype). The term
"atopy" should be used only when there is evidence of IgE-mediated allergy. Some
allergic disorders clearly are predominantly atopic, such as hay fever or peanut
allergy. However, diseases such as asthma and perennial rhinitis may or may not be
atopic. Indeed, even in atopic allergic diseases, an IgE-initiated mechanism is part of
a complex cascade of cellular and humoral immune responses after allergen exposure.1
In adults, asthma and rhinitis are classified as nonallergic when total IgE is normal
and/or specific IgE to common allergens is not detected in the serum or on skin-prick
test. Even in children, when atopy is presumed to be the cause in the vast majority of
children, similar symptoms occur in nonatopic individuals.2 The relationship of atopy
to asthma and other allergic diseases is not understood clearly.2,3 Atopic eczema is,
by definition, related to atopy; however, the cause-and-effect relationship is not
established. Eczema and sensitization to food and inhalant allergens both are
common in early childhood.4
In an individual, the presence of atopy may be confirmed by high levels of
specific IgE or total IgE in the serum or by positive responses to skin-prick test. A
number of studies examined the association between asthma and atopy in both adults
and children.25-8 Some of these studies were in large unselected populations,2,5,7,8
whereas others were smaller case-control studies.6 One birth cohort study from New
Zealand examined the association of childhood asthma with sensitization to common
aeroallergens, based on skin-prick testing performed at 13 years of age.9-11 The
authors reported that sensitivity to house dust mite and to cat were significant risk
factors for asthma, whereas sensitivity to grass pollen was not significant.9 Our birth
cohort study describes the relationship of atopy to symptoms of allergic disease in
early childhood.
In 1989 to 1990, a whole-population birth cohort was recruited on the Isle of
Wight to study the development of and risk factors for allergic disorders through
childhood. These children were followed up at 1, 2, and 4 years to determine the
presence of allergic disorders and atopy, as assessed by positive skin-prick test to 1 or
more common allergens. Previous reports of the 4-year follow-up examined the risk
factors for allergic diseases4 and the influence of cord IgE.12 This analysis specifically
describes the pattern of sensitization to common allergens at the age of 4 years and the
relationship of atopy to allergic diseases.

METHODS

For a period of 14 months (January 1989 to February 1990), the parents of

all children born on the Isle of Wight (n = 1536) were approached, and an interview-

21
administered questionnaire was completed. The study was approved by the local
research ethics committee, and informed consent was obtained from all parents. After
excluding adoptions, perinatal deaths, nonresidents, and refusals, 1456 children
were available for inclusion in this prospective study. At birth, information was
obtained on family history of allergic diseases, presence of pets, smoking in the house,
and birth weight. Data on social class were available for 723 children from the
maternity records, as this information was not sought at the time of recruitment.
These children were reviewed at 1,13 2,14 and 44,12 years of age. At 1 and 2
years, a questionnaire seeking information on symptoms suggestive of allergic
disease in the child was completed. Those with symptoms of allergic disease were
seen in the clinic and administered a skin-prick test. At 4 years of age, all children
and their parents were invited to attend the allergy clinic. A total of 981 children
(67% of the original cohort) attended the clinic, and an interview-administered
questionnaire was completed, physical examination was conducted, and skin-prick
tests were performed on these children. Questionnaire (postal or telephone)
information was available for an additional 237 children (n = 1218; 84% of the
original cohort). Some of the families had moved from the Isle of Wight, and others
did not want the child to be skin-prick tested. Questionnaire information related to
the presence or otherwise of allergic disease and details of environmental factors
such as parental smoking, exposure to pets, housing conditions, and birth order were
updated.

Diagnostic Criteria for Atopic Disease

Information was obtained by the study physicians (E.A.H., S.M.T., S.H.A.)

regarding the presence of allergic symptoms. For asthma, information included the
presence and frequency of cough and wheezing, physician-diagnosed asthma, and
treatment given. For eczema, the presence of typical rash and its distribution and
duration were established. For rhinoconjunctivitis, the presence of nasal (discharge,
blockage, and recurrent sneezing) and eye (itching, watering) symptoms was
recorded. A physical examination was performed for the relevant signs. A clinical
diagnosis was made as to the presence of asthma, eczema, and rhinitis. The minimum
criteria for the diagnosis of asthma included 3 or more separate episodes of wheeze
and/or cough, each lasting at least 3 days. Eczema constituted recurrent, scaly,
pruritic, erythematous rash in a typical distribution lasting for 6 weeks or more. A
diagnosis of rhinitis required frequent or seasonal symptoms of nasal discharge and/or
blockage and recurrent sneezing.

Skin-Prick Tests

A panel of 6 inhalant and 6 food allergens was used. These included house
dust mite (Dermatophagoides pteronyssinus), grass pollen mix, cat, dog, Alternaria
alternata, Cladosporium herbarum, cow's milk, hen's egg, soya, cod, wheat, and peanut.
Standardized extracts were used when available. All extracts were from
Biodiagnostics (Reinbek, Germany). Histamine (0.1%) in phosphate-buffered saline
and physiologic saline were used as positive and negative controls, respectively. Two
study nurses performed all of the tests. Children were advised not to take
antihistamines for 72 hours before the clinic appointment. Commercially available
lancets (Medipoint, Inc, Mineola, NY) were used to prick the epidermis through the
allergen extract drops. The tests were read at 15 minutes, and mean wheal diameters

22
were calculated (sum of the longest diameter and the diameter perpendicular to it
divided by 2). In the presence of a positive control (>= 3 mm), a mean wheal
diameter of at least 3 mm greater than the negative control was taken as positive.
Surrounding erythema was ignored. The data also were analyzed using a 2-mm
cutoff, as has been used in some studies.9

Statistical Analysis

All data were coded and entered into the database module of the statistics
software SPSS PC+ V4 (SPSS Inc, Chicago, IL). All subsequent analysis was
performed using this package. X² tests were used to test the univariate association
between each allergic disease and positive skin-prick test (Fisher's exact test was used
when appropriate). Multiple logistic regression analysis was performed to obtain the
adjusted odds ratios (OR) and 95% confidence intervals (CI) for the independent effect
of sensitization to each allergen on allergic disease, adjusting for the effect of
sensitization to other allergens. In the regression model, asthma, rhinitis, and
eczema were entered as the dependent variable and the results of skin-prick tests to
allergens included in the standard battery were entered as covariates. To assess how
much of allergic disease is attributable to atopy (defined as positive skin-prick test)
in this population, we estimated the population-attributable risk.3 This was calculated
with the formula P(R - 1)/R, where R is the OR for the allergic disease under
consideration and P is the proportion of atopy in children with that disease.

RESULTS

Information on the prevalence of allergic diseases was available on 1218

(84%) children. This analysis is confined to the 981 (67%) of the original population,
who also had skin-prick tests to the standard battery. Table 1 shows the characteristics
of children with and without skin-prick tests. There were no significant differences in
gender, family history of allergic disease, birth characteristics, exposure to
environmental tobacco smoke, and presence of pets. Allergic disorders (asthma,
rhinitis, or eczema) were present in 317 of the 1218 (26%) when information was
available and 276 (28.1%) of 981 who were skin-prick tested at 4 years. A total of 238
children were not seen at the 4-year follow-up. Information was available on 231 of
these children from the previous follow-ups at 1 and 2 years (Table 1).
Disproportionately more of these children belonged to a lower socioeconomic group.
When allergic disease at 1 or 2 years was compared, there was little difference
between those who were not seen at 4 years and those who were not skin-prick tested.
However, children who were skin-prick tested at 4 year showed a higher prevalence
of allergic disease at 1 and 2 years as well.

TABLE 1
Characteristics of Children Who Completed Questionnaire and Were Skin Tested, Who
Completed Questionnaire but Were Not Skin Tested, and Who Were Not Seen at 4-
Year Follow-Up

23
 SPT Done SPT Not Done Not Seen at 4 Years
Characteristic
[n/Total n (%)] [n/Total n (%)] [n/Total n (%)]

Family history of allergic

disease
Maternal 332/977 (34.0) 79/236 (33.5) 88/238 (37.0)
Paternal 254/977 (26.0) 57/235 (24.3) 62/231 (26.8)
Sibling 212/564 (37.6) 38/114 (33.3) 53/138 (38.4)
Maternal IgE (mean [SE]) 112.91 (7.52) 117.39 (16.08) 109.71 (15.97)
(n = 680) (n = 162) (n = 152)
Allergic diseases at 4 y
Asthma 161/981 (16.4) 20/234 (8.5) NA
Rhinitis 60/980 (6.1) 5/234 (2.1) NA
Eczema 124/981 (12.6) 21/233 (9.0) NA
Any allergic disease* 276/981 (28.1) 41/236 (17.4) NA
Allergic diseases at 1 or
2y
Asthma 144/946 (15.2) 21/200 (10.5) 32/231 (13.9)
Rhinitis 169/946 (17.9) 19/200 (9.5) 29/231 (12.6)
Eczema 161/946 (17.0) 21/200 (10.5) 14/231 (6.1)
Any allergic disease* 336/946 (35.5) 48/200 (24.0) 52/231 (22.5)
Male gender 497/981 (50.7) 127/237 (53.6) 122/238 (51.3)
High cord IgE (>0.5 ku/L) 112/858 (13.1) 27/206 (13.1) ND
Low birth weight (<2.5 38/954 (4.0) 5/231 (2.2) 9/231 (3.9)
kg)
Exposure to cigarette 373/981 (38.0) 92/237 (38.8) NA
smoke
Low socioeconomic 308/586 (52.6) 66/137 (48.2) 93/135 (68.9)
group
Cat in the house 374/954 (39.2) 76/204 (37.3) NA
Dog in the house 283/956 (29.6) 69/200 (34.5) NA

NA indicates information not available at 4 year; ND, not done.

*
Asthma and/or rhinitis and/or eczema.
Social classes 4 and 5 according to the Registrar General's classification, information
collected at recruitment.

A total of 192 children (19.6%) were atopic (positive reaction to 1 or more

allergens); using a cutoff of 2 mm increased the number of children regarded as atopic
to 202 (20.6%). Sensitization to inhalant allergens was relatively common (19.2%) as
compared with food allergens (3.5%). There were only 3 children who were sensitized
solely to a food allergen. House dust mite (11.9%), grass pollen (7.8%), and cat

24
(5.8%) were the most common positive reactions (Fig 1). The proportion of children
who were sensitized to cat was not higher in households with cat ownership
(households with cat: 5.1% [19 of 374], households without cat: 6.2% [36 of 580]; not
significant). Similarly, no difference was seen in sensitization to dog in households
with and without dogs (households with dog: 1.8% [5 of 282]; households without dog:
2.8% [19 of 673]; not significant). The 4 most common allergens (house dust mite,
grass pollen, cat, and A alternata) could detect 94% of the atopic children.

Fig. 1. Sensitization to common food and inhalant allergens in an unselected

population of children aged 4 years (% indicates percentage of children whose tests
were positive to the respective allergen in the population studied).

Sensitization to the 4 most common allergens was strongly associated with the
presence of allergic disorders (Table 2); using a cutoff of 2 mm for skin-prick test
positivity did not have a significant effect on this association. For example, 59 (36.5%)
children with asthma were sensitized to house dust mite with a 3-mm cutoff. The
corresponding figure for a 2-mm cutoff was 64 (39.8%). Sensitization to other
inhalant allergens (dog and C herbarum) and some of the food allergens also
showed an association (data not shown). There was a graded effect with the potent
allergens, such as house dust mite, having the greatest impact. For example, 50% of
children who were sensitized to house dust mite had asthma, as opposed to 44% who
were sensitized to cat, 42% who were sensitized to grass pollen, and 32% who were
sensitized to A alternata (Table 3). Overall, 68.4% children who were sensitized to
house dust mite had asthma, eczema, and/or rhinitis.

TABLE 2
Allergic Sensitization in 4-Year-Old Children With Common Allergic Disorders

25
 (Univariate Analysis)

Sensitization Yes [n (%)] No [n (%)] OR (95% CI)

Asthma n = 161 n = 820

Any allergen 71 (44.1) 121 (14.8) 4.56 (3.16-6.57)
House dust mite 59 (36.6) 58 (7.1) 7.60 (5.00-11.53)
Grass pollen 32 (19.9) 45 (5.5) 4.27 (2.62-6.97)
Cat 25 (15.5) 32 (3.9) 4.53 (2.60-7.88)
Alternaria 15 (9.4) 32 (3.9) 2.55 (1.35-4.82)
Rhinitis n = 60 n = 920
Any allergen 33 (55.0) 159 (17.3) 5.85 (3.42-10.00)
House dust mite 24 (40.0) 93 (10.1) 5.93 (3.39-10.37)
Grass pollen 19 (31.7) 58 (6.3) 6.89 (3.76-12.62)
Cat 9 (15.0) 48 (5.2) 3.21 (1.49-6.90)
Alternaria 7 (11.7) 40 (4.4) 2.90 (1.24-6.79)
Eczema n = 124 n = 857
Any allergen 53 (42.7) 139 (16.2) 3.86 (2.59-5.75)
House dust mite 35 (28.2) 82 (9.6) 3.72 (2.36-5.84)
Grass pollen 30 (24.2) 47 (5.5) 5.50 (3.32-9.12)
Cat 24 (19.4) 33 (3.9) 5.99 (3.41-10.55)
Alternaria 15 (12.2) 32 (3.7) 3.58 (1.88-6.83)

TABLE 3
Skin-Prick Test Positivity to Common Allergens and Point Prevalence of Asthma,
Eczema, Rhinitis, and Any Allergic Disease

Asthma Rhinitis Eczema Any Allergic Disease

Allergen
[n (%)] [n (%)] [n (%)] [n (%)]

House dust mite

Positive (n = 117) 59 (50.4) 24 (20.5) 35 (29.9) 80 (68.4)
Negative (n = 864) 102 (11.8) 36 (4.2) 89 (10.3) 196 (22.7)
Grass pollen
Positive (n = 77) 32 (41.6) 19 (24.7) 30 (39) 50 (64.9)
Negative (n = 904) 129 (14.3) 41 (4.5) 94 (10.4) 226 (25.0)
Cat

26
 Positive (n = 57) 25 (43.9) 9 (15.8)* 24 (42.1) 38 (66.7)
Negative (n = 924) 136 (14.7) 51 (5.5) 100 (10.8) 238 (25.8)
Alternaria
Positive (n = 47) 15 (31.9)* 7 (14.9)* 15 (31.9) 27 (57.4)
Negative (n = 933) 145 (15.5) 53 (5.7) 108 (11.6) 248 (26.6)
Peanut
Positive (n = 11) 4 (36.4)NS 3 (27.3)* 6 (54.5) 6 (54.5)
Negative (n = 967) 156 (16.1) 57 (5.9) 117 (12.1) 269 (27.8)
Egg
Positive (n = 8) 3 (37.5)NS 5 (62.5) 4 (50.0)* 6 (75)*
Negative (n = 972) 157 (16.1) 55 (5.7) 119 (12.2) 269 (27.7)

NS indicates not significant. P < .001 except where indicated by*or .

*
P < .01.
P < .05.

Boys were atopic more often than girls at this age (boys: 112 of 497 [22.5%] vs
girls: 80 of 484 [16.5%]; OR: 1.47; CI: 1.07-2.02; P = .02). Male preponderance was
observed with most allergens, but this was statistically significant for house dust mite
(boys: 75 of 497 [15.1%] vs girls: 42 of 484 [8.7%]; OR: 1.87; CI: 1.25-2.79; P =
.002) and grass pollen (boys: 51 of 497 [10.3%] vs girls: 26 of 484 [5.4%]; OR: 2.01;
CI: 1.23-3.29; P = .004).
An independent effect of allergen sensitization on asthma was observed only
with house dust mite (OR: 8.07; Table 4). For rhinitis, grass pollen and egg were
independent risk factors. The development of eczema was influenced by sensitization
to 3 major inhalant (house dust mite, grass pollen, and cat) and 2 food (egg and peanut)
allergens, confirming the atopic nature of eczema at this age.

TABLE 4
Adjusted OR and CI for the Independent Risk of Allergic Disorder With Sensitization
to Common Allergens (Logistic Regression Analysis, n = 842)
Asthma Rhinitis Eczema
Allergen
(OR [CI]) (OR [CI]) (OR [CI])

House dust mite

Positive (n = 97) 8.07 (4.60-14.14) 2.19 (0.92-5.17) 1.95 (1.04-3.66)*
Negative (n = 745)
Grass pollen
Positive (n = 71) 1.53 (0.76-3.08) 5.02 (2.21-11.41) 2.92 (1.49-5.72)

27
 Negative (n = 771)
Cat
Positive (n = 53) 0.89 (0.40-1.97) 0.68 (0.23-2.05) 2.70 (1.23-5.92)
Negative (n = 789)
Peanut
Positive (n = 11) 0.65 (0.13-3.36) 2.98 (0.54-16.54) 4.65 (1.02-21.34)*
Negative (n = 831)
Egg
Positive (n = 6) 1.85 (0.28-12.37) 18.43 (2.06-164.71) 6.08 (0.88-42.01)
Negative (n = 836)

Sensitization to other allergen, included in the model but found to be nonsignificant

were, dog, Alternaria, Cladosporium, milk, wheat, cod, and soya.
*
P < .05.
P < .01.
P < .001.

The majority of children (98 of 192) were sensitized to >1 allergen. A graded
effect was observed with the risk of allergic disease in the child increasing with the
number of positive skin-prick test reactions (Fig 2). This effect was consistent
throughout the spectrum of allergic diseases (asthma, eczema, and rhinitis). Nearly
80% of children with positive skin-prick test reactions to 4 or more allergens had
asthma, eczema, and/or rhinitis compared with 20% if they were nonatopic.

Fig. 2. Risk of allergic diseases in a child increases with the number of positive skin-
prick tests.

28
 The prevalence of atopy in children with asthma was 44% (Table 2). With an
OR of 4.56, the population-attributable risk was calculated to be 34%. There was
essentially no change in the population-attributable risk (34.6%) when a 2-mm cutoff
was used (atopy in children with asthma: 45%; OR: 4.34). Fifty-five percent of
children with rhinitis were atopic (OR: 5.85). Therefore, 46% cases of rhinitis could
be attributable to atopy. The population-attributable risk of atopy for eczema was
32% (prevalence: 43%; OR: 3.86).

DISCUSSION

Overall 475 children (33%) either were not seen or did not have a skin-prick
test at 4 years (Table 1). The prevalence of allergic disease was higher in children
who were skin-prick tested compared with those who were not skin-prick tested. There
was minimal difference in the prevalence of allergic disease at 1 or 2 years in those
who did not have a skin-prick test and those who were not seen at 4 years. Family
history of allergic disease and environmental risk factors (except for social class)
were similar in all groups. It is likely that children who were not seen at 4 years had
a similar prevalence of allergic disorders to those who were seen but not skin-prick
tested. This may have skewed our results toward a higher prevalence of atopy in
children who were skin-prick tested and biased the results toward a stronger
association of atopy with allergic disease. However, the prevalence of atopy (19.6%)
in those who were skin-prick tested was lower than reported in children in other
studies,9,15,16 which argues against the possibility that a highly sensitized
subpopulation came forward for skin-prick testing. Children who were not seen at 4
years more commonly belonged to a lower socioeconomic group, but this is unlikely to
have significantly effected the prevalence of atopy.4

As this cohort was recruited during a period of 14 months, with inclusion of

January and February births over 2 consecutive years, there was a higher number of
winter births (winter: 381; spring: 295; summer: 279; autumn: 263). This potentially
could introduce a bias with regard to the season of birth effect. In this cohort,
however, season of birth had influenced neither the development of allergic disorders
nor allergen sensitization at 4 years of age.4

Foods are common allergens in early childhood. As the child grows, foods are
replaced by inhalant allergens.17 Our study confirms that sensitization to food
allergens becomes relatively uncommon (3%) by the age of 4. A recent report16
describing the natural course of sensitization to food and aeroallergens showed a
decrease in the sensitization to food allergen from 10% at 1 year to 3% at 6 years. At
the same time, sensitization to inhalant allergens increased from 1.5% at 1 year to
26% at 6 years of age. In our study, 60% of the atopic children could be identified
with skin-prick test to house dust mite alone and 94% when 4 common inhalant
allergens were included in the skin-prick test battery. This is a useful guide when
screening children for atopy.

The prevalence of atopy of 19.6% was somewhat lower than reported in other
studies.9,15,16 Some authors, using a smaller wheal size of >= 2 mm as the cutoff
for skin-prick test positivity, reported a higher prevalence of atopy.9 Using a cutoff

29
of 2 mm in this population did not increase the prevalence of atopy significantly,
either in the whole population or among children with asthma. The lowest limit of
skin-prick test reactivity that reliably predicts radioallergosorbent assay test
positivity is, in fact, a larger wheal size of 4 to 5 mm.18 Therefore, a 3-mm cutoff for
skin-prick test positivity, which is used commonly in clinical and epidemiologic
studies,19-22 was thought to be more appropriate. Most other studies assessed
children who were 6 years or older.8,9,19-22 An explanation for somewhat lower
prevalence rate could be the age of our childhood population. At the age of 4,
children have grown out of food sensitization (as confirmed by this study) but may not
yet have acquired sensitization to aeroallergens.

Some less common inhalant allergens, such as tree pollen, horse, or

Aspergillus, were not included in the standard battery. The need to include common
food allergens in the battery at this age meant that the number of inhalant allergens
had to be restricted. Although, in theory, it is possible that a child may be sensitized
solely to an uncommon allergen not included in the battery, this would be a rare
occurrence. We believe that by using this panel, we were able to detect most of the
atopic children among those given skin-prick tests in this cohort. Unfortunately, serum
total and specific IgE levels were not measured to strengthen the validity of skin-prick
test responses. However, total IgE may be within the age-adjusted normal range in
some atopic individuals.23

Several studies 9,24 noted a positive correlation between the prevalence and
severity of asthma and the number and size of positive skin-prick tests. Our findings
are similar, showing a linear relationship with a higher prevalence of allergic disease
in children who react to >1 allergen (Fig 2). Unfortunately, a valid correlation of the
number of skin-prick test responses to clinical indicators of severity of allergic
diseases could not be made because only a minority had severe disease.

Our study confirms previous reports of a higher prevalence of atopic

sensitization in boys than in girls.10,20,25 A statistically significant difference was
observed only with house dust mite and grass pollen sensitization, although the trend
was similar for all allergens tested.

It is a common belief that the allergic disorders are almost always atopic,
especially in children. Evidence supporting this hypothesis is the clustering of the
disorders in families and the presence of allergic sensitization in a majority of children
with these disorders. A number of studies suggested an association of atopy with
asthma.25-9,25 Indeed, for asthma, there is considerable epidemiologic evidence for
the causative role of IgE.6,8,26 However, there are few studies in which this
relationship was studied in a homogenous, unselected population recruited at birth.7,9
Overall, these studies suggest a positive relationship between atopy, as assessed by
skin-prick test responses or IgE, and asthma. Sears et al9 showed a strong independent
risk of house dust mite and cat but not grass pollen sensitization on the development of
asthma and bronchial hyperresponsiveness. Our study confirms this observation and
extends it to other allergic diseases (rhinitis and eczema). House dust mite
sensitization was found to be the most important risk for asthma, with an OR of 8.07.
This is consistent with the humid climate of Isle of Wight. We previously showed house
dust mite concentrations in homes in the Isle of Wight to be extremely high.27 Peat et
al,15 in their study of different regions of Australia, found house dust mite to be the

30
most important risk factor in coastal regions, whereas A alternata acquired a higher
significance in the inland with a dry climate. In Isle of Wight, cat or grass pollen
sensitization was not an independent risk factor of asthma, although grass pollen
sensitization was closely associated with rhinitis.

The relationship of allergen exposure, sensitization, and the development of

allergy-related disease is complex. In a recent study, Lau et al7 reported a strong
association of dust mite and cat allergen sensitization with respiratory symptoms and
bronchial hyperresponsiveness during the first 7 years of life. However, they failed to
demonstrate a consistent relationship between dust mite and cat allergen exposure and
respiratory allergic manifestation. Platts-Mills et al8 confirmed, as does our study and
previous reports,9,22 that mite and cat sensitization are strong independent risk factors
for asthma. However, whereas increased mite allergen exposure leads to increased
sensitization, increased cat allergen exposure stimulates IgG antibody production and
decreases the risk of sensitization to cat allergen.8 In our study, having a cat or a dog
at home did not influence the prevalence of sensitization to their allergens. Our data
also support the suggestion that sensitization to various indoor allergens has a
differential effect on the development of allergic diseases, with house dust mite having
the highest risk and molds the lowest. Sensitization to the common molds A alternata
and C herbarum was observed in a number of children who had no evidence of
clinical disease.28

Although it generally is agreed that atopy is an important risk factor for

allergic disease, the extent to which atopy accounts for these diseases is controversial.
Simple IgE-mediated disorders, such as hay fever and peanut allergy, clearly are
attributable to sensitization to pollen and peanut, respectively. Asthma, eczema, and
perennial rhinitis are, however, more complex disorders. Evidence supporting the
role of total IgE in asthma includes the correlation of elevated serum levels of IgE
with self-reported asthma symptoms29 and airway hyperresponsiveness.26,30
However, other studies cast doubt on the role of total IgE as an important indicator of
respiratory allergic diseases.31 In the African population, serum levels of IgE have
been reported to be higher in people who do not have asthma that in people who do.32
Similar symptoms occur in the absence of sensitization (nonallergic or intrinsic
disease). Even in allergic eczema, non-IgE-mediated inflammatory mechanisms
may play a significant role. For asthma, rhinitis, and eczema, it may be argued that
the primary abnormality is genetically determined and affects the airway/nasal
epithelium33 and/or dermis/epidermis.34

So how much of allergic disease is attributable to atopy? Pearce et al3

attempted to solve this, in relation to asthma, by a meta-analysis of the published
articles describing the association of asthma and atopy. Their analysis included studies
in which atopy was defined as either positive skin-prick test responses or high serum
IgE. They concluded that the proportion of asthma cases that attributable to atopy
averaged between 30% and 40%, in both adults and children. Our results confirm this
observation in 4-year-old children not only for asthma but also for rhinitis and eczema.
We propose a model for the development of allergic disorders, in which 30% to 40% of
cases of chronic allergic disease in early childhood are attributable to atopy and 60%
to 70% of cases could be accounted for by organ-based and other factors.

31
 ACKNOWLEDGMENTS

This study was funded by the Isle of Wight Health Authority Trust Funds.

We are grateful to the invaluable guidance and support of Dr. David Wallace
Hide (deceased) in the initiation and successful running of this birth cohort study. We
acknowledge the help of Roger Twiselton in performing cord blood IgE measurements.

FOOTNOTES

Received for publication Jun 27, 2000; accepted Apr 10, 2001.

Reprint requests to (S.H.A.) David Hide Asthma and Allergy Research Centre,
St Mary's Hospital, Isle of Wight PO30 5TG, United Kingdom. E-mail:
sha@soton.ac.uk

ABBREVIATIONS

IgE, immunoglobulin E; OR, odds ratio; CI, confidence interval.

REFERENCES

1. Macaubas C, Prescott S, Smallacombe T, et al. Perinatal and Early Childhood

Cytokine Responses to Environmental Allergens. New York, NY: Marcel
Dekker; 1999
2. Gergen PJ, Turkeltaub PC. The association of individual allergen reactivity with
respiratory disease in a national sample: data from the second National Health
and Nutrition Examination Survey, 1976-80 (NHANES-II). J Allergy Clin
Immunol. 1992:90:579-588
3. Pearce N, Pekkanen J, Beasley R How much asthma is really attributable to
atopy? Thorax 1999; 54:268-272
4. Tariq SM, Matthews SM, Hakim EA, Stevens M, Arshad SH, Hide DW The
prevalence of and risk factors for atopy in early childhood: a whole population
birth cohort study. J Allergy Clin Immunol 1998; 101:587-593
5. Norman E, Rosenhall L, Nystrom L, Jonsson E, Stjemberg N Prevalence of
positive skin prick tests, allergic asthma, and rhinoconjunctivitis in teenagers in
northern Sweden. Allergy 1994; 49:808-815
6. Duff AL, Pomeranz ES, Gelber LE, Risk factors for acute wheezing in infants
and children: viruses, passive smoke and IgE antibodies to inhalant allergens.
Pediatrics 1993; 92:535-540
7. Lau S, Illi S, Sommerfeld C, Early exposure to house-dust mite and cat allergen
and development of childhood asthma: a cohort study. Lancet 2000; 356:1392-
1397

32
8. Platts-Mills T, Vaughan J, Squillace S, Woodfolk J, Sporik R Sensitisation,
asthma, and a modified Th2 response in children exposed to cat allergen: a
population-based cross-sectional study. Lancet 2001; 357:752-756
9. Sears MR, Herbison GP, Holdaway MD, Hewitt CJ, Flannery EM, Silva PA The
relative risks of sensitivity to grass pollen, house dust mite and cat dander in the
development of childhood asthma. Clin Exp Allergy 1989; 19:419-424
10. Sears MR, Burrows B, Flannery EM, Herbison GP, Holdaway MD Atopy in
childhood. I. Gender and allergen related risks for development of hay fever and
asthma. Clin Exp Allergy 1993; 23:941-948
11. Sears MR, Burrows B, Herbison GP, Holdaway MD, Flannery EM Atopy in
childhood. II. Relationship to airway responsiveness, hay fever and asthma. Clin
Exp Allergy 1993; 23:949-956
12. Tariq SM, Arshad SH, Matthews SM, Hakim EA Elevated cord IgE increases
the risk of aero-allergen sensitisation without increasing respiratory allergic
symptoms during early childhood. Clin Exp Allergy 1999; 29:1042-1048
13. Arshad SH, Hide DW Effect of environmental factors on the development of
allergic disorders in infancy. J Allergy Clin Immunol 1992; 90:235-241
14. Arshad SH, Stevens M, Hide DW The effect of genetic and environmental
factors on the prevalence of allergic disorders at the age of two years. Clin Exp
Allergy 1993; 23:504-511
15. Peat JK, Toelle BG, Gray EJ, Prevalence and severity of childhood asthma and
allergic sensitisation in seven climatic regions of New South Wales. Med J Aust
1995; 163:22-26
16. Kulig M, Bergmann R, Klettke U, Wahn V, Tacke U, Wahn U Natural course of
sensitization to food and inhalant allergens during the first 6 years of life. J
Allergy Clin Immunol 1999; 103:1173-1179
17. Nickel R, Kulig M, Forster J, Sensitization to hen's egg at twelve months is
predictive of allergic sensitization to common indoor and outdoor allergens at
the age of three years. J Allergy Clin Immunol 1997; 99:613-617
18. Pastorello EA Skin tests for diagnosis of IgE-mediated allergy. Allergy 1993;
48:57-59
19. Yemaneberhan H, Bekele Z, Venn A, Lewis S, Parry E, Britton J Prevalence of
wheeze and asthma and relation to atopy in urban and rural Ethiopia. Lancet
1997; 350:85-90
20. Keur J, Frischer T, Karamaus W, Early childhood risk factors for sensitization at
school age. J Allergy Clin Immunol 1992; 90:358-363
21. Leung R, Ho P, Lam CWK, Lai CKW Sensitization to inhaled allergens as a risk
factor for asthma and allergic disease in Chinese population. J Allergy Clin
Immunol 1997; 99:594-599
22. Wickens K, Pearce N, Seibers R, Indoor environment, atopy and the risk of
asthma in children in New Zealand. Pediatr Allergy Immunol 1999; 10:199-208
23. Williams PB, Dolen WK, Koepke JW, Comparison of skin testing and three in
vitro assays for specific IgE in the clinical evaluation of immediate
hypersensitivity. Ann Allergy 1992; 68:35-45
24. Zimmerman B, Feanny S, Reisman J, Allergy in asthma. I. The dose relationship
of allergy to severity of childhood asthma. J Allergy Clin Immunol 1988; 81:63-
70
25. Mensinga TT, Schouten JP, Rijcken B, Weiss ST, Speizer FE, Lende R The
relationship of eosinophilia and positive skin test reactivity to respiratory

33
 symptom prevalence in a community-based population study. J Allergy Clin
Immunol 1990; 86:99-107
26. Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Holdaway MD
Relation between airway responsiveness and serum IgE in children with asthma
and in apparently normal children. N Engl J Med 1991; 325:1067-1071
27. Arshad SH, Matthews S, Gant C, Hide DW Effect of food and house-dust mite
allergen avoidance on development of allergic disorders in infancy. Lancet
1992; 339:1493-1497
28. Tariq SM, Matthews S, Hakim E, Stevens M, Hide DW Sensitisation to
Alternaria and Cladosporium at age 4 years. Clin Exp Allergy 1996; 26:794-798
29. Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG Association of
asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med
1989; 320:271-277
30. Sunyer J, Anto JM, Sabria J, Relationship between serum IgE and airway
responsiveness in adults with asthma. J Allergy Clin Immunol 1995; 95:699-706
31. Tschopp JM, Sistek D, Schindler C, Current allergic asthma and rhinitis:
diagnostic efficiency of three commonly used atopic markers (IgE, skin prick
tests, and Phadiatop). Results from 8329 randomized adults from the
SAPALDIA Study. Swiss Study on Air Pollution and Lung Diseases in Adults.
Allergy 1998; 53:608-613
32. Scrivener S, Britton J Immunoglobulin E and allergic disease in Africa. Clin
Exp Allergy 2000; 30:304-307
33. Doull IJM, Lawrence S, Watson M, Allelic association of gene markers on
chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness. Am J
Respir Crit Care Med 1996; 153:1280-1284
34. Olesen AB, Ellingsen AR, Olesen H, Juul S, Thestrup-Pedersen K Atopic
dermatitis and birth factors: historical follow-up by record linkage. BMJ 1997;
314:1004-1008

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