Sensitization to Common Allergens and Its Association With Allergic Disorders at Age 4 Years: A Whole Population Birth Cohort Study
Authors: Arshad Syed Hasan , Tariq Syed Mohammed , Matthews Sharon , Hakim Eluzai 
Published: August 2004

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.
χ2 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 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, andA 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 &gt;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 &lt;50%. We propose a model for the development of allergic disorders, where 30% to 40% of cases of allergic disease (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.