Sensitization to common allergens and its association with allergic disorders at age 4 years: A whole population birth cohort study

Background. Atopy is defined as the genetic propensity to develop immunoglo bulin E antibodies in response to exposure to allergens and assessed by ski n prick test responses to common allergens. Although it is generally agreed that atopy is an important risk factor for allergic diseases such as asthm a, rhinitis, and eczema, the extent to which atopy accounts for these disea ses is controversial. Objective. We aim to describe the prevalence of sensitization to common all ergens and investigate the degree of association of atopy (as defined by po sitive 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 peri od (1989-1990). These children have been seen previously at 1 and 2 years o f age. At 4 years, 1218 children were reviewed and an interview was adminis tered or postal questionnaire was completed for the presence of allergic di seases (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, c at, 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 grea ter than the negative control was taken as positive. This analysis is confi ned to the 981 (67% of the original population) who also had skin prick tes ts to the standard battery. chi (2) tests were used to test the univariate association between each all ergic 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 allerge n on allergic disease, adjusting for the effect of sensitization to other a llergens. To ascertain how much of allergic disease is attributable to atop y, 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 cons ideration 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 mos t characteristics to the rest of the population, except that they had a hig her prevalence of allergic disease. Allergic disorders (asthma, rhinitis, a nd 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). Sensiti zation 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 c at (5.8%) were the most common positive reactions. A test to the 4 most com mon allergens (house dust mite, grass pollen, cat, and A alternata) could d etect 94% of the atopic children. Sensitization to the 4 most common allerg ens was strongly associated with the presence of allergic disorders. There was a graded effect with the potent allergens, such as house dust mite, hav ing the greatest impact. For example, 50% of children sensitized to house d ust 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 res pective figures for grass pollen, cat, and A alternata were 64.9%, 66.7%, a nd 57.4%. The proportion of children sensitized to cat was not higher in ho useholds with cat ownership (households with cats: 5.1% [19/374]; household s without cats: 6.2% [36/580]; not significant [NS]). Similarly, no differe nce was seen in sensitization to dog in households with and without dogs (h ouseholds 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 pre ponderance was observed with most allergens, but this was statistically sig nificant 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 f emale: 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 inde pendent 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 increasi ng with the number of positive skin prick test reactions. This effect was c onsistent 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 perce nt 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 o f atopy in children with eczema: 43%; and the OR for the development of ecz ema: 3.86). Conclusion. Atopy is closely associated with asthma, rhinitis, and eczema a t 4 years of age, with a direct and linear relationship. However, the propo rtion of cases of allergic disease attributable to atopy is <50%. We propos e a model for the development of allergic disorders, where 30% to 40% of ca ses of allergic disease (asthma, eczema, and rhinitis) in early childhood a re attributable to atopy and 60% to 70% of cases could be accounted for by organ-based and other factors.