Early Predictors for Developing Allergic Disease and Asthma: Examining Separate Steps in the “Allergic March”
Authors: Kewalramani Anu 
Published: October 2008

PURPOSE OF THE STUDY.
The authors sought to detect early childhood predictors of the development of allergen sensitization. As a secondary objective, they examined the relationship of early sensitization with later onset of wheeze, asthma, rhinitis, and eczema.

STUDY POPULATION.
The Children Asthma Prevention Study (CAPS) evaluated 616 infants with a family history of asthma or current wheeze. They were followed from birth until 5 years of age.

METHODS.
Clinical outcome assessments were performed at 18 months and 3 and 5 years of age with parent interviews by using a standard questionnaire. Data on environmental tobacco exposure and breastfeeding were obtained. Children had skin-prick tests for several environmental and food allergens at 18 months and 5 years. At 18 months, total immunoglobulin E (IgE) levels were measured, and at 5 years of age, prebronchodilator and postbronchodilator spirometry was performed. Two populations emerged and were investigated. One group included children who were not sensitized at 18 months and were followed-up at 5 years of age; the second group included all children in the cohort who did not have wheeze, asthma, eczema, or rhinitis at 18 months and had complete data on clinical outcomes at 5 years of age.

RESULTS.
There were 375 nonsensitized children at 18 months who had valid skin-prick test results at 5 years of age. Of these children, 132 (35.2%) developed sensitization to ≥1 allergen by 5 years of age, with house dust mite being the most common allergen. Among these children, eczema at 18 months predicted subsequent sensitization at 5 years, with an adjusted relative risk (RR) of 1.67. A serum total IgE level greater than the median value (20.5 kU/L) was also associated with subsequent sensitization at 5 years of age (RR: 1.51). Wheeze, asthma, and rhinitis at 18 months were not associated with subsequent sensitization. There were 177 children with no wheeze, asthma, or rhinitis at 18 months of age, and of these children, 26 (15%) were sensitized to allergen. This subpopulation had an increased risk of developing wheeze (RR: 2.41), asthma (RR: 4.66), and rhinitis (RR: 1.77) by 5 years of age, but not eczema.

CONCLUSIONS.
Eczema, but not wheeze, asthma, or rhinitis, in nonsensitized young children seems to be a risk factor for the development of subsequent allergen sensitization. Sensitization at a young age was a predictor of subsequent wheeze, asthma, and rhinitis but not eczema.

REVIEWER COMMENTS.
Studies have shown that early allergic sensitization can be associated with later development of atopic diseases. This study confirms this observation with the small subpopulation of sensitized infants going on to develop wheeze, asthma, and rhinitis. Development of eczema in this subpopulation was not seen, but the “allergic march” usually begins in early infancy with atopic dermatitis and food allergy and then progresses to allergic rhinitis and asthma by 5 years of age. Less is known about early clinical predictors of sensitization developing later in childhood. This study concentrated on a group of nonsensitized 18-month-olds and found that eczema was a risk factor for the subsequent development of sensitization. It is important to remember that although sensitization (evidence of IgE antibodies to an allergen) was confirmed, clinical allergy was not. It also should be noted that this population of children was selected because of their positive family histories of asthma or current wheeze, so these results may not apply to the general population.