Abstracts from the 3rd International Severe Asthma Forum (ISAF)

Respiratory symptoms are common in preschool children. However, which of these wheezers will develop asthma at school age, and what phenotype they will develop remains difficult to predict. Current models such as the asthma prediction index (API) are based on clinical parameters and have only modest predictive accuracy. Expression levels of well replicated asthma genes could potentially form novel biomarkers for asthma prediction. IL1RL1 is an asthma susceptibility gene, and has also been linked to eosinophilia. Therefore, we hypothesized that expression levels of IL1RL1 in the form of soluble IL-1RL1-a measured in serum from wheezing preschool children contribute to the prediction of asthma at school age. Moreover, since IL1RL1 was previously associated with blood eosinophilia, our second aim was to determine whether serum IL-1RL1-a levels predict eosinophilic asthma. Method: We used logistic predictive modeling in a prospective Dutch birth cohort (n = 202 wheezers), and calculated the area under the curve (AUC) of the sensitivity/1-specificity curves of potential models. Results: Neither IL-1RL1-a serum levels at age 2-3 years alone nor its combination with the API had predictive value for doctors' diagnosed asthma at age 6y (IL-1RL1-a alone: AUC = 0.50 [95 CI 0.41-0.59, P = 0.98], API + IL-1RL1-a: AUC = 0.57 [95 CI 0.49-0.66, P = 0.12]). However, IL-1RL1-a serum levels at age 2-3 years correlated with the severity of airway eosinophilia (determined by levels of exhaled fraction of NO, [FeNO]) in children who had developed asthma at age 6y (Pearson's R = -0.24, P = 0.046, N = 59). Logistic predictive modeling of eosinophilic asthma at age 6y (asthma with FeNO 20 ppb) showed that IL-1RL1-a serum levels itself and in combination with the API could predict this eosinophilic subphenotype of asthma (IL-1RL1-a alone: AUC = 0.65 [95 CI 0.52-0.79, P = 0.04], API + IL-1RL1a: AUC = 0.70 [95 CI 0.56-0.84, P = 0.01]). Interestingly, IL-1RL1-a levels had a negative direction of effect.