Component‐resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Component‐resolved diagnosis (<jats:styled-content style="fixed-case">CRD</jats:styled-content>) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double‐blind placebo‐controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (<jats:styled-content style="fixed-case">CRD</jats:styled-content>‐ and extract‐based). Odds ratios (<jats:styled-content style="fixed-case">OR</jats:styled-content>s) and areas under receiver‐operating characteristic (<jats:styled-content style="fixed-case">ROC</jats:styled-content>) curves (<jats:styled-content style="fixed-case">AUC</jats:styled-content>s) were used to evaluate their predictive value.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Cor a 9 and 14 were positively (<jats:styled-content style="fixed-case">OR</jats:styled-content> 10.5 and 10.1, respectively), and Cor a 1 negatively (<jats:styled-content style="fixed-case">OR</jats:styled-content> 0.14) associated with severe symptoms during <jats:styled-content style="fixed-case">DBPCFC</jats:styled-content>, with <jats:styled-content style="fixed-case">AUC</jats:styled-content>s of 0.70‐073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the <jats:styled-content style="fixed-case">AUC</jats:styled-content> to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>A model combining <jats:styled-content style="fixed-case">CRD</jats:styled-content> with clinical background and extract‐based serology is superior to <jats:styled-content style="fixed-case">CRD</jats:styled-content> alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.</jats:p></jats:sec>