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

BACKGROUND: Component-resolved diagnosis (CRD) 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. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: 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 (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs 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 AUC 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. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics.

BACKGROUND: In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it. METHODS: We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster(®), Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), "top responders", were then compared with those below the 25th percentile (n = 15) "poor responders". RESULTS: On average, the 59 patients completing the study (mean age ± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P < 0.001), but not in the inflammatory indicators (EBT, CRP and Eos). However, when comparing the "top responders" with the "poor responders", significant improvement in these inflammatory indicators was observed: EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[°C] to 33.57 ± 0.33, P = 0.003, Eos in blood fell from 381.7 ± 91.2 [cells/µL] to 244.2 ± 43.2, P = 0.02. Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders (Mann-Whitney test, P = 0.04). CONCLUSION: Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation. These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping. Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment. However, improved compliance due to the "promise of a new drug" effect should also be considered as contributing to the treatment results.