Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

Prospective validation of 'Allergy-Control-SCORE(TM)': a novel symptom-medication score for clinical trials.

BACKGROUND: Combined symptom and medication scores (SMS) are recommended as primary endpoints in clinical trials. Several SMS have been created, but none has been formally validated. OBJECTIVE: To evaluate the validity of the 'Allergy-Control-SCORE© (ACS)', a novel instrument to assess patient's allergy severity by recording symptoms and rescue medication. METHODS: One hundred and twenty-one consenting subjects (age 18-65 year), including 81 patients with allergic rhino-conjunctivitis and/or asthma and 40 healthy controls, participated in the study. They recorded daily nasal, eye, and lung symptoms using a 4-point scale (none, mild, moderate, and severe) and use of anti-symptomatic medication. Pollen counts were monitored during the study period. Symptom and medication scores values were compared to global allergy severity, quality of life, and allergy-related medical consultations. Feasibility was tested through a questionnaire on comprehensibility, easiness of use, and completeness. Retest reliability was assessed by testing consistency, in relation to pollen exposure, and for values recorded during each of 2 consecutive weeks. RESULTS: Convergent reliability analysis indicated a highly significant correlation between ACS© and global allergy severity (P < 0.0001), quality of life (P < 0.0001), and allergy-related medical consultations (P < 0.0001). Scores were highly related to pollen counts. Allergy-Control-SCORE© showed a good retest reliability (r = 0.81; P < 0.0001) and discriminated extremely well between patients with allergy and healthy controls (6.1 ± 4.8 vs 0.2 ± 0.5; t = 10.82; P < 0.0001) with a sensitivity of 97% and a specificity of 87%. Study participants evaluated the feasibility of the SMS as excellent. CONCLUSIONS: Allergy-Control-SCORE© is a valid and reliable instrument to assess allergy severity in clinical trials and observational studies of respiratory allergic diseases.

Primary versus secondary immunoglobulin E sensitization to soy and wheat in the Multi-Centre Allergy Study cohort.

BACKGROUND: IgE sensitization to soy and wheat is classified as 'primary' when generated by food ingestion and 'secondary' when it as a consequence of primary sensitization to cross-reacting pollen antigens via inhalation. The age-specific relevance of these categories of sensitization throughout childhood is unknown. OBJECTIVE: To monitor the natural course of IgE sensitization against common food allergens in childhood in relation to sensitization against cross-reactive airborne allergens. METHODS: The German Multi-Centre Allergy Study with follow-up from birth to age 13 recruited initially 1314 children. IgE antibody levels against cow's milk, hen's egg, soy, wheat, mites, cat and dog dander, birch and grass pollens were tested. Longitudinal data were analysed from the 273 children with sera obtained at age 2, 5, 7 and 10 years of age. RESULTS: The point prevalence of sensitization (>1.0 kU/L) to milk and egg allergens progressively decreased from about 4% at 2 years to <1% at 10 years. By contrast, the prevalence of IgE to wheat and soy progressively increased with age, from 2% to 7% (soy) and from 2% to 9% (wheat). At 10 years of age, IgE to grass pollen was detected in 97% and 98% of the children reacting against soy and wheat, respectively; IgE to birch pollen was observed in 86% and 82% of the children reacting against soy and wheat, respectively. Early IgE sensitization to soy or wheat preceded that to grass or birch pollen in only 4% and 8% of participants sensitized to soy and wheat, respectively. CONCLUSION: IgE sensitization to soy and wheat is relatively uncommon and mostly primary in early infancy, more frequent and mostly secondary to pollen sensitization at school age. Clinical Implications Awareness should be raised to avoid unnecessary diet restrictions due to the high frequency of clinically irrelevant, secondary sensitization to soy and wheat in schoolchildren with pollinosis.