Component-resolved diagnostics demonstrates that most peanut-allergic individuals could potentially introduce tree nuts to their diet.

BACKGROUND: Nut allergy varies from pollen cross-allergy, to primary severe allergy with life-threatening symptoms. The screening of IgE antibodies to a wide spectrum of allergens, including species-specific and cross-reactive allergens, is made possible via microarray analysis. OBJECTIVE: We sought to study the association of variable IgE sensitization profiles to clinical response in peanut-challenged children and adolescents in a birch-endemic region. In addition, we studied the avoidance of tree nuts and species-specific sensitizations. METHODS: We studied 102 peanut-sensitized patients who underwent a double-blind placebo-controlled challenge to peanut. We analysed ISAC ImmunoCAP microarray to 112 allergens, singleplex ImmunoCAPs for hazelnut Cor a 14 and cashew Ana o 3, and performed skin prick tests to peanut, tree nuts and sesame seed. We surveyed avoidance diets with a questionnaire. RESULTS: Sensitization to PR-10 proteins was frequent (Bet v 1 90%), but equally high in the challenge negatives and positives. IgE to Ara h 2 and Ara h 6 discriminated peanut allergic (n = 69) and tolerant (n = 33) the best. Avoidance of tree nuts was common (52% to 96%), but only 6% to 44% presented species-specific sensitizations to tree nuts, so a great number could potentially introduce these species into their diet. CONCLUSIONS AND CLINICAL RELEVANCE: PR-10-sensitizations were frequent and strong regardless of peanut allergy status. Component-resolved diagnostics can be employed to demonstrate to patients that sensitization to seed storage proteins of tree nuts is uncommon. Several tree nuts could potentially be reintroduced to the diet.

Burden of allergy diets in Finnish day care reduced by change in practices.

BACKGROUND: Nonessential allergy diets in children with mild symptoms may harm the development of immunological tolerance and impose a burden on families and day care. We aimed to reduce the high prevalence of allergy diets in day care by reforming the practices for inquiring about need of special diets from parents. METHODS: We developed a new special diet form and an information leaflet based on the new allergy guidelines. The new form was implemented into 40 Finnish day care centres in the capital region in 2013-2015. The questionnaires on practices concerning special diets in day care centres and allergy knowledge were collected from the personnel. RESULTS: After 2 years, the new special diet form was used by 64% of families with food-allergic children, and the prevalence of allergy diets in day care centres decreased by 43% to 4.3% (IQ range 3.05-5.96). A significant decrease was found in the prevalence of all basic (milk, grains, egg) and most other allergy diets (P for trend < 0.01). The new practice was well accepted by day care and kitchen personnel. Lack of updated allergy knowledge was noted among day care personnel. CONCLUSIONS: The burden of allergy diets in day care settings could be decreased by simple pragmatic changes based on current allergy guidelines. Old allergy attitudes persisted among day care personnel, indicating the need for continuous education.

Cross-sensitization profiles of edible nuts in a birch-endemic area.

BACKGROUND: Sensitization to birch pollen causes cross-sensitization to nuts, but rarely leads to clinical nut allergy. The aim was to study sensitizations to nuts in individuals sensitized to birch pollen and examine cross-reactivities between birch and nut species. METHODS: All subjects with skin prick tests (SPTs) for birch pollen conducted during 1997-2013 in the Skin and Allergy Hospital in Helsinki (n = 114 572) and their available SPTs for nuts (n = 50 604) were included. Nut sensitizations were analyzed both with and without cosensitization to birch and stratified into age-categories. Cross-reactivities were analyzed with hierarchical clustering. One group of 1589 patients was surveyed for symptoms. Data were gathered also from Lapland to examine sensitizations in an area with less birch-pollen exposure. RESULTS: Of subjects with birch sensitization, 84% were cosensitized to hazelnut, 71% to almond, and 60% to peanut. In a subgroup without birch sensitization, young children (<5 years) were most commonly nut-sensitized (8-40%); and this prevalence decreased in adolescents and further in adults (4-12%). Cashew and pistachio (ρ = 0.66; P < 0.001) and pecan and walnut (ρ = 0.65; P < 0.001) correlated the strongest. The majority of nut-sensitized patients (71% hazelnut, 83% almond, 73% peanut) reported no or mild symptoms. Cosensitizations between nuts and birch were similar in Lapland with its lower birch-pollen exposure. CONCLUSION: Birch-sensitized individuals are frequently cosensitized to hazelnut, almond, and peanut. Among the birch-negatives, prevalences of nut sensitizations decrease from early childhood to adolescence. Cashew and pistachio, and pecan and walnut cross-react the most.

Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: a double-blind placebo-controlled study.

BACKGROUND: Component-resolved diagnostics offers a modern tool in peanut allergy, but studies applying consistently double-blind placebo-controlled challenges are lacking. We aimed to optimize diagnostics for moderate-to-severe peanut allergy in a birch-endemic region and to create an oral-peanut challenge with its allergen activity characterized. METHODS: We performed double-blind placebo-controlled peanut challenges for a referred sample of 6- to 18-year-olds with peanut sensitization or a high suspicion of peanut allergy, including anaphylaxis. We measured specific IgE (sIgE) to Ara h 1, 2, 3, 6, 8, and 9. Testing of allergen activity of the challenge products was by IgE microarray inhibition. RESULTS: Of the 102 patients, 69 were challenge positive: 25 (36%) had severe, 36 (52%) moderate, and 8 (12%) mild symptoms; 38 (37%) received adrenalin. SIgE to Ara h 6 AUC 0.98 (95%CI, 0.96-1.00) was the best marker of moderate-to-severe allergy. When sIgE to Ara h 2 and Ara h 6 was measured together, all (100%) severe reactions at low doses were successfully diagnosable. SIgE to Ara h 8 had no diagnostic value, AUC 0.42 (95%CI, 0.30-0.52). Both nonroasted and roasted peanut inhibited 100% of IgE binding to Ara h 1, 2, 3, and 6. Nonroasted peanut inhibited 87% of IgE binding to Ara h 8, roasted inhibited 30%. The products lacked Ara h 9 activity. CONCLUSION: Co-sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. SIgE to Ara h 8 added no diagnostic value. Component-resolved diagnostics reduce the need for oral challenges in peanut allergy.

Intestinal defensin secretion in infancy is associated with the emergence of sensitization and atopic dermatitis.

BACKGROUND: Intestinal flora and innate immunity, and their interactions impact adaptive immunity. OBJECTIVE: To study the association of fecal defensin levels in infancy with synbiotic treatment and with the emergence of atopy. METHODS: The randomly selected group of 102 infants belonged to a randomized, double-blind placebo-controlled trial where 1223 infants in high risk for allergy received, from birth to 6 months, a mixture of synbiotics, or placebo. Clinical trials registration number for the clinical trial is NCT00298337. In the subgroup, 45 received active treatment and 56 received placebo treatment. Follow-up for the emergence of sensitization and allergic diseases lasted 5 years. At the age of 3 (n = 96) and 6 (n = 87) months, we measured fecal levels of human neutrophil peptide (HNP) 1-3 and of ß-defensin 2 (HBD2) using enzyme linked immunosorbent assays and concentrations of lactic acid bacteria on MRS agar. We used multifactorial regression in data analysis. RESULTS: Fecal levels of HNP1-3 and HBD2 decreased from the age of 3-6 months (P < 0.0001). HBD2 levels decreased less in the synbiotics group compared with placebo (P < 0.02). High fecal HBD2 levels at 6 months were associated with an increased risk for sensitization by the age of 5 years (OR 2.5, 95% confidence interval 1.1-5.8, P < 0.03). High fecal HNP1-3 levels at 6 months were associated with a decreased risk for atopic dermatitis (OR 0.4, 95% CI 0.1-1.0, P < 0.05). Samples with very low or high HBD2 levels at 6 months had low concentrations of lactic acid bacteria (P < 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Early innate immunity responses in the gut are associated with the emergence of sensitization and atopic dermatitis later in childhood.

Ovalbumin-specific immunoglobulins A and G levels at age 2 years are associated with the occurrence of atopic disorders.

BACKGROUND: Humoral responses to food antigens may reflect the propensity of a child's immune system to develop tolerance to innocuous antigens. Early nutrition as well as probiotics may influence these immunological responses. OBJECTIVE: To study the association of humoral responses to early food antigens with the administration of prebiotics and probiotics, with the occurrence of allergy, and with the length of exclusive breastfeeding. METHODS: In a randomized double-blind allergy prevention trial in high-risk children, 1018 mothers took probiotics or placebo from the 36th week of gestation, and their newborn infants received probiotics and prebiotics or placebo during 6 months. At 2 and 5 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, rhinitis) and sensitization (skin prick test ≥3 mm or serum antigen-specific IgE>0.7 kU/L). In 688 infants at age 2, we measured in sera-specific IgA, IgG, IgG1, and IgG4 antibody levels to cow's milk (CM), α-casein (CAS), ß-lactoglobulin (BLG), and ovalbumin (OVA) with ELISA, and specific IgE levels to CM and hen's egg with UniCap. RESULTS: Probiotic treatment (n=342) compared with placebo (n=346) showed no effect on serum food-specific IgA, IgG, IgG1, or IgG4 concentrations at age 2. Atopic children had higher OVA-IgA (P<0.001), OVA-IgG (P=0.001), OVA-IgG1 (P<0.001), and egg-IgE but lower OVA-IgG4/egg-IgE ratio (P<0.001) than non-atopic children. Longer duration of exclusive breastfeeding (≥4 vs. <4 months) was associated with reduced CM- and CAS-specific serum IgA (P<0.001) and IgG levels (P<0.001; P=0.003). CONCLUSION AND CLINICAL RELEVANCE: Allergy was associated with more intense IgA and IgG responses to OVA. Breastfeeding depressed humoral responses, whereas prebiotics and probiotics supplementation showed no immunomodulatory effect. The effect of probiotics on allergies is not mediated through food-specific antibody responses. Furthermore, OVA-specific IgA and IgG antibodies may help in assessing the risk for atopy.

Randomized trial comparing natural and synthetic surfactant: increased infection rate after natural surfactant?

The efficacy of a natural porcine surfactant and a synthetic surfactant were compared in a randomized trial. In three neonatal intensive care units, 228 neonates with respiratory distress and a ratio of arterial to alveolar partial pressure of oxygen <0.22 were randomly assigned to receive either Curosurf 100 mgkg-1 or Exosurf Neonatal 5 ml.kg-1. After Curosurf, the fraction of inspired oxygen was lower from 15 min (0.45 +/- 0.22 vs 0.70 +/- 0.22, p = 0.0001) to 6 h (0.48 +/- 0.26 vs 0.64 +/- 0.23, p = 0.0001) and the mean airway pressure was lower at 1 h (8.3 +/- 3.2 mm H20 vs 9.4 +/- 3.1 mm H20, p = 0.01). Thereafter the respiratory parameters were similar. The duration of mechanical ventilation (median 6 vs 5 d) and the duration of oxygen supplementation (median 5 vs 4 d) were similar for Curosurf and Exosurf. After Curosurf, C-reactive protein value over 40 mg l-1 occurred in 45% (vs 12%; RR 3.62, 95%CI 2.12-6.17, p = 0.001), leukopenia in 52% (vs 28%; RR 1.85, 95% CI 1.31-2.61, p = 0.001) and bacteraemia in 11% (vs 4%; RR 3.17, 95% CI 1.05-9.52, p < 0.05). We conclude that when given as rescue therapy Curosurf had no advantage compared with Exosurf in addition to the more effective initial response. Curosurf may increase the risk of infection.