Predictors of anaphylaxis to peanut and tree nuts in a Mediterranean population.

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.

Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults.

BACKGROUND: Tree nut allergy may cause anaphylaxis. There are limited population-based studies on prevalence and early-life risk factors. METHODS: We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population-based cohort study and assessed early-life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early-life risk factors. RESULTS: Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non-mild symptoms). Sixty-three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15-33.6), eczema (ORadj 2.53 95% CI 1.21-5.32) and asthma (ORadj 5.59 95% CI 2.35-13.3)) at pre-school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. CONCLUSIONS: In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.

Real-world tree nut consumption in peanut-allergic individuals.

BACKGROUND: Individuals with peanut allergy often avoid tree nuts, yet true rates of tree nut allergy in peanut-allergic individuals are as low as 7%. OBJECTIVE: To examine tree nut sensitization patterns in peanut-allergic individuals, patient and family choice regarding tree nut consumption, and factors that influence consumption of tree nuts. METHODS: All patients presenting for peanut allergy evaluation to an outpatient allergy office were included during a 4-month period. In addition to demographic information, sensitization to tree nuts and tree nut consumption were collected. Logistic regression was performed to generate odds ratios with 95% CIs in univariate and multivariate analyses for variables that predict tree nut consumption. RESULTS: A total of 258 individuals with peanut allergy were enrolled. Ninety-five (36.8%) consumed all tree nuts ad libitum, 63 (24.4%) consumed some but not all tree nuts, and 100 (38.8%) consumed no tree nuts. Of the 100 electively avoiding all tree nuts, the most commonly reported reason was fear of cross-contact (50%). Although there was no difference between rates of sensitization between individual tree nuts (P = .056), cashew and pistachio had higher serum specific IgE levels compared with other tree nuts (P < .001). The tree nut most commonly consumed by peanut-allergic individuals was almond (P < .001). Consumption of foods with precautionary labeling was the strongest predictor of tree nut consumption in peanut allergic individuals (P < .001) CONCLUSION: Our data highlight the potential for safe introduction of tree nuts in peanut-allergic individuals and indicate that peanut-allergic individuals who consume foods with precautionary labeling are most likely to consume tree nuts.

Effect of fatty fish or nut consumption on concentrations of persistent organic pollutants in overweight or obese men and women: A randomized controlled clinical trial.

BACKGROUND AND AIMS: While excess energy intake and physical inactivity constitute the obvious causes of body fat accumulation, persistent organic pollutants (POPs) are novel factors that have been linked to cardiometabolic disorders. Major sources of POPs are animal fats including fatty fish. Given the putative protective effects of fish on cardiovascular disease, we explored whether high consumption of fatty fish increased serum concentrations of POPs. METHODS AND RESULTS: Men and women aged 35-70 years with body mass index between 25 and 38 kg/m2 and at least 1 cardiometabolic component were randomized to high intakes of fatty fish (mostly farmed salmon, ∼630 g/week; n = 45), high intakes of nuts (∼200 g/week; n = 42) or a control group following their usual diet but restricting fatty fish and nuts for 6 months (n = 44). Concentrations of 15 POPs (5 organochlorinated compounds, 2 dioxin-like polychlorinated biphenyls and 8 non-dioxin-like polychlorinated biphenyls) and cardiometabolic risk factors were measured at baseline and end of the study. Results showed that changes in concentrations of individual and classes of POPs did not differ between the dietary groups and controls (p > 0.05). Among cardiometabolic risk factors HDL-cholesterol increased in the fatty fish group compared to controls (+0.10 mmol/L, CI (0.05-0.20); p = 0.005) while no changes were observed in the group consuming nuts. CONCLUSION: Fatty fish consumption for 6 months did not increase the serum concentrations of POPs in individuals with overweight or obesity and metabolic risk. While this finding appears reassuring regarding short-term intakes of farmed salmon, long term variations in POPs in adipose stores require further study.

Influence of Instant Controlled Pressure Drop (DIC) on Allergenic Potential of Tree Nuts.

Pistachio and cashew contain allergenic proteins, which causes them to be removed from the diet of allergic people. Previous studies have demonstrated that food processing (thermal and non-thermal) can produce structural and/or conformational changes in proteins by altering their allergenic capacity. In this study, the influence of instant controlled pressure drop (DIC) on pistachio and cashew allergenic capacity has been studied. Western blot was carried out using IgG anti-11S and anti-2S and IgE antibodies from sera of patients sensitized to pistachio and cashew. DIC processing causes changes in the electrophoretic pattern, reducing the number and intensity of protein bands, as the pressure and temperature treatment increment, which results in a remarkable decrease in detection of potentially allergenic proteins. The harshest conditions of DIC (7 bar, 120 s) markedly reduce the immunodetection of allergenic proteins, not only by using IgG (anti 11S and anti 2S) but also when IgE sera from sensitized patients were used for Western blots. Such immunodetection is more affected in pistachio than in cashew nuts, but is not completely removed. Therefore, cashew proteins are possibly more resistant than pistachio proteins. According these findings, instant controlled pressure drop (DIC) can be considered a suitable technique in order to obtain hypoallergenic tree nut flour to be used in the food industry.

Evidence of Cross-Reactivity between Different Seed Storage Proteins from Hazelnut (Corylus avellana) and Walnut (Juglans regia) Using Recombinant Allergen Proteins.

Seed storage proteins are extremely stable allergens in nuts, seeds, and legumes and are responsible for the most severe allergic reactions to these foods. The cross-reactivity between seed storage proteins from different sources has not been studied at a molecular level so far. This study aimed to ascertain the cross-reactivity between walnut and hazelnut seed storage proteins using recombinant allergens. Sera from 13 consecutive patients with severe primary walnut and/or hazelnut allergy and hypersensitive to both nuts were studied. IgE specific for rCor a 9, rCor a 14, and rJug r 1 was measured, and inhibition experiments were carried out by measuring IgE reactivity after absorption of patients' sera with freshly prepared walnut extract. All 13 sera showed strong IgE reactivity against walnut 2S albumin, Jug r 1, 12 reacted to hazelnut 2S albumin, Cor a 14, and 8 to the hazelnut legumin, Cor a 9. In inhibition experiments, absorption of sera with whole walnut extract led to the complete disappearance of IgE reactivity to Jug r 1 in 12/13 cases, as expected, but also to the complete disappearance of specific IgE to Cor a 14 in 9/12 sera, and of IgE reactivity to Cor a 9 in 7/8. In the remaining cases a dramatic drop in IgE reactivity was observed. The study shows that patients primarily allergic to either walnut or hazelnut showing a skin or serological reactivity to the other nut also are potentially at risk of severe allergic reactions caused by cross-reactivity between 2S albumins and legumins.

IgE Cross-Reactivity of Cashew Nut Allergens.

BACKGROUND: Allergic sensitisation towards cashew nut often happens without a clear history of eating cashew nut. IgE cross-reactivity between cashew and pistachio nut is well described; however, the ability of cashew nut-specific IgE to cross-react to common tree nut species and other Anacardiaceae, like mango, pink peppercorn, or sumac is largely unknown. OBJECTIVES: Cashew nut allergic individuals may cross-react to foods that are phylogenetically related to cashew. We aimed to determine IgE cross-sensitisation and cross-reactivity profiles in cashew nut-sensitised subjects, towards botanically related proteins of other Anacardiaceae family members and related tree nut species. METHOD: Sera from children with a suspected cashew nut allergy (n = 56) were assessed for IgE sensitisation to common tree nuts, mango, pink peppercorn, and sumac using dot blot technique. Allergen cross-reactivity patterns between Anacardiaceae species were subsequently examined by SDS-PAGE and immunoblot inhibition, and IgE-reactive allergens were identified by LC-MS/MS. RESULTS: From the 56 subjects analysed, 36 were positive on dot blot for cashew nut (63%). Of these, 50% were mono-sensitised to cashew nuts, 19% were co-sensitised to Anacardiaceae species, and 31% were co-sensitised to tree nuts. Subjects co-sensitised to Anacardiaceae species displayed a different allergen recognition pattern than subjects sensitised to common tree nuts. In pink peppercorn, putative albumin- and legumin-type seed storage proteins were found to cross-react with serum of cashew nut-sensitised subjects in vitro. In addition, a putative luminal binding protein was identified, which, among others, may be involved in cross-reactivity between several Anacardiaceae species. CONCLUSIONS: Results demonstrate the in vitro presence of IgE cross-sensitisation in children towards multiple Anacardiaceae species. In this study, putative novel allergens were identified in cashew, pistachio, and pink peppercorn, which may pose factors that underlie the observed cross-sensitivity to these species. The clinical relevance of this widespread cross-sensitisation is unknown.

Long-term association of nut consumption and cardiometabolic risk factors.

BACKGROUND AND AIMS: Long-term associations between nut consumption and cardiometabolic risk factors are not well known. We investigated the relationship between nut consumption and cardiometabolic risk factors including dyslipidemia, hypertension, diabetes mellitus (DM), and obesity in a cohort of Iranian adults. METHODS AND RESULTS: The study was conducted within the framework of the Isfahan Cohort Study on 1387 healthy participants. The participants were followed up for 12 years. A validated food frequency questionnaire was completed, and anthropometric measurements, blood pressure, and fasting serum lipids and blood sugar were evaluated in three phases. Mixed-effects binary logistic regression was applied to examine the associations between nut consumption and cardiometabolic risk factors. The participants were classified according to the tertiles of nut consumption as cut-points, and associations were evaluated between the thirds of nut intake. Subjects in the last third were less likely to have hypercholesterolemia [OR (95% CI): 0.76 (0.60-0.97)], hypertriglyceridemia [OR (95% CI): 0.74 (0.58-0.93)], and obesity [OR (95% CI): 0.79 (0.50-0.98)] but more likely to have DM [OR (95% CI): 1.85 (1.27-2.68)] than those in the first third. However, after adjustment for various potential confounders, the associations remained significant only for obesity [OR (95% CI): 0.67 (0.48-0.94)] and DM [OR (95% CI): 2.23 (1.37-3.64)]. CONCLUSION: After adjustment for potential confounders, we observed an inverse association for nut consumption and obesity but positive association for DM and nut intake. On the basis of our findings, it is suggested that incorporation of nuts into people's usual diet may have beneficial effects for individuals with lower risk such as subjects without DM.

Factors predicting anaphylaxis in children with tree nut allergies.

Background: Tree nut (TN) allergies are the most common cause of fatal anaphylaxis and generally are ongoing food allergies throughout life. Objective: To investigate the predicting factors for TN anaphylaxis in children. Methods: Children with TN allergy were divided into anaphylactic and nonanaphylactic groups, those who had an anaphylactic reaction with at least one type of TN and those with any type of reaction other than anaphylaxis with TNs, respectively. Children with TN allergies were evaluated for the predictors of anaphylaxis by using multivariate logistic regression analysis. Results: A total of 184 children (ages 4.9 years; 3.2-6.9 years) with TN allergy were included in the study. Of these, 90 experienced an anaphylactic type of reaction on exposure to at least one type of TNs. Comparisons of the two groups showed that concomitant asthma, skin-prick test, specific immunoglobulin E, total immunoglobulin E, and serum basal tryptase (sBT) levels were significantly higher in the anaphylactic group compared with the nonanaphylactic group. In multivariate analysis, female gender (odds ratio [OR] 4.905 [95% confidence interval {CI}, 1.266-19.001], p = 0.021), sBT levels (OR 2.287 [95% CI, 1.431-3.654], p < 0.001), concomitant egg white allergy (OR 4.135 [95% CI, 1.016-16.481], p = 0.048), and concomitant asthma (OR 3.874 [95% CI, 1.109-13.526], p = 0.034) were risk factors for anaphylaxis. The optimal cutoff value for sBT was 2.06 ng/mL, with a sensitivity of 85.9% and a specificity of 69%, as well as an area under the curve 0.810 (95% CI, 0.717-0.903, p < 0.001). The sBT levels of 1.94 ng/mL and 5.30 ng/mL predicted clinical reactivity at 50% and 95% probabilities. Conclusion: Different aspects, including gender, higher mast cell load and/or activation, and a stronger atopic background (e.g., coexisting egg allergy, asthma), contributed to the development of anaphylactic reactions to TNs in children.

Tree nut allergies: Allergen homology, cross-reactivity, and implications for therapy.

Tree nut allergy is a potentially life-threatening disease that is increasing in prevalence, now affecting 1% of the general population in the United States. While other food allergies often resolve spontaneously, tree nut allergies are outgrown in less than 10% of cases. Due to the likelihood of cross-sensitization to multiple tree nut allergens, the current treatment guideline is strict avoidance of all nuts once one tree nut allergy has been diagnosed. For example, walnut and pecan are highly cross-reactive, along with cashew and pistachio, but the extent of clinical, IgE-mediated cross-reactivity among other tree nuts remains unclear, therefore making avoidance of all tree nuts a safe approach. There have been recent advances in immunotherapy for food allergies. For instance, there are investigational immunotherapies for milk, egg and peanut allergies, specifically oral immunotherapy, sublingual immunotherapy and epicutaneous immunotherapy. However, there are no large randomized controlled clinical trials for tree nut allergies. Even though there has been less research into tree nut allergy immunotherapies, the evidence of T-cell cross-reactivity among tree nuts exists in animal models and in T cells from allergic patients indicates that immunotherapeutic interventions may be possible. Here, we review the literature regarding epidemiology, allergen homology and cross-reactivity among tree nuts, and explore how current findings can be employed for effective therapy.

Comparing the eating out experiences of consumers seeking to avoid different food allergens.

BACKGROUND: Eating outside the home is challenging for consumers with food allergy (FA) and intolerance (FI) and lack of allergen information provision in eating out venues can lead to unnecessary restrictions. Following European legislation (2014) designed to improve allergen information provision, little is known about differences in information provision experienced by consumers seeking to avoid particular allergens, or how this impacts on their eating out experiences. This study compared the information provision that consumers with FA/FI to different allergens experience when eating out. METHODS: Using mixed methods, participants were recruited from across the UK and took part in self-report surveys or in-depth interviews. Surveys were completed by 232 participants avoiding either gluten (n = 66), nuts (peanuts/tree nuts) (n = 94), or milk (n = 74), and responses were subject to quantitative analyses. Interviews were carried out with 49 participants avoiding either gluten (n = 13), nuts (n = 14), milk (n = 13) or a combination of these allergens (n = 9), and analysed using the framework approach. RESULTS: Although general improvements in information provision following the legislation were reported, variations in provision between allergen groups led participants seeking to avoid milk to conclude that their dietary needs were less well-understood and seen as less important. These perceptions were reflected in a reluctance to involve eating out venue staff in deliberations about the potential for milk-free meal options. CONCLUSIONS: The provision of visual indicators of the presence of milk and of staff trained in allergen-awareness would improve the eating out experiences of consumers seeking to avoid milk. Medical professions can play a key role in encouraging these patients to pursue their right to make enquiries about allergens in order to avoid accidental milk ingestion when eating out.

Correlation of negative skin-prick test results for tree nuts and successful tree nut challenges among children with peanut allergy.

Background: Children with peanut allergy are regularly instructed to avoid all tree nuts. However, children with peanut allergy are likely not allergic to all tree nuts. Objective: In our cohort of patients with peanut anaphylaxis and who underwent oral immunotherapy, we sought to determine the correlation of skin-prick testing (SPT) results for tree nuts and the likelihood of successfully passing a tree nut challenge. Methods: SPT was performed for peanut and tree nuts (macadamia, pine nut, coconut, hazelnut, brazil nut, cashew, pecan, walnut, pistachio, almond) in 27 patients with known peanut allergy. The probability of a negative SPT result (wheal < 3 mm) for each nut was determined. Results: All the patients demonstrated positive results in peanut allergy diagnostics in SPT, component testing, or food challenge. Only 15.4% of the patients had a positive SPT result to peanut alone. Macadamia, pine nut, and coconut SPT had a probability of negative SPT results of 0.97, 0.97, and 0.91, respectively. The odds ratio for this group having a negative SPT was 46.22. For hazelnut, brazil nut, and cashew, the probability of a negative SPT result was 0.81, 0.77, and 0.73, respectively. Pecan, walnut, and pistachio had odds ratios of 0.68, 0.68, and 0.64, respectively. All the patients with macadamia, pine nut, and coconut negative SPT results subsequently passed 9-g food challenges without oral immunotherapy. Conclusion: Despite current recommendations to avoid all tree nuts for patients with peanut allergy, the majority of patients with peanut allergy had negative SPTs and food challenges to certain tree nuts, especially macadamia, pine nut, and coconut. This pattern was seen despite most patients having multiple nut sensitizations.

'Everybody has to think - do I have any peanuts and nuts in my lunch?' School nurses, collective adherence, and children's food allergies.

Developing robust explanations for patients' non-adherence to medical treatments is a pressing clinical concern. Social scientists have emphasised the importance of taking a 'patient-centred' approach to the study of illness management. Using data from a qualitative study of the management of children's food allergies, I found that school nurses created what I term collective adherence - the translation of individual medical recommendations into prescriptions to be followed by entire communities. School nurses secured collective adherence by aligning physicians, schools, and families around a particular interpretation of medical recommendations, setting guidelines of behaviour for the entire school community to follow, and balancing the diverging needs of illness sufferers and non-illness sufferers. This study contributes to the study of adherence by examining the medical recommendation as a dynamic prescription, extending adherence to the study of ancillary providers' interaction with medical recommendations, and examining the impact of illness on non-family ties. I conclude with a discussion of implications for the field of school nursing; and potential applications of the collective adherence framework to the management of health conditions and health risks.

sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children sensitized to cashew nuts.

BACKGROUND: The double-blind, placebo-controlled food challenge test (DBPCFC) is the gold standard in cashew nut allergy. This test is costly, time consuming and not without side effects. Analysis of IgE reactivity to cashew nut components may reduce the need for food challenge tests. METHODS: In a prospective and multicentre study, children with suspected cashew nut allergy underwent a DBPCFC with cashew nut. Specific IgE to cashew nut and to the components Ana o 1, 2 and 3 were determined. A skin prick test (SPT) with cashew nut extract was performed. The association between the outcome of the food challenge test and specific IgE to Ana o 1, 2 and 3 was assessed with logistic regression analyses, unadjusted and adjusted for other diagnostic variables. Discriminative ability was quantified with a concordance index (c). RESULTS: A total of 173 children (103 boys, 60%) with a median age of 9 years were included. About 79% had a positive challenge test outcome. A steep rise in the risk of a positive challenge was observed for specific IgE to each individual component Ana o 1, 2 and 3 with estimated risks up to approximately 100%. Median values of Ana o 1, 2, 3 were 1.29 kU/l (range 0-100 kU/l), 4.77 kU/l (range 0-100 kU/l) and 8.33 kU/l (range 0-100 kU/l) respectively and varied significantly (p < 0.001). Specific IgE to Ana o 1, 2 and 3 was better distinguished between cashew-allergic and tolerant children (c = 0.87, 0.85 and 0.89, respectively) than specific IgE to cashew nut or SPT (c = 0.76 and 0.83, respectively). CONCLUSION: The major cashew nut allergens Ana o 1, 2 and 3 are each individually predictive for the outcome of food challenge tests in cashew-allergic children.