Estimating the Risk of Severe Peanut Allergy Using Clinical Background and IgE Sensitization Profiles.

Background: It is not well-understood why symptom severity varies between patients with peanut allergy (PA). Objective: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity. Methods: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity. Results: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54-0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC. Conclusions: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient.

Predicting food allergy: The value of patient history reinforced.

BACKGROUND: EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy-focused questionnaires. OBJECTIVE: To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food-related adverse reactions. METHODS: Adult and school-age participants in the standardized EuroPrevall population surveys, with self-reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with "probable" FA, defined as a food-specific case history supported by relevant IgE sensitization. RESULTS: In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29-1.41]), oral allergy symptoms (OAS) (4.46 [4.19-4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68-2.95]), asthma comorbidity (1.38 [1.30-1.46]) and male sex (1.50 [1.41-1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85-0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross-validation. In children (N = 670), OAS (2.26 [2.09-2.44]) and AR comorbidity (1.47 [CI 1.39-1.55]) contributed most to prediction of probable FA, with a combined cross-validation-based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. CONCLUSIONS: In both adults and school-age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA.

Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Predictors of Food Sensitization in Children and Adults Across Europe.

BACKGROUND: The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences. OBJECTIVE: To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures. METHODS: Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non-cross-reactive) FS. RESULTS: Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS. CONCLUSIONS: Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed.

Prevalence of Food Sensitization and Food Allergy in Children Across Europe.

BACKGROUND: For adults, prevalence estimates of food sensitization (FS) and food allergy (FA) have been obtained in a standardized manner across Europe. For children, such estimates are lacking. OBJECTIVES: To determine the prevalence of self-reported FA, FS, probable FA (symptoms plus IgE sensitization), and challenge-confirmed FA in European school-age children. METHODS: Data on self-reported FA were collected through a screening questionnaire sent to a random sample of the general population of 7- to 10-year-old children in 8 European centers in phase I of the EuroPrevall study. Data on FS and probable FA were obtained in phase II, comprising an extensive questionnaire on reactions to 24 commonly implicated foods, and serology testing. Food challenge was performed in phase III. RESULTS: Prevalence (95% CI) of self-reported FA ranged from 6.5% (5.4-7.6) in Athens to 24.6% (22.8-26.5) in Lodz; prevalence of FS ranged from 11.0% (9.7-12.3) in Reykjavik to 28.7% (26.9-30.6) in Zurich; and prevalence of probable FA ranged from 1.9% (0.8-3.5) in Reykjavik to 5.6% (3.6-8.1) in Lodz. In all centers, most food-sensitized subjects had primary (non-cross-reactive) FS. However, FS due to birch pollen related cross-reactivity was also common in Central-Northern Europe. Probable FA to milk and egg occurred frequently throughout Europe; to fish and shrimp mainly in the Mediterranean and Reykjavik. Peach, kiwi, and peanut were prominent sources of plant FA in most countries, along with notably hazelnut, apple, carrot, and celery in Central-Northern Europe and lentils and walnut in the Mediterranean. CONCLUSIONS: There are large geograhical differences in the prevalence of FS and FA in school-age children across Europe. Both primary and cross-reactive FS and FA occur frequently.

Food Allergy in Adults: Substantial Variation in Prevalence and Causative Foods Across Europe.

BACKGROUND: According to the community-based EuroPrevall surveys, prevalence of self-reported food allergy (FA) in adults across Europe ranges from 2% to 37% for any food and 1% to 19% for 24 selected foods. OBJECTIVE: To determine the prevalence of probable FA (symptoms plus specific IgE-sensitization) and challenge-confirmed FA in European adults, along with symptoms and causative foods. METHODS: In phase I of the EuroPrevall project, a screening questionnaire was sent to a random sample of the general adult population in 8 European centers. Phase II consisted of an extensive questionnaire on reactions to 24 preselected commonly implicated foods, and measurement of specific IgE levels. Multiple imputation was performed to estimate missing symptom and serology information for nonresponders. In the final phase, subjects with probable FA were invited for double-blind placebo-controlled food challenge. RESULTS: Prevalence of probable FA in adults in Athens, Reykjavik, Utrecht, Lodz, Madrid, and Zurich was respectively 0.3%, 1.4%, 2.1%, 2.8%, 3.3%, and 5.6%. Oral allergy symptoms were reported most frequently (81.6%), followed by skin symptoms (38.2%) and rhinoconjunctivitis (29.5%). Hazelnut, peach, and apple were the most common causative foods in Lodz, Utrecht, and Zurich. Peach was also among the top 3 causative foods in Athens and Madrid. Shrimp and fish allergies were relatively common in Madrid and Reykjavik. Of the 55 food challenges performed, 72.8% were classified as positive. CONCLUSIONS: FA shows substantial geographical variation in prevalence and causative foods across Europe. Although probable FA is less common than self-reported FA, prevalence still reaches almost 6% in parts of Europe.

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey.

BACKGROUND: Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens. OBJECTIVE: Establishing a molecular map of hazelnut allergy across Europe. METHODS: In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. RESULTS: Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. CONCLUSIONS: In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

Health-related quality of life in food-allergic adults from eight European countries.

BACKGROUND: Food allergy can impair health-related quality of life (HRQL). Food Allergy Quality of Life Questionnaires (FAQLQs) have been developed and validated, including an adult form (FAQLQ-AF). HRQL has not, to date, been measured across different European countries using a uniform methodology. OBJECTIVE: To translate and validate the FAQLQ-AF for use in 8 European countries (Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden). METHODS: The English FAQLQ-AF was translated, back-translated, and compared for use in the 8 relevant European languages. Adults with a perceived food allergy were recruited from outpatient departments and through a community survey. Participants completed the FAQLQ-AF, the Food Allergy Independent Measure, and questions concerning participants' characteristics. Validity of the FAQLQ-AF was analyzed for use in the 8 countries. RESULTS: The FAQLQ-AF had strong construct validity (r > 0.59) and an excellent internal consistency (Cronbach α > 0.95) in all countries. Total FAQLQ-AF scores (range 3.2-5.0) were significantly different across participating countries. CONCLUSION: The FAQLQ-AF is a suitable and valid instrument for measuring HRQL in food-allergic adults in Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden. The impact of food allergy on HRQL seems to differ among adults from the 8 participating European countries.

Kiwifruit allergy across Europe: clinical manifestation and IgE recognition patterns to kiwifruit allergens.

BACKGROUND: Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions. OBJECTIVE: We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated. METHODS: This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP. RESULTS: Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract. CONCLUSION: Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy.

Agreement between information provided by stroke patients and their relatives on psychophysical and vascular risk factors.

BACKGROUND: In studies examining vascular risk factors and the effects of stress in stroke patients, information sometimes has to be provided by a close relative. OBJECTIVES: The present study was designed to assess agreement between the information provided by a stroke patient and his/her next-of-kin or other close relative on prior vascular risk factors and situations of psychophysical stress based on a standardized interview within 72 h after stroke. DESIGN: Case-control observational study. PARTICIPANTS AND SETTINGS: All patients with incident stroke aged 18-65 years admitted to our centre were enrolled as cases, and their coinhabiting relatives as controls. The study was conducted from January to June 2008. METHODS: A structured questionnaire about vascular risk factors and psychophysical stress factors were obtained from the participants within 72 h after stroke. Subjects were required to grade themselves or their relatives using validated Spanish versions of the Life Events Stress Scale of Holmes and Rahe, Goldberg's General Health Questionnaire GHQ-28 and the SF-12 Health Survey, as well as the Spanish Type A Behaviour Scale. The questionnaires were self-administered. Cases and controls completed the same questionnaires and which were administered with a time difference of no longer than 24 h between the two groups of subjects. Risk factors were analyzed by determining kappa statistics and interclass correlation coefficients (ICC). Bland-Altman plots were used to examine the scores obtained in graded scales. RESULTS: 25 patients and 25 relatives were recruited. Agreement between cases and controls was good for reported atrial fibrillation, diabetes, alcohol consumption and smoking (range 0.83-1.0). ICC were low for the questionnaires Holmes-Rahe Life Events (0.26; 95%CI: 0.08-0.57), General Health GHQ-28 (0.39; 95%CI: 0.03-0.67) and SF12 Health Survey (0.52; 95%CI: 0.16-0.76 and 0.35; 95%CI: 0.06-0.66), and good for the Type A Behaviour Scale ERCTA (0.62; 95%CI: 0.32-0.81). CONCLUSIONS: The information obtained from family members on patient risk factors could be considered reliable, while that related to psychophysical aspects was not sufficiently reliable for research purposes. Agreement assessments could be useful to avoid misclassification biases.

Safety and efficacy of drug-eluting stents versus bare-metal stents in saphenous vein grafts lesions: a meta-analysis.

AIMS: Controversy exists about the safety and efficacy of drug-eluting stents (DES) in saphenous vein bypass grafts (SVGs). The aim of this study was to perform a meta-analysis of all published studies comparing DES and bare-metal stents (BMS) in patients with SVGs disease. METHODS AND RESULTS: We included 22 studies comparing DES versus BMS in 5,543 patients with SVGs disease. The primary efficacy endpoint was target vessel revascularisation (TVR). The primary safety endpoint was mortality. Other outcomes of interest were cardiac mortality, myocardial infarction, target lesion revascularisation (TLR), stent thrombosis and a combined of major adverse cardiac events (MACE). DES significantly reduced the risk of TVR, OR=0.56 (95% CI, 0.41-0.76, p=0.0003) and TLR, OR=0.58 (95% CI, 0.41-0.81; p=0.001). Total mortality and cardiac mortality were significantly lower in DES versus BMS, OR=0.69 (95% CI, 0.49-0.98, p=0.04) and OR=0.71 (95% CI, 0.51-0.99; p=0.04), respectively. The overall risk of stent thrombosis, and myocardial infarction were not significantly different for patients receiving DES vs. BMS. Total MACE were significantly lower in patients receiving DES, OR=0.55 (95% CI, 0.42-0.71; p<0.00001). CONCLUSIONS: This meta-analysis suggests that the use of DES in patients with SVG lesions is associated with a reduction of the need of reintervention and mortality compared with BMS.

Lower levels of in-stent late loss are not associated with the risk of stent thrombosis in patients receiving drug-eluting stents.

AIMS: The aim of this study was to evaluate whether there is any relationship between in-stent late loss (ISLL) and the risk of stent thrombosis (ST) in patients treated with drug eluting stents (DES). The benefit of DES in reducing binary angiographic restenosis and the need for new revascularisation procedures is due to a reduction on ISLL. It has been hypothesised, however, that neointimal hyperplasia could preclude ST, and thus a very low ISLL could increase the risk of ST. METHODS AND RESULTS: We selected 26 randomised clinical trials comparing bare metal stents and DES or different DES types, and including clinical and angiographic follow-up. In order to evaluate the association between risk of ST and ISLL, meta-regression analyses were conducted, weighting for the number of patients of each study. Twenty-six studies were included, retrieving 36 subgroups for analysis and 8,971 patients treated with DES. The incidence for ST and LST was 0.81% and 0.17%. Using meta-regression techniques, neither the risk of ST nor the risk of LST were found to be significantly associated with ISLL, accounting for -0.82 and -0.002 meta-regression estimates respectively (IC 95%: -1.92 to 0.28 for ST and -0.008 to 0.003 for LST). CONCLUSIONS: The risk of ST and LST after DES implantation is not related with ISLL values. A very low mean value of ISLL is nor associated with a higher risk of ST.

Risk of late-acquired incomplete stent apposition after drug-eluting stent versus bare-metal stent. A meta-analysis from 12 randomized trials.

BACKGROUND: Incomplete stent apposition (ISA) is an unusual finding of intravascular ultrasound (IVUS) that may occur both after drug-eluting stent (DES) or bare-metal stent (BMS) implantation and could be associated with late stent thrombosis. Controversy still remains about whether the risk of late-acquired ISA is increased after DES implantation. This meta-analysis aimed to clarify whether DES implantation is associated with an increased risk of late-acquired ISA. METHODS: We performed a meta-analysis from 12 randomized trials that compared DES and BMS and included IVUS follow up: TAXUS II (n = 469), TAXUS IV (n = 187), TAXUS V (n = 213) and VI (n = 147), ASPECT (n = 81), DELIVER (n = 65), SIRIUS (n = 141), DIABETES (n = 140), ENDEAVOR II (n = 250), FUTURE I and II (n = 83), and SPIRIT-I (n = 58). In these trials, 1,834 patients (972 DES, and 862 BMS) underwent immediate and follow-up IVUS examination. RESULTS: There was no heterogeneity among the trials (Q-test for heterogeneity: Chi2: 7.69; (p = 0.26), I2: 22%. Out of the 1,834 patients undergoing serial IVUS examination, 85 developed late-acquired ISA (4.6%). This incidence was significantly higher in DES compared with BMS (6.5% vs. 2.6%, respectively; odds ratio [OR] 2.48, 95% confidence interval [CI] 1.26 to 4.87; p = 0.008). That means that the risk of developing late-acquired ISA is 2.5 times higher after DES versus BMS implantation. No stent thrombosis occurred in the patients diagnosed with ISA over a period up to 12 months. CONCLUSION: DES implantation could be associated with an increased risk of late ISA in comparison with BMS. The clinical implication of late ISA in the long term remains to be clarified.