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.

Treatment with azelastine hydrochloride and fluticasone propionate in a single delivery device of young children and adolescents with allergic rhinitis.

Background: Allergic rhinitis (AR) is the most common chronic noncommunicable disease worldwide that affects any age during the human life span but raises particular concerns among the parents and caregivers of the children who are affected. H1-receptor antagonists and corticosteroids provide the most effective way of bringing the condition under control. Intranasal application of these medications has the advantage of a faster onset of action and avoids systemic unwanted adverse effects. The only combination treatment, which comprises azelastine hydrochloride and fluticasone propionate, so far in a single advanced delivery system has proven its efficacy and safety in clinical trials of adult patients with AR. Objective: To critically review and identify gaps in the existing data for children in all different strata of pediatric ages. Methods: We searched the specialized medical literature for publications on the efficacy and safety of the combined formulation of azelastine and fluticasone in a single delivery device in adolescents (ages < 18 years) and children (ages < 12 years). Results: Altogether, 12 peer-reviewed articles have been published about trials that also involved subjects in different strata of the pediatric ages, seven of the articles pooled adolescents and adults. Three articles presented the results of studies in children ages 4 to 11 years specifically designed to overcome the difficulties that children experience in expressing themselves verbally. Conclusion: All the trials with the novel combination product that involved young children and adolescents documented its efficacy, effectiveness, and safety. However, the numbers of the youngest children (ages 4 and 5 years) were low, which suggested that further data about safety and efficacy in this age group are needed.

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.

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.

Food allergy in adults in Europe: what can we learn from geographical differences?

PURPOSE OF REVIEW: The aim of this article is to characterize the present state-of-the-art on the topic of food allergies across Europe. RECENT FINDINGS: A systematic review and metaanalysis on the epidemiology of food allergy in Europe have been performed by the Food Allergy and Anaphylaxis Guidelines Group of the European Academy of Allergology and Clinical Immunology. The authors had made an extensive search of four different electronic databases which retrieved thousands of hits. A critical appraisal of the documents reduced their number to just over 100 articles covering the period 2000-2012, revealing striking methodological inhomogeneity and blank areas on the map of the continent, particularly for the adult population. A major new development intending to fill in the gaps in the field of food allergy is the launch and implementation of the European Union-funded project 'Prevalence, Cost and Basis of Food Allergy Across Europe,' acronym 'EuroPrevall.' Among the deliverable of the project are several seminal articles on food allergy in adults which are presented in this review. SUMMARY: The EuroPrevall project confirmed much more reliably and in more detail the existing inhomogeneity in the prevalence of food allergy, which reflects environmental and climate differences between the separate countries, but possibly also the level of public awareness.

Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry.

BACKGROUND: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. METHODS: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. RESULTS: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. CONCLUSIONS: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.

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.

Clinical characteristics of patients seeking medical advice for nasal symptoms in Bulgaria with special focus on children.

BACKGROUND: In an attempt to circumvent low response rates and high cost of classical epidemiological trials, we carried out a real-life survey among practicing physicians consulting patients for nasal symptoms. In this fragment of our work we analyze similarities and differences between children and adults and within the different strata of pediatric age. METHODS: A survey was carried out by 69 physicians across Bulgaria (general practitioners, allergists and otorhinolaryngologists) and made possible calculation of the proportion of subjects with nasal symptoms from all other patients seen. Its structure allowed classification of rhinitis according the ARIA guidelines. RESULTS: Out of the 1685 completed survey forms, 506 pertained to the age group below 18 years. The gender predominance differed in children and adults: 57.3 % vs. 42.8 % of males respectively, P < 0.001. The prevalence of persistent rhinitis in children was 55.7 %, lower than in adults, 63.3 %, P = 0.004. In both pediatric and adult patients moderately severe and severe forms of rhinitis prevailed, 93.7 % vs. 94.6 %, with nasal obstruction as leading symptom: 59.9 % vs. 58.8 %. Cough was significantly more prevalent among children, 72.5 %, gradually decreasing until reaching adulthood, 58.7 %, P < 0.001. Prevalence of doctor diagnosed asthma was also higher among children, 25.1 %, than in adults, 19.5 %, P = 0.011. A gradient for characteristics, which were different in children, emerged across the pediatric age strata. DISCUSSION: Our study uses an unorthodox design targeting the patient population visiting physicians' offices because of nasal symptoms, achieving a much higher level of credibility of the results at minimal expense. As we base our survey on international guidelines, we believe this approach demonstrates the applicability of such consensus documents for practical purposes when in the hands of qualified physicians. CONCLUSIONS: Moderate and severe rhinitis symptoms motivate patients and their guardians to seek medical advice. While nasal congestion is a leading bothersome symptom in both adults and children, specific other features characterize the pediatric age and differ across its strata.

Objective approach for fending off the sublingual immunotherapy placebo effect in subjects with pollenosis: double-blinded, placebo-controlled trial.

BACKGROUND: Symptom scoring for the assessment of allergen immunotherapy is associated with a substantial placebo effect. OBJECTIVE: To assess the ability of exhaled breath temperature (EBT), a putative marker of airway inflammation, to evaluate objectively the efficacy of grass pollen sublingual immunotherapy in a proof-of-concept study. METHODS: This was a double-blinded, placebo-controlled clinical trial in 56 subjects (mean ± SD 30 ± 12 years old, 33 men) sensitized to grass pollen. The objective measurements were EBT, spirometry, and periostin and high-sensitivity C-reactive protein in blood. Overall discomfort scored on a visual analog scale was used as a proxy for subjective symptoms. Evaluations were performed before, during, and after the grass pollen season. RESULTS: Fifty-one subjects (25 and 26 in the active treatment and placebo groups, respectively) were assessed before and during the pollen season. The mean pre- vs in-season increase in EBT was significantly smaller (by 59.1%) in the active treatment than in the placebo group (P = .030). Of the other objective markers, only the blood periostin level increased significantly during the pollen season (P = .047), but without intergroup differences. Subjectively, the mean pre- vs in-season increase in the visual analog scale score was 32.3% smaller in the active treatment than in the placebo group, although this difference did not reach statistical significance (P = .116). CONCLUSION: These results suggest that the efficacy of grass pollen sublingual immunotherapy can be assessed by EBT, a putative quantitative measurement of airway inflammation, which is superior in its power to discriminate between active and placebo treatment than a subjective assessment of symptoms assessed on a visual analog scale. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01785394.

Circadian changes in the sputum of asthmatic subjects and healthy controls.

BACKGROUND: : Asthma is exhibiting classical circadian fluctuations of clinical symptoms and airflow measurements, presumably influenced by the underlying airway inflammation and the endogenous cortisol secretion. The aim of our study was to examine the cellular and eosinophilic cationic protein (ECP) contents of sputum, collected andfrozen at 2 opposite time points of the day-and-night cycle, and tocorrelate them to blood cortisol levels. METHODS: : Thirteen subjects with uncontrolled asthma (8 men, aged 25-54 years) and 10 healthy subjects (6 men, aged 25-50 years) volunteered for the study. They were induced with hypertonic saline to produce sputum between 8:00 am and 9:00 am and between 8:00 pm and 9:00 pm, when blood was also withdrawn to measure cortisol levels. RESULTS: : Asthmatic subjects did not display significant morning/evening differences in their sputum total cell counts ([TCCs] median, 2.06 × 10 cells/mL; range 0.50-5.66 cells/mL vs median, 1.29 cells/mL; range, 0.24-9.26 cells/mL, P > 0.1), whereas controls had a well-defined morning peak (median, 0.75 cells/mL; range, 0.31-2.25 cells/mL vs median, 0.33 cells/mL; range, 0.1-0.97 cells/mL, P < 0.001). Asthmatic subjects had significantly higher sputum TCC than controls in the evening (P < 0.001), but their morning TCC did not significantly exceed those of the healthy subjects. Asthmatic subjects had significantly more sputum eosinophils and higher ECP levels than controls but failed to demonstrate significant morning/evening differences in contrast to the controls who had higher morning eosinophils and ECP. Macrophages were relatively increased in theevening samples of both asthmatic subjects and controls. No significant correlations between the circadian cortisol shift and any of the sputum indices were found. CONCLUSIONS: : Sputum undergoes circadian changes, which are different in health and in asthma and do not correlate with endogenous cortisol levels.