Food allergy in adolescents: validation of the food allergy independent measure and the EuroPrevall food allergy quality of life questionnaire into Spanish

Background: Different questionnaires have been developed globally to assess and compare the impact of food allergy on the quality of life. The aim of this study was to validate a Spanish translation of the Food Allergy Independent Measure (FAIM) and the EuroPrevall Food Allergy–Quality of Life Questionnaire–Teenage Form (FAQLQ-TF) for adolescents aged 13–17 years. Methods: Sixty adolescents diagnosed with immunoglobulin E-mediated allergy to food completed the questionnaires. Cronbach’s alpha was used to assess internal consistency; correlation between FAQLQ-TF and FAIM was used to test construct validity. The discriminant validity was evaluated by comparison with the number of offending foods, the perceived impact on social life, the diagnosis of anaphylaxis, and the previous prescription of adrenaline auto--injectors (AAI). Results: No question fulfilled criteria to be removed from the questionnaire. For FAIM, Cronbach’s alpha = 0.763, and for the four domains of FAQLQ-TF, Cronbach’s alpha = 0.797–0.847. A significant correlation existed between FAQLQ-TF and FAIM, and of both of them with anaphylaxis and the prescription of AAI (P ˂ 0.05 for all comparisons). Conclusions: This Spanish translation of FAIM and FAQLQ-TF for adolescents had good internal consistency and construct validity as well as ability to discriminate patients according to the number of foods to avoid, impact on social life, diagnosis of anaphylaxis, and AAI prescription (AU)

First-in-human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy.

BACKGROUND: Polymerized allergens conjugated to non-oxidized mannan (PM-allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM-allergoids are readily taken up by DCs and induce Treg cells. This first-in-human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM-allergoid (PM-HDM) administered subcutaneously (SC) or sublingually (SL). METHODS: In a randomized, double-blind, double-dummy, placebo-controlled trial, 196 subjects received placebo or PM-HDM at 500, 1000, 3000, or 5000 mannan-conjugated therapeutic units (mTU)/mL in 9-arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. RESULTS: No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. CONCLUSIONS: PM-HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.

Validation of the food allergy independent measure and the EuroPrevall food allergy quality of life questionnaire for children 8–12 years translated into Spanish

Background Different questionnaires have been developed to measure quality of life (QoL) in patients with food allergy. Our aim was to validate a Spanish translation of the Food Allergy Independent Measure (FAIM) and the EuroPrevall Food Allergy Quality of Life Questionnaire—Child Form (FAQLQ-CF) for children aged 8–12 years.Methods Sixty children with a diagnosis of IgE-mediated allergy to food completed the questionnaires. The internal consistency was evaluated with Cronbach’s alpha. The correlation of FAQLQ-CF with FAIM was assessed to test construct validity. We compared both values with the diagnosis of anaphylaxis to evaluate discriminant validity.Results Cronbach’s alpha was in the range of 0.654–0.863 for the four domains of FAQLQ-CF and 0.779 for FAIM. There were no criteria to remove questions from the questionnaires. Significant correlations could be found between FAQLQ-CF and the number of offending foods and the impact on social life (all r > 0.33, P < 0.01), and between FAIM and anaphylaxis.Conclusions The Spanish translation of FAQLQ-CF showed acceptable internal consistency, good construct validity, and capacity to discriminate patients depending on the number of foods to avoid and the impact on social life. FAIM showed good discriminant capacity for anaphylaxis (AU).

Validation of the food allergy independent measure and the EuroPrevall food allergy quality of life questionnaire for children 8-12 years translated into Spanish.

BACKGROUND: Different questionnaires have been developed to measure quality of life (QoL) in patients with food allergy. Our aim was to validate a Spanish translation of the Food Allergy Independent Measure (FAIM) and the EuroPrevall Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF) for children aged 8-12 years. METHODS: Sixty children with a diagnosis of IgE-mediated allergy to food completed the questionnaires. The internal consistency was evaluated with Cronbach's alpha. The correlation of FAQLQ-CF with FAIM was assessed to test construct validity. We compared both values with the diagnosis of anaphylaxis to evaluate discriminant validity. RESULTS: Cronbach's alpha was in the range of 0.654-0.863 for the four domains of FAQLQ-CF and 0.779 for FAIM. There were no criteria to remove questions from the questionnaires. Significant correlations could be found between FAQLQ-CF and the number of offending foods and the impact on social life (all r > 0.33, P < 0.01), and between FAIM and anaphylaxis. CONCLUSIONS: The Spanish translation of FAQLQ-CF showed acceptable internal consistency, good construct validity, and capacity to discriminate patients depending on the number of foods to avoid and the impact on social life. FAIM showed good discriminant capacity for anaphylaxis.

Bacterial Mucosal Immunotherapy with MV130 Prevents Recurrent Wheezing in Children: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

Rationale: Recurrent wheezing in children represents a severe public health concern. Wheezing attacks (WA), mainly associated with viral infections, lack effective preventive therapies. Objectives: To evaluate the efficacy and safety of mucosal sublingual immunotherapy based on whole inactivated bacteria (MV130) in preventing WA in children. Methods: A Phase 3 randomized, double-blind, placebo-controlled, parallel-group trial including a cohort of 120 children <3 years old with ⩾3 WA during the previous year was conducted. Children with a positive skin test to common aeroallergens in the area where the clinical trial was performed were excluded from the trial. Subjects received MV130 or placebo daily for 6 months. The primary endpoint was the number of WA within 1 year after the first dose comparing MV130 and placebo. Measurements and Main Results: There was a significant lower number of WA in MV130 versus the placebo group, 3.0 (interquartile range [IQR], 2.0-4.0) versus 5.0 (IQR, 3.0-7.0) (P < 0.001). As secondary outcomes, a decrease in the duration of WA and a reduction in symptoms and medication scores in the MV130 versus placebo group were found. No adverse events were reported related to the active treatment. Conclusions: Mucosal bacterial immunotherapy with MV130 shows safety and clinical efficacy against recurrent WA in children.Clinical trial registered with www.clinicaltrials.gov (NCT01734811).

Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

The clinical evidence of second-generation H1-antihistamines in the treatment of allergic rhinitis and urticaria in children over 2 years with a special focus on rupatadine.

INTRODUCTION: Many obstacles limit the development of pharmacologic studies in children, in particular ethical and practical issues. Therefore, although second-generation H1-antihistamines (sgAH) are recommended by international guidelines as first-line therapy in childhood allergies, most data on the efficacy of antihistamines in children has been extrapolated from studies in adult patients. AREAS COVERED: The current review focuses on rupatadine, a well-studied modern sgAH that has dual affinity for histamine H1-receptors and PAF receptors. In recent years, clinical efficacy and safety controlled-clinical trials on rupatadine were conducted in children and were based on latest current guidelines using validated tools of allergic rhinitis and urticaria. EXPERT OPINION: Children are not little adults since they present specific physiologic, metabolic, and developmental differences that should be evaluated in specific trials. The clinical evidence with rupatadine in children is the most recent and validated in accordance with current recommendations, with extensive direct data on efficacy and safety in pediatric populations over 2 years old.

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

BACKGROUND: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. OBJECTIVE: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. METHODS: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. RESULTS: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). CONCLUSION: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.

Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study.

BACKGROUND: Peanut, tree nut, and sesame allergies are responsible for most life-threatening food-induced allergic reactions. Rates of coexistent allergy between these foods have been from mostly retrospective studies that include only a limited number of tree nuts or were not based on oral food challenges. OBJECTIVE: The Pronuts study is a multicenter European study (London, Geneva, and Valencia) assessing the challenge-proven rate of coexistent peanut, tree nut, and/or sesame seed allergy. METHODS: Children aged 0 to 16 years with at least 1 confirmed nut or sesame seed allergy underwent sequential diagnostic food challenges to all other nuts and sesame seed. RESULTS: Overall, the rate of coexistent peanut, tree nut, and sesame seed allergy was 60.7% (n = 74/122; 95% CI, 51.4% to 69.4%). Peanut allergy was more common in London, cashew and pistachio nut allergies were more common in Geneva, and walnut and pecan allergies were more common in Valencia. Strong correlations were found between cashew-pistachio, walnut-pecan, and walnut-pecan-hazelnut-macadamia clusters. Age (>36 months) and center (Valencia > Geneva > London) were associated with an increased odds of multiple nut allergies. By pursuing the diagnostic protocol to demonstrate tolerance to other nuts, participants were able to introduce a median of 9 nuts. CONCLUSION: We found a higher rate of coexistent nut and sesame seed allergies than previously reported. Performing sequential food challenges was labor intensive and could result in severe allergic reactions; however, it reduced dietary restrictions. Age was a significant predictor of multiple nut allergies, and thus the secondary spread of nut allergies occurred in older children.

Managing Nut Allergy: A Remaining Clinical Challenge.

Peanut and tree nut allergies have become a public health problem over the last 2 decades. The diagnostic procedure relies on a suggestive history, as well as on evidence of sensitization (skin prick testing and/or specific IgE blood testing), followed in selected cases by a food challenge. Standard IgE tests may be positive to more than 1 nut, due to cross-reactivity (allergens common to several nuts) or cosensitivity (frequently associated positive test results without cross-reactivity). Thus, many patients with a peanut or a tree nut allergy avoid all nuts, relying on positive test results without clinical evidence of reactivity. In addition, coexisting pollen sensitivity may add to diagnostic uncertainty due to potential cross-reactivity between pollens and nuts. In this article, we discuss challenges in diagnosis and clinical management of peanut and tree nut allergy related to cross-reactivity and cosensitization, as well as the avoidance of nuts tested positive to reduce the risk of reactions by cross-contamination. Studies to provide more accurate characterization of genuine clinically relevant cross-reactivity or cosensitivity to multiple nuts are needed.

[Progresses in the diagnosis of allergy]. / Progresos en el diagnóstico de la alergia.

The traditional diagnosis of allergy by Prick tests and/or RAST offers very limited information about the real nature of allergic problems and of their clinical, therapeutic and prognostic implications. The diagnosis by allergic components (natural or recombinant) suppose a great qualitative step leading a great improving in the diagnosis and treatment of allergic patients, because its use with clinical history and other diagnostic in vivo or in vitro methods improve importantly the diagnostic accuracy.

El diagnóstico tradicional de la alergia mediante pruebas por punción, RAST, o ambas, ofrece información muy limitada respecto a la auténtica naturaleza de los problemas alérgicos y de sus implicaciones clínicas, terapéuticas y de pronóstico. El diagnóstico por componentes alergénicos (naturales o recombinantes) supone un gran salto cualitativo que está permitiendo gran mejoría en el diagnóstico y tratamiento de los pacientes alérgicos, porque su uso concomitante con la historia clínica y otros métodos diagnósticos in vivo e in vitro mejora de manera relevante la precisión diagnóstica.

Allergy and asthma prevention 2014.

Asthma and allergic diseases have become one of the epidemics of the 21st century in developed countries. Much of the success of other areas of medicine, such as infectious diseases, lies on preventive measures. Thus, much effort is also being placed lately in the prevention of asthma and allergy. This manuscript reviews the current evidence, divided into four areas of activity. Interventions modifying environmental exposure to allergens have provided inconsistent results, with multifaceted interventions being more effective in the prevention of asthma. Regarding nutrition, the use of hydrolyzed formulas in high-risk infants reduces the incidence of atopic dermatitis, while there is for now not enough evidence to recommend other dietary modifications, prebiotics, probiotics, or other microbial products. Pharmacologic agents used until now for prevention have not proved useful, while there is hope that antiviral vaccines could be useful in the future. Allergen-specific immunotherapy is effective for the treatment of allergic patients with symptoms; the study of its value for primary and secondary prevention of asthma and allergy is in its very preliminary phases. The lack of success in the prevention of these disorders lies on their complexity, which involves many genetic, epigenetic, and environmental interactions. There is a need to identify target populations, involved mechanisms and interactions, and the best interventions. These must be effective, feasible, implementable, and affordable.

Pediatric allergy and immunology in Spain.

The data of the ISAAC project in Spain show a prevalence of childhood asthma ranging from 7.1% to 15.3%, with regional differences; a higher prevalence, 22.6% to 35.8%, is described for rhinitis, and atopic dermatitis is found in 4.1% to 7.6% of children. The prevalence of food allergy is 3%. All children in Spain have the right to be visited in the National Health System. The medical care at the primary level is provided by pediatricians, who have obtained their titles through a 4-yr medical residency training program. The education on pediatric allergy during that period is not compulsory and thus very variable. There are currently 112 certified European pediatric allergists in Spain, who have obtained the accreditation of the European Union of Medical Specialist for proven skills and experience in pediatric allergy. Future specialists in pediatric allergy should obtain their titles through a specific education program to be developed in one of the four accredited training units on pediatric allergy, after obtaining the title on pediatrics. The Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) gathers over 350 pediatric allergists and pediatricians working in this field. SEICAP has a growing activity including yearly congresses, continued education courses, elaboration of technical clinical documents and protocols, education of patients, and collaboration with other scientific societies and associations of patients. The official journal of SEICAP is Allergologia et Immunophatologia, published every 2 months since 1972. The web site of SEICAP, http://www.seicap.es, open since 2004, offers information for professionals and extensive information on pediatric allergic and immunologic disorders for the lay public; the web site is receiving 750 daily visits during 2011. The pediatric allergy units are very active in clinical work, procedures as immunotherapy or induction of oral tolerance in food allergy, contribution to scientific literature, and collaboration in international projects.

Sublingual immunotherapy for allergic respiratory diseases: an evaluation of meta-analyses.

BACKGROUND: Five published meta-analyses (MAs) seem to prove the efficacy of sublingual immunotherapy in allergic asthma and rhinoconjunctivitis. OBJECTIVE: We aimed to assess the consistency, magnitude, and robustness of the results of these MAs. METHODS: The data reported in the MAs were checked with the data reported in the original studies. Funnel plots were performed to test for potential publication bias, and the trim-and-fill method was used to assess and correct the estimate of the effects if asymmetry was present. RESULTS: The 5 MAs included 43 studies; 17 were used in more than one MA. There were discrepancies among the MAs in the data reported from the same original studies: the MAs reported different estimates for the same outcome or the same estimates for different outcomes in 16 of those 17 studies. The MAs evaluated 15 main outcomes, 10 of which showed benefits that reached statistical significance. Funnel plots showed asymmetry in 7 outcomes, and correction by using the trim-and-fill method led to a decrease in their effect estimates and even to a loss of statistical significance in 4 of the previously significant outcomes. There was inconsistency among the MAs in the benefits when considering age, disease, allergen, or symptoms and medication use. CONCLUSION: Because of discrepancies, inconsistencies, and lack of robustness, the MAs on sublingual immunotherapy do not provide enough evidence to support its current routine management in patients with allergic asthma or rhinoconjunctivitis. Sensitivity to potential publication bias should be tested and reported in all MAs.

Frequent IgE sensitization to latex, cow's milk, and egg in children with short bowel syndrome.

Children with short bowel syndrome (SBS) undergo frequent operations, so they are at risk for sensitizing to latex. There have been isolated reports of sensitization to food in these children. In a cross-sectional study, we assessed sensitization to latex, cow's milk, and egg with skin prick tests (SPT) and serum-specific immunoglobulin E (IgE) in 14 children with SBS. Data were collected about the number of operations with latex devices, serum total IgE, and history of feeding with milk formula. Ten children were sensitized to latex (specific IgE median: 6.7 kU/l, range: 0.5-33). Compared with those non-sensitized, sensitized children had significantly (p < 0.05) higher levels of serum total IgE in z-units (mean rank 3.25 vs. 9.2, respectively), and more operations with latex devices (mean rank 3.75 vs. 9). Eight children were sensitized to cow's milk, one with only positive SPT, the other seven with serum-specific IgE (median: 3.5, range: 0.5-21.1 kU/l), and five to egg (specific IgE median: 0.68, range: 0.58-2.17 kU/l). Except for some isolated days with cow's milk formula, the children had been initially fed with a diet without intact cow's milk proteins. Sensitization to latex, cow's milk, and egg is very frequent in children with SBS. They should be treated in a latex-free environment since the very early stages of the disease, and should be routinely studied regarding food sensitization, as this might contribute as an added factor in the chronic diarrhea of these patients.

Adverse effects of inhaled corticosteroids in funded and nonfunded studies.

BACKGROUND: Evidence regarding the safety profile of drugs may vary depending on study sponsorship. We aimed to evaluate differences between studies funded by the pharmaceutical manufacturer of the drug (PF) and those with no pharmaceutical funding (NoPF) regarding the finding and interpretation of adverse effects of inhaled corticosteroids. METHODS: We assessed the safety reporting of inhaled corticosteroids in 275 PF and 229 NoPF studies identified by a MEDLINE search using prespecified criteria. RESULTS: Overall, the finding of statistically significant differences for adverse effects was significantly less frequent in PF (34.5%) than in NoPF (65.1%) studies (prevalence ratio, 0.53; 95% confidence interval, 0.44-0.64). This association became nonsignificant (prevalence ratio, 0.94; 95% confidence interval, 0.77-1.15) after controlling for design features (such as dose or use of parallel groups) that tended to be associated with less frequent finding of adverse effects and were more common in PF studies. Among studies finding a statistically significant increase in adverse effects associated with the study drug, the authors of PF articles concluded that the drug was "safe" more frequently than the authors of NoPF studies (prevalence ratio, 3.68; 95% confidence interval, 2.14-6.33). CONCLUSIONS: The type of funding may have determinant effects on the design of studies and on the interpretation of findings: funding by the industry is associated with design features less likely to lead to finding statistically significant adverse effects and with a more favorable clinical interpretation of such findings. Disclosure of conflicts of interest should be strengthened for a more balanced opinion on the safety of drugs.