Validation of the Finnish version of the food allergy quality of life questionnaire-parent form (F-FAQLQ-PF).

AIM: Specific questionnaires about food allergy and health-related quality of life (HRQoL) have been developed and validated in several languages, but not Finnish. We aimed to validate the Finnish Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) for children under age 13 years. METHODS: The original FAQLQ-PF and Food Allergy Independent Measure (FAIM) were translated into Finnish per World Health Organisation guidelines and tested by 72 parents of children under age 13 years with suspected severe peanut or tree nut allergy who were recruited at Allergy Centre in Tampere University Hospital in Tampere, Finland. We calculated the construct validity of the questionnaire by calculating the coefficients between the two measures and used Cronbach's alpha to establish the internal consistency. RESULTS: The FAQLQ-PF showed strong correlations with domain structure and internal consistency, based on Spearman's correlations (rho) for the HRQoL questions, FAIM questions and FAIM mean values. The total questionnaire score correlated significantly with the mean FAIM (rho = 0.95, p < 0.001) and individual FAIM questions. The FAQLQ-PF and domains had good or excellent internal consistency (Cronbach's alpha >0.70). CONCLUSION: The Finnish FAQLQ-PF demonstrated good construct validity and excellent internal consistency for measuring food allergy HRQoL in children under age 13 years.

Haemostatic differences between SARS-CoV-2 PCR-positive and negative patients at the time of hospital admission.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombosis. We conducted a cohort study of consecutive patients, suspected of SARS-CoV-2 infection presented to the emergency department. We investigated haemostatic differences between SARS-CoV-2 PCR positive and negative patients, with dedicated coagulation analysis. The 519 included patients had a median age of 66 years, and 52.5% of the patients were male. Twenty-six percent of the patients were PCR-positive for SARS-CoV-2.PCR positive patients had increased levels of fibrinogen and (active) von Willebrand Factor (VWF) and decreased levels of protein C and α2-macroglobulin compared to the PCR negative patients. In addition, we found acquired activated protein C resistance in PCR positive patients. Furthermore, we found that elevated levels of factor VIII and VWF and decreased levels of ADAMTS-13 were associated with an increased incidence of thrombosis in PCR positive patients. In conclusion, we found that PCR positive patients had a pronounced prothrombotic phenotype, mainly due to an increase of endothelial activation upon admission to the hospital. These findings show that coagulation tests may be considered useful to discriminate severe cases of COVID-19 at risk for thrombosis.

Quality of spirometry and related diagnosis in primary care with a focus on clinical use.

American and European societies' (ATS/ERS) criteria for spirometry are often not met in primary care. Yet, it is unknown if quality is sufficient for daily clinical use. We evaluated quality of spirometry in primary care based on clinical usefulness, meeting ATS/ERS criteria and agreement on diagnosis between general practitioners (GPs) and pulmonologists. GPs included ten consecutive spirometry tests and detailed history questionnaires of patients who underwent spirometry as part of usual care. GPs and two pulmonologists assessed the spirometry tests and questionnaires on clinical usefulness and formulated a diagnosis. In total, 149 participants covering 15 GPs were included. Low agreements were found on diagnosis between GPs and pulmonologists 1 (κ = 0.39) and 2 (κ = 0.44). GPs and pulmonologists rated >88% of the tests as clinically useful, although 13% met ATS/ERS criteria. This real-life study demonstrated that clinical usefulness of routine primary care spirometry tests was high, although agreement on diagnosis was low.

Long-term follow-up of bladder outlet procedures in children with neurogenic urinary incontinence.

INTRODUCTION: Achieving continence in children with neurogenic sphincteric incompetence is a challenge. Awareness of the long-term outcome in this young patient population is important. In the past 25 years, the study institution has built experience in bladder outlet procedures such as bladder neck sling and bladder neck reconstructions. OBJECTIVE: The objective of this study was to evaluate the long-term outcome on continence and re-intervention rate of bladder outlet procedures in children with neurogenic urinary incontinence at the study institution. DESIGN: All children who underwent a bladder neck procedure between 1992 and 2017 at the study institution were retrospectively reviewed. Continence at the end of follow-up was the primary endpoint, defined as 'dry' when there was an interval of a minimum of 4 h without urinary leakage. Non-parametric tests were used for statistical analysis. RESULTS: During this 25-year period, a total of 60 children underwent a bladder outlet procedure, either a bladder neck sling (n = 43) or a bladder neck reconstruction (n = 17). The median age at surgery was 11.6 years (interquartile range [IQR] 7.8-13.9). Concomitant surgery consisted of bladder augmentation in 80% and continent catheterizable urinary channel in 97% of children. Dry rate within 1 year was 38%. After a median follow-up of 10.4 years (IQR 6.5-15.5), 77% of all children were dry. Twenty-five children (42%) needed one or more re-interventions, including redo of the bladder outlet procedure, other type of outlet procedure, bulking agents, bladder augmentation, and bladder neck closure. DISCUSSION: This study confirms that achieving continence is a challenge. The inconsistent use of the definition of urinary continence creates confusion in the literature and makes comparison of outcome with other studies difficult. Openness of (long-term) results in achieving urinary continence is important and helpful for future patients. CONCLUSION: On the long term, the majority of children with neurogenic urinary incontinence were dry after a bladder outlet procedure, but a considerable number of patients had a re-intervention. The initial outcome on continence was slightly disappointing. Reporting long-term results is essential and helpful for patient counseling.

Retrospective observational cohort study regarding the effect of breastfeeding on challenge-proven food allergy.

BACKGROUND/OBJECTIVES: Human breast milk is generally regarded as the best nutrition for infants in their first months of life. Whether breastfeeding has a protective effect on food allergy is a point of debate and the subject of this study. SUBJECTS/METHODS: This retrospective study was conducted in 649 children who underwent a double-blind placebo-controlled food challenge (DBPCFC) as part of routine care in a tertiary care clinic. Food allergy was defined as having at least one positive DBPCFC to any food. The association between both "any" breastfeeding (yes/no) and its duration in months with food allergy was studied by logistic regression analysis with correction for confounding variables. RESULTS: The prevalence of food allergy was 58.9% (n = 382). Of all subjects, 75.8% (n = 492) was breastfed and 24.2% (n = 157) bottle-fed. There was no significant association between food allergy and breastfeeding versus bottle-feeding after correction for the confounding effect of increased breastfeeding by atopic parents and a history of asthma in the child (OR = 1.24, 95% CI = 0.85-1.79, p = 0.27). However, in breastfed children, every additional month of breastfeeding lowered the risk for food allergy by ~4% (OR = 0.96, 95% CI = 0.93-0.99, p = 0.02). No confounders were identified in this association. CONCLUSION: These results show for the first time that in children investigated for possible food allergy, every additional month of breastfeeding is associated with a lower risk of developing clinical food allergy as diagnosed by DBPCFC. However, overall, there was no association between the prevalence of food allergy and breastfeeding versus bottle-feeding in this tertiary care population.

Prediction of the severity of allergic reactions to foods.

BACKGROUND: There is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted. OBJECTIVE: To identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact. METHODS: The study population consisted of children with a double-blind, placebo-controlled food challenge (DBPCFC)-confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions. RESULTS: A total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B = 0.30, P < .001), eliciting dose (B = -0.09, P < .001), level of specific immunoglobulin E (B = 0.15, P < .001), reaction time during the DBPCFC (B = -0.01, P = .004), and severity of accidental reaction (B = 0.08, P = .015). The total explained variance of this model was 23.5%, and the eliciting dose only contributed 4.4% to the model. Independent predictors for more severe accidental reactions with an explained variance of 7.3% were age (B = 0.03, P = .014), milk as causative food (B = 0.77, P < .001), cashew as causative food (B = 0.54, P < .001), history of atopic dermatitis (B = -0.47, P = .006), and severity of DBPCFC reaction (B = 0.12, P = .003). CONCLUSIONS: The severity of DBPCFCs and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk-related management decisions.

Bacillus Calmette-Guérin vaccination at birth and in vitro cytokine responses to non-specific stimulation. A randomized clinical trial.

Several studies have shown increased in vitro cytokine responses to non-related pathogens after Bacillus Calmette-Guérin (BCG) vaccination. A total of 158 infants (80 BCG administered within 7 days of birth; 78 controls) were bled 4 days post-randomization, and at age 3 and 13 months. Geometric mean concentrations of IL-1ß, TNF-α, IL-6 (24 h stimulation) and IFN-γ, IL-10, IL-17, IL-22 (96 h stimulation) in response to in vitro stimulation with RPMI, LPS, PHA, Escherichia coli, Streptococcus pneumoniae, Candida albicans and BCG were compared among BCG vaccinated children and controls. BCG vaccination did not affect in vitro cytokine production, except IFN-γ and IL-22 response to BCG. Stratifying for 'age at randomization' we found a potentiating effect of BCG on cytokine production (TNF-α, IL-6, IL-10) in the 4 days post randomization stimulations, among children who were vaccinated at age 2-7 days versus age 0-1 days. BCG vaccination did not potentiate cytokine production to non-BCG antigens. At 4 days post randomization, BCG was associated with higher cytokine production in the later randomized children.

Brain activity on fMRI associated with urinary bladder filling in patients with a complete spinal cord injury.

OBJECTIVE: Patients with complete spinal cord injury (SCI) may maintain some perception of bladder fullness. The aim of the study was to evaluate brain activation arising from anticipated extraspinal sensory pathways. METHODS: Fourteen patients ages 24-54 years were enrolled, all having experienced a complete SCI (ASIA A) at C7 to T5 an average of 17 months before study entry. Urodynamic equipment was used for repeated bladder filling and detrusor activity evaluation. All functional magnetic resonance imaging measurements were performed using a Siemens Trio 3T scanner with the GRE-EPI sequence (field of view = 192 × 192 mm, voxel 3 × 3 × 3 mm, TR/TE = 3000/30 ms, 45 slices). Nine hundred dynamic scans were acquired over 45 min. Statistical analysis was done in SPM8 using a general linear model. Statistics using t-tests were thresholded at P = 0.001. RESULTS: We excluded results from two patients because of activation artifacts. In 8 of 12 patients, significant brain activity was observed during urinary bladder filling. We found significant activation clusters at the nucleus of the solitary tract (NTS) (3/8), parabrachial nucleus (PBN) (4/8), hypothalamus (4/8), thalamus (6/8), amygdala (7/8), insular lobe (5/8), anterior cingulate gyrus (5/8), and prefrontal cortex (8/8). Activations in nuclei involved in afferents likely from the vagal nerve (NTS and PBN) correlated significantly with reported bladder sensations. CONCLUSIONS: These data suggest that extraspinal sensory pathways may develop following SCI and that vagal nerve may play a role in re-innervation of the urinary bladder. Neurourol. Urodynam. 36:155-159, 2017. © 2015 Wiley Periodicals, Inc.

Incomplete and incorrect epinephrine auto-injector training to food-allergic patients by pharmacists in the Netherlands.

BACKGROUND: Successful treatment of anaphylaxis in the community relies on early and correct use of epinephrine auto-injectors (EAI). In the Netherlands, pharmacists supply EAIs to patients and have a crucial role in instructing patients in how and when to use EAI. However, there are currently no data in Europe on the quality of such instruction provided by pharmacists. Therefore, the aims of this study were to investigate the knowledge, attitudes, and beliefs regarding food allergy among pharmacists in the Netherlands and to investigate the quality of EAI instructions and demonstrations to patients by pharmacists. METHODS: Pharmacists were asked to complete an online questionnaire. Quality of instructions and demonstration accuracy were assessed in mystery guest visits to randomly selected pharmacies. For the statistical analysis, descriptive methods were used. RESULTS: In total, 25 of 115 questionnaires were completed. Only two (8%) respondents gave correct answers concerning the proper EAI demonstration. Twenty-one (84%) respondents thought that the provision of instructions was the responsibility of pharmacists. In total, ten pharmacies were included in simulated patient visits. Five of them (50%) demonstrated the EAI. None of them demonstrated the EAI use correctly. CONCLUSION: Food-allergic patients at high risk for anaphylaxis who receive their EAI from a community pharmacy are often not instructed on how to use an EAI or receive incorrect instructions. Pharmacists show considerable gaps in knowledge about food allergy and its management. These data suggest that opportunities exist to improve the quality of care provided by pharmacies to high-risk food-allergic patients.

No difference in health-related quality of life, after a food challenge with cashew nut in children participating in a clinical trial.

BACKGROUND: Previous studies showed that health-related quality of life (HRQL) significantly improved after the food challenge, with greater improvements in HRQL after a negative outcome than after a positive outcome. It is currently unknown whether this also occurs in patients undergoing DBPCFCs with cashew nut in the context of a clinical trial. METHODS: Quality of life was studied in children enrolled in a cashew nut study using Food Allergy Quality of Life Questionnaires (FAQLQs). Children, teenagers and parents of the children completed the questionnaires before the challenge test and 6 months after the DBPCFC with cashew nut. The difference in the change in HRQL between the children with a positive and negative DBPCFC outcome was studied by Mann-Whitney U-test. RESULTS: In total, 112 children (67 boys, median age of 9 years) were included. The children, teenagers and parents of the children completed 143 sets of questionnaires in total. There were no significant differences in baseline total and domain scores compared to the follow-up scores in the FAQLQ-CF, FAQLQ-TF and FAQLQ-PF. In children, the delta FAIM score in the negative DBPCFC tested group was significantly better than the delta FAIM score in the positive challenged group (p = 0.026). There were no significant differences in the changes in the scores of the FAQLQ-CF and FAQLQ-PF in the children with a positive challenge outcome, compared to the children with a negative challenge result. However, there was a significant difference in the change in score between the latter groups in the domain 'accidental exposure' of the FAQLQ-TF (p = 0.049). CONCLUSION: This study showed no difference in the change in HRQL scores after a DBPCFC with cashew nut in children participating in a clinical trial. The utility of HRQL as an outcome for clinical trials in food allergy may be limited if participant baseline HRQL is relatively unimpaired.

Translation to Portuguese and cultural adaptation of Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF).

Food allergy is a health problem with significant negative impact in Quality of Life (QoL). We aimed to translate into Portuguese and culturally adapt to our population the Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF). Cross-cultural translation was performed according to guidelines. Linguistic validation consisted in 3 steps: forward translation, backward translation and comprehensibility testing. A consensual version was obtained and tested in parents of food allergic children by cognitive debriefing. Twelve questionnaires were fulfilled, all completed in ≤ 15 min. No comments, doubts or suggestions were posed, except for 2 parents regarding a question about the number of food their children had to avoid. Two gave special positive feedback about the utility of FAQLQ-PF. Changes have been included after this pre-test in accordance to doubts and suggestions of participants, and the Portuguese version is now able to be used in clinics and research.

Patient-reported disease-specific quality-of-life and symptom severity in systemic mastocytosis.

BACKGROUND: Presently, no validated data exist on symptom severity and disease-specific quality-of-life (QoL) for patients with mastocytosis. Simultaneously, clinical trials and drug application processes increasingly mandate reporting patients' perspectives on symptoms and QoL. We report on the development and validation of the mastocytosis quality-of-life questionnaire (MQLQ) and the mastocytosis symptom assessment form (MSAF). METHODS: Both outcome measures were developed in a standardized stepwise method, starting with the identification of items in focus groups (n = 12), item reduction and subsequent cross-sectional validation in a 63% female cohort of 164 adult patients with indolent systemic mastocytosis. RESULTS: The MSAF reveals that fatigue is the severest mastocytosis symptom while the MQLQ indicates that fear of anaphylaxis mostly impacts QoL. Cross-sectional validity was assessed by correlating both individual domains and the total scores of the MQLQ and MSAF with independent measures of mastocytosis. The total scores of both the MQLQ (P < 0.001; Spearman's r: 0.568) and the MSAF (P < 0.001; Spearman's r: 0.559) correlated significantly with the consensus on physician-scored mediator symptoms. The MQLQ domains displayed a high internal consistency (Cronbach's alpha: 0.841-0.958) and the domains 'bones', 'skin symptoms' and 'anaphylaxis' differed significantly between patients with and without osteoporosis, urticaria pigmentosa or anaphylaxis, respectively (P < 0.001). CONCLUSIONS: The MQLQ is the first disease-specific QoL questionnaire for mastocytosis and is complemented by the MSAF, a short and convenient symptom scoring form. Both patient-reported outcome measures are valid, reliable and discriminate between patients with different disease characteristics, making them useful instruments for clinical research.

Late reactions in food-allergic children and adolescents after double-blind, placebo-controlled food challenges.

The time during which children are observed following a double-blind, placebo-controlled food challenge (DBPCFC) varies in clinical practice. There are little data on late reactions (LRs) following DBPCFCs. Therefore, we determined the prevalence, severity and clinical characteristics of late reactions in food-allergic children and adolescents after DBPCFC, and ascertained which factors are associated with, and may predict, LRs. Logistic regression analyses were performed to investigate which factors were associated with LRs and to develop the association and prediction models. A total of 1142 children underwent DBPCFCs (child-test combinations). Of these 1142 child-test combinations, 400 reported LRs following the DBPCFC. LRs in food-allergic children after DBPCFC are poorly predictable and are generally not severe. All LRs, including those on the placebo day, are more frequently reported in younger children. Children who do not experience severe immediate reactions may be safely discharged home 2 h after a DBPCFC.

The compliance and burden of treatment with the epinephrine auto-injector in food-allergic adolescents.

BACKGROUND: Food-allergic patients at high risk of potential fatal anaphylaxis should carry an epinephrine auto-injector (EAI) at all times. This treatment may be perceived as burdensome and this may affect compliance and health-related quality of life (HRQL). The aims of the study were (1) to determine the burden of treatment (BoT) of an EAI, (2) to examine the relationship between this burden and compliance, and (3) to analyze which factors contribute to the BoT of the EAI as perceived by food-allergic adolescents and their parents. METHODS: Dutch food-allergic adolescents prescribed an EAI, and their parents completed a questionnaire package (n = 55). Relationships between BoT and HRQL, illness severity and perception, and anxiety measures were investigated. RESULTS: Food-allergic adolescents and their parents were (extremely) positive about the EAI (54.5%; 72.7%, respectively) (=low BoT). The BoT measure showed a significantly greater burden in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times than adolescents who reported they did. The BoT scores of both adolescents and their parents were not associated with HRQL, illness severity and perception, or trait anxiety. CONCLUSIONS: The majority of food-allergic adolescents and their parents were positive about the EAI (=low BoT). However, the BoT was significantly associated with self-reported compliance with carrying the EAI. The BoT was higher in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times. The BoT measure seems to be a useful tool to study compliance with carrying an EAI. The BoT of an EAI is not associated with HRQL. The BoT measures a distinct concept related to compliance behavior.

Epinephrine auto-injector prescriptions to food-allergic patients in primary care in The Netherlands.

BACKGROUND: The knowledge of general practitioner(s) (GPs) regarding food allergy and anaphylaxis and practices in the prescription of epinephrine auto-injector(s) (EAIs) among GPs has previously only been studied using questionnaires and hypothetical cases. Therefore, there are currently no data as to whether or not GPs prescribe EAIs to high risk food-allergic patients presenting to primary care practices. The aim of this study was therefore to describe and evaluate practice in EAI prescription by GPs to food-allergic patients in The Netherlands. METHODS: Patients aged 12-23 years who consulted their GP for allergic symptoms were identified in a primary care database. Patients were classified as probably or unlikely to be food-allergic. A risk factor assessment was done to identify probably food-allergic patients at high risk for anaphylaxis to assess the need for an EAI. RESULTS: One hundred forty-eight out of 1015 patients consulted their GP for allergic symptoms due to food. Eighty patients were excluded from analysis because of incomplete records. Thirty-four patients were classified as probably food-allergic. Twenty-seven of them were considered high risk patients and candidates for an EAI. Importantly, only 10 of them had actually been prescribed an EAI by their GP. CONCLUSIONS: This study shows that high risk food-allergic patients that visit their GPs are often not prescribed an EAI. Thus, previously identified low rates of EAI ownership may be partly due to GPs not prescribing this medication to patients for whom it would be appropriate to do so. These data suggest that there is a need for improvement of the quality of care for high risk food-allergic patients in primary care.

The measurement properties of the five-item International Index of Erectile Function (IIEF-5): a Dutch validation study.

Erectile dysfunction (ED), affecting men worldwide, is associated with worse mental health. The severity of ED as well as the effect of its treatment can be assessed using valid self-reported outcome measures. A widely used measure is the International Index of Erectile Function short form (IIEF-5) which is not yet validated in Dutch. The objective of this study was to translate the IIEF-5 into Dutch and to investigate its reliability and validity to provide a useful evaluation tool. The IIEF-5 was translated into Dutch following standardized forward-backward procedures. To conduct this observational study, men with symptoms of ED completed the Dutch IIEF-5 at inclusion, 1 week later, and 6 months after inclusion. A population-based sample (reference group) completed the IIEF-5 once. The quality domains reliability and validity were addressed by testing the measurement properties internal consistency, reliability, measurement error, and content validity. Data of 82 patients and 253 reference group participants were analyzed. Internal consistency was adequate with Cronbach's alpha of 0.94 in both patient and reference group. In patients, the test-retest reliability was adequate with an intra-class correlation coefficient for agreement of 0.88. A floor effect was present in the patient group (42%), though not in the reference group (3%). There was no ceiling effect in patients (0%), while this was present in the reference group (17%). Analysis of responsiveness was not possible due to the limited number of patients receiving treatment. The Dutch IIEF-5 is a reliable and valid measure to determine severity of symptoms of ED. This evaluation tool is valuable for clinical use and interpreting results across international clinical studies. The context of a patient's sexual life is, however, indispensable and should be taken into account.

Validation of the Spanish Version of the Food Allergy Quality of Life Questionnaire-Adult Form (S-FAQLQ-AF).

INTRODUCTION: Specific food allergy quality of life questionnaires have been developed within the context of the EuroPrevall project. We aimed to adapt and validate the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) in the Spanish language. METHODS: The original English questionnaire was translated and culturally adapted into Spanish following World Health Organization guidelines. The final Spanish version of the FAQLQ-AF (S-FAQLQ-AF) was approved by the original authors. Consecutive patients ( 18 years old) who fulfilled the following criteria were recruited: 1) diagnosis of food allergy defined as immediate allergic symptoms and a positive prick test or IgE against the culprit food(s) and 2) physician-assessed ability to complete the questionnaires. Patients completed the S-FAQLQ-AF and a Spanish version of the SF-12 questionnaire. Reliability was assessed 10 to 14 days after completion of the first questionnaire. RESULTS: Eighty-two consecutive outpatients were recruited and cross-sectional validity was.assessed based on the correlation between the S-FAQLQ-AF and the Food Allergy Independent Measure (FAIM) in this population (rho = 0.83, P < .0001). The S-FAQLQ-AF showed excellent internal consistency (Cronbach α, 0.95). S-FAQLQ-AF domains also had excellent internal consistency: α = 0.93 for allergen avoidance-dietary restrictions; α = 0.83 for emotional impact; α = 0.85 for risk of accidental exposure, and α = 0.66 for food allergy related health. Limited correlation was found between the S-FAQLQ-AF and the SF-12. CONCLUSION: The S-FAQLQ-AF is a valid, short, easy-to-use, and reliable instrument that discriminates between patients with different atopic phenotypes and is suitable for assessing the impact of IgE-mediated food allergy on patient quality of life.

First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar.

BACKGROUND: Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals. METHODS: We performed oral food challenges in 21 apple-allergic individuals with Elstar apples which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual analogue scale (VAS). RESULTS: Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges with these downregulated apple lines produced significantly less intense maximal symptoms to the first dose (Vmax1) than with Elstar (Vmax1 Elstar 3.0 mm vs 0.0 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm vs 0.2 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043). Only one subject (5%) remained symptom-free when challenged with the Elstar apple, whereas 43% did so with e-DR1 and 63% with e-DR2. CONCLUSION: These data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 gene expression in the fruit and reduction of symptoms when these apples are ingested by allergic subjects. Approximately half of the subjects developed no symptoms whatsoever, and virtually all subjects wished to consume the apple again in the future.

The effects of food allergy on quality of life.

The majority of research on food allergy has been bio-medical in orientation, focusing on issues such as the molecular structure of allergens, or aimed at methods of diagnosis. In the last decade, there has been a growing interest in the development of questionnaires that measure the impact of food allergy on health-related quality of life (HRQL). These studies have provided insight into the everyday burden of living with food allergy and have suggested ways that HRQL can be improved. The EuroPrevall project (europrevall@bbsrc.ac.uk) has given great impetus to research in the area of HRQL. In addition to clinical research on the prevalence, mechanisms and causes of food allergy, research output in the area of psycho-social impact has included HRQL measures for all age groups and examination of the socio-economic impact of food allergy. In this chapter, we review the literature on the impact of food allergy on children, teens and their parents; the majority of this data was generated over the life of the EuroPrevall project. We then examine both quantitative and qualitative research findings to provide an in-depth picture of the impact of food allergy on the concerns and everyday lives of children, teens, adults and parents. Research on factors that are related to and impact HRQL is also discussed. There is a strong emphasis throughout the chapter on developmental considerations of food allergy, spanning from infants to adults. We conclude by discussing methodological issues in relation to the measurement of HRQL in relation to food allergy. We offer some recommendations for future research and practice on HRQL so that HRQL measures can reach their full potential in research, practice and policy, with the help of the findings in this review. Overall, the findings suggest that food allergy has a strong impact on HRQL in terms of social, dietary, and psychological factors. 'Rules' and restrictions ostensibly apply to food, but because food is such an integral part of everyday life, these restrictions extend far beyond 'mealtimes'. Therefore, social events are experienced differently and have a different meaning for those living with food allergy, giving rise to feelings of exclusion and difference when compared to those without allergy. Children, teens, and parents need to cope with normal developmental changes as well as with the food allergy, placing them under increased psycho-social stress and leading to adverse effects on HRQL and coping. To address and attempt to alleviate such stressors, both quantitative and qualitative research suggests that targeting uncertainty should be a major goal for health professionals working with children, teens and families with a food allergy. Remarkable similarities in response to food allergy across countries suggest that policies and programmes that address quality of life issues may be relevant to many different populations. An in-depth understanding of the relationship between a diagnosis of food allergy and HRQL, as well as the factors that impact it, will ultimately lead to the promotion of earlier, more effective preventive strategies and interventions that are focused on maximising optimal health development and quality of life.