The longitudinal impact of probiotic and peanut oral immunotherapy on health‐related quality of life.
BACKGROUND: We previously reported that probiotic and peanut oral immunotherapy (PPOIT) was effective at inducing sustained unresponsiveness compared with placebo in a double-blind, placebo-controlled randomized trial. This study evaluated the impact of PPOIT on health-related quality of life (HRQL). METHOD: Fifty-one participants (PPOIT 24; placebo 27) from the PPOIT trial completed Food Allergy Quality of Life Questionnaire (FAQLQ-PF) and Food Allergy Independent Measure (FAIM) at pre-treatment, end-of-treatment and 3 months after end-of-treatment. A total of 42 participants (20 PPOIT; 22 placebo) completed measures at 12 months post-treatment. Changes over time in PPOIT and placebo groups were examined by repeated-measures analysis of variance and paired t tests. RESULTS: Probiotic and peanut oral immunotherapy was associated with significant improvement in FAQLQ-PF (F = 3.63, P = .02), with mean difference 0.8 at 3 months post-treatment (P = .05) and 1.3 at 12 months post-treatment (P = .005), exceeding the 0.5 minimal clinically important difference for FAQLQ-PF. For FAIM, mean difference was 0.5 (P = .03) at 3 months and 0.4 (P = .04) at 12 months post-treatment. In placebo group, post-treatment FAQLQ and FAIM remained unchanged from pretreatment. Improvement in FAQLQ-PF and FAIM scores related specifically to acquisition of sustained unresponsiveness rather than to receiving PPOIT treatment or participation in the trial. CONCLUSIONS: Probiotic and peanut oral immunotherapy has a sustained beneficial effect on psychosocial impact of food allergy at 3 and 12 months after end-of-treatment. Treatment was not associated with reduced HRQL relative to baseline in either PPOIT or placebo groups, indicating that PPOIT was well tolerated and psychological well-being was not negatively impacted. Improved HRQL was specifically associated with acquisition of sustained unresponsiveness.
EAACI Guidelines on Allergen Immunotherapy: IgE‐mediated Food Allergy.
Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.
NUT Co Reactivity‐Acquiring Knowledge for Elimination Recommendations (NUT CRACKER) Study.
BACKGROUND: Ambiguities exist regarding the diagnosis of tree-nut allergy, necessitating either elimination or performance of oral food challenges (OFC). OBJECTIVE: To examine the co-incidences of allergies among tree-nuts and improve diagnostic testing to minimize the need for OFC. METHODS: Eighty three patients prospectively evaluated for walnut, pecan, cashew, pistachio, hazelnut and almond allergy. A history of previous reactions was obtained and standardized skin prick tests (SPT) using finely ground tree-nut solution and basophil activation tests (BAT) were performed. Patients underwent OFC for each tree-nut they eliminated and to which a reaction in the previous 2 years was not documented. RESULTS: While most patients were sensitized to 5-6 tree-nuts, over 50% were allergic to only 1-2 tree-nuts. The highest rate of allergy in sensitized patients was observed for walnut (74.6%) and cashew (65.6%). The rate of co-allergy for most tree-nuts was < 30%. Two thirds of walnut- and cashew-allergic patients were also allergic to pecan and pistachio, respectively, while all pecan- and pistachio-allergic patients were allergic to walnut and cashew, respectively. Receiver operating characteristic analysis for SPT and BAT was tree-nut dependent and yielded area under the curve (AUC) values ranging from 0.75-0.94. Knowledge of co-incident allergies in these pairs along with the combination of SPT and BAT correctly distinguished allergic from tolerant patients for walnut (87%), pecan (66%), cashew (71%) and pistachio (79%). CONCLUSION: The data presented here should assist in differentiating between allergic and tolerant patients, decrease the need for OFC and allow for appropriate elimination recommendations.
CRD and beyond: multivariable regression models to predict severity of hazelnut allergy.
BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n=423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during DBPCFC) were categorized in mild, moderate and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (OR) and areas under receiver operating characteristic (ROC) curves (AUC) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1 respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk), increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3% and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.
Changes in patient quality of life during oral immunotherapy for food allergy.
BACKGROUND: Quality of life is (QOL) impaired in patients with food allergy and improves following oral immunotherapy (OIT). However, the treatment itself is prolonged and demanding. We examined changes in patient QOL during OIT for food allergy. METHODS: The FAQLQ-PF was administered to children aged 4-12 years undergoing OIT for milk, peanut or egg allergy, at the beginning and after 4 months of treatment. Patients were categorized as improved, unchanged, or diminished FAQLQ-PF (>0.5 point decrease, a change of ≤0.5 points, or >0.5 increase, respectively) and compared. Food-allergic patients not undergoing OIT served as controls. RESULTS: The Food Anxiety, Social and Dietary limitation and total FAQLQ-PF scores improved significantly during the study period (p=0.001, p=0.018 and p=0.01, respectively) in treated but not in control patients, while the Emotional Impact did not. The change in the FAQLQ-PF was independent of the maximal tolerated dose at baseline or following four months of treatment, the pace of dose-increase or of number or severity of reactions experienced. The total FAQLQ-PF score was inversely associated with the score at baseline on multi-variate analysis (regression coefficient = -0.56, p<0.001). That was driven primarily by improvement in QOL scores in patients with high score (worse QOL) at baseline. Some patients with low FAQLQ-PF score (better QOL) at baseline, deteriorated. CONCLUSIONS: QOL of patients with food allergy improves in some but deteriorates in others during OIT. Patients with impaired QOL at baseline, improve significantly despite the treatment-burden. Some patients with better QOL at baseline, might deteriorate during OIT.
A prospective microbiome‐wide association study of food sensitization and food allergy in early childhood.
BACKGROUND: Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development. METHODS:
Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high dose Vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; p-values were adjusted for multiple comparisons. RESULTS: Complete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log2 fold change -2.15, p=0.003), Dialister (log2 fold change -2.22, p=0.009), Dorea (log2 fold change -1.65, p=0.02) and Clostridium (log2 fold change -1.47, p=0.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log2 fold change -3.41, p=0.03), Oscillospira (log2 fold change -2.80, p=0.03), Lactococcus (log2 fold change -3.19, p=0.05) and Dorea (log2 fold change -3.00, p=0.05) were underrepresented among subjects with food allergy. CONCLUSIONS: The temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy.
A comparative study on basophil activation test, histamine release assay and passive sensitization histamine release assay in the diagnosis of peanut allergy.
BACKGROUND: Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR) and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy. METHODS: BAT, HR, and passive HR were performed on eleven peanut allergic and fourteen non-allergic subjects. Blood was incubated with peanut extract or anti-IgE and tests performed as follows: BAT - CD63-upregulation assessed by flow cytometry; HR - released histamine quantified by a glass fiber-based fluorometric method; Passive HR - IgE-stripped donor basophils were incubated with participants' serum and histamine release quantified as HR. RESULTS: CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1 ± 17.4) compared to HR (23.4 ± 10.31) and passive HR (11.1 ± 2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82%, and specificity of 100%, 100%, and 100%, respectively when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10 and passive HR 9. Likewise, BAT recognized 12 of 14 non-allergic subjects, HR 10 and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, non-releasers in HR but not in BAT had lower basophil count compared to releasers (249 vs. 630 counts/min). CONCLUSION: BAT displayed a significant higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR.