Partial Egg Consumption Modifies the Diagnostic Performance of Allergy Tests to Predict Outcome of Double-Blind Placebo-Controlled Food Challenges to Egg.

BACKGROUND: Many children are consuming some egg when they are diagnosed with egg allergy. We hypothesized that egg consumption could modify the diagnostic performance of allergy tests. OBJECTIVE: To stratify diagnostic performance of tests according to egg consumption status. METHODS: The BAT2 study (NCT03309488) participants underwent oral food challenge (OFC), food-frequency questionnaires, skin prick test (SPT), specific immunoglobulin E (sIgE) and specific immunoglobulin G4 (sIgG4) and basophil activation test (BAT). RESULTS: At study entry, 45% of participants reported partial egg consumption ("consumers") and 55% were avoiding egg strictly ("avoiders"). Avoiders had larger SPT (P < .001), higher BAT to egg (P < .001), sIgE to egg white (EW; P = .001) and to ovalbumin (OVA; P = .001), but not to ovomucoid (P = .231). Consumers had higher levels of sIgG4 to all egg allergens (P < .001) than avoiders. In consumers, the test with the best diagnostic performance was BAT (area under the curve [AUC] = .912) followed by SPT to raw egg (AUC = 0.805), EW-sIgE (AUC = 0.738), and OVA-sIgE (AUC = 0.732). In avoiders, the best tests were BAT (AUC = 0.834) and EW-sIgE (AUC = 0.833) followed by OVA-sIgE (AUC = 0.793) and SPT to EW (AUC=0.789). Using 100% sensitivity and 100% specificity cut-offs, the proportion of patients requiring OFC were 33% for BAT, 53% for SPT to raw egg, 61% for OVA-sIgE, and 73% for EW-sIgE for consumers; and 73% for BAT, 79% for EW-sIgE, and 93% for SPT to EW for avoiders. CONCLUSIONS: The diagnostic performance of tests is influenced by the immunomodulatory effect of egg consumption. BAT is the most reliable test and reduced the need for OFC, particularly in partial egg consumers.

The role of basophil activation test and component-resolved diagnostics in the workup of egg allergy in children at low risk for severe allergic reactions: A real-life study.

BACKGROUND: The gold standard for diagnosing egg allergy in children is the oral food challenge (OFC). However, OFCs are time-consuming and risky procedures. Our study aimed to evaluate the utility of the basophil activation test (BAT) and component-resolved diagnostic in the diagnostic workup of children with egg allergy. METHODS: Overall, 86 children aged 6 months to 17 years, suspected of egg allergy, underwent OFC with boiled egg according to international standardized protocols. BAT and specific immunoglobulin E (sIgE) testing to component egg proteins (Gal d 1-4) were also performed. RESULTS: Of the 22 children who reacted to boiled egg, only one experienced anaphylaxis during the challenge. BAT was performed in samples obtained by 75 of the 86 patients of our cohort. Egg white and yolk protein extracts induced CD63 upregulation in the egg-allergic (EA) children compared with sensitized children that tolerated boiled egg (we registered an overall mean of CD63 expression in the EA population of 44.4% [SD 34.1] for egg white and 34.7% [SD 31.3] for egg yolk vs. 12.5% [SD 19.1] and 10.0% [SD 16.0] in sensitized children). BAT could discriminate between true egg allergy and egg sensitization in our population. As a second-line diagnostic step, the positivity of BAT for egg white or Gal d 1-sIgE resulted in a 40.9% OFC reduction, especially for those with a positive outcome. CONCLUSION: The BAT may be implemented in the diagnostic workup of egg allergy in children and, in a stepwise approach, separately or combined with Gal d 1-sIgE, may predict the allergic status and reduce the number of positive OFCs in children with egg allergy at low risk for severe reactions.

[Early introduction of potentially allergenic foods in pediatric patients under six months of age]. / Introducción temprana de alimentos potencialmente alergénicos en pacientes pediátricos menores de seis meses de edad.

OBJECTIVE: To review the available evidence on the early introduction of allergenic foods and the possible protection in the development of food allergy in later stages. METHODS: An exploratory review of randomized clinical trials whose study population included infants less than 6 months of age at enrollment with or without a diagnosis of food allergy was conducted. For the purposes of this review, eggs, peanuts, and wheat were included as potentially allergenic foods. The following databases were consulted: Medline, EBSCO, OVID, Science Direct and JSTOR (Journal Storage), Scielo, LILACS, Redalyc and Imbiomed from August to December 2021. RESULTS: 429 articles were identified, 412 were excluded, and the final analysis included 9 studies that met the inclusion criteria. Six trials correspond to allergy to eggs, two to peanuts and one to wheat. The age of introduction differs in all trials. The earliest exposure was at 3.5 months and the latest at 5.5 months. The reduction in the risk of developing food allergy occurred in children at risk of allergy. Adverse reactions were common, particularly with the introduction of egg. CONCLUSIONS: We found no evidence that early introduction (< 6 months of age) of allergenic foods reduces the risk of developing food allergy in infants without risk factors.

OBJECTIVO: Revisar la evidencia disponible acerca de la introducción temprana de alimentos alergénicos y la posible protección en la aparición de alergia alimentaria en etapas posteriores. MÉTODOS: Se realizó una revisión exploratoria de ensayos clínicos aleatorizados, cuya población de estudio incluyera lactantes menores de 6 meses al momento del reclutamiento con o sin diagnóstico de alergia alimentaria. Se incluyeron como alimentos potencialmente alergénicos el huevo, cacahuate y trigo. Se consultaron las bases de datos: Medline, EBSCO, OVID, Science Direct y JSTOR (Journal Storage), Scielo, LILACS, Redalyc e Imbiomed del mes de agosto a diciembre de 2021. RESULTADOS: Se identificaron 429 artículos, se excluyeron 412 y el análisis final incluyó 9 estudios que cumplieron con los criterios de inclusión. Seis ensayos corresponden a alergia al huevo, dos al cacahuate y uno a trigo. La edad de introducción difiere en todos los ensayos. La exposición más temprana fue a los 3.5 y la más tardía a los 5.5 meses. La reducción del riesgo de alergia alimentaria se presentó en niños con riesgo de alergia. Las reacciones adversas fueron comunes, particularmente con la introducción de huevo. CONCLUSIONES: No existe evidencia que la introducción temprana (< 6 meses de edad) de alimentos alergénicos reduzca el riesgo de alergia alimentaria en lactantes sin factores de riesgo.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

BACKGROUND: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. METHODS: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. RESULTS: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. CONCLUSIONS: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

Egg Intake Is Associated with Lower Risks of Impaired Fasting Glucose and High Blood Pressure in Framingham Offspring Study Adults.

The association between egg consumption and cardiometabolic risk factors such as high blood pressure (HBP) and impaired fasting glucose (IFG) or type 2 diabetes (T2D) is still under debate. This study examines the association between egg consumption and these outcomes among 2349 30-64 year-old adults in the prospective Framingham Offspring Study. Diet was assessed using three-day dietary records. Potential confounders retained in the final models included age, sex, body mass index, and other dietary factors. The analysis of covariance and Cox proportional hazard's models were used to assess the relevant continuous (i.e., FG, SBP, DBP) and categorical (i.e., T2D, HBP) outcomes. Consuming ≥5 eggs per week was associated with lower mean FG (p = 0.0004) and SBP (p = 0.0284) after four years of follow-up. Higher egg intakes led to lower risks of developing IFG or T2D (HR: 0.72; 95% CI: 0.51-1.03) and high blood pressure (HBP) (HR: 0.68; 0.50-0.93). The beneficial effects of egg consumption were stronger in combination with other healthy dietary patterns. This study found that regular egg consumption as part of a healthy diet had long-term beneficial effects on blood pressure and glucose metabolism and lowered the long-term risks of high blood pressure and diabetes.

Dietary Effects on Chronic Venous Disease.

BACKGROUND: Diet is fundamental to maintaining and improving human health. There is ample evidence identifying the beneficial and/or harmful effects of diet on noncommunicable diseases such as obesity, diabetes mellitus, and cardiovascular disease. However, the associations of the diet to chronic venous disease has not been fully described. METHODS: Data were collected through a cross-sectional survey conducted on 1,571 community-dwelling adults in 2018. Diet intake frequency was assessed using valid food group consumption frequency questionnaires. Multivariable logistic regression models were used to evaluate the association of diet with chronic venous disease. RESULTS: In total, 857 participants were diagnosed with chronic venous disease. Those who ate soybean products daily and 4-6 days/week had a 51-31% lower risk of chronic venous disease compared with those who only occasionally consumed soybean food, respectively. Participants who consumed eggs and egg products 1-3 days/week versus those who only occasionally ate eggs showed a lower risk of chronic venous disease [odds ratio (OR) 0.542, 95% confidence interval (CI) 0.375-0.782]. Eating fried food 4-6 days each week was associated with an increased risk of chronic venous disease (OR 3.872, 95% CI 1.263-11.599) compared with those who only occasionally ate fried foods. There is a decreasing tendency of the adjusted OR for eating soybean products daily with the severity of disease [chronic venous disease (C0-C2): OR 0.575, 95% CI 0.408-0.812; chronic venous insufficiency (C3-C6): OR 0.222, 95% CI 0.114-0.435]. CONCLUSIONS: A higher frequency in the consumption of soybean products and eggs were associated with a lower risk of chronic venous disease. High level of fried food consumption was positively associated with risk of chronic venous disease. There are certain specific trends in relation to dietary consumption and severity of disease, although these trends were less strong. These associations are largely independent of other dietary and nondietary factors.

Home Introduction of Baked Egg After Oral Food Challenge.

BACKGROUND: Baked egg (BE) introduction may accelerate resolution of egg allergy. Long-term data regarding the safety and success of BE introduction in the real world are limited. OBJECTIVE: To identify predictors of future egg consumption and barriers to advancement based on characteristics during and after BE oral food challenges (OFCs). METHODS: We performed a retrospective review of consecutive BE OFCs with a minimum 24-month follow-up. Goal doses ranged from 1/16 to 1/4 egg. Outcomes were categorized as pass (no reaction), fail (but allowed BE introduction), or fail (avoid). Status of egg introduction and reactions were recorded. RESULTS: A total of 243 patients were included; 134 passed and 109 failed (70 of whom were instructed to introduce BE). At follow-up (median, 47 months), 90 (37%) were consuming direct egg, 26 (11%) lightly cooked egg, 39 (16%) BE, and 88 (36%) avoiding; 58% who failed versus 81% who passed were consuming some form of egg. Median egg white IgE level was significantly higher among avoiders versus introducers (8.7 vs 5.8; P = .008). Lower egg white IgE level and younger age were predictors of egg consumption in some form at follow-up (median IgE, 5.8 vs 8.4; P = .03; median age, 4.0 vs 8.0 years; P < .001). A total of 94 patients had a total of 136 reactions (132 mild, 4 severe); 22 (16.2%) were accidental exposures, 42 (30.9%) planned escalations, and 72 (52.9%) with previously tolerated doses. CONCLUSIONS: Most patients who underwent a BE OFC continued to consume some form of egg, often advancing to direct egg. However, many reverted to avoidance and adverse reactions were common.

Egg consumption and risk of acute stroke in the Million Veteran Program.

BACKGROUND: While observational data suggest a higher risk of coronary artery disease with frequent egg consumption, only limited and inconsistent data are available on the relation of egg consumption with stroke. OBJECTIVE: The primary objective was to assess whether egg consumption is associated with a higher risk of ischemic and hemorrhagic stroke among US veterans. METHODS: In a prospective cohort study of US veterans from the Million Veteran Program (MVP), egg intake was collected through a self-reported food frequency questionnaire at baseline. Incidence of stroke was ascertained via ICD9/ICD10 codes from the electronic health records. Multivariable Cox proportional hazard models were used to estimate the multivariable adjusted hazard ratios. RESULTS: A total of 233,792 veterans (91.6% men) were studied with a mean age of 65.6 ± 11.7 years. During a mean follow-up of 3.3 years, a total of 5740 cases of fatal and non-fatal ischemic stroke and 423 cases of fatal and non-fatal hemorrhagic stroke occurred. Median egg consumption was 2-4 eggs/week. Crude incidence rates for acute ischemic stroke were 6.5, 7.2, 7.1, 7.4, 8.0, 8.1, and 8.6 cases per 1000 person-years for egg consumption of <1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, 1/day, and ≥2/day, respectively. Corresponding multivariable adjusted hazard ratios (95% CI) were 1.00 (ref), 1.10 (0.96-1.25), 1.09 (0.96-1.23), 1.10 (0.98-1.25), 1.16 (1.01-1.33), 1.20 (1.03-1.40), and 1.22 (1.03-1.45) controlling for age, sex, ethnicity, body mass index, diabetes, smoking, alcohol intake, modified DASH score, and education (p linear trend 0.0085). For hemorrhagic stroke, multivariable adjusted hazard ratios (95% CI) after controlling for age, sex, ethnicity, body mass index, modified DASH score, and level of education were 1.00 (ref), 1.28 (0.96-1.72), 1.22 (0.93-1.61), and 1.19 (0.88-1.61) for egg consumption of <1/week, 1/week, 2-4/week, 5+/week, respectively. CONCLUSION: Our data are consistent with a positive association of egg consumption with acute ischemic stroke but not hemorrhagic stroke among veterans.

Prospective evaluation of tolerance to unheated milk-boiled egg after baked milk-egg tolerance under 2 years.

BACKGROUND: The time to acquisition of tolerance to unheated milk and regular egg after achievement of tolerance to baked goods is not known. OBJECTIVE: To determine the time to acquisition of unheated-milk-regular-egg tolerance, after the tolerance of the baked forms, in children younger than 2 years. METHODS: An initial oral food challenge with baked milk (BM) and baked egg (BE) was performed on patients who were reactive to unheated milk-regular egg, respectively. Patients who were BM-BE tolerant were offered unheated-milk-regular-egg challenges, and patients who were BM-BE reactive were offered BM-BE challenges at an average of 3-month intervals. Food-induced atopic dermatitis was included. RESULTS: Thirty-six children with unheated-milk allergy (median age, 7.3 months [interquartile range (IQR), 6.0-13.5]) and 65 with regular-egg allergy (median age, 7 months [IQR, 5.8-11.0]) were included. Seven of 13 children who were BM tolerant acquired unheated-milk tolerance after a median 4.0 months (IQR, 2.0-7.0). Twelve of 23 children who were BM reactive acquired unheated-milk tolerance after a median 5.0 months (IQR, 3.0-8.0) after BM tolerance. Twenty-one of 29 children who were BE tolerant acquired regular-egg tolerance after a median 3.0 months (IQR, 1.0-6.0). Sixteen of 36 children who were BE reactive acquired regular-egg tolerance after a median 4.0 months (IQR, 2.0-6.8) after BE tolerance. CONCLUSION: Different tolerance rates were determined for baked products at different time points in the first 2 years of life. Unheated-milk-regular-egg allergy resolved in up to 65.5% and 75.5% of cases, respectively, in an average 4 to 5 months after acquisition of BM-BE tolerance. Baked-milk-baked-egg tolerance may be regarded as a precursor of tolerance.

Egg Allergy in Children and Weaning Diet.

Eggs are a fundamental food in the human diet, and together with cow's milk, they are the most common food allergen. This work highlights the main nutritional characteristics of eggs to show how their absence from a child's diet can constitute a serious deficiency. We then analyze the risk factors that facilitate the onset of egg allergy. The third part of the paper reports possible interventions to lower the appearance of food allergy that have been occurred in trials. The last part of the paper is a synthesis of this research study that has been taken from several of the latest guidelines or from position papers.

Associations of Dietary Cholesterol, Serum Cholesterol, and Egg Consumption With Overall and Cause-Specific Mortality: Systematic Review and Updated Meta-Analysis.

BACKGROUND: Despite substantial research highlighting the importance of exogenous dietary cholesterol intake and endogenous serum cholesterol level in human health, a thorough evaluation of the associations is lacking. Our study objective was to examine overall and cause-specific mortality in relation to dietary and serum cholesterol, as well as egg consumption, and conduct an updated meta-regression analysis of cohort studies. METHODS: We conducted a prospective analysis of 27 078 men in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). Multivariable-controlled cause-specific Cox proportional hazards regression models were used to calculate hazard ratios and 31-year absolute mortality risk differences. A systematic review and meta-analysis of cohort studies was also performed (PROSPERO [URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021272756]). RESULTS: Based on 482 316 person-years of follow-up, we identified 22 035 deaths, including 9110 deaths from cardiovascular disease (CVD). Greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Hazard ratios for each additional 300 mg cholesterol intake per day were 1.10 and 1.13 for overall and CVD-related mortality, respectively; for each additional 50-g egg consumed daily, hazard ratios were 1.06 and 1.09, respectively, for overall and CVD-related mortality (all P values<0.0001). After multivariable adjustment, higher serum total cholesterol concentrations were associated with increased risk of CVD-related mortality (hazard ratios per 1 SD increment, 1.14; P<0.0001). The observed associations were generally similar across cohort subgroups. The updated meta-analysis of cohort studies on the basis of 49 risk estimates, 3 601 401 participants, and 255 479 events showed consumption of 1 additional 50-g egg daily was associated with significantly increased CVD risk (pooled relative risk, 1.04 [95% CI, 1.00-1.08]; I2=80.1%). In the subgroup analysis of geographic regions (Pinteraction=0.02), an increase of 50-g egg consumed daily was associated with a higher risk of CVD in US cohorts (pooled relative risk, 1.08 [95% CI, 1.02-1.14]) and appeared related to a higher CVD risk in European cohorts with borderline significance (pooled relative risk, 1.05), but was not associated with CVD risk in Asian cohorts. CONCLUSIONS: In this prospective cohort study and updated meta-analysis, greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Our findings support restricted consumption of dietary cholesterol as a means to improve long-term health and longevity.

Egg consumption and risk of cardiovascular events among Iranians: results from Isfahan Cohort Study (ICS).

PURPOSE: The association between egg consumption and cardiovascular events remains controversial. This study aims to evaluate this association in cardiovascular events including myocardial infarction (MI), ischemic coronary heart disease (ICHD), stroke, cardiovascular disease (CVD), and CVD mortality in an Iranian population. METHODS: This prospective cohort study included 6504 adults (age ≥ 35 years) with no history of CVD event at baseline. The frequency of egg consumption was assessed using a validated food frequency questionnaire. Participants were followed for 12 years and incidence of new CVD cases were determined through active examinations and linkages to multiple registries. Cox frailty models were conducted to calculate adjusted hazard ratios (HR)s for cardiovascular events associated with egg consumption. RESULTS: Over a median follow-up of 12 years, fully adjusted model [adjusted for age, sex, education, residency, smoking, daily physical activity, family history of CVD, metabolic syndrome, aspirin, body mass index and Global Dietary Index] revealed a null association between egg and cardiovascular events. Compared with non-consumers (&lt;1 time/week), higher egg consumption (≥3 time/week) was not associated with incident MI (HR = 1.44, 95% CI: 0.86, 2.41; P = 0.48), ICHD (HR = 1.26, 95% CI: 0.80, 1.99; P = 0.41), stroke (HR = 0.79, 95% CI: 0.46, 1.38; P = 0.71) and CVD (HR = 1.05, 95% CI: 0.79, 1.40; P = 0.93). CONCLUSION: These findings suggest that higher egg consumption is not associated with increased risk of MI, ICHD, stroke, and CVD among Iranians. Larger studies with longer duration of follow-up are warranted to explore these associations in populations with higher egg consumption.

Dietary cholesterol and egg intake are associated with the risk of gestational diabetes: a prospective study from Southwest China.

BACKGROUND: An increasing body of evidence suggests that cholesterol intake increases during pregnancy and may influence the risk of gestational diabetes mellitus (GDM). However, existing evidence remains controversial and limited. The present study aimed to determine the relation among dietary cholesterol, specifically egg consumption, in pregnant Chinese women and their risk of GDM. METHODS: A population-based study that included 1617 pregnant women was conducted in 2017. At baseline, dietary information was collected by 24-hour dietary recalls over three days. GDM was diagnosed by a 75 g 2-hr oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Logistic regression models were used to examine the associations of dietary cholesterol and egg intake with GDM. In addition, path analysis including cholesterol intake, plasma lipid profiles and GDM risk was conducted. RESULTS: The average total cholesterol intake was 340.8 mg/d, and cholesterol from eggs accounted for 59.2%. The odds ratio (OR) of GDM risk was 1.48 for the highest quartile of total cholesterol intake compared to the lowest quartile (95% CI 1.10-2.00; P trend = 0.015) after adjustment for potential risk factors for GDM. Moreover, cholesterol from eggs rather than from other foods was positively associated with incident GDM (OR=1.09, 95% CI 1.03-1.17). Each additional egg consumed per day was positively correlated with a higher risk of GDM (OR=1.32, 95% CI 1.11-1.58). Path analysis indicated that cholesterol intake not only increased the risk of GDM by elevating plasma total cholesterol (TC), but also increased the risk of GDM through other non hyperlipidemia pathways. CONCLUSIONS: Maternal dietary cholesterol intake was significantly associated with incident GDM, and egg consumption was a major driver of the association in this population. More studies are needed to substantiate these findings and to explore the underlying mechanisms.

Utility of Gal d 1-Specific IgE Levels in Predicting Reactivity to Boiled Egg in Chinese Children.

BACKGROUND: Many researchers have reported predicting the outcome of oral food challenges (OFCs) on the basis of specific IgE (sIgE) levels. However, the clinical usefulness of the determination of IgE antibodies to egg allergen components in Chinese children with suspected boiled egg allergy is not well studied. OBJECTIVE: Our objective was to assess the diagnostic performance of sIgE to egg white and Gal d 1, 2, 3, and 5 based on the open challenge outcome for boiled egg. METHODS: A total of 48 child patients with a suspect of boiled egg allergy were included. Serum egg white and Gal d 1, 2, 3, and 5 sIgE were measured by ImmunoCAP. Diagnostic value was assessed by area under the receiver operating characteristic curves (AUC). RESULTS: Using the OFC results as the reference parameter, Gal d 1 sIgE had the highest AUC (0.84) compared with egg white (0.77) and other investigated components (ranging from 0.51 to 0.71). The clinical sensitivity and specificity for the sIgE to Gal d 1 at optimal cutoff (6.15 kUA/L) were 73.7% and 96.7%, respectively. Sensitization to Gal d 1 with a cutoff value of >7.48 kUA/L indicated a 90% probability of positive challenge. CONCLUSION: Quantitative measurements of Gal d 1 sIgE antibodies using ImmunoCAP are useful in the management of boiled egg allergy in Chinese children.