Improving In Vitro Detection of Sensitization to Lipid Transfer Proteins: A New Molecular Multiplex IgE Assay.

SCOPE: LTP-syndrome is characterized by sensitization (IgE) to multiple non-specific lipid transfer proteins (nsLTPs) with a variable clinical outcome. The treatment is primarily based on offending food avoidance. However, the determination of Pru p 3-specific IgE is currently the main diagnostic tool to assess sensitization to nsLTPs. Herein, the study evaluates improvement of LTP-syndrome diagnosis and clinical management using a new IgE multiplex-immunoblot assay with a high diversity of food nsLTPs. METHODS AND RESULTS: An EUROLINE-LTP strip with 28 recombinant nsLTPs from 18 allergenic sources is designed. In total the study investigates 38 patients with LTP-syndrome and compares results from the nsLTPs (LTP-strip) with the respective food extracts of Prick-by-prick (PbP) testing. The agreement exceeds 70% for most nsLTPs, e.g., Pru p 3 (100%), Mal d 3 (97%), Pru av 3 (89%), Pha v 3 isoforms (87%/84%), Ara h 9 (82%), Cor a 8 (82%), and Jug r 3 (82%). The functionality and allergenic relevance of nine recombinant nsLTPs are proven by Basophil activation testing (BAT). CONCLUSIONS: The new IgE multiplex-immunoblot nsLTP assay shows a good diagnostic performance allowing culprit food assessment. Negative results from LTP-strip may indicate potentially tolerable foods, improving diet intervention and patients' quality of life.

Detection of the peripheral blood antigens and clinical value in recurrent aphthous ulcer: A cross-section study.

Abstract Background/purpose: Recurrent aphthous ulcer (RAU) is one of the most common diseases of oral mucosa, which is generally believed to be related to immunity, though the etiology is still unclear. It is suspected that allergies are directly related to RAU. So we sought to explore the relationship between hypersensitivity and RAU. Materials and methods: 40 RAU patients who were in ulceration period and 40 people who were in good health were selected from Jan 2016 to Feb 2017, matched in age and sex. The peripheral blood antigens of 40 RAU patients and 40 healthy people was tested, and serum specific IgE (sIgE) with 6 groups of antigens and total IgE (tIgE) analysis was performed to identify IgE-mediated allergic reaction possibly affecting RAU. We then investigated the food intolerance and IgG levels to discover the correlation between non-IgE mediated allergic reaction and RAU. Results: The positive cases and rate of sIgE in RAU group was higher than that of control, but the difference was not statistically significant (P＞0.05). Positive grade of animal fur scraps (EX1), house dust mixed (HX2) and the serum tIgE concentration of the RAU group were significantly higher than the control group (P＜0.05).The number of food intolerance in RAU group was significantly higher than that in control group (P＜0.05). Conclusion: Our findings suggested certain correlation between RAU and anaphylaxis. Daily contact allergens and food intolerance may be one of the causes of RAU. Moreover, this provides reference value for clinical diagnosis and treatment.

Low Levels Matter: Clinical Relevance of Low Pru p 3 sIgE in Patients With Peach Allergy.

Many clinical lab settings still use 0.35 KUA/L as the cut-off for serum specific-IgE (sIgE) immunoassays, while the detection limit is 0.1 KUA/L. The clinical relevance of -low-level sIgE (0.1-0.35 KUA/L) remains controversial. Pru p 3 sIgE is considered to be the main routine tool for assessing lipid transfer protein (LTP) sensitization. We aimed to evaluate the clinical relevance of Pru p 3 sIgE low levels in a population diagnosed with LTP allergy. Adults diagnosed with LTP allergy and Pru p 3 sIgE ≥ 0.1 KUA/L between 2012 and 2019 were included. Clinical data were reviewed. nPru p 3 basophil activation test (BAT) was performed and basophil reactivity (BR) and sensitivity (BS) correlated with the peach allergy symptoms. Pru p 3 sIgE from 496 subjects was recorded, 114 (23.0%) between 0.1 and 0.34 KUA/L (grLOW), the rest ≥ 0.35 KUA/L (grB). A total of 44.7% in grLOW and 59.9% in grB were allergic. Urticaria was more frequent in grLOW. In grLOW, Pru p 3 sIgE was higher in patients with local compared with systemic symptoms. In grB, Pru p 3 sIgE was higher in allergic patients. Pru p 3/Total IgE ratios were higher in allergic vs. tolerant in both groups. In BAT, BR was similar in both groups. In grLOW, it was higher on allergic compared with tolerant (p = 0.0286), and on those having systemic vs. local symptoms (p = 0.0286). BS showed no significant difference between groups. Patients with low levels represent a non-negligible fraction and around 45% are peach allergic. BAT showed functional sIgE in them. Pru p 3 sensitizations should be carefully evaluated even when sIgE levels are low.

Skin Testing Is Useful in Assessing Aeroallergen Sensitization in IgE Deficient Patients with Environmental Allergy-Like Symptoms.

BACKGROUND: The value of aeroallergen skin testing is not known in IgE deficient individuals (IgE<2.5 kU/L). OBJECTIVE: To investigate the utility of skin prick (SPT), intradermal skin testing (IDST) and measuring serum specific IgE (ssIgE) in IgE deficient patients presenting with environmental allergy-like symptoms. METHODS: Individuals with IgE deficiency who had both SPT and IDST performed between 2010 to 2020 were matched (age and gender) to three different groups of non-IgE deficient patients with IgE≥2.5 kU/L (normal IgE [2.5 ≤ IgE<100], high IgE [100≤IgE<1000] and very high IgE levels [≥1000 kU/L]) who also had skin testing performed for evaluation of environmental allergy-like symptoms. RESULTS: Among 34 IgE deficient patients who completed SPT and IDST, 52.9% (18/34) had at least one positive skin test (4 ± 3 positive tests/patient), compared with 91.2% in those with normal, 94.1% with high or 97.1% with very high IgE levels (p < 0.01). In contrast, only one of the IgE deficient patients had detectable ssIgE, while ssIgE levels were significantly higher in all other IgE subgroups. Allergic immunotherapy was prescribed for 22.2% of the IgE-deficient patients with positive skin tests, similar to those with normal (2/31, 6.5%, p = 0.21), high IgE (9/32, 28.1%, p = 0.25) and very high IgE levels (8/33, 23.5%, p = 0.07), with similar efficacy in their symptoms control. CONCLUSION: Individuals with IgE deficiency may present with environmental allergy-like symptoms. A combination of SPT and IDST is useful for diagnosing aeroallergen sensitizations in these patients, indicating the presence of skin mast cell-bound IgE in some of these individuals, despite very low serum IgE levels. Further studies are needed to assess the exact significance of positive skin tests and the benefits of immunotherapy in this group.

The Importance of Nasal Provocation Testing in the Diagnosis of Dermatophagoides pteronyssinus-Induced Allergic Rhinitis.

BACKGROUND: Allergen identification is the first step for allergen-specific immunotherapy (AIT) of allergic rhinitis (AR). Currently, the diagnosis of AR is based mainly on the positive results of the skin prick test (SPT) and/or serum specific immunoglobulin E (sIgE) measurement. However, the results of these two tests may not always directly correlate with AR. OBJECTIVE: To investigate the importance of nasal provocation testing (NPT) in the diagnosis of Dermatophagoides pteronyssinus (Der p)-induced AR. METHODS: Rhinitis patients willing to undergo AIT (n = 171) were enrolled. The correlations of Der p SPT, sIgE, NPT, and clinical symptom severity were assessed. RESULTS: NPT-positive responses were more common in patients with higher SPT and sIgE levels. The optimal cut-off value for a NPT-positive response for SPT was 5.5 mm and for sIgE was 2.77 kUA/L, based on the respective receiver operating characteristic (ROC) curves. The area under the curve (AUC) of the ROCs was 0.814 (SPT only) and 0.794 (sIgE only) and increased to 0.828 with the combination of SPT and sIgE. The Der p-NPT concentration was inversely correlated with SPT and sIgE levels (r = -0.477, P < .001, and r = -0.461, P < .001, respectively), but none was correlated with the total nasal symptom score. CONCLUSION: For patients who are willing to receive Der p AIT, NPT is a useful and safe test to confirm diagnosis prior to treatment initiation, especially in patients with lower levels of Der p SPT (< 5.5 mm) or sIgE (< 2.77 kUA/L).

Nut Allergy: Clinical and Allergological Features in Italian Children.

BACKGROUND: Nut allergies are an increasingly frequent health issue in the pediatric population. Tree nuts (TN) and peanuts are the second cause of food anaphylaxis in Italy. Unfortunately, knowledge of the clinical characteristics of a TN allergy in Italian children is limited. Our study aimed to identify the clinical and allergological characteristics of Italian children with a nut allergy (TN and peanut). METHODS: A retrospective observational analysis was performed on the clinical charts of children with a history of nut reaction referred to the allergy unit of the hospital from 2015 to 2019. The studied population was represented by children with a confirmed nut allergy based on positive prick by prick and/or serum-specific IgE to nut plus a positive nut oral food challenge. Demographic, clinical, and allergological features were studied and compared among different nuts. RESULTS: In total, 318 clinical charts were reviewed. Nut allergy was confirmed in 113 patients. Most patients (85/113, 75%) had a familial history of allergy and/or a concomitant allergic disorder (77/113, 68%). Hazelnut and walnut were the more common culprit nuts observed in allergic children. Anaphylaxis was the first clinical manifestation of nut allergy in a high percentage of children (54/113, 48%). The mean age of the first nut reaction was statistically higher with pine nuts. Over 75% of children reported a single nut reaction. During the OFCs, the signs and symptoms involved mainly the gastrointestinal system (82/113, 73%) and resolved spontaneously in most cases. Severe reactions were not frequent (22/113, 19%). CONCLUSION: To our knowledge, this is the first Italian study that provided a comprehensive characterization of children with a nut allergy. These results are important for clinicians treating children with a nut allergy.

Clinical Predictors and Outcomes of Oral Food Challenges Illustrate Differences Among Individual Tree Nuts.

BACKGROUND: Although allergy to tree nuts is often considered a single entity, there is heterogeneity in patient reactivity and immune response to different tree nuts. OBJECTIVE: We sought to characterize tree nut oral food challenges (OFCs) in a pediatric population performed at a single center over a 12-year period and determine differences in OFC outcome to different tree nuts. METHODS: A retrospective chart review was conducted in patients (0-20 years) who completed an unblinded OFC to any tree nut from 2007 to 2019 at Lurie Chlildren's Hospital of Chicago. Differences among almond, cashew, hazelnut, and walnut challenges were compared, and probability curves were used to estimate positive predictive values (PPVs) of specific IgE at OFC. RESULTS: A total of 531 tree nut OFCs were included. The mean age at OFC was 7.77 years (standard deviation, 4.33). Overall, 74.0% of children passed clinically indicated OFCs. Of the 4 most commonly challenged tree nuts, almost all patients passed OFC to almond (97.3%) and hazelnut (87.9%). Pass rates were lower for cashew (65.3%) and walnut (57.0%), P < .0001. The odds of failure were 0.83 times lower for patients who were avoiding without a previous reaction compared with those who had previously reacted (P = .0025). CONCLUSIONS: The majority of patients pass low-risk almond and hazelnut OFCs. PPVs at the 50th percentile for walnut (2.84 kU/L) and cashew (3.35 kU/L) were lower than those previous studies have suggested.

Cow's Milk Protein Allergy as a Model of Food Allergies.

Cow's milk allergy (CMA) is one of the most common food allergies in infants, and its prevalence has increased over recent years. In the present paper, we focus on CMA as a model of food allergies in children. Understanding the diagnostic features of CMA is essential in order to manage patients with this disorder, guide the use of an elimination diet, and find the best moment to start an oral food challenge (OFC) and liberalize the diet. To date, no shared tolerance markers for the diagnosis of food allergy have been identified, and OFC remains the gold standard. Recently, oral immunotherapy (OIT) has emerged as a new therapeutic strategy and has changed the natural history of CMA. Before this, patients had to strictly avoid the food allergen, resulting in a decline in quality of life and subsequent nutritional, social, and psychological impairments. Thanks to the introduction of OIT, the passive approach involving rigid exclusion has changed to a proactive one. Both the heterogeneity in the diagnostic process among the studies and the variability of OIT data limit the comprehension of the real epidemiology of CMA, and, consequentially, its natural history. Therefore, well-planned randomized controlled trials are needed to standardize CMA diagnosis, prevention, and treatment strategies.

Evaluation of safety and consistency of inhaled allergen extracts in the diagnosis of allergic diseases in children / 中华实用儿科临床杂志

Objective:To investigate the safety and consistency of domestic inhaled allergen extracts in the diagnosis of allergic diseases in children.Methods:Nine thousand five hundred and sixty-three children diagnosed with allergic diseases from September 2018 to June 2020 in Children′s Hospital Affiliated to Capital Institute of Pedia-trics were selected in this study, and all of them were subjected to skin prick test(SPT), and 415 of them were subjected to serum specific IgE (sIgE) test at the same time.The adverse events during SPT were recorded and the consistency of the results between SPT and sIgE test was analyzed.Results:There were 14 cases with adverse events in 9 563 patients, and the overall incidence was 0.15%.The incidence of adverse events was 0.07% (2/2 581 cases) in the 1-5 years old group, 0.19% (12/6 197 cases) in the 6-11 years old and 0 in the 12-17 years old group.The severity of all these events was grade Ⅰ.Out of the 14 cases with adverse events, only 1 case was considered to be related to allergen preparations, with the incidence being 0.01% (1/9 563 cases). The Kappa index showed that the results of dermatophagoides pteronyssinus, dermatophagoides farinae, alternaria and artemisia measured by SPT and sIgE were almost the same.There was high consistency between tree pollens and ragweed ( P<0.01), and moderate consistency between aspergillus fumigatus ( P<0.01). When the results of sIgE were used as the diagnostic criteria, the Youden index for the results of SPT ranged from 0.76 to 0.89, with aspergillus fumigatus (0.76) and tree pollens mixture (0.79) as the lowest.The positive likelihood ratio for most of the inhaled allergens was more than 10 except for tree pollens mixture (7.12) and dermatophagoides farinae (9.10). The negative likelihood ratio for most of the inhaled allergens was less than or equal to 0.1 except for aspergillus fumigatus (0.19). Conclusions:The domestic inhaled allergen extracts had high safety in the clinical application of SPT, and their results of SPT had good consistency with those of serum sIgE, which was conducive to the diagnosis and evaluation of allergic diseases in children.

Distribution of serum specific IgE in children with allergic conjunctivitis and analysis of its concomitant allergic diseases.

BACKGROUND: Allergic conjunctivitis (AC) is predominantly caused by serum specific-IgE (sIgE)-mediated type I allergy. This study aims to analyze the distribution of sIgE in children with AC, and the concomitant allergic diseases. METHODS: The clinical data from 310 children, diagnosed with AC and admitted to our hospital from January 2017 to January 2019 were retrospectively collected. The children were divided into three groups: infant group (2 months to 1 year old, 91 cases), child group (1 to 3 years old, 112 cases), and preschool group (3 to 6 years old, 107 cases). Children in every group were analyzed for positive rates, the number of positive sIgE types, the distribution of positive inhaling and ingesting allergens and concomitant allergic diseases. RESULTS: The sIgE positive rate of infant was significantly lower than that of the other two groups, and the number of 18.75% sIgE positive species was 1. The number of sIgE positive species in the child group and preschool group was more than 2 (78.30%, 71.15%). The positive rate of sIgE to dust mites, house dust, animal dander, eggs, beef, mutton and mango in the preschool group was significantly higher than the other groups (P<0.05). The positive rate of sIgE to milk in infant group was significantly higher than the other two groups (P<0.05). Children in the preschool group showed the highest incidence of AC, AC + allergic rhinitis, AC + allergic rhinitis + wheezing, while those in the infant group displayed the lowest incidence (P<0.05). AC + gastrointestinal allergy, AC + atopic dermatitis, AC + gastrointestinal allergy + atopic dermatitis in infant group was significantly higher than the other two groups (P<0.05). Patients in the child group displayed a significantly higher incidence of AC + infant wheezing than the other two groups (P<0.05). CONCLUSIONS: We correlated children's age with the positive rate and gradual increase in types of AC allergens. Concomitant allergic diseases of children with AC at different ages conform to the natural course of allergic diseases. In clinic, improving the diagnostic efficiency of AC in children, and early interventional treatment will positively contribute to their prognosis, and reduce the risk of other allergic diseases.

Diagnosis of Sesame Allergy: Analysis of Current Practice and Exploration of Sesame Component Ses i 1.

BACKGROUND: Sesame is an allergen of increasing importance. OBJECTIVE: We sought to characterize the outcomes of oral food challenges (OFCs) to sesame and evaluate the diagnostic accuracy of skin prick testing (SPT), sesame, and Ses i 1-specific IgE (sIgE). METHODS: We reviewed sesame OFCs performed at the Mount Sinai pediatric allergy clinic between January 2010 and April 2018. We assessed the accuracy of diagnostic tests by calculating the area under the curve (AUC) of the receiver operating characteristic curves. The association between OFC outcome and sesame sensitization was analyzed using a logistic regression, which was then used to estimate the 95% positive predictive value (PPV) of these tests. RESULTS: We identified 341 patients (69% male, mean age 7.7 years) who underwent sesame OFC. Among 106 (31%) positive OFCs, the median cumulative eliciting dose was 500 mg sesame protein (1/2 teaspoon tahini). Sesame SPT wheal ≥6 mm had sensitivity 54.1% and specificity 87.8%; AUC 0.756 (95% confidence interval [CI], 0.699-0.814). SPT wheal size ≥14 mm had 95% PPV. Sesame-sIgE level did not correlate with OFC outcome. Ses i-sIgE levels were analyzed in 30 patients using the Immuno Solid-phase Allergen Chip (ISAC) microarray and were significantly associated with OFC outcome (AUC: 0.715 [95% CI, 0.541-0.890]). Ses i 1-sIgE ≥0.3 ISAC Standardized Units had sensitivity 58.3% and specificity 83.3%. CONCLUSIONS: This is the largest study of sesame allergy to date. Sesame SPT is a more accurate predictor of sesame allergy compared with sesame sIgE. Ses i 1-sIgE appears promising but requires further study regarding diagnostic accuracy.

[Characteristic analysis of aeroallergens of allergic rhinitis patients in Wuhan].

Objective:To analyze the distribution characteristics of common aeroallergens in patients with allergic rhinitis（AR）in Wuhan. Method:Serum specific IgE（ssIgE）was detected in 1 983 patients with clinically diagnosed AR by Midiwiss Allergen Screen system. Data was analyzed statistically. Result:Among the 1 983 patients，1 507（76.0%）had at least one positive ssIgE. The most common aeroallergens were Dermatophagoides pteronyssinus（62.0%），mixed fungi（32.1%）and house dust（27.3%）.Single positive allergen（43.8%），dual positive allergen（28.1%）and triple positive allergen（15.4%）were the most common combinations. The proportion of single positive allergens in the juvenile group（1 to 17 years old）（35.2%）was lower than adult group（≥18 years old）（46.7%），while the proportion of multiple positive allergens was higher than adult group. The positive rates of mulberry and mixed grass in male group were higher than female group. The positive rates of house dust，cat fur and dog fur in the juvenile group were higher than the adult group，while the positive rate of mulberry，cockroach and mixed grass were lower than the adult group. In the elder group（60-88 years old），the positive rates of Dermatophagoides pteronyssinus and mixed fungi were higher than the other three groups. The positive rates of Dermatophagoides pteronyssinus in summer and autumn were higher than that in winter and spring. The positive rate of mixed grass in autumn was much higher and the positive rate of mixed trees and mulberry trees in spring was higher than summer and autumn. Conclusion:Dermatophagoides pteronyssinus，mixed fungi and house dust were the most common aeroallergens among patients with allergic rhinitis in Wuhan. The distribution characteristics in different genders，ages and seasons were different..

Association of serum specific IgE levels with asthma in autumn pollen-induced allergic rhinitis: A retrospective analysis.

BACKGROUND: Artemisia and Humulus pollen are the two most important aeroallergens of autumn allergies in North China. Cross-sectional data in 2001 have shown that allergic rhinitis often preceded or occurred at the same time as asthma in patients with autumn pollinosis in North China. OBJECTIVE: We used this cross-sectional data to investigate the association of serum specific IgE (sIgE) levels to Humulus and/or Artemisia pollen with the onset of asthma in patients with autumn pollen-induced allergic rhinitis. METHODS: 1096 patients with autumn pollinosis were face-to-face interviewed and underwent sIgE tests to Artemisia and Humulus. The temporal sequence of allergic rhinitis and asthma was documented. 1013 patients were positive to Artemisia and/or Humulus by sIgE. Multinomial logistic regression and survival analysis were used to examine the potential implication of sIgE levels for the progression of asthma in autumn pollen-induced allergic rhinitis. RESULTS: Of the 1013 participants with a positive sIgE test to Artemisia and/or Humulus, 563 (55.6%) had a history of allergic rhinitis which preceded or occurred at the same time as asthma. 450 (44.4%) had allergic rhinitis alone. After controlling of sex, age at onset of allergic rhinitis, and parental asthma, the risk of developing asthma increased with the levels of sIgE to both Artemisia and Humulus (p < 0.05). In Kaplan-Meier analysis, IgE classes 5-6 to Humulus or Artemisia increased the risk of asthma development (p < 0.05). CONCLUSION: Autumn pollen-induced allergic rhinitis often coexists with seasonal asthma. The incidence of asthma is more pronounced when the sIgE level was higher.

[Analysis of allergen spectrum and sensitization factors in children with allergic rhinitis].

Objective:The aim of this study is to analyze the distribution of common allergens in allergic rhinitis patients aged 2-15 in Zhangjiagang area,in order to provide a path to know the epidemic features of children with AR, and supports epidemiological materials to find better prevention, diagnosis and treatment for them.Method:From July.2015 to July.2018,1 320 children aged 2-15 who were suspected with allergic rhinitis by the doctors of ENT clinic in the Zhangjiagang Affiliated Hospital,were enrolled in this project.Using the serum specific IgE detection methods to detect common allergens in those patients,then analyze the relationship among allergens and gender,age and visiting time of every single patient.Result:The total positive rate of 1 320 children was 82.50%,and the total positive rate of 8 common inhaled allergens was 82.50%.The main allergens were dust mites and dogs. The total positive rate of Children aged in 7-12 was the highest,and the positive rate of dust mites of male was higher than female.The common food allergens total positive rate was 9.09%.And the top three food allergens were milk,shrimp,crab.The number of visitors in July and August was the most in a year.The dust mite had the highest positive rate among common inhaled allergen in a year,and the maximum value appeared in July.The rate of patients who were allergic to one inhalant allergen were lower than those who were allergic to two or more inhalant allergens.Conclusion:The dust mite is the major allergen above all.The total positive rate of Children aged in 7-12 was the highest,and the positive rate of dust mites of male was higher than female;the maximum value appeared in July and August.The rate of patients who were allergic to one inhalant allergen were lower than those who were allergic to two or more inhalant allergens.

The use of specific immunoglobulin E in nasal secretions for the diagnosis of allergic rhinitis.

OBJECTIVE: Although local specific immunoglobulin (sIgE) has been employed as a diagnostic criterion for allergic rhinitis (AR), the use of local sIgE has not been fully evaluated in the diagnosis of allergic rhinitis. The aim of this study was to evaluate the use of nasal secretion sIgE in the diagnosis of allergic rhinitis. METHODS: A total of 51 patients (27 males and 24 females, mean age = 33.3 years) with rhinitis symptoms were enrolled consecutively from the allergy-rhinology clinic of Beijing TongRen Hospital (Beijing, People's Republic of China). Questionnaires were completed by each participant at recruitment to record demographic data, nasal symptom severity, and physician-diagnosed comorbid asthma. The severity of nasal obstruction, rhinorrhea, sneezing, and nasal/eye itching was recorded according to a visual analogue scale (VAS) of 10 cm. Sensitization to Dermatophagoides pteronyssinus, Dermatophagoides farinae, mugwort, Candida albicans, Penicillium notatum, Alternaria, Cladosporium, and Aspergillus were assessed according to presence of sIgE antibodies to these allergens in serum and nasal secretions. RESULTS: VAS scores of the participants ranged from 11 to 25 (mean = 17), and 14 (27.5%) patients had comorbid asthma. Based on serum sIgE, 31 (60.8%) patients were allergic to mugwort, 14 (27.5%) to Dermatophagoides, and three (5.9%) to fungal allergens. Based on nasal secretion sIgE, 32 (62.7%) patients were allergic to mugwort, 12 (23.5%) to Dermatophagoides, and three (5.9%) to fungal allergens. The local mugwort sIgE level and serum mugwort sIgE level were positively correlated with each other and with VAS scores. CONCLUSION: sIgE level in nasal secretions of subjects with rhinitis is a reliable noninvasive alternative to serum sIgE for diagnosis of allergic rhinitis. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:E311-E315, 2018.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Diagnosis of Food Allergy.

Food allergy diagnosis remains challenging. Most standard methods are unable to differentiate sensitization from clinical allergy. Recognizing food allergy is of utmost importance to prevent life-threatening reactions. On the other hand, faulty interpretation of tests leads to overdiagnosis and unnecessary food avoidances. Highly predictive models have been established for major food allergens based on skin prick testing and food-specific immunoglobulin E but are lacking for most other foods. Although many newer diagnostic techniques are improving the accuracy of food allergy diagnostics, an oral food challenge remains the only definitive method of confirming a food allergy.

[Diagnostic accuracy of specific IgE antibodies measurements in occupational airway allergy to high molecular weight agents]. / Trafnosc diagnostyczna oznaczen alergenowo swoistych przeciwcial IgE w zawodowej alergii dróg oddechowych na czynniki o duzej masie czasteczkowej.

BACKGROUND: The performance of specific inhalation challenge test (SICT) - reference method in diagnostics of occupational allergy - has some limitations due to health status of a particular patient. Therefore, it is extremely important to identify usefulness of other tests, and the evaluation of diagnostic accuracy of commercially available serum specific immunoglobulin E (sIgE) kits to the most common high molecular weight agents has been launched. MATERIAL AND METHODS: The study group comprised 141 subjects - 110 bakers and 31 farmers - with suspicion of occupational airway allergy. All patients underwent evaluation of serum sIgE to occupational allergens with the use of Phadia and Allergopharma kits: in bakers to flour mix and α-amylase, in farmers to epithelium of cow, pig and feathers. Specific inhalation challenge test with workplace allergens performed in all subjects was a reference method for further analysis. RESULTS: Serum specific IgE to flour mix had the highest sensitivity (Phadia - 95.6%, Allergopharma - 88.3%), while its specificity was relatively low (Phadia - 47.8%, Allergopharma - 25%). There were numerous discrepancies between the results of sIgE estimation for particular single allergens (k87, e4, e83), as well as for their mixtures (fx901, fx20, ex71), performed with the kits of both companies (Phadia vs. Allergopharma). CONCLUSIONS: Evaluation of serum specific IgE is characterized by inadequate sensitivity, specificity and predictive value to take the place of specific inhalation challenge test in diagnostics of occupational respiratory allergy. Med Pr 2017;68(1):31-43.

Clinical characteristics of total IgE in pediatric allergic disease

PURPOSE: Serum total and specific IgE levels have been widely used to diagnose allergic disease. However, it has recently been suggested that serum total IgE does not properly reflect specific IgE. Therefore, we evaluated the clinical significance of serum total IgE in pediatric allergic disease. METHODS: This study included 633 patients who visited Kyungpook National University Children's Hospital between March 2013 and April 2015. We used immunoCAP, an inhalant multiple allergen simultaneous test (MAST), and food MAST to measure specific IgE. We used a skin prick test in some patients and measured serum total IgE, eosinophil count, and serum eosinophil cationic protein in all patients. RESULTS: There was a positive correlation between serum total IgE and antigen level in the inhalant immunoCAP test. Specifically, the sum of immunoCAP levels was highly correlated with serum total IgE (r=0.631, P<0.001). Moreover, there was a positive correlation between serum total IgE and the sum of food immunoCAP levels (r=0.323, P<0.001). Among the food immunoCAP antigens, milk was highly correlated with serum total IgE (r=0.558, P<0.001). There was a positive correlation between serum total IgE and the sum of class levels of inhalant/food MAST tests (r=0.709, P<0.001 and r=0.686, P<0.001, respectively). There was also a positive correlation between serum total IgE and the number of positive skin prick tests (r=0.445, P<0.001). CONCLUSION: Serum total IgE may reflect the sum of serum specific IgE levels in pediatric allergic disease.

A new framework for the interpretation of IgE sensitization tests.

IgE sensitization tests, such as skin prick testing and serum-specific IgE, have been used to diagnose IgE-mediated clinical allergy for many years. Their prime drawback is that they detect sensitization which is only loosely related to clinical allergy. Many patients therefore require provocation tests to make a definitive diagnosis; these are often expensive and potentially associated with severe reactions. The likelihood of clinical allergy can be semi-quantified from an IgE sensitization test results. This relationship varies though according to the patients' age, ethnicity, nature of the putative allergic reaction and coexisting clinical diseases such as eczema. The likelihood of clinical allergy can be more precisely estimated from an IgE sensitization test result, by taking into account the patient's presenting features (pretest probability). The presence of each of these patient-specific factors may mean that a patient is more or less likely to have clinical allergy with a given test result (post-test probability). We present two approaches to include pretest probabilities in the interpretation of results. These approaches are currently limited by a lack of data to allow us to derive pretest probabilities for diverse setting, regions and allergens. Also, cofactors, such as exercise, may be necessary for exposure to an allergen to result in an allergic reaction in specific IgE-positive patients. The diagnosis of IgE-mediated allergy is now being aided by the introduction of allergen component testing which may identify clinically relevant sensitization. Other approaches are in development with basophil activation testing being closest to clinical application.