Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

Nasal allergen-neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis.

BACKGROUND: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients. METHODS: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months. Both groups subsequently received SCIT for 12 months at Year 2. Nasal and serum antibodies (IgG4, IgA1 and IgA2) and their inhibitory capacity were measured at multiple timepoints. RESULTS: The allergen concentration tolerated increased significantly at 6 months (Group A; p = .047) and 24 months (Group B; p = .049) compared with baseline and persisted until the end of the study. Induction of serum sIgA1 to Phl p was seen in Groups A and B, albeit the former being induced earlier (1.71-fold, p = .027). A significant induction in sIgG4 to Phl p 1 and 5 was observed in serum of Group A (p = .047 and p = .0039) and sIgA2 to Phl p in Group B (p = .032 and p = .0098) at 18 and 24 months, respectively. Both local and systemic blocking antibodies can inhibit allergen-IgE complexes binding to CD23 on B cells, and this correlated with level of allergen tolerated intra-nasally in Group A (serum; 𝜌 = -.47, p = .0006, nasal; 𝜌 = -.38, p = .0294). CONCLUSIONS: Grass pollen SCIT induced functional systemic blocking antibodies that correlate with the concentration of allergen tolerated following NAC, highlighting their potential as a biomarker of SCIT in LAR.

The contribution of milk substitutes to the nutritional status of children with cow's milk allergy.

BACKGROUND: The impact of alternative milk substitutes on the nutritional status of children with cow's milk allergy (CMA), the prevailing cause of food allergies, is unresolved. METHODS: A cross-sectional study was performed in children older than 2 years with IgE-mediated CMA. Patients' clinical characteristics, anthropometric measurements, dietary intake (by 3-day food diary), and biochemical markers of nutritional status were assessed. RESULTS: One hundred two children with CMA (68.6% boys; median age, 3.7 years; 51% multiple food allergies) were evaluated. 44.1% of the children consumed plant-based beverages (PBB), 19.6% therapeutic formula and 36.3% did not consume any milk substitutes. In all age groups, dietary calcium, riboflavin, and vitamin D intake of those who did not use milk substitutes were lower than those who consumed formula or PBB (p < .01). Also in the 2-3 years old age group, dietary zinc (p = .011) and iron intake (p = .004) of the formula-fed group was higher. Formula-fed patients had higher levels of 25-OH vitamin D (µg/L) and serum vitamin B12 (ng/L) than PBB-fed patients (respectively; p < .001, p = .005) and those who did not consume any milk substitute (p < .001). Patients of all ages who did not utilize a milk substitute failed to obtain an adequate amount of dietary calcium. CONCLUSION: The use of milk substitutes positively affects dietary calcium, riboflavin, and vitamin D intake in CMA, but their contribution is variable. Those who do not use milk substitutes are at greater risk inadequate of dietary calcium intake. Personalized nutritional advice, given the clinical diversity and the impact of individual differences, is required.

Mite allergen sensitization patterns in Turkish children: Age-related changes and molecular correlations.

BACKGROUND: Mites are ubiquitous aeroallergens found worldwide. Elucidating individual mite allergen sensitization patterns provides critical insights for managing allergic diseases. This study aimed to investigate molecular allergen (MA) sensitization patterns across different age groups and explore cluster relationships among mite-sensitized children. METHODS: We analyzed 76 children who exhibited sensitization to at least one of the 17 distinct mite MAs through microarray testing. RESULTS: Dermatophagoides farinae exhibited a slightly higher prevalence of sensitization compared with Dermatophagoides pteronyssinus. Der p 1/2 and Der f 1/2 demonstrated an almost 40% sensitization rate, while Der p 10/Blo t 10, Der p 20, Der p 23, and Gly d 2/Lep d 2 displayed an approximately 20% sensitization rate. Sensitization levels and ratios increased significantly with age for Der p 23 but showed numerical rises for other MAs, except for Der p 10/Blo t 10. The presence of various types of atopic diseases had only a minimal impact on sensitization profiles. Strong correlations emerged between Der f 2 and Der p 2, Der p 10 and Blo t 10, Der p 21 and Blo t 5, as well as Gly d 2 and Lep d 2. Hierarchical cluster analysis substantiated these relationships. Der p 10 and its homolog Blo t 10-sensitive patients (15/76) were mostly seen as mono sensitization(12/15). Ten patients exhibited monosensitization to Der p 20, suggesting a possible association with scabies infection. CONCLUSION: In children, mite sensitization diversity and levels increased with age. The presence of significant correlations/cluster relationships among these sensitizations underscores homologies among specific MAs.

Plasma Extracellular Vesicles Derived from Pediatric COVID-19 Patients Modulate Monocyte and T Cell Immune Responses Based on Disease Severity.

BACKGROUND: The COVID-19 pandemic has caused significant morbidity and mortality globally. The role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients remains unclear. METHODS: We isolated EVs from healthy controls (n = 13) and pediatric COVID-19 patients (n = 104) with varying severity during acute and convalescent phases using serial ultracentrifugation. EV effects on healthy PBMCs, naïve CD4+ T cells, and monocytes were assessed through in vitro assays, flow cytometry, and ELISA. RESULTS: Our findings indicate that COVID-19 severity correlates with diverse immune responses. Severe acute cases exhibited increased cytokine levels, decreased IFNγ levels, and lower CD4+ T cell and monocyte counts, suggesting immunosuppression. EVs from severe acute patients stimulated healthy cells to express higher PDL1, increased Th2 and Treg cells, reduced IFNγ secretion, and altered Th1/Th17 ratios. Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes (p < .001 for mild, p = .0025 for severe cases) and decreased CD4+ T cell (p = .043) and monocyte (p = .033) populations in stimulated healthy PBMCs. CONCLUSION: This study reveals the complex relationship between immunological responses and EV-mediated effects, emphasizing the impact of COVID-19 severity. We highlight the potential role of plasma-derived EVs in early-stage immunosuppression in severe COVID-19 patients.

Understanding of lipid transfer protein sensitization patterns and its clinical significance in children.

Background: Lipid transfer proteins (LTP) are the most common food allergens in the Mediterranean region. Objective: The study aimed to investigate co-sensitization patterns and cluster relationships between LTP allergen molecules across a broad range of allergen-specific sensitization patterns, and clinical outcomes in eastern Mediterranean children. Methods: Among 496 children evaluated for multiple sensitizations with multiplex testing, 105 children (21%) with 16 different LTP sensitizations were analyzed. Clinical reactivity was examined based on clear-cut history of immunoglobulin E mediated symptoms (oral allergy syndrome [OAS], systemic reactions, and anaphylaxis). Results: All children included were sensitive to food LTPs, but 56% were sensitive to pollen LTPs. The number of children with OAS and clinical reactivity was 12 and 59, respectively, and no cofactors were reported. The most common sensitizations were Pru p 3 (74%) and Cor a 8 (66%). Significant correlations were observed in the heatmap between the LTP molecules other than Par j 2 and Tri a 14. Overall, clinical reactivity was associated with increased age and number of LTP molecule positivity. Conclusion: In the eastern Mediterranean region, 21% of children with multiple food and/or pollen sensitizations were found to have LTP sensitization; however, almost half reported clinical reactivity. The hierarchical pathway highlights that distinct LTP allergen molecules can act as primary sensitizers. Clinical reactivity is linked to increasing numbers of LTP molecule positivity and increasing age.

Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

Recognition of nuts and seeds in children with/without food allergies and their mothers: A reflection of culinary culture.

BACKGROUND: Nuts and seeds are among the leading causes of food allergy. Effective food allergy management hinges on the ability to identify and avoid relevant foods. AIM: To evaluate the nut/seed recognition ability in both children and mothers. METHODS: Primary caregivers (mothers) and their children (6-18 years old) with/without food allergies were shown photographs of nuts/seeds, and their products with visible/hidden allergens to assess their ability to recognize accurately. RESULTS: A total of 196 children and 184 mothers participated. The median ages of the children and mothers were 7.6 (6.8-10) and 37.8 (33.1-41.5) years, respectively. Over 75% of the children/adolescents and over 90% of the mothers accurately identified the kernel forms of nuts/seeds, except pine nuts. Walnuts, hazelnuts, almonds, and cashews were the most accurately recognized kernel forms by both populations. Generally, the kernel forms were recognized 5-20% more accurately than their in-shell forms, followed by products with visible and hidden forms, respectively. Some Turkish culinary-specific products with visible/hidden allergens were recognized as frequently as the kernel/in-shell forms by both study groups. Although there was a similar recognition pattern between study groups and subgroups (nut/seed allergy, other food allergy, controls), higher rates of recognition were found in mothers than in their children and adolescents than in schoolchildren. CONCLUSION: In Eastern Mediterranean region, nuts and sesame seeds are highly recognized by both mothers and their children. Accurate identification of these foods is likely a culinary feature, but not the result of increased awareness. More information is needed on whether this ability reduces the risk of exposure.

Exploring the Heterogeneity of IgE-Mediated Food Allergy through Latent Class Analysis.

INTRODUCTION: Food allergy (FA) is a heterogeneous disease with multiple morbidities and a huge burden for patients and healthcare systems. Variable manifestations, comorbidities (atopic dermatitis [AD], asthma, and/or allergic rhinitis [AR]), severity (anaphylaxis), and outcomes suggest the existence of different endotypes that cluster analyses may reveal. In this study, we aimed to investigate distinct subgroups among patients with FAs using data from 524 children/adolescents. METHODS: 524 patients with IgE-mediated FA (353 male [67%]; median age 4.4 years [IQR:3.0-6.8]), 354 (68%) had multiple FA. The history of AD, asthma, AR, and anaphylaxis was recorded in 59.4%, 35.5%, 24.2%, and 51.2% of the patients, respectively. Latent class analysis was carried out to distinguish clinical FA phenotypes using five potential markers of allergy severity (single/multiple FA, never/inactive/current asthma and AD, AR, and anaphylaxis). RESULTS: Three distinct phenotypes were identified: (1) multiple FA with eczema and respiratory multimorbidity (42%), (2) multiple FA with persistent eczema (34%), and (3) single FA with respiratory multimorbidity without eczema (24%). Compared with the single FA cluster, the prevalence of AD was significantly higher in multiple FA groups. Cluster 1 had the highest frequency of AR and allergic asthma, and the lowest rate of total tolerance of FA. DISCUSSION: We put forward the hypothesis of underlying pathogenesis according to the clinical phenotypes. While skin barrier defect may play a dominant role in the pathogenesis in Cluster 2, immune dysregulation may be dominant in Cluster 3. In Cluster 1, the most severe group, a combination of both skin barrier defects and immune dysregulation may be responsible for the clinical features.

In Chronic Spontaneous Urticaria, Complete Response to Antihistamine Treatment Is Linked to Low Disease Activity.

INTRODUCTION: The use of predictors of response to a specific treatment in patients with chronic spontaneous urticaria (CSU) can improve disease management, help prevent unnecessary healthcare costs, and save time. In this study, we aimed to identify predictors of complete response to standard-dosed and higher than standard-dosed antihistamine treatments in patients with CSU. METHODS: Medical records of 475 CSU patients, 120 of them <18 years old, from 3 different centers were analyzed. We used 15 machine learning (ML) models as well as traditional statistical methods to predict complete response to standard-dosed and higher than standard-dosed antihistamine treatment based on 17 clinical parameters. RESULTS: CSU disease activity, which was assessed by urticaria activity score (UAS), was the only clinical parameter that predicted complete response to standard-dosed and higher than standard-dosed antihistamine treatment, with ML models and traditional statistics, for all age groups. Based on ROC analyses, optimal cut-off values of disease activity to predict complete response were UAS <3 and UAS <4 for standard-dosed (area under the ROC curve [AUC] = 0.69; p = 0.001) and higher than standard-dosed (AUC = 0.79; p = 0.001) antihistamine treatments, respectively. Also, ML models identified lower total IgE (<150 IU/mL) as a predictor of complete response to a standard-dosed antihistamine and lower CRP (<3.4 mg/mL) as a predictor of complete response to higher than standard-dose antihistamine treatment. DISCUSSION: In this study, we showed that patients with UAS <3 are highly likely to have complete response to standard-dosed AH and those with a UAS <4 are highly likely to have complete response to higher than standard-dosed AH treatment. Low CSU disease activity is the only universal predictor of complete response to AH treatment with both ML models and traditional statistics for all age groups.

Eosinophilia in children: characteristics, etiology and diagnostic algorithm.

Eosinophilia is common in children and may be caused by various disorders. Large-cohort studies, including mild cases, are limited in children. This study aimed to reveal underlying etiologies of childhood eosinophilia and to create a diagnostic algorithm. Children (< 18 years) with absolute eosinophil counts (AECs) ≥ 0.5 × 109/L were reviewed from medical files. Clinical characteristics and laboratory values were recorded. Patients were grouped based on the severity of eosinophilia as mild (0.5-1.5 × 109/L), moderate (≥ 1.5 × 109/L) and severe (≥ 5.0 × 109/L). An algorithm was formed to evaluate these patients. We included 1178 children with mild (80.8%), moderate (17.8%) and severe eosinophilia (1.4%). The most common reasons of eosinophilia were allergic diseases (80%), primary immunodeficiency (PID) (8.5%), infectious diseases (5.8%), malignancies (0.8%) and rheumatic diseases (0.7%). Only 0.3% of children presented with idiopatic hypereosinophilic syndrome. Allergic diseases and PIDs were the most common etiologies in mild/moderate and severe groups, respectively. The median duration of eosinophilia was 7.0 (3.0-17.0) months in the study population and was the shortest in severe cases (2.0 (2.0-5.0) months). Multiple logistic regression analysis demonstrated food allergy [OR:1.866, 95%CI:1.225-2.842, p = 0.004] and PIDs [OR:2.200, 95%CI:1.213-3.992, p = 0.009] as independent factors for childhood eosinophilia. A diagnostic algorithm including mild form was presented for childhood eosinophilia.    Conclusion: Eosinophilia was frequently determined due to secondary causes; allergic diseases in mild/moderate eosinophilia, PIDs in severe group. Etiology of eosinophilia was diverse, and an algorithm concerning the severity of eosinophilia would be practical and rational. What is Known: • In children, eosinophilia is common, and mild eosinophilia occurs frequently. • Malignancies presents frequently with severe eosinophilia. What is New: • Primary immunodeficiencies were not a rare cause of eosinophilia, especially in countries such as the Middle East and eastern Mediterranean countries, where the countries consanguineous marriages are common, and should be investigated in children with eosinophilia who do not have allergic or infectious diseases. • In literature, there are many algorithms about childhood hypereosinophilia. However, mild eosinophilia is extremely important in children. Because all patients with malignancy and most of the patients with rheumatic diseases presented with mild eosinophilia. Therefore, we proposed an algorithm for childhood eosinophilia that includes mild eosinophilia besides moderate and severe cases.

Characteristics of tree nut, peanut, and seed consumption in the eastern Mediterranean region.

BACKGROUND: Nuts and seeds are among the most common causes of food allergy (FA), and consumption differences across cultures and geographic regions are thought to account for the diversity of these allergies. METHODS: Caregivers of infants (age 12-24 months) with or without FA were questioned in face-to-face interviews to identify the nut and seed consumption practices in the household, during pregnancy, breastfeeding, and early childhood. RESULTS: Of the 171 infants (median age: 17.3 months) included in the study, 75 were healthy and 96 had FA. More than two-thirds of the infants in the whole group started to be fed with walnuts, sesame/tahini, hazelnuts, almonds, and sunflower seeds. The percentages of healthy infants who were not fed with tree nuts, seeds, and peanuts were 4%, 4%, and 49.3%, respectively, for the healthy infants, and 11.8%, 11.8%, and 67.8% for those with FA. In the FA group, sesame and peanut consumption was initiated at a younger age, and walnut, hazelnut, and almond consumption at an older age compared to the healthy infants (p < 0.05 for each). Walnuts and sesame/tahini were the most consumed nuts at home, and peanuts and pumpkin seeds were the least consumed. Mothers reported that they increased tree nut consumption during pregnancy due to their positive effect on health and sesame/tahini consumption during breastfeeding to increase breast milk, respectively. CONCLUSION: The uniqueness of Turkish culinary culture is characterized by the frequent consumption of tree nuts and seeds, with further increases during pregnancy/lactation and early introduction to the diet of infants.

Determination of the effects of advanced glycation end products receptor polymorphisms and its activation on structural cell responses and inflammation in asthma.

BACKGROUND: Advanced glycation end products receptor (RAGE) is a pattern recognition receptor which attracted attention in chronic airway diseases recently. This study aimed to determine the association of RAGE with asthma and the cellular responses resulting from RAGE signaling pathway activation. METHODS: Asthmatic (n = 362) and healthy (n = 134) children were genotyped by PCR-RFLP. Plasma sRAGE levels were determined by ELISA. Lung structural cells were stimulated with AGEs (advanced glycation end products) and control BSA. Expressions of cytokines and protein levels were determined by real-time PCR and ELISA. RESULTS: : Gly82Ser and -374 T/A polymorphisms in RAGE gene were associated with lower plasma sRAGE levels (p < 0.001 and p < 0.025, respectively). AGE stimulation increased the expression of RAGE (p = 0.002), ICAM-1 (p = 0.010) and VCAM-1 (p = 0.002) in endothelial cells; TIMP-1 (p = 0.003) and MCP-1 (p = 0.005) in fibroblasts. AGE stimulation increased protein levels of IL-6 (p < 0.001) in endothelial cells; VEGF (p = 0.025) and IL-8 (p < 0.001) in fibroblasts; IL-1b (p < 0.001) and VEGF (p = 0.007) in epithelial cells. DISCUSSION: Activation of RAGE pathway may contribute to asthma pathogenesis by increasing the expression of several asthmarelated genes. These findings suggest that suppression of RAGE signaling may be an alternative candidate for treating asthma.

Cupressus arizonica: an emerging aeroallergen for East Mediterranean children.

Background/aim: Cupressus sempervirens is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to Cupressus arizonica pollen, which is not native to Anatolia. Materials and methods: Patients aged 5-18 years who underwent respiratory allergy screening in Türkiye's largest referral center over a 1-year period were reviewed retrospectively for a diagnostic study of Cupressus allergy. Results: Of 246 patients, 207 (67.6% male) with a median age of 11.7 (IQR 9.2-15) years were found to be aeroallergen-sensitive and C. arizonica (32%) was the second most common sensitivity after grass pollen (83.6%). In the C. arizonica-sensitive subgroup, only 3% (2/67) were monosensitive, and grass (77.6%), cat (38.8%), and weeds (38.8%) were the most common co-sensitivities. Cup a 1 specific IgE (sIgE) was measured in 26 patients with C. arizonica sensitivity and all were found to be positive. A nasal allergen challenge (NAC) was performed for 44 of 67 patients with C. arizonica sensitivity, and 13 of 44 patients had a positive outcome (NAC+) at the highest two extract concentrations. The Cupressus wheal sizes and Cup a 1 sIgE levels of the NAC+ subgroup were higher than those of the NAC- subgroup but reached significance only for wheal size [6 (5-7.5) vs. 4.5 (4-6), p=0.004]. The NAC+ subgroup reported more frequent nasal discharge, congestion, and eye symptoms than the NAC- subgroup during the relevant pollen season. Conclusion: C. arizonica sensitivity has increased in the East Mediterranean region, similarly to North Mediterranean data, and this is associated with the presence of allergy both clinically and in laboratory findings. C. arizonica should be included in the aeroallergen screening panels of children from the East Mediterranean.

Nutritional risks in children with food allergy.

BACKGROUND: Food allergies (FA) are a growing problem in the pediatric population and clinical features differ according to the underlying immunological mechanisms. While the primary management strategy is to eliminate the culprit food from the diet, assessment of the potential nutritional risks of elimination is also an integral part of management. In cases that do not improve over time; if you have basic food allergies and multiple food allergies, this can also lead to negative nutritional consequences. The contribution of basic nutrients, economical and easily accessible foods to the diet, is critical and has an important place in meeting the daily adequate intake of many nutrients. In the presence of food allergy, it is necessary to meet the vitamins and minerals that cannot be obtained from allergic foods, with alternative sources or supplements. For example, insufficient calcium intake in cow's milk allergy (CMA), the most common FA in early childhood, is very likely if an alternative supplement has not been introduced. In the management of CMA, choosing the appropriate formula and/or supplement for the clinical characteristics of children, when necessary, has an important place. In conclusion, nutritional risk assessment of children with FA requires a comprehensive, detailed, and multidisciplinary approach.

IgE mediated legume allergy in east Mediterranean children: A reflection of multiple food allergies.

BACKGROUND: Legumes are nutritionally valuable as an inexpensive protein source, but may cause severe allergic reactions. This study aimed to identify the characteristics of legume allergies (LAs) in Turkish children. METHODS: A total of 87 children (4.9 (3.1-7.0) years) with LAs confirmed by either oral food challenge (OFC) or consistent history were reviewed. RESULTS: The median age of onset was 19 (12-38) months. The most frequent LA was lentil (n = 57, 66%), followed by peanut (n = 53, 61%), chickpea (n = 24, 28%), pea (n = 21, 24%), bean (n = 7, 8%), and soybean (n = 1, 1%). From these, it was observed that 60% had multilegume (≥2) allergies and the age of onset occurred earlier compared with the single LA subgroup (18 (11-30) vs. 28 (17-42) months, p = .042). Single LA was present in peanut (51%) and lentil (16%) allergies, but not chickpea, pea, and bean. Fifteen patients had tolerated lentils before their first allergic reaction. The majority of children with LA (91.9%) were allergic to multiple foods including tree nuts (71%), hen's egg (66%), and cow's milk (49%). Seventy-eight patients (89.7%) also presented with atopic comorbidities concerning atopic dermatitis (70%), asthma (40%), and allergic rhinitis (30%). Patients with anaphylactic type of reaction (20%) had higher frequency of aeroallergen sensitization (p = .001). Lip dose challenge with legume paste predicted the result of OFC with a diagnostic accuracy of 81.82% and a positive likelihood ratio of 10.8. CONCLUSION: In Turkey, LA is a reflection of multiple food allergies and the presence of allergy to a least frequently encountered legume is a sign of multiple LA.

Safety and efficacy of rapid drug desensitization in children.

BACKGROUND: Any drug taken at the recommended dosage may cause hypersensitivity reactions (DHR). Rapid drug desensitization (RDD) protocols have been developed in the case of a confirmed or highly suspected HSR to allow safe administration of the medicine when there is no alternative drug or in the presence of a less effective or more toxic alternative. The aim of this study was to evaluate the characteristics of children who underwent desensitization, the safety and efficacy of RDD in children, as well as, the characteristics and management of breakthrough reactions. METHOD: This retrospective study concerned children who underwent RDD due to physician-diagnosed HSRs during or up to 48 hours after the infusion of various drugs between February 2010-February 2021. Patients with a chronic disease needing chronic drug usage and acute infections seen in patients with chronic diseases were included. The results of RDD were documented. RESULTS: The study included 48 patients [8.1(IQR = 3.32-13.4) years, 60.4% male] with 58 HSRs of which 62.1% were classified as moderate and 5.2% as severe. Most of the patients were being treated for leukemia (41.7%), solid tumors (29.2%), and infections (6.3%). Skin tests were done for 41 out of 58 HSRs in 35 patients, and twenty of them were positive. A total of 269 RDDs were performed for 18 different drugs. Ninety percent of desensitizations were achieved with no reaction, and 3.7% and 5.6% with mild and moderate reactions, respectively. In multivariate analysis, skin test positivity was the only risk factor for breakthrough reactions (OR = 8.5, CI = 1.72-42.15, p = .009). CONCLUSION: We demonstrated the safety and efficacy of RDD in childhood, thereby offered the first line treatment options to children with chronic diseases with hypersensitivity reactions (HSRs).

The controversy of drug hypersensitivity in patients with cystic fibrosis and review of the literature.

BACKGROUND: Cystic fibrosis (CF) is reported to be a risk factor for drug hypersensitivity. However, there are conflicting data about true prevalence of drug hypersensitivity in children with CF. METHODS: The suspicious drug hypersensitivity reactions (DHRs) of children with CF were enquired by the European Network for Drug Allergy (ENDA) questionnaire, and skin tests and/or drug provocation tests were performed according to the established guidelines. RESULTS: Two hundred and nineteen children (48.9% boys; median [IQR] age, 8.4 years [4.8-12.4 years]) with cystic fibrosis were included in the study, among which 22 patients with 24 suspected DHRs were evaluated. Most of the suspected DHRs were of non-immediate (n = 16, 66.6%) type, and the offending drugs were amoxicillin-clavulanic acid (n = 7), macrolides (n = 4), trimethoprim-sulfamethoxazole (TMP/SMX) (n = 2), piperacillin-tazobactam (n = 1), pancrelipase (n = 1), and ursodeoxycholic acid (n = 1). Eight (33.3%) of the DHRs were classified as immediate (ceftriaxone [n = 2], ceftazidime [n = 2], meropenem [n = 1], AmBisome [n = 2], and vancomycin [n = 1]). The main clinical presentations were maculopapular eruption (41.6%) and urticaria (37.5%), accompanied by angioedema (8.3%), flushing (12.5%), and vomiting (8.3%). Nine skin tests (with beta-lactam protocol in 6 patients) and 24 DPTs were performed, and none of the skin tests revealed a positive result; however, 2 DPTs with TMP/SMX were positive. CONCLUSION: Actual drug hypersensitivity was demonstrated in 2 of 219 patients (0.9%) with non-beta-lactam antibiotics. These results conflict with previous researches that showed higher drug hypersensitivity rates but are consistent with some recent studies. Allergological diagnostic workup is mandatory in patients with cystic fibrosis in case of a suspicious DHR.

The role of diagnostic tests and oral food challenge results to predict sesame allergy.

BACKGROUND: The presence of sesame allergy and its importance are increasing. OBJECTIVE: To determine the results of sesame and tahini oral food challenges (OFCs) and whether sesame-specific immunoglobulin E and skin prick tests (SPTs) accurately predicted sesame allergy in children. METHODS: Patients with suspected sesame allergy between June 1, 2018, and June 1, 2020, were examined. RESULTS: Of 92 patients (n = 65, 70.7% of the patients were boys) with a median age of 2 years (interquartile range, 1.2-3.8 years), 64 were reactive to tahini. Of 64 patients, 41 had a positive OFC result and 23 had a consistent history. Of 54 sesame OFCs, 10 patients had a positive outcome. Of 44 with a negative outcome of sesame OFC, 4 experienced allergic reactions with tahini at home and 22 patients had a positive result for tahini OFC. In multivariate logistic regression analysis, clinical reactivity of sesame (either a consistent history or a positive OFC) was positively associated with sesame SPT (odds ratio, 2.120; 95% confidence interval, 1.136-3.957; P = .01) and tahini SPT (odds ratio, 1.661; 95% confidence interval, 1.143-2.413; P = .008). Nevertheless, sesame-specific immunoglobulin E did not predict clinical reactivity. Tahini OFC outcomes were well predicted for both sesame and tahini SPTs (area under the curves of 0.937 and 0.896, respectively, P < .001 for both). A sesame SPT wheal size of 5.25 mm had 90.6% sensitivity, 82.1% specificity, and 5.1 positive likelihood ratio. For tahini SPT, the 6-mm threshold had 100% sensitivity, 82.1% specificity, and 5.6 positive likelihood ratio. CONCLUSION: In the OFC, tahini emerged as a more optimal diagnostic tool to avoid false negatives. Furthermore, both high sesame and tahini SPT levels individually can help predict the diagnosis of sesame allergy.

Psychological burden of asthma in adolescents and their parents.

INTRODUCTION: Asthma, a common chronic disease in adolescents is impacted by factors affecting quality of life. This study aimed to determine the psychosocial factors of adolescents with asthma and their parents. METHODS: The study included 122 adolescents with asthma, 82 healthy controls, and their parents who completed the Asthma Control Test (ACT), Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Brief Symptom Inventory (BSI). RESULTS: The mean age was 14.2 ± 1.9 years. ACT score was high and depression was low in patients with good treatment compliance. As the age of the first asthma symptoms/diagnosis increased, somatization, anxiety, hostility and general psychopathology scores increased, as did the somatization score of parents. Parental anxiety score was not related with adolescent BSI scores in the controls but in the study group when it was higher, the anxiety, depression, somatization, and general psychopathology scores were higher. PAQLQ showed that anxiety, negative self-esteem, somatization, depression, and general psychopathology were higher in patients concerned about asthma. Depression and somatization scores were higher in the parents of patients who perceived that "Treatment does not contribute to asthma control." Somatization scores were higher among parents of patients who noted: "Asthma will not pass in the long-term" and "I cannot control asthma." CONCLUSION: Higher scores of asthma patients who were anxious about the disease and families who were despondent about treatment demonstrate that health care providers should spend more time informing patients and caregivers. Increasing patient treatment compliance during early adolescence will lessen the psychological burden of the disease.