Factors affecting formula compliance of infants with IgE mediated cow's milk protein allergy during the pandemic.

Introduction: Cow's milk protein allergy (CMPA) is the most commonly encountered food allergy in the world, usually seen in infants under the age of 2 years. This study aims to determine the factors including COVID-19 affecting formula compliance of CMPA patients. Methods: This study is a prospective, observational study based on 10 different Paediatric Allergy-Immunology clinics in Turkey. Patients aged between 6 months and 2 years, who were followed up with IgE-mediated CMPA treatment or newly diagnosed and using breast milk and/or formula were included in the study. The sociodemographic characteristics of the patients, their symptoms, the treatments they received, and the effects of the COVID-19 pandemic on adherence to formula were evaluated with a questionnaire administered to the parents. Results: The compliance rate for formula-based treatment was 30.8% (IQR: 28.3, SD: 21.86). The number of patients with a single and multiple food allergy was 127 (51.6%) and 71 (28.9%), respectively. Breastfeeding duration, daily amount of prescribed formula and addition of sweetener to the formula were found to reduce compliance (p = 0.010, p = 0.003, and p = 0.004, respectively). However, it was determined that the patient's height, weight, age at diagnosis, and age of formula onset did not have a significant effect on compliance. Conclusion: It was found that the duration of breastfeeding, the increase in the daily amount of formula requirement, and the addition of sweeteners had adverse effects on formula compliance. There was no significant correlation between the formula adherence of CMPA patients and the pandemic.

An Expert Panel Statement on the Beneficial Effects of Human Milk Oligosaccharides (HMOs) in Early Life and Potential Utility of HMO-Supplemented Infant Formula in Cow's Milk Protein Allergy.

This review by pediatric gastroenterology and allergy-immunology experts aimed to address the biological roles of human milk oligosaccharides (HMOs) and the potential utility of HMOs in prevention of allergy with particular emphasis on cow's milk protein allergy (CMPA). The participating experts consider HMOs amongst the most critical bioactive components of human milk, which act as antimicrobials and antivirals by preventing pathogen adhesion to epithelial cells, as intestinal epithelial cell modulators by enhancing maturation of intestinal mucosa and intestinal epithelial barrier function, as prebiotics by promoting healthy microbiota composition and as immunomodulators by modulating immune cells indirectly and directly. Accordingly, the participating experts consider the proposed link between HMOs and prevention of allergy to be primarily based on the impact of HMO on gut microbiota, intestinal mucosal barrier, immunomodulation and immune maturation. Along with the lower risk of respiratory and gastrointestinal infections, HMO-supplemented formulas seem to be promising alternatives in the management of CMPA. Nonetheless, the effects of individual as well as complex mixtures of HMO in terms of clear clinical and immunological effects and tolerance development need to be further explored to fully realize the immunomodulatory mechanisms and the potential for HMOs in prevention of allergic diseases and CMPA.

Clinical phenotypes of childhood food allergies based on immune mechanisms: A multicenter study.

Background: Food allergies (FA) are an important public health concern that place a major burden on the lives of children and their families. The complex pathogenesis of FAs results in multisystemic and heterogenous clinical presentations. Objective: To evaluate, according to immune mechanisms, the characteristics and risk factors of childhood FA in Turkey. Methods: This descriptive multicenter study included 1248 children with FA, aged < 18 years,, who were evaluated by pediatric allergists in 26 different centers. Results: Immune mechanisms of FA were immunoglobulin E (IgE) mediated in 71.8%, non-IgE mediated in 15.5%, and mixed IgE/non-IgE mediated in 12.7% of the patients. An episode of anaphylaxis had occurred in 17.6% of IgE-mediated FA. The most common food allergens were classified into five categories (in order of decreasing frequency): cow's milk, egg, tree nuts and/or peanut, wheat, and seafood. Allergies to cow's milk and egg declined significantly with age, whereas tree nuts and/or peanut allergies increased with age. The 0-2 year age group accounted for 62.5% of the cases. The most frequent cause of FA and food anaphylaxis was cow's milk before age 13 years and tree nuts and/or peanut during adolescence (ages 13-18 years). Compared with other phenotypes, male sex (odds ratio [OR] 1.486; p = 0.032), sibling(s) (OR 1.581; p = 0.021), and maternal atopy (OR 1.531; p = 0.045) increased the likelihood of IgE-mediated FA, whereas high household income (OR 1.862; p = 0.026) increased the likelihood of non-IgE-mediated FA in multivariate regression analysis. Conclusion: This study showed that the clinical findings of FA were highly variable, depending on age and underlying immune mechanism. Knowing the population characteristics will enable better management of FA in children.

Current Trends in Tolerance Induction in Cow's Milk Allergy: From Passive to Proactive Strategies.

This review addresses the current strategies of inducing tolerance development in infant and childhood cow's milk protein allergy (CMPA). The change in prevention strategies for CMPA has been emphasized based on the lack of evidence to support the efficacy of food allergen avoidance in infancy and the concept of the dual-allergen-exposure hypothesis, which suggests that allergen exposure through the skin leads to sensitization, whereas early oral consumption of allergenic food protein induces oral tolerance. The new approach is based on the likelihood of early introduction of allergenic foods to the infant's diet to reduce the development of food allergies through oral tolerance induction. The latest treatment guidelines recommend the continuation of breast feeding and the elimination of cow's milk and products from the maternal diet in exclusively breast-fed infants with CMPA, the use of an extensively hydrolyzed infant formula (eHF) with proven efficacy in CMPA as the first elimination diet in formula-fed infants with CMPA and the use of amino acid-based formula (AAF) in severe cases, such as anaphylaxis, enteropathy, eosinophilic esophagitis, and food protein-induced enterocolitis syndrome (FPIES), as well as cases of multiple system involvement, multiple food allergies, and intolerance to extensively hydrolyzed formula (eHF). In conclusion, this paper presents the current knowledge on tolerance development in infants and children with CMPA to increase the awareness of the clinicians concerning the new approaches in CMPA treatment Tolerance development is considered a relatively new concept in CMPA, inducing a shift in interventions in CMPA from a passive (avoidance of responsible allergen) toward a proactive (tolerance induction) strategy.

The Utility of Next-Generation Sequencing for Primary Immunodeficiency Disorders: Experience from a Clinical Diagnostic Laboratory.

INTRODUCTION: Primary immune deficiency disorders (PIDs) are a group of diseases with profound defects in immune cells. The traditional diagnostics have evolved from clinical evaluation, flow cytometry, western blotting, and Sanger sequencing to focusing on small groups of genes. However, this is not sufficient to confirm the suspicion of certain PIDs. Our innovative approach to diagnostics outlines the algorithm for PIDs and the clinical utility of immunophenotyping with a custom-designed multigene panel. MATERIALS AND METHODS: We have designed a diagnostic algorithm based on flow cytometry studies to classify the patients; then the selected multigene panel was sequenced. In silico analysis for mutations was carried out using SIFT, Polyphen-2, and MutationTaster. RESULTS AND DISCUSSION: The causative mutation was identified in 46% of PIDs. Based on these results, this new algorithm including immune phenotyping and NGS for PIDs was suggested for the clinical use. CONCLUSIONS: This study provides a thorough validation of diagnostic algorithm and indicates that still the traditional methods can be used to collect significant information related to design of most current diagnostics. The benefits of such testing are for diagnosis and prevention including the prenatal and preimplantation diagnosis, prognosis, treatment, and research.

The Trend of Change of Allergic Diseases over the Years: Three Repeated Surveys from 1994 to 2014.

BACKGROUND: Although it is known that there has been an increase in asthma and allergic diseases among school-aged children, results vary between countries. The aim of this study was to examine trends in the prevalence of these diseases in the city of Adana (south Turkey) over the last 20 years based on the results of 3 cross-sectional studies. METHODS: Three cross-sectional surveys were performed 10 years apart in south Turkey. Here, we compare the surveys conducted among children between the ages of 6 and 14 years from 1994, 2004, and 2014. The participants were randomly chosen among children attending participating primary schools in Adana. The questionnaire in the first survey contained almost the same questions as the ISAAC. In the 2 latter surveys, we used the ISAAC questionnaire to investigate the prevalence of asthma and other allergic diseases. RESULTS: A total of 2,334 children in 1994, 3,728 children in 2004, and 3,209 children in 2014 were included in the final analysis. The results showed a statistically significant increase in the prevalence of physician-diagnosed allergic diseases across the years, respectively: asthma (5, 4.6, and 8.9%), allergic rhinitis (8.8, 11.4, and 15.6%), and atopic dermatitis (5, 9.9, and 7%). In contrast, the prevalence of parent-reported current wheeze (16.2, 13.2%) decreased in the last 10 years. CONCLUSIONS: Our findings were consistent with the increased prevalence of childhood asthma and other allergic diseases. However, this pattern did not occur in respiratory symptoms.

Fraction of exhaled nitric oxide as a predictor in juvenile idiopathic arthritis progression.

In this study, the relation between the nitric oxide (NO) levels in the serum and fraction of exhaled nitric oxide (FENO) in children with juvenile idiopathic arthritis (JIA) and the activation criteria of the disease has been investigated. The study group consisted of 35 JIA-diagnosed patients and 18 healthy children. According to the clinical and laboratory findings, the patients with JIA were divided into two groups, active (group I) and in remission (group II). The healthy children were classified as group III. The activation criteria of the disease were determined for each patient. The serum NO level and FENO level were measured in all the patients. In the group with JIA, correlation was detected between FENO level and number of involved joints and number of joints with limited motion. In addition, correlation was determined between the FENO level and number of involved joints in group I and the serum NO level and activity score in group II. However, it was seen that there is no statistical difference in the serum NO level and FENO level of the patients with JIA and the control group and groups I and II. This study demonstrated the correlation between FENO level and number of involved joints and number of joints with limited motion in patients with JIA. Our results matter in terms of FENO being a noninvasive laboratory marker in following the progression of the disease.

Clinical Features of Food Allergy during the 1st Year of Life: The ADAPAR Birth Cohort Study.

BACKGROUND: Although food allergies (FAs) occur most commonly during the 1st year of life, there is limited information available regarding the epidemiology of FAs. In this study, we investigated the incidence of FA and the associated risk factors during the 1st year of life in southeast Turkey. METHODS: This study is a prospective evaluation of 1,377 infants born at the Balcali Hospital (Çukurova University) and includes four routine follow-up assessments until the age of 1 year. At birth, a physical examination was performed, cord blood samples were taken, and parents completed a baseline questionnaire. Follow-up visits were scheduled at 3, 6 and 12 months and included the infants' physical examination and a follow-up questionnaire. A skin prick test (SPT) was performed and food-specific IgE levels were measured at 6 and 12 months. Telephone interviews were conducted when the infants were 9 months of age, and the questionnaire was administered. The diagnosis of FA was based on food-specific IgE levels, positive SPT results, associated clinical findings and an oral food challenge (OFC) test. RESULTS: Patient histories, physical examinations and laboratory results indicated a possible FA in 90 infants (6.5%) during the 1st year of life. All of them underwent OFC testing with the suspected foods, and FA was confirmed in 33 cases (2.4%). Cow's milk allergy was the major cause of FA. Skin reactions were major clinical findings in FA. A family history of atopy was identified as the major risk factor for FA. CONCLUSIONS: The prevalence and risk factors of FA in our region are consistent with those reported in the literature.

The ADAPAR Birth Cohort Study: Food Allergy Results at Five Years and New Insights.

BACKGROUND: Although food allergy (FA) is often a transient condition during childhood, when and in whom FA will resolve can be affected by many factors. In this study, we analyzed the data at 5 years on 33 children diagnosed with FA in the ADAPAR (Adana Pediatric Allergy Research) birth cohort study in southern Turkey. METHODS: Thirty-three infants detected as having FA at the end of their first year in the ADAPAR study were assessed every 6 months until the age of 5 years. Each follow-up included a clinical examination, questionnaire, blood sampling and a skin-prick test. RESULTS: Culprit allergens were cow's milk (n = 20), eggs (n = 17), chicken meat (n = 1) and bananas (n = 1). Of the 17 patients with egg allergy, 14 developed complete tolerance and 1 developed partial tolerance (i.e. tolerance to baked food). Of the 20 patients with milk allergy, complete tolerance was observed in 16 and partial tolerance in 1. The mean age of tolerance to egg was 22.4 ± 7.5 months and to cow's milk, it was 20.9 ± 1.1 months. Complete tolerance developed in 1 case allergic to chicken meat and in 1 case allergic to banana. Other allergic conditions were also determined: allergic rhinitis in 27.2%, atopic dermatitis in 21.2%, asthma in 9%, urticaria in 9% and drugs in 9%. CONCLUSIONS: Our results confirm early and high tolerance rates before school age in children with food allergies that started in infancy. This will help pediatricians to give more informed advice to parents of infants with cow's milk or hen's egg allergy.