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MicroRNAs (miRNAs) are noncoding RNAs that play an important role in the regulation of inflammation and have not been evaluated in exhaled breath condensates (EBC) of patients with esophageal atresia and tracheoesophageal fistula (EA–TEF). It is aimed to evaluate the levels of miRNA-21 and miRNA-24 in EBC of patients with EA–TEF. Patients who received surgery for EA–TEF (EA) were assessed for age, sex, types of anomaly, surgical treatments, and respiratory problems. A 500–1000 mL of EBC was obtained from each participant with EcoScreen. The levels of miRNA-21 and miRNA-24 in the EBC were analyzed by real-time polymerase chain reaction and compared between the EA group and the control group consisting of healthy children with no history of respiratory problems (n  = 17). The levels of miRNAs in relation to respiratory problems and gastroesophageal reflux (GER) were also assessed. A total of 19 patients were enrolled in the EA group with a mean age of 7.8 ± 3.2 years and a male-to-female ratio of 10:9 EA cases had significantly lower levels of miRNA-21 (P  < 0.05) compared to that in control group. The miRNA-24 levels did not differ between groups (P  > 0.05). EA patients with positive pH testing for GER (n  = 6) and fundoplication (n  = 6) had higher levels of miRNA-21 than those with normal pH testing and without fundoplication, respectively (n  = 13, P  < 0.05). The levels of miRNA-21 and miRNA-24 did not differ between patients with and without proton pump inhibitor treatment (P  > 0.05). The lower levels of miRNA-21 in the EBC of EA patients suggest a hyperreactive airway problem, which may be associated with GER and its surgical treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The ability to predict the function and structure of complex molecular mechanisms underlying cellular behaviour is one of the main aims of systems biology. To achieve it, we need to understand the evolutionary routes leading to a specific response dynamics that can underlie a given function and how biophysical and environmental factors affect which route is taken. Here, we apply such an evolutionary approach to the bacterial chemotaxis pathway, which is documented to display considerable complexity and diversity. Results We construct evolutionarily accessible response dynamics starting from a linear response to absolute levels of attractant, to those observed in current-day Escherichia coli. We explicitly consider bacterial movement as a two-state process composed of non-instantaneous tumbling and swimming modes. We find that a linear response to attractant results in significant chemotaxis when sensitivity to attractant is low and when time spent tumbling is large. More importantly, such linear response is optimal in a regime where signalling has low sensitivity. As sensitivity increases, an adaptive response as seen in Escherichia coli becomes optimal and leads to 'perfect' chemotaxis with a low tumbling time. We find that as tumbling time decreases and sensitivity increases, there exist a parameter regime where the chemotaxis performance of the linear and adaptive responses overlap, suggesting that evolution of chemotaxis responses might provide an example for the principle of functional change in structural continuity. Conclusions Our findings explain several results from diverse bacteria and lead to testable predictions regarding chemotaxis responses evolved in bacteria living under different biophysical constraints and with specific motility machinery. Further, they shed light on the potential evolutionary paths for the evolution of complex behaviours from simpler ones in incremental fashion.

Abstract Background Low levels of asthma control worldwide point to the possibility of sub-optimal management; therefore, documentation of physicians' perception is critical for future interventions. Our aim was to examine self-reported management abilities of Turkish physicians dealing with children with asthma, document the factors affecting appropriate decisions and compare the results with those of a previous survey. Methods Physicians were surveyed via a questionnaire aimed to document self-perceived asthma knowledge and attitudes in asthma management. Results The majority of physicians were male (63%) and examined 234 ± 9 patients per week. Infrequent use of objective parameters in asthma diagnosis and attack severity assessment was reported and most preferred nebulized corticosteroids to the systemic form in acute asthma. Even though self-perceived overall asthma knowledge did not differ between genders (p = 0.098), male physicians scored higher than females for inhaled steroids for acute asthma (2.8 ± 0.12 vs 2.17 ± 0.2, respectively, p = 0.007), while female physicians recorded more frequent use of inhaled steroids for chronic asthma (3.72 ± 0.08 vs 3.43 ± 0.07, respectively, p = 0.006). Female physicians' scoring for "symptom control" as the main aim of asthma management was higher than that of their male counterparts (3.88 ± 0.04 vs 3.65 ± 0.06, respectively, p = 0.002). Conclusion Although there were some discrepancies between guidelines and clinical practice, most applications of Turkish physicians dealing with children with asthma were appropriate. Interestingly, when scores of female versus male physicians were compared, it can be suggested that female physicians have a more appropriate perception of asthma, indicating a significant contribution of gender-related factors in clinical attitudes and beliefs.

Abstract Background While detection and analysis of functional modules in biological systems have received great attention in recent years, we still lack a complete understanding of how such modules emerge. One theory is that systems must encounter a varying selection (i.e. environment) in order for modularity to emerge. Here, we provide an alternative and simpler explanation using a realistic model of biological signaling pathways and simulating their evolution. Results These evolutionary simulations start with a homogenous population of a minimal pathway containing two effectors coupled to two signals via a single receptor. This population is allowed to evolve under a constant selection pressure for mediating two separate responses. Results of these evolutionary simulations show that under such a selective pressure, mutational processes easily lead to the emergence of pathways with two separate sub-pathways (i.e. modules) each mediating a distinct response only to one of the signals. Such functional modules are maintained as long as mutations leading to new interactions among existing proteins in the pathway are rare. Conclusion While supporting a neutralistic view for the emergence of modularity in biological systems, these findings highlight the relevant rate of different mutational processes and the distribution of functional pathways in the topology space as key factors for its maintenance.

Background: Atopic dermatitis (AD) substantially burdens individuals, families, and healthcare systems. We aimed to document the treatment journey of pediatric patients with moderate-to-severe AD in a referral center based in our country., Methods: This retrospective study reviewed patients aged 1-18 years diagnosed with AD, seeking systemic treatment recommendations from the "pediatric allergy and dermatology multidisciplinary team meeting"., Results: Over the 14-month study period, 30 (12.5%) of 240 AD patients were evaluated in the pediatric dermato-allergy team meetings. The median age of the patients was 13.66 years (Q1-Q3: 7.94-17.27), of whom 60% were male. The median annual healthcare visits for AD were 4 (Q1-Q3: 1.00-8.75). Among the study group, 70% were sensitized to aeroallergens, and admission markers included total IgE (median: 1980 IU/mL, Q1-Q3: 794.50-5446), and eosinophil counts (median: 650, Q1-Q3: 275-1275). All patients utilized intermittent and/or continuous topical corticosteroids (CS), with 56.6% employing short-term/long-term topical tacrolimus. Over the past two years, systemic CSs were utilized in 93.3% of the patients, whereas 57.1% received more than one course. Approximately 43.3% of the patients agreed to receive systemic cyclosporine treatment, with only 30.8% benefiting and 3.3% reporting adverse effects (hypertrichosis and cellulitis). Three patients self-funded dupilumab, all benefiting without adverse effects. Omalizumab, mycophenolate mofetil and narrow-band  ultraviolet (UV) treatments were used in one patient each, with limited benefit observed. Health insurance did not grant approval for a Janus kinase inhibitor for one patient., Conclusions: Managing moderate to severe AD is complex and costly, considering disease heterogeneity, comorbidities, care pathways, and health system challenges. Addressing the unmet needs should be a priority in Türkiye's healthcare systems., Competing Interests: The authors declare that there is no conflict of interest.

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., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Conflict of interest statement: The authors declare that there was no conflictwere no conflicts of interest and no funding., (© TÜBİTAK.)

Hereditary angioedema (HAE) is characterized by recurrent angioedema attacks with no urticaria. This disease has a high mortality due to asphyxia. Level of complement component 4 (C4), C1 esterase inhibitor (C1-INH) level and function, and genetic mutations determine different endotypes of HAE. Clinical presentation and the triggers of vasogenic edema may change according to the endotypes. An adolescent girl with oligomenorrhea, obesity, hirsutism, and acanthosis nigricans was diagnosed with polycystic ovary syndrome and prescribed ethinyl estradiol and cyproterone acetate containing oral contraceptive (OC). On the sixteenth day of treatment, she developed angioedema of the face, neck, and chest leading to dyspnea. Adrenaline, antihistamine, and corticosteroid treatments were ineffective. In the family history, the patient’s mother and two cousins had a history of angioedema. C1-INH concentrate was administered with a diagnosis of HAE. C4 and C1-INH level and activity were normal. Genetic analysis identified a mutation in the factor 12 ( F12 ) gene, and the diagnosis of F12-related HAE was made. OC treatment was discontinued. She has had no additional angioedema attacks in the follow-up period of two years. OC containing estrogen may induce the life-threatening first attack of F12-related HAE even in children. Recurring angioedema attacks in the family should be asked before prescribing estrogen-containing OC pills., (©Copyright 2023 by Turkish Society for Pediatric Endocrinology and Diabetes | The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Introduction: There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively., Methods: Twenty-three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)-G, Aspergillus IgE, Aspergillus polymerase chain reaction (PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1-year follow-up., Results: Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z-scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity  (p = 0.939), and the median FEV 1% decline (0.0%/year vs. -4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar., Conclusion: Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1-year follow-up., (© 2023 Wiley Periodicals LLC.)

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., (© 2023 S. Karger AG, Basel.)

Objectives: Cell-free DNA has been found in all body fluids, but DNAs emerging from locations that are not in direct contact with breath in exhaled breath condensate (EBC) are yet to be found. The potential of EBC for prenatal and cancer screening prompted us to investigate whether fetal DNA is present in maternal EBC., Method: A total of 20 pregnant women's EBC and blood samples were collected. Four Y chromosome-specific assays were tested on all EBC and plasma samples by quantitative PCR (qPCR). The best-performing assay was used for digital droplet PCR (ddPCR) on all EBC and the six plasma samples., Results: The sex of the fetuses was accurately determined from plasma samples. DNA sequences could not be properly amplified in EBC samples by the qPCR. By ddPCR, the Y chromosome sequence was amplified in two of the 11 EBC samples, from women carrying male fetuses (2/11), and the Y chromosome sequence was not amplified in the EBC of women carrying female fetuses (9/9). Exhaled breath condensate ddPCR result's specificity was 100%, the detection rate of Y chromosome was 18.18% (2/11), and the corrected accuracy was 59.09%., Conclusion: Our finding of "the presence of fetal DNA in maternal EBC", despite the low detection rate, might have a major impact on prenatal diagnosis and cancer screening., (© 2022 John Wiley & Sons Ltd.)

Background: The incidence of food allergies is increasing all over the world. Prevention strategies intend to reduce food sensitization risk and subsequent allergies. In this review, we will discuss the recent data concerning different geographic regions for the prevention of food allergies in children., Methods: This review provides recommendations for the prevention of food allergies based on the recent data available in the PUBMED database in English (up to December 2022)., Results: The best strategy to prevent food allergies is regarded as the early introduction of allergenic foods to an infant`s diet. A healthy and diverse diet is recommended for infants and their mothers, in accordance with the family`s eating habits and regional food culture, rather than avoiding certain foods or using supplements. Avoiding common food allergens in the maternal diet during pregnancy and/or breastfeeding is not recommended. Exclusive breastfeeding is generally recommended for all mothers for at least 6 months. There is no specific association between exclusive breastfeeding and the primary prevention of any specific food allergy. Where a breastmilk substitute is needed, the best alternative should be chosen according to the infant`s nutritional needs. There is no substantial evidence to support the use of hydrolyzed or soy formula in infancy against food allergies or sensitization., Conclusions: Feeding patterns in infancy play an important role in the risk of developing food allergies. Existing strategies to prevent allergies are relatively ineffective and further research is needed to figure out strategies for food allergy prevention, particularly in high-risk infants.

Background: Optimum management of food allergy (FA) includes consideration of co-allergies and multimorbidities and tolerance assessment. Documentation of FA practices may pave the way for better practice., Methods: Patients aged 3-18 years, with persistent IgE-mediated hen`s egg allergy were reviewed., Results: A total of 102 children with a median age of 59 months (IQR= 40-84) (72.2% males) were included. All were diagnosed during infancy and the initial symptoms were atopic dermatitis (65.6%), urticaria (18.6%), and anaphylaxis (5.9%). Of the total population, 21 (20.6%) experienced anaphylaxis with hen`s eggs, and 79.4%, 89.2%, and 30.4% had multiple FAs (≥2 food categories), ever atopic dermatitis, and asthma, respectively. The most common co-allergies were tree nuts, cow`s milk, and seeds, respectively. From 52 heated egg yolk and 47 baked egg oral food challenges, 48 (92.3%) and 41 (87.2%) were found as tolerant, respectively. The baked egg nontolerant group had a greater egg white skin prick test diameter [9 mm (IQR: 6-11.5) vs. 6 mm (IQR: 4.5-9); (p=0.009)] and specific IgE [12.6 kU/L (IQR: 4.11-45.4) vs. 6.2 kU/L (IQR: 1.9-12.4) (p=0.009)], respectively. In the multivariate analysis, baked egg tolerance was more likely in those with egg yolk-tolerant subgroup (OR: 6.480, 95% CI: 2.524-16.638; p < 0.001) and heated egg tolerance in those with baked egg tolerance (OR: 6.943, 95% CI: 1.554-31.017; p=0.011)., Conclusions: Persistent hen`s egg allergy is characterized by multiple food allergies and age-related multimorbidities. Baked egg and heated egg yolk tolerance were more likely to be considered in a subgroup with a high expectation for finding a way to eliminate their allergy.

Atopic dermatitis (AD) is a very common skin disease caused by inflammatory reactions, in which the main symptoms of severe itching and recurrent eczema diminish quality of life. As epidermal barrier function and the immune system play a critical role in atopic dermatitis, promoting IgE-mediated sensitization can be the main targets of AD treatment. The goal of AD treatment should be to eliminate the symptoms and obtain longterm eczema control with a multi-step approach adapted to the severity of the disease. Basic management for all patients comprises the use of moisturisers and avoiding triggers. While topical therapy is effective for most children diagnosed with AD, there may also be children who require systemic therapy. The aim of this paper was to present an extensive review of the systemic agents commonly used in childhood atopic dermatitis which mainly target cutaneous inflammation.

Bullous lung diseases may cause primary spontaneous pneumothorax (PSP) in children. The microRNAs (miRNAs) are non-coding RNAs that participate in regulation of inflammation and cancer. We hypothesized that children with bullous lung disease and PSP may have altered miRNA expressions in their exhaled breath condensates (EBCs). Therefore, a prospective study was performed to evaluate the miRNA-24 and 21 expression, and the matrix metalloproteinase-7 (MMP-7) levels in EBC of children with PSP. Children with PSP were evaluated for age, gender, clinical features and results of surgical treatment. EBC samples (500-1000 ml) were collected to evaluate the miRNA-21, 24 expressions, and MMP-7, and tissue-inhibitor-MMP-1 (TIMP-1) levels. miRNA expressions and MMP levels of patients were compared with healthy controls (control group (CG), n = 12). Subjects ( n = 16) with a mean age of 15 years (10-19 years), and a male-to-female ratio of 14:2 were enrolled in this study. The most common presenting symptom was sudden chest pain ( n = 14). In 62.5% of the cases an underlying bullous lung disease were detected. During an average of 16.6 months (1-60 months) follow up period, four subjects relapsed. The mean MMP-7 (1.74-1.57 ng ml -1 ), and TIMP-1 (1.92-1.84 ng ml -1 ) levels were similar between both groups ( p > 0.05). miRNA-24 expression was significantly decreased in the PSP group, when compared to the CG (0.16-1 2 -ΔΔCT , p < 0.05). In addition, the miRNA-21 expression was not different between the two groups ( p > 0.05). In conclusion, the miRNA-24 levels were significantly decreased in children with PSP. Taken together, children with PSP, especially those with bullous disease, should be closely monitored in the long-term period., (© 2022 IOP Publishing Ltd.)

Background: Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients., Methods: Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index., Results: In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy., Conclusion: Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.

Background: MicroRNAs (miRNA) are small non-coding molecules that play a significant regulatory role in several allergic diseases. However, their role in allergic rhinitis is still not clearly understood. The aim of this study was to identify the candidate miRNAs that can discriminate between different forms of allergic rhinitis and also differ in and out of the allergen season., Methods: The study included 20 healthy children, 20 patients with seasonal allergic rhinitis (SAR), 20 non-atopic asthmatics (NA-A), and 12 patients with perennial allergic rhinitis (PAR). Patients with SAR were evaluated comparatively in and outside the allergen season. The changes in the expressions of selected miRNAs (miR- 125b, miR-126, miR-133b, miR-181a, and miR-206) that were found related to the allergic diseases according to the literature were determined using quantitative polymerase chain reaction., Results: In the SAR group, expression levels of miR-125b (p=0.040) and miR181a (p=0.014) were lower than in the controls outside of the allergen season. Expression levels of miR-181a were different between patients with SAR and NA-A (p=0.003), also between the SAR and PAR (p=0.001) groups in multiple comparisons. In contrast, the expression of miR-206 was found to be decreased in patients with NA-A and PAR compared with the controls (p=0.005 and p=0.024, respectively). In correlation analysis, expression levels of miR-125b and peak expiratory flow (PEF) values were found to be negatively correlated in the SAR (p=0.013) and PAR (p=0.029) groups. The expression level of miR-206 was positively correlated with total IgE levels in PAR (p=0.007). Receiver operating characteristic analysis revealed that miR-125b and miR-181a predicted the risk of SAR (p=0.040 and p=0.014, respectively), and miR-206 for NA-A and PAR (p=0.005 and p=0.024, respectively)., Conclusions: Our study showed that expression levels of miRNAs were different according to the type of allergic diseases and the presence of allergens. miR-181a and miR-125b can be candidate biomarkers for SAR, and miR-206 for NA-A and PAR.

Background: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks., Objective: Documentation of the rate, spectrum, and predictors of positive reactions is instructive., Methods: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed., Results: A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly considered food groups were cow's milk (31.8%), hen's egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow's milk, 4.9% with hen's egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03-14.90]), wheat (OR: 3.80, [CI: 1.64-8.84]), and tree nuts (OR: 2.78, [CI: 1.83-4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27-10.28]) was more likely to elicit anaphylaxis., Conclusion: In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC., Competing Interests: Authors declare that there is no conflict of interest and there was no funding provided.

Background: Previous studies demonstrated critical deficits in diagnosis and management of childhood food allergy (FA), and recent developments in FA research support adopting a proactive approach in FA management. Our objective was to describe FA knowledge and management patterns of pediatricians., Method: We applied a 24-item survey to 170 general pediatricians, pediatric allergists and pediatric gastroenterologists practicing in Turkey., Results: Some IgE-mediated symptoms of FA such as cough, urticaria, wheezing and anaphylaxis were falsely recognized as symptoms of non-IgE-mediated FA by 30%, 29%, 25% and 19% of the participants, respectively. By contrast, 50% of the participants falsely recognized bloody stool, a finding of IgE-mediated FA. Most frequently and least frequently used diagnostic tools were specific IgE (30.5%) and oral food challenge test (1.7%), respectively. Maternal diet restrictions and infant diet restrictions were advised by 82% and 82%, respectively. Percentages of physicians eliminating only 1 food were 21%, 19%; 2 foods were 15%, 11%; 3 foods were 7%, 8%; 4-5 foods were 8%, 11%; 5 to 10 foods were 21%, 26%; and > 10 foods were 28%, 25% from the maternal and infant diet, respectively. Cow`s milk, cheese, butter, yoghurt, baked milk products and hen`s egg were the most commonly restricted items., Conclusion: Overall, FA knowledge of pediatricians was fair. Pediatricians utilize an overly restrictive approach when advising diet eliminations in FA. Recent developments favor a more proactive approach to induce immune tolerance and need to be encouraged in pediatric clinical practice. Future educational efforts should focus on emphasizing the deleterious effects of injudicious and extensive eliminations.

Background: Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma, and venom allergy. Compliance is essential for SCIT to obtain maximal benefit as it is a long-term treatment., Objectives: This study aimed to determine the level of real-life SCIT compliance in pediatric patients and the associated factors. Additional aims were to determine how SCIT compliance was affected by the COVID-19 pandemic and why some patients dropped out SCIT., Method: Pediatric patients diagnosed with allergic rhinitis, allergic asthma, or venom allergy that received SCIT between September 2012 and July 2020 were analyzed., Results: The study included 201 children (66.7% male) with a median (interquartile range) age of 12.8 years (9.4-15.2) at the time of the first SCIT injection. The overall compliance rate before COVID-19 pandemic was 86.1%. Short SCIT follow-up time and venom anaphylaxis were found to be risk factors for drop out. The leading causes of drop outs were moving to another city/country (32.1%), symptom improvement (17.8%), treatment ineffectiveness (14.2%), and adverse reactions (14.2%). Among the 108 patients that were still receiving SCIT during the COVID-19 pandemic, 31 (28.7%) dropped out the therapy. The most frequent reasons for drop-out were fear of being infected with COVID-19 (35.4%) and thinking that the AIT practise stopped due to COVID-19 pandemic (29%). Male gender and older age were found to be the independent risk factors for drop-out of SCIT., Conclusions: Real life compliance in children was found 13.9% and it was higher than adults. Nearly one-third of children dropped out during the CO-VID-19 pandemic. Male gender and older age are associated with SCIT drop-out during the COVID-19 pandemic., (© 2021 S. Karger AG, Basel.)

Background: Food allergies (FAs) potentially differ across cultures., Methods: All medical records of 534 children and adolescents with IgE-mediated FA over a 5-year period were reviewed to document the regional characteristics with regard to spectrum and outcome., Results: According to their last visit, the most common FAs were tree nuts (TNs) (52.4%), cow`s milk (27.3%), seeds (24.7%), egg white (23.2%) and peanuts (14.9%). Hazelnut and Anacardia nuts were the most common etiologies for TN allergies, whereas lentils and chickpeas for legumes and sesame and pumpkin seed for seeds were most common, respectively. TN allergy was in first place in school-age children (55.3%) and adolescents (57.1%) while in the second place in preschoolers (57.7%) after egg white (60%). Of these 534 children, 59.2% had at least one resolved FA (mainly egg white, cow`s milk) and 21% had no residual FA during the study period. Emerging FAs (fish, shellfish, fruit, TN and seed) after the age of 3 years was reported in 94 children. The prevalence of current asthma (22.3%, 38.2%, 40%) and allergic rhinitis (11.6%, 45.2%, 60%) increased, while current atopic dermatitis (17.5%, 8.6%, 8,6%) decreased in preschoolers, school age children and adolescents, respectively., Conclusions: The FA spectrum of Turkish children and adolescents differs from many regions of the world with high rates of TN (hazelnut, Anacardia nuts), seed (sesame, pumpkin seed) and lentils, and low rates of soy, peanut and seafood allergies. However, resolution, emergence and persistence of allergies and comorbidities are similar, which points to the limited role of the environment in the outcome.

Background: Recurrent angioedema is a rare entity during childhood. This study aimed to clarify differences between hereditary angioedema (HAE) and histaminergic angioedema (HA) in children., Methods: Fifty-seven children with HAE (male 36.8%, 8.9 years [5.4-12.5]) and 42 children with recurrent HA (male 42.9%, 11.5 years [8.1-16.8]) were analyzed., Results: The median age at symptom onset (6 [3-10]; 7.8 [4.5-13] years), frequency of angioedema episodes within last year (3 [2-5]; 5 [2-10]), and duration of symptoms (48 [24-48]; 24 [12-48] hours) were similar in the HAE and HA group, respectively. Recurrent urticaria was observed in 7.3% (n = 3) of patients in the HAE group and in 45.2% (n = 19) of the HA group (P < .001). While angioedema episodes involving the lips (n = 30; 71.4%; P = .035) and eyelids (n = 28; 66.7%; P = .012) were observed more frequently in the HA group, gastrointestinal involvement/abdominal pain (n = 15; 36.6%) was more common in HAE (P < .001). Itching as a prodromal symptom was detected in 47.6% (n = 20) of HA patients versus 14.6% (n = 6) of those with HAE (P = .002). In the logistic regression analysis for the diagnosis of HAE, a family history of angioedema (OR = 58.289 [95% CI 10.656-318.853], P < 001) and trauma (OR = 35.208 [95% CI [4.368-283.794]], P = .001) as a triggering factor were determined to be independent variables., Conclusion: A family history of angioedema, trauma as a triggering factor, and abdominal pain should suggest the diagnosis of HAE and the need for further investigation., (© 2020 Wiley Periodicals LLC.)

Background/aim: Filaggrin is a protein complex involved in epidermal differentiation and skin barrier formation. Mutations of the filaggrin gene (FLG) are associated with allergen sensitization and allergic diseases like atopic dermatitis (AD), allergic rhinitis, food allergy (FA), and asthma. The aim of the study is to reveal the frequency of change in the FLG gene and determine the association between FLG loss-of-function (LOF) mutations and FA and/or AD in Turkish children., Materials and Methods: Four FLG loss-of-function (LOF) mutations known to be common in European populations were analyzed in 128 healthy children, 405 food-allergic children with or without atopic dermatitis, and 61 children with atopic dermatitis. PCR-RFLP was performed for genotyping R501X, 2282del4, and R2447X mutations; S3247Xwas genotyped using a TaqMan-based allelic discrimination assay. Results were confirmed by DNA sequence analysis in 50 randomly chosen patients for all mutations., Results: A total of 466 patients [(67% male, 1 (0.7–2.8) years] and 128 healthy controls [59% male, 2.4 (1.4–3.5) years)] were included in this study. Two patients were heterozygous carriers of wild-type R501X, but none of the controls carried this mutation. Three patients and one healthy control were heterozygous carriers of wild-type 2282del4. Neither patients nor controls carried R2447X or S3247X FLGmutations. There were no combined mutations determined in heterozygous mutation carriers., Conclusions: Although R501X, 2282del4, R2447X, and S3247X mutations are very common in European populations, we found that FLG mutations were infrequent and there is no significant association with food allergy and/or atopic dermatitis in Turkish individuals., Competing Interests: The authors have no conflicts of interest to declare., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Despite the fact that childhood asthma poses an important burden, especially on the families, little is known about the emotional experiences of mothers. This article describes the predominant emotional challenges and experiences reported by mothers of children with asthma., Methods: Individual, semi-structured, in-depth interviews with a qualitative study method was used in collection of the data. Face-to-face interviews with mothers of children with asthma were conducted using sociodemographic data form and semi-structured interview forms developed by the investigators. The transcribed interview texts were analyzed according to a qualitative content analysis., Results: A total of 20 mothers were interviewed. We found that the experience of mothers of the children with asthma was a strenuous journey of overriding an emotional rollercoaster, that is, from being thrown into a chaotic situation to later processing the difficult situation affected by the asthma. First moment at diagnosis, relaxation against uncertainties, anxiety, fear, truly acceptance, sadness were the predominant emotions. Mothers described experiences and challenges of frequent admission to emergency, administration of medication and treatments, school problems, limitations in physical activity and spouse relationship problems. Experiences of problems contributed to hopelessness, abandoned, angry and burnout. Mothers had concerns about the chronic nature of the disease, side effects of medications, complications that might develop, factors influencing the disease, and future plans., Conclusions: Mothers of children with asthma described complex emotional journeys. This has implications for healthcare providers who need to be aware of the complexity of these emotional journeys to support parents more effectively, thereby helping improve patient outcomes. Parents should be trained for symptoms and disease management with a written action plan. It is imperative to realize multi-disciplinary team collaboration and to regularly review training and information. Future research should concentrate on promoting awareness, education, advocacy, and support for parents of asthmatic children.

Objective: Precise diagnosis of allergy requires knowledge of the population's food allergy (FA) spectrum and predictors., Methods: Medical charts of Turkish children aged 0-2 years with FA and/or atopic dermatitis (AD) were reviewed., Results: A total of 1,389 patients, 912 with FA and 1,140 with AD, were included. In the FA group, the most frequently diagnosed FAs were egg white (75.9%), cow's milk (55.7%), tree nuts (31.5%) and sesame (20.6%). The detection of FA in 99% of children with any kind of FA necessitate testing with egg white, cow's milk, hazelnut, sesame, walnut, cashew, and pistachio. In the FA group, 72.7 and 56.8% had AD and multiple FA respectively. Multiple FA (56.8 vs. 49.8%) and hen's egg allergy (85.5 vs. 50.2%, p < 0.005) were more common and cow's milk allergy (51.4 vs. 67.1%, p < 0.005) less common in the AD subgroup of the FA group than in the non-AD subgroup. Multiple FA likelihood increases parallel to the severity of AD (p < 0.05). In the AD group, 58.2% had an immunoglobulin E-mediated FA. The risk of concomitant FA increased as the age at symptom onset of AD decreased (OR 0.800 [95% CI 0.731-0.875]; p < 0.001) and the severity of AD increased (OR 2.350 [95% CI 1.898-2.911]; p < 0.001)., Conclusion: Although severe and early-onset AD is a predictor of the presence and magnitude of FA in infancy, the spectrum of FA is a reflection of cultural characteristics. The clinical presentations of both AD and FA may in fact be an expression of the extent of the immune dysregulation underlying atopy and allergy., (© 2020 S. Karger AG, Basel.)

Background/aim: The aim of this study was to compare the effect of salbutamol delivered to children by jet nebulizer (JN) and mesh nebulizer (MN)., Materials and Methods: Children admitted with acute asthma were treated with 3 doses of nebulized salbutamol, 1 given by MN. The patients’ vital signs, lung function measurements, modified pulmonary index score (MPIS), and whole body plethysmography (WBP) measurements were evaluated before and 20 min after each dose of salbutamol., Results: Thirty-onechildren [9.5 (6.4–17.2) years, 67.7% male, 32.3% female] with mild (67.7%) and moderate (32.3%) asthma attacks were included in the study. The improvements with MN were comparable with JN in terms of changes in pretreatment and posttreatment forced expiratory volume in the first second (FEV1) (2.57 ± 4.57, 3.65 ± 5.44; P = 0.44), forced vital capacity (FVC) (2.52 ± 5.29, 4.17 ± 7.54; P = 0.28), heart rate (7.33 ± 10.21, 4.14 ± 9.32; P = 0.24), peripheral capillary oxygen saturation (SpO2) (0.38 ± 0.23, 0.43 ± 0.15; P = 0.83), and modified pulmonary index score (MPIS) (−6.30 ± 22.70, −8.77 ± 25.46; P = 0.70). The pre- and posttreatment values of total lung capacity (TLC), residual volume (RV), specific conductance (sGaw), and RV/TLC were similar for the JN and MN groups. Adverse effects were not different: however, complaints of palpitation were significantly higher in the posttreatment MN group than the pretreatment MN group (32.3% vs 9.7%, respectively, P = 0.016)., Conclusion: These findings support the previous evidence found in studies of adults that MN is as effective as and as safe as JN in the treatment of acute asthma in children, (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background: Venom immunotherapy (VIT) is safe in children, although adverse effects can occur., Objective: To document adverse effects and to determine re-sting reactions and the efficacy of VIT in childhood., Methods: We retrospectively analyzed data from children who had taken VIT from 2002 through 2015. These patients were queried by telephone to determine reactions after re-stings during or after VIT., Results: In total 107 children with a systemic reaction after Hymenoptera sting and with proved immunoglobulin E-mediated sensitization were enrolled. Participants had a median age of 10.0 years (7.2-12.4 years) at the beginning of immunotherapy. Fifty-two participants had allergic reactions during VIT; 40 of these reactions were local (37.4%), 5 were large local (4.7%), and 7 were systemic (6.5%). Of the 52 patients with adverse reactions, most reactions were local (n = 40, 89%) and were observed mainly in dose-increase periods (n = 25, 60%; P < .001). Although local reactions were more frequently seen with Vespula treatment (P = .047), systemic reactions were common with Apis treatment (P = .031). Sixty-eight patients (63.5%) were queried for re-sting, 33 (48.5%) had a re-sting and 24 (72.7%) of these 33 patients developed allergic reactions. The reactions were local (n = 19), large local (n = 1), and systemic (n = 4). Risk analysis for local and systemic reactions during VIT showed pre-existing asthma as an independent risk factor (odds ratio 4.1, 95% confidence interval 1.3-12.7, P = .016)., Conclusion: In children, VIT appears to be safe and protective against severe reactions after re-sting. However, pre-existing asthma was identified as a risk factor for systemic and large local reactions during VIT in children., (Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Although the pathophysiology of gastroesophageal reflux disease (GERD) remains unclear, it is accepted as a multifactorial disease. It is thought that some of the interventions that might cause alterations in the normal gastrointestinal tract anatomy and diseases that affect the lower esophageal sphincter, esophageal clearance, and stomach motility (gastric emptying) might lay a foundation for GERD development. Moreover, it is common knowledge that GERD might cause various extraesophageal symptoms and complications. A possible connection between GERD and sarcoidosis, amyloidosis, hypothyroidism, rheumatoid arthritis, mixed connective tissue disorders, Sjögren's syndrome, systemic sclerosis, diabetes mellitus, cholecystectomy, sleeve gastrectomy, sleep apnea syndrome, chronic obstructive pulmonary disease, and asthma were summarized in this literature review.

Gastroesophageal reflux disease (GERD) is one of the most commonly diagnosed conditions in the daily practice of gastroenterologists. Due to variations in symptoms and clinical findings, differences in the severity of the disease in each patient and the fact that diverse methods are used for making a diagnosis makes a single and standard classification of this disease impossible. Here a step-approach suitable for GERD classification is summarized.

Objective: Familial Mediterranean fever (FMF) is the most common form of autoinflammatory diseases. We aimed to evaluate the small bowel mucosa by capsule endoscopy (CE) in FMF patients for investigation of other possible causes of abdominal pain., Material and Methods: The study group consisted of 41 patients with FMF. A standard questionnaire was used to record the gastrointestinal symptoms, other clinical findings, Mediterranean fever gene (MEFV) mutations, and history of medications including non-steroidal anti-inflammatory drugs (NSAIDs). Gastroscopy, colonoscopy and small bowel CE were performed in all patients, and biopsies were taken from terminal ileum and duodenum., Results: The mean age of the patients was 34 ± 11 years, 63% of them were female, and 76.5% of them were carrying MEFV exon 10 mutations. Only one patient used NSAIDs in addition to colchicine. In endoscopic investigations, gastric erosion was detected in only one patient, and no significant findings were detected in colonoscopy. CE showed small bowel mucosal defects in 44% (erosions in 26.8%, ulcer in 17.1%) and edema in 29.3% of the patients. Most (64%) of the ulcer and erosions were localized to jejunum, and only 24% were in ileum. Mitotic changes as an indirect finding of colchicine toxicity were not different from the changes observed in samples of independent group of patients with irritable bowel syndrome., Conclusion: Mucosal defect was observed in half of the FMF patients, which may be associated with underlying inflammation or chronic colchicine exposure. Detection of nonspecific chronic inflammation without mitotic changes supports that mucosal defects may be associated with the autoinflammatory process.

Animal epithelia and saliva contain a substantial amount of aeroallergen material, causing both acute onset of symptoms related to hypersensitivity, and chronic inflammation of the airways leading to allergic rhinitis or asthma. Although allergy to horses is generally considered to be more prevalent in rural areas, sensitization to horse allergens is more frequent than might be expected in urban residents without any direct or occupational exposure to horses. However, horse allergy is seldom mentioned among animal-induced allergic reactions. Anaphylaxis due to horse exposure is reported even more rarely. Here, a pediatric patient with a hypersensitivity reaction after horse allergen exposure is reported, and the definition of the type of reaction is discussed, as it may be the whole set of locally induced multisystemic reactions that resembles anaphylaxis.