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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., (© 2022 S. Karger AG, Basel.)

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.

Introduction: Children with food allergy are at increased risk for asthma and asthma morbidity. Since leukotrienes are implicated in the pathogenesis of both asthma and probably in food allergies, we hypothesized that asthmatic children with concomitant food allergy may have a favorable response to antileukotriene treatment., Methods: Asthmatic children aged 6-18 years with and without food allergy were treated with montelukast and placebo in a double-blind, placebo-controlled cross-over parallel-group study. The primary outcome of the study was improvement in FEV1%. Asthma control tests, spirometry and methacholine challenges were performed as well as Fractional Exhaled Nitric Oxide (FeNO) levels. PGD2, CystLT, and lipoxin levels were measured in exhaled breath condensate (EBC)., Results: A total of 113 children were enrolled and 87 completed the study in accordance with the protocol. At baseline, children with food allergy and asthma (FAA) had higher levels of PGD2 and CysLT levels in the EBC than children with asthma alone (AA) (p < 0.001 for each). In the montelukast arm, although FEV1% was significantly higher in the FAA group compared to AA (p = 0.005), this effect was linked to the baseline difference of FEV1% between both arms. Montelukast treatment failed to improve FEV1% in both groups compared to the placebo. No effect of montelukast was observed in the remaining study parameters., Conclusion: Although children with FAA do not show a more favorable response to montelukast treatment compared to AA, a significant difference between baseline PGD2 and CystLT levels between FAA and AA groups may point to a different endotype of childhood asthma., (© 2021 S. Karger AG, Basel.)

Interferon Regulatory Factor-3 (IRF-3) is one of the key players in the inflammatory response mediated by the innate immune system. Although many studies have implicated a role for IRF-3 in the pathogenesis of inflammatory airway diseases, information about the possible association of IRF-3 genetic variants with asthma is scarce. We aimed to investigate the potential effects of IRF-3 polymorphisms in childhood asthma and asthma-related phenotypes. IRF-3 polymorphisms were first determined by sequencing 25 asthmatic and 25 healthy children. For further analysis, 609 asthmatic children and 191 healthy controls were screened for the genetic variants, such as rs2304204, rs2304205, rs320440, rs34739574, and rs7251. In addition, the relationship between these polymorphisms and asthma-related phenotypic features, including forced expiratory volume in one second values, eosinophil counts, and IgE levels was determined. rs7251 was associated with asthma in the codominant ( P  = 0.049) and G dominant ( P  = 0.025) model, however this significance was lost after False Discovery Rate analysis. Other investigated single nucleotide polymorphisms (SNPs) showed no significant association with asthma or asthma-related phenotypes. In conclusion, the seven SNPs of IRF-3 gene are not associated with asthma or asthma-related phenotypes in Turkish asthmatic children.

Aim: We aimed to identify the frequency, magnitude and risk factors of salbutamol-induced hypoxia in children with acute asthma., Methods: This study was conducted at Hacettepe University on children who presented to the paediatric allergy clinic or the paediatric emergency room with acute asthma between July 2014 and June 2015. Vital signs, pulse oximetry-defined oxygen saturation and modified pulmonary index scores were evaluated before and after the first, second and third doses of nebulised salbutamol and repeated one and 10 days later., Results: We included 304 patients (65.7% male) from median age of 5.3 years (range 1-18 years). Salbutamol-induced hypoxia was detected in 14.7%, 3.9% and 1.3%, respectively, after the first, second and third doses of salbutamol. The risk factors for hypoxia were younger age and a higher modified pulmonary index score, but the risk factors for salbutamol-induced hypoxia were the number of salbutamol doses given in the last six hours and the presence of aeroallergen sensitisation. The maximum decrease in oxygen saturation after salbutamol was %5., Conclusion: Although bronchodilators are the first-line treatment for acute asthma, they caused modest hypoxaemia, especially at repeated doses and, or, in patients with aeroallergen sensitisation., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objectives: Results of previous studies have established several factors related with the natural course of childhood asthma. The aim of this study is to investigate the prognosis of childhood asthma and to determine possible risk factors for disease persistence., Methods: An outpatient cohort with a median (interquartile range) follow-up duration of 19.4 (17.7-21.8) years was re-evaluated. Current clinical remission (CR) was defined as no asthma symptoms and no use of controller medication within the past year., Results: Out of 115 patients, 78 could be surveyed with questionnaire and 46 patients with a median age of 25.3 (23.9-27.0) years were further investigated with clinical work-up. Nineteen (24.4%) patients were in CR in both visits (adolescence and young adulthood). A further 7 patients (9.0%) who were not in CR at adolescence were in CR at the young adulthood visit. However, 21 patients (26.9%) who were in CR at adolescence were not in CR at the young adulthood visit. Thirty-one patients (39.7%) with persistent symptoms at adolescence were not in CR at young adulthood, either. In multivariate logistic models, the presence of obstructive pattern (forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) <80% vs. ≥80%) in pulmonary function tests during the adolescence period (odds ratio; [95% confidence interval] (6.71 [1.65-27.29]; p=0.008) and later-onset rhinitis (10.27 [1.18-89.13]; p=0.035) predicted the absence of CR at young adulthood., Conclusion: A substantial number of patients who were in CR during adolescence have re-emerging disease. The presence of obstructive pattern in adolescence and later-onset rhinitis were associated with the absence of CR in young adults with asthma. Awareness of risk factors along with early interventions may provide better results in childhood asthma., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aeroallergens may trigger symptoms in sensitized children with asthma. Documentation of sensitization is crucial to enable effective implementation of measures to prevent asthma exacerbations. To document the sensitization patterns of very young children (≤2 years) with asthma, we retrospectively analyzed the skin-prick test (SPT) results of the largest referral center in the country. During a 4-year period, 432 children (median age, 1.21 years; male/female, 2.35) were referred. All patients had recurrent wheezing attacks and good response to inhaled bronchodilators and were diagnosed with asthma by their referring physician. SPT with eight aeroallergens (grass mix, weed mix, tree mix, mold mix, house-dust mite, cockroach, cat, and dog) was performed in 209 patients (full panel group) and the remaining 223 were tested only with a mixture of two house-dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae; house-dust mite group). The sensitization rates in house-dust mite and full panel groups were 3.2% (7/223) and 3.3% (7/209), respectively. Univariate and multivariate modeling was unable to identify a predictor for the presence of aeroallergen sensitization. During first 2 years of life, low rates of aeroallergen sensitization and lack of predictors of sensitization in children with asthma suggest that skin testing for aeroallergens may not be a routine procedure. When there is a high index of suspicion, testing only for indoor aeroallergens including house-dust mites, molds, and pets may identify the majority of sensitized children.

Objective: It is difficult to determine if preschool children with recurrent wheezing are suffering from asthma or will suffer from asthma in the future. The aim of this study was to investigate the prognosis and risk factors of recurrent wheezing in children, beginning in the first 3 years of life., Method: Children who were referred because of recurrent wheezing episodes during the first 3 years of life were evaluated for the presence of asthma over a 4-year period. A child without any symptoms within the last 12 months was considered to be in remission., Results: The study included 529 (male/female: 2.17) children with a median (inter-quartile) age of 0.6 years (0.3-1.0) at symptom onset. The median follow-up and symptom durations were 2.93 years (1.74-4.76) and 4.30 years (2.91-5.97), respectively. Remission/recovery was achieved in 1.7%, 8.0%, and 14.4% of the children within 12, 24, and 36 months, respectively. A negative "stringent asthma predictive index" (API) significantly shortened the time to recovery of wheezing compared to the positive API (p = .036). Maternal smoking during pregnancy (OR = 4.35; 95% CI = 1.29-14.63); p = .018) and the number of emergency room admissions within the first 3 years of life (OR = 1.10; 95% CI = 1.01-1.19); p = .031) were found to be independent risk factors for the persistence of wheezing symptoms., Conclusion: Most of the children who were referred with frequent wheezing remain symptomatic 3 years after the initial wheezing episodes. A negative API is related to a shorter wheezing duration. Maternal smoking during pregnancy and the severity of the wheezing episodes appeared to be significant risk factors for the persistence of wheezing symptoms.

Background: International guidelines highlight the importance of assessing asthma control status in children with asthma, and research on practical and objective instruments for assessing asthma control is ongoing., Objective: To determine the role of the Childhood Asthma Control Test (C-ACT) and fractional concentration of exhaled nitric oxide (FeNO) in identifying children with not well-controlled asthma., Methods: Children 6 to 11 years of age with asthma were enrolled in the study. They completed C-ACT and underwent FeNO and spirometric measurements during the monthly clinic visits. An asthma specialist assessed asthma control according to the gold standard Global Initiative for Asthma guideline and decided the treatment of the patients., Results: Seventy-six children with a mean (SD) age of 8.7 (1.4) years were evaluated in the first visit, whereas 64 and 51 children were admitted for second and third visits, respectively. A C-ACT score of 22 or less had 69% sensitivity and 77% specificity in determining not well-controlled asthma, whereas an FeNO value of 19 ppb or higher had 61% sensitivity and 59% specificity in patients who completed 3 visits. Receiver operating characteristic curve analysis revealed that the C-ACT was better than FeNO for identifying patients with not well-controlled asthma (area under the curve, 0.79; P < .001 [C-ACT] vs .58, P = .10 [FeNO]) Results of multivariate generalized estimating equation analysis revealed that a C-ACT score of 22 or less (odds ratio, 8.75; 95% confidence interval, 4.35-17.59; P < .001) and an FeNO of 19 ppb or greater (odds ratio, 2.60; 95% confidence interval, 1.07-6.29; P = .03) were significant indicators for the presence of not well-controlled asthma., Conclusion: The C-ACT is superior to FeNO in determining the control status of children with asthma and may be used as a complementary tool in clinical practice to detect children with not well-controlled asthma., (Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The safety of long-acting beta-2-adrenergic agonists is increasingly questioned by physicians. Although formoterol is frequently used in childhood, its effects on the autonomic cardiovascular system have not been studied., Objective: To investigate the effects of inhaled formoterol on autonomic nervous system using heart rate variability in adolescents with persistent asthma., Methods: Electrocardiography of 20 asthmatic adolescents (12-20 years) was monitored for 5 specific days. The first day served as basal measurement, and the 2nd and 3rd days reflected the effects of a single and 2 doses of formoterol, respectively. From days 4 to 29, patients received regular treatment with formoterol/budesonide and were monitored on days 30 and 31 to evaluate the development of cardiac and respiratory tolerance after single-dose and 2 doses of formoterol, respectively. Electrocardiographs were analyzed for heart rate, heart rate variability (both time and frequency domain parameters), and spirometry tests were performed., Results: Inhalation of single-dose formoterol increased heart rate and decreased heart rate variability parameters (ratio of the normal-to-normal [NN] interals changing in excess of 50 ms to total of NN intervals [pNN50], total power [TP][ms], TP[ln]) compared with the corresponding baseline values during the first 12 hours of the day. The heart rate variability parameters (pNN50, TP[ms], TP[ln], root mean square of differences between adjacent NN intervals) during the first 12 hours were increased on the 30th day compared with the 2nd day and decreased on the 31st day compared with the 30th day., Conclusion: Single-dose formoterol inhalation decreases cardiovagal responsiveness and increases the sympathetic tone in cardiac autonomous control, and regular use of formoterol causes development of tolerance to these effects. However, additive doses of formoterol cause loss of this tolerance., (Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Systemic inflammation, attacks, deterioration of thoracic region mechanics, medications used, and decreased physical activity level (PAL) and fitness negatively may affect respiratory muscle strength. The primary aim of this study was to evaluate dynamic inspiratory muscle strength (S-index), PAL, and physical fitness in children with asthma compared to healthy peers. The secondary aim of this study was to investigate the relationships between S-index and peak inspiratory flow (PIF) values and functional parameters in childhood asthma. Methods: This cross-sectional prospective study consisted of participants of 6–11 years of age, specifically, 20 children with asthma and 20 healthy peers. The device (POWERbreathe K5) evaluated PIF and S-index variables. PAL was determined with the Physical Activity Questionnaire-Child (PAQ-C) and fitness was evaluated with the FITNESSGRAM test battery. Results: The PIF Average (Avg): 1.8 ± 0.6, Best: 2.6 ± 0.6 (asthmatic children) vs. Avg: 2.4 ± 0.7, Best: 3.1 ± 0.9 (healthy children); p = 0.017, p = 0.027, respectively) and S-index (Avg: 34.1 ± 10.3, Best: 45.6 ± 9.9 (asthmatic children) vs. Avg: 43.2 ± 12.1, Best: 56.6 ± 14.7 (healthy children); p = 0.015, p = 0.008 respectively) values of children with asthma were significantly lower compared to healthy peers. The PAL and physical fitness of asthmatic and healthy peers were similar (p > 0.05). There were significant relationships between S-indexavg and S-indexbest with the PAQ-C score (r = 0.498, p < 0.025 r = 0.547, p < 0.013, respectively) and PIFavg and PIFbest with the PAQ-C score (r = 0.490, p < 0.028 r = 0.602, p < 0.005) in children with asthma. Conclusions: Dynamic respiratory muscle strength is negatively affected in children with asthma whereas their physical activity and fitness levels are comparable to their peers. However, it was found that children with a higher S-index and PIF rate had higher PALs. These findings suggest that pulmonary rehabilitation interventions to improve respiratory muscle function should be considered an important strategy to maintain and increase physical activity levels in children with asthma. [ABSTRACT FROM AUTHOR]