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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.
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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.
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Hipersensibilidade a Leite , Substitutos do Leite , Estado Nutricional , Vitamina D , Humanos , Hipersensibilidade a Leite/dietoterapia , Hipersensibilidade a Leite/imunologia , Feminino , Estudos Transversais , Masculino , Pré-Escolar , Criança , Animais , Vitamina D/sangue , Cálcio da Dieta/administração & dosagem , Riboflavina , Bovinos , Vitamina B 12/sangueRESUMO
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.
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Venenos de Artrópodes , Dessensibilização Imunológica , Imunoglobulina E , Humanos , Criança , Adulto , Dessensibilização Imunológica/métodos , Masculino , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Venenos de Artrópodes/imunologia , Adolescente , Animais , Pessoa de Meia-Idade , Adulto Jovem , Índice de Gravidade de Doença , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Hipersensibilidade/terapia , Hipersensibilidade/imunologia , Hipersensibilidade/diagnóstico , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/terapia , Pré-Escolar , Alérgenos/imunologia , Himenópteros/imunologia , Estudos Prospectivos , Triptases/sangue , BiomarcadoresRESUMO
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.
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Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/terapia , Estudos Retrospectivos , Masculino , Feminino , Criança , Adolescente , Pré-Escolar , Lactente , Índice de Gravidade de Doença , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND: Recent advancements in molecular diagnostics have unveiled a multitude of allergen molecules (AMs) associated with animal sensitizations, revealing significant cross- and co-sensitization patterns among these seemingly distinct allergens. METHOD: We investigated the sensitization profiles of 120 children, sensitized to at least one of the 14 AMs from cat, dog, or horse using the Alex test, employing correlations and hierarchical clusters to explore relationship between sensitizations. RESULTS: Sensitizations to Fel d 1, Can f 4/5, and Equ c 4 differ from other cat, dog, and horse AM sensitizations, suggesting they may represent genuine sensitizations for their respective animals. High correlations were observed among various AMs, including lipocalins (Can f 1/2/6, Fel d 4/7, and Equ c 1), serum albumins (Fel d 2, Can f 3, and Equ c 3), and uteroglobins (Fel d 1 and Can f_Fd1). Hierarchical clustering of sensitizations identified two similarity clusters and one dissimilarity cluster, providing an estimation of the likelihood of cross-reactivity. Additionally, our method facilitated speculation regarding cross-, co-, or genuine sensitization. Moreover, we noted a potential increase in the number and level of sensitized animal AMs concurrent with increased sensitization to other aeroallergens with advancing age. No significant difference was detected for the presence or absence of various types of allergic comorbidities. CONCLUSION: Correlations and hierarchical clustering can unveil the extent and magnitude of cross-, co-, and genuine sensitization relationships among animal AMs. These insights can be leveraged to enhance artificial intelligence algorithms, improving diagnostic accuracy through the integration of other measures of sensitization.
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Alérgenos , Hipersensibilidade , Cães , Animais , Alérgenos/imunologia , Gatos/imunologia , Criança , Cavalos/imunologia , Humanos , Feminino , Masculino , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Pré-Escolar , Adolescente , Reações Cruzadas/imunologia , Lactente , Imunização , Imunoglobulina E/imunologia , Imunoglobulina E/sangueRESUMO
Pollen from Salsola kali, i.e., saltwort, Russian thistle, is a major allergen source in the coastal regions of southern Europe, in Turkey, Central Asia, and Iran. S. kali-allergic patients mainly suffer from hay-fever (i.e., rhinitis and conjunctivitis), asthma, and allergic skin symptoms. The aim of this study was to investigate the importance of individual S. kali allergen molecules. Sal k 1, Sal k 2, Sal k 3, Sal k 4, Sal k 5, and Sal k 6 were expressed in Escherichia coli as recombinant proteins containing a C-terminal hexahistidine tag and purified by nickel affinity chromatography. The purity of the recombinant allergens was analyzed by SDS-PAGE. Their molecular weight was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and their fold and secondary structure were studied by circular dichroism (CD) spectroscopy. Sera from clinically well-characterized S. kali-allergic patients were used for IgE reactivity and basophil activation experiments. S. kali allergen-specific IgE levels and IgE levels specific for the highly IgE cross-reactive profilin and the calcium-binding allergen from timothy grass pollen, Phl p 12 and Phl p 7, respectively, were measured by ImmunoCAP. The allergenic activity of natural S. kali pollen allergens was studied in basophil activation experiments. Recombinant S. kali allergens were folded when studied by CD analysis. The sum of recombinant allergen-specific IgE levels and allergen-extract-specific IgE levels was highly correlated. Sal k 1 and profilin, reactive with IgE from 64% and 49% of patients, respectively, were the most important allergens, whereas the other S. kali allergens were less frequently recognized. Specific IgE levels were highest for profilin. Of note, 37% of patients who were negative for Sal k 1 showed IgE reactivity to Phl p 12, emphasizing the importance of the ubiquitous cytoskeletal actin-binding protein, profilin, for the diagnosis of IgE sensitization in S. kali-allergic patients. rPhl p 12 and rSal k 4 showed equivalent IgE reactivity, and the clinical importance of profilin was underlined by the fact that profilin-monosensitized patients suffered from symptoms of respiratory allergy to saltwort. Accordingly, profilin should be included in the panel of allergen molecules for diagnosis and in molecular allergy vaccines for the treatment and prevention of S. kali allergy.
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Alérgenos , Reações Cruzadas , Imunoglobulina E , Pólen , Profilinas , Salsola , Humanos , Profilinas/imunologia , Profilinas/química , Imunoglobulina E/imunologia , Alérgenos/imunologia , Alérgenos/genética , Salsola/imunologia , Feminino , Pólen/imunologia , Masculino , Reações Cruzadas/imunologia , Adulto , Proteínas Recombinantes/imunologia , Rinite Alérgica Sazonal/imunologia , Pessoa de Meia-Idade , Basófilos/imunologia , Basófilos/metabolismo , Antígenos de Plantas/imunologia , Antígenos de Plantas/genética , Adulto Jovem , Adolescente , Proteínas de Plantas/imunologia , Proteínas de Plantas/genéticaRESUMO
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.
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Anafilaxia , Proteínas de Transporte , Relevância Clínica , Criança , Humanos , Alimentos , AlérgenosRESUMO
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.
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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.
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Hipersensibilidade , Piridinolcarbamato , Criança , Humanos , Análise por ConglomeradosRESUMO
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.
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Hipersensibilidade Alimentar , Hipersensibilidade a Leite , Animais , Feminino , Bovinos , Humanos , Criança , Pré-Escolar , Lactente , Hipersensibilidade Alimentar/epidemiologia , Dieta , Suplementos Nutricionais , AlérgenosRESUMO
Urticaria is a common disease that can affect individuals of all age groups, with approximately one-quarter of the population experiencing it at least once in their lifetime. Lesions characterized by erythema and itchy hives can appear anywhere on the body. These can vary in size ranging from millimeters to centimeters, and typically clear within 24â h. About 40% of patients with urticaria have accompanying angioedema, which involves localized deep tissue swelling. Urticaria usually occurs spontaneously and is classified into acute and chronic forms, with the latter referring to a condition that lasts for more than 6 weeks. The prevalence of chronic urticaria in the general population ranges from 0.5% to 5%, and it can either be inducible or spontaneous. The most common form of pediatric urticaria is acute and is usually self-limiting. However, a broad differential diagnosis should be considered in children with urticaria, particularly if they also have accompanying systemic complaints. Differential diagnoses of pediatric urticaria include chronic spontaneous urticaria, chronic inducible urticaria, serum sickness-like reaction, urticarial vasculitis, and mast cell disorders. Conditions that can mimic urticaria, including but not limited to cryopyrinopathies, hyper IgD syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA), Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPs), and Schnitzler syndrome should also be considered. The many faces of pediatric urticaria can be both easy and confusing. A pragmatic approach relies on clinical foresight and understanding the various forms of urticaria and their potential mimickers. This approach can pave the way for an accurate and optimized diagnostic approach in children with urticaria.
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BACKGROUND: Indacaterol acetate (IND), a long-acting ß2-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma. METHODS: In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥ 6 to < 12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler® in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV1) after two weeks of treatment. RESULTS: In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV1 from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV1 after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 µg group and 25% patients in IND 150 µg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥ 0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile. CONCLUSIONS: Once-daily IND 75 µg and IND 150 µg via Breezhaler® in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 µg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02892019; 08-Sep-2016).
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Asma , Humanos , Criança , Asma/diagnóstico , Asma/tratamento farmacológico , Método Duplo-Cego , Volume Expiratório Forçado , AcetatosRESUMO
Objective: To evaluate growth, tolerance and safety outcomes with use of an extensively hydrolyzed casein-based formula (eHCF) in infants with cow's milk protein allergy (CMPA). Methods: A total of 226 infants (mean ± SD age: 106.5 ± 39.5 days, 52.7% were girls) with CMPA who received eHCF comprising at least half of the daily dietary intake were included. Data on anthropometrics [weight for age (WFA), length for age (LFA) and weight for length (WFL) z-scores] were recorded at baseline (visit 1), while data on infant feeding and stool records, anthropometrics and Infant Feeding and Stool Patterns and Formula Satisfaction Questionnaires were recorded at visit 2 (on Days 15 ± 5) and visit 3 (on Days 30 ± 5). Results: From baseline to visit 2 and visit 3, WFA z-scores (from -0.60 ± 1.13 to -0.54 ± 1.09 at visit 2, and to -0.44 ± 1.05 at visit 3, p < 0.001) and WFL z-scores (from -0.80 ± 1.30 to -0.71 ± 1.22 at visit 2, and to -0.64 ± 1.13 at visit 3, p = 0.002) were significantly increased. At least half of infants never experienced irritability or feeding refusal (55.7%) and spit-up after feeding (50.2%). The majority of mothers were satisfied with the study formula (93.2%), and wished to continue using it (92.2%). Conclusions: In conclusion, eHCF was well-accepted and tolerated by an intended use population of infants ≤ 6 months of age with CMPA and enabled adequate volume consumption and improved growth indices within 30 days of utilization alongside a favorable gastrointestinal tolerance and a high level of parental satisfaction.
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BACKGROUND: Chronic spontaneous urticaria (CSU), a long-lasting disease in children, impacts their quality of life. We report the results of a phase 2b dose-finding trial of ligelizumab (NCT03437278) and a high-affinity humanized monoclonal anti-IgE antibody, in adolescents with CSU, supported by modeling and simulation analyses, mitigating challenges in pediatric drug development. METHODS: This multicenter, double-blind, placebo-controlled trial, randomized H1-antihistamine-refractory adolescent CSU patients (12-18 years) 2:1:1 to ligelizumab 24 mg, 120 mg, or placebo every 4 weeks for 24 weeks. Patients on placebo transitioned to ligelizumab 120 mg at week 12. Integrating data from the previous adult and present adolescent trial of ligelizumab, a nonlinear mixed-effects modeling described the longitudinal changes in ligelizumab pharmacokinetics, and its effect on weekly Urticaria Activity Score (UAS7). RESULTS: Baseline UAS7 (mean ± SD) was 30.5 ± 7.3 (n = 24), 29.3 ± 7.7 (n = 13), and 32.5 ± 9.0 (n = 12) for patients (median age, 15 years) on ligelizumab 24 mg, 120 mg, and placebo, respectively. Change from baseline in UAS7 at week 12 with ligelizumab 24 mg, 120 mg, and placebo was -15.7 ± 10.9, -18.4 ± 12.3, and -13.0 ± 13.0, respectively. Ligelizumab was well-tolerated. The modeling analysis showed that body weight, but not age, affected ligelizumab's apparent clearance. No significant differences between adolescents and adults were detected on the model-estimated maximum effect and potency. CONCLUSIONS: Ligelizumab exhibited efficacy and safety in adolescent CSU patients, consistent with that in adults. The PK and potency of ligelizumab were not impacted by age, and the same dose of ligelizumab can be used for treating adolescents and adults with CSU. Our study shows how modeling and simulation can complement pediatric drug development.
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Antialérgicos , Urticária Crônica , Urticária , Adulto , Humanos , Adolescente , Criança , Antialérgicos/uso terapêutico , Omalizumab/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Doença Crônica , Urticária/tratamento farmacológico , Urticária Crônica/tratamento farmacológicoRESUMO
OBJECTIVE: Plastic bronchitis (PB) is a rare disease in children, and reliable data are scarce. Here, we aimed to analyze the clinical features, management, and outcomes in children with PB. METHODS: The medical data of patients who were followed up with a diagnosis of PB between January 2010 and March 2022 were retrospectively analyzed. RESULTS: The median age of 15 patients was 9 (interquartile range: 4-10) years with a male/female ratio of 12/3. Initial symptoms included recurrent pneumonia (33.3%), persistent atelectasis (33.3%), cast expectoration (26.6%), and intense, persistent cough (6.6%). The most common underlying diagnosis was asthma (n = 12, 80%), and six of the patients were newly diagnosed. The most common radiological findings were atelectasis as a consequence of major airway obstruction on chest X-ray or computed tomography. Five patients, all diagnosed as having asthma, had recurrent PB and required multiple airway procedures for treatment and diagnosis. During a median 7-year follow-up of five patients, occasionally cast expectoration was observed in one patient with asthma who had poor compliance with inhaled corticosteroids. CONCLUSION: PB is a common reflection of the different underlying etiologies in the pediatric age group, and treatment and outcomes are closely related to these. It should be kept in mind that asthma can be a predisposing factor for the development of PB.
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Asma , Bronquite , Atelectasia Pulmonar , Humanos , Criança , Masculino , Feminino , Pré-Escolar , Estudos Retrospectivos , Broncoscopia/efeitos adversos , Bronquite/complicações , Bronquite/terapia , Asma/complicações , Asma/terapia , Asma/diagnóstico , Atelectasia Pulmonar/etiologia , Causalidade , PlásticosRESUMO
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.
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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.
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Síndrome Hipereosinofílica , Hipersensibilidade , Humanos , Criança , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/epidemiologia , Síndrome Hipereosinofílica/etiologia , Hipersensibilidade/diagnóstico , Contagem de Leucócitos , Diagnóstico Diferencial , AlgoritmosRESUMO
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.