Diagnostic evaluation of hypersensitivity reactions to arylpropionic acid derivatives: a descriptive observational study focusing on clinical characteristics and potential risk factors in children.

BACKGROUND: Arylpropionic acid derivatives (APs) are the main triggers of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Data on clinical patterns and risk factors for AP hypersensitivity in children are quite limited. AIM: To assess the clinical characteristics and potential risk factors for proven AP hypersensitivity in children. METHOD: Patients with a history of AP hypersensitivity were retrospectively assessed using a standardized diagnostic algorithm. Children with confirmed hypersensitivity were defined as selective responders or cross-intolerants based on the result of drug provocation tests and further categorized according to the EAACI/ENDA classification. A multivariable logistic regression analysis was performed to analyze the potential risk factors for proven AP hypersensitivity. RESULTS: A total of 166 patients (51.2% male, median age of six years) with a history of AP hypersensitivity were included. Ibuprofen (89.2%) was the most frequently reported AP in the patients' histories. The reported hypersensitivity of 40 (22.4%) patients was confirmed by diagnostic testing: eight (13.6%) patients with a history of reaction only to APs and 32 (29.9%) patients with a history of reactions to multiple NSAIDs, including chemically unrelated NSAIDs in addition to APs. Five (12.5%) patients were classified as selective responders and 35 (87.5%) were cross-intolerants. Overall, five (12.5%) of the confirmed cases could not be categorized according to the EAACI/ENDA classification. Older age (aOR: 1.11, 95% CI 1.02-1.21, p = 0.015), chronic urticaria as an underlying disease (aOR: 2.87, 95% CI 1.09-7.54, p = 0.033) and a history of anaphylaxis (aOR: 7.84, 95% CI 1.86-33.04, p = 0.005) were related to confirmed AP hypersensitivity. CONCLUSION: Almost a quarter of children and adolescents were confirmed to have AP hypersensitivity. Older age, the presence of chronic urticaria and a history of anaphylaxis were potential risk factors for proven AP hypersensitivity.

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

A Bayesian Network Meta-Analysis of the Effect of Targeted Therapies on the Total Length of Hospital Stay in Children with Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare potentially life-threatening hypersensitivity disorders characterized by widespread skin and mucosal involvement. However, there is no standardized evidence-based treatment to reduce the complications of SJS/TEN. This article aims to compare the efficacy of different treatments for pediatric SJS/TEN in terms of length of hospital stay (LOS) using a Bayesian network meta-analysis (NMA). A Bayesian NMA is used to compare and combine evidence from multiple studies and allows clinicians to estimate the relative effectiveness of different treatments/interventions while accounting for heterogeneity in the available evidence. Methods: We conducted a comprehensive electronic database search for studies compatible with our inclusion criteria. Six studies with 103 patients were included in the NMA; of them, 37 patients were treated with intravenous immunoglobulin (IVIG), 37 with systemic corticosteroids (CS), 23 with IVIG + CS, and 3 with Etanercept (ET) + CS. Patients with a median age of 10 years were included in the study. Results: CS had the highest probability of being the most optimal treatment for SJS/TEN in terms of shorter LOS based on the Surface Under the Cumulative Ranking curve levels, and CS + IVIG was associated with a statistically nonsignificant trend toward shorter LOS than IVIG alone. Remarkably, none of the treatments showed a significant benefit over the other interventions in terms of LOS. Conclusion: Current evidence suggests that coadministration of CS and IVIG may be associated with a shorter LOS than IVIG alone. Further research with larger randomized controlled trials is needed to reach a definitive conclusion about the efficacy of specific therapy on LOS in pediatric SJS/TEN and to establish more definitive treatment guidelines.

Toxic Skin Reactions Should Be Differentiated from Allergic Reactions to Chemotherapeutic Drugs in Children: A Case Series and Review of the Literature.

Background: Chemotherapeutic drugs can lead to a wide spectrum of cutaneous findings, ranging from nonimmune toxic reactions to severe immune-mediated hypersensitivity reactions. The aim of this study was to evaluate the clinical, histopathological features, and prognosis of toxic skin reactions to chemotherapeutic drugs and to compare them with characteristics of immune-mediated reactions in children with malignancies. Methods: The medical records of all children with cancer who experienced skin reactions after chemotherapy administration and diagnosed as a toxic skin reaction between 2010 and 2022 were retrospectively analyzed. The diagnosis was re-evaluated and differentiated from other similar disorders by using clinical manifestations, photodocumentation, and histopathological findings. Results: A total of 17 children aged 2-17 years were involved: toxic erythema of chemotherapy (TEC) in 14 children, methotrexate-induced epidermal necrosis in 2 children, and toxic epidermal necrolysis (TEN)-like TEC in 1 child. The most commonly implicated drug was methotrexate. Most patients recovered rapidly after drug cessation and supportive measures. In 10 of the 17 patients, reintroduction of the culprit chemotherapeutic drug at reduced doses or increased dosage intervals was possible without any recurrence. Six patients could not receive further doses since they deceased due to sepsis and other complications. Conclusions: Cutaneous toxic eruptions to chemotherapeutic drugs may present with a severe phenotype resembling Stevens-Johnson syndrome/TEN. An accurate diagnosis prevents potentially harmful therapeutic interventions, withholding of chemotherapy, and erroneous assignment of drug allergies.

Evaluation of Pediatric Chronic Urticaria with Emphasis on Clinical and Laboratory Characteristics and Treatment Response to Omalizumab: A Real-Life Experience from a Tertiary Allergy Center.

Pediatric data on the clinical and etiologic features, treatment response, and use of omalizumab for chronic urticaria (CU) are quite limited. The aim of this study was to evaluate the clinical and demographic characteristics, laboratory findings, and response to treatment of CU in children. Children with a diagnosis of CU between 2019 and 2023 were included in the study. Information on demographic characteristics, clinical features, laboratory tests, provocation tests for inducible urticaria, urticaria activity scores (UAS7), and treatment responses were obtained from patients' medical records. A total of 150 children (50.7% male) with CU were enrolled in the study. A total of 14 (9.3%) patients had autoimmune diseases of which 11 (7.3%) had autoimmune thyroiditis. Overall, 97 (64.7%) patients had chronic spontaneous urticaria (CSU) and 53 (35.3%) had chronic inducible urticaria. A total of 16 patients who remained symptomatic despite high-dose antihistamines were treated with omalizumab, with a good response in 13 (81.3%) and a partial response in 3 (18.7%) patients. CSU accounts for the majority of pediatric CU, with the etiology being in part related to an autoimmune background. This study provides an overview of CU in children and demonstrates the safety and efficacy of treatment with omalizumab.

Evaluation of different protocols for classification of pediatric hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: Children with underlying allergic disease should be a separate subgroup.

Background: Different recommendations for the classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions (NSHSR) in children have been reported but a shortage still exists. Objective: The aim of the present study was to evaluate the inclusivity of two European Academy of Allergy and Clinical Immunology (EAACI) position paper classifications and to characterize the factors that underlie classification discordance in children. Methods: Patients with a history of NSHSR were evaluated with a standardized diagnostic protocol according to EAACI/ European Network for Drug Allergy (ENDA) recommendations. Children were classified and compared according to the EAACI 2013 and the pediatric EAACI/ENDA 2018 classifications. Subjects who were unclassified and those who were classified were compared. Results: Of 232 patients (median [interquartile range] age 6 years (4-11 years) with a history of NSHSR, 52 (22.4%) were confirmed with diagnostic tests. Thirty-six (69.2%) were classified as having cross-intolerance, whereas 16 patients (30.8%) were classified as selective responders. Eleven of the confirmed cases (21.2%) could not be categorized according to the 2013 EAACI classification, whereas this number was six adolescents (11.5%) when the 2018 EAACI/ENDA pediatric classification was used. Patients who were unclassified and who were all cross-intolerant were more likely to have atopic sensitization (p = 0.001) and asthma as an underlying disease (p = 0.03), higher serum eosinophil count (p = 0.022), and total immunoglobulin E levels (p = 0.007) compared with those who fit well into the classification. In multivariate regression analysis, the presence of atopic sensitization (adjusted odds ratio 20.36 [95% confidence interval, 2.14-193.48]; p = 0.009) was found to be the only significant underlying factor for an unclassified and/or blended phenotype. Conclusion: The 2013 EAACI classification resulted in a high rate of subjects who were unclassified. Despite better clinical utility, the recent pediatric EAACI/ENDA classification system still has shortcomings in terms of inclusivity for adolescents. Mostly, children with underlying allergic diseases could not be classified by the current guidelines. We propose to classify them as a separate pediatric cross-intolerance subgroup because the underlying mechanism may involve more than cyclooxygenase 1 inhibition.

Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

Management of Anaphylaxis in Pediatric Population.

Although an increase in the incidence of childhood anaphylaxis has been reported, it remains underdiagnosed. Foods are the most common triggers for anaphylaxis, particularly cow's milk, hen's egg, and nuts. Other common causes of anaphylaxis in children and adolescents include venom and drugs. The skin is the most commonly affected organ, but approximately 10% of patients with anaphylaxis may present without skin symptoms, which can lead to misdiagnosis. Recognition of anaphylaxis is a great challenge in children, possibly due to a lack of vigilance among patients, caregivers, and healthcare professionals, but also in part due to discrepancies in the clinical definition of anaphylaxis. In addition, anaphylaxis in infants often poses a distinct challenge because the wide spectrum of clinical manifestations and the inability of infants to describe their symptoms may hinder prompt diagnosis and treatment. Given the rapid onset of anaphylaxis and its unpredictable severity, rapid assessment and appropriate treatment are critical. Although the morbidity and mortality associated with anaphylaxis are potentially preventable with the timely administration of life-saving epinephrine, anaphylaxis is still undertreated worldwide. Long-term management of pediatric anaphylaxis is a patientcentered, multidimensional approach that focuses on the recognition of anaphylaxis, the use of epinephrine auto- injectors, and prevention of recurrences. Therefore, close communication and collaboration between the child, caregivers, healthcare professionals, and schools are the cornerstone of long-term care. This paper is designed to provide a comprehensive overview of current perspectives and concepts related to anaphylaxis in the pediatric population in light of recent guidelines and literature.

New diagnostic perspectives in the management of pediatric beta-lactam allergy.

Since overdiagnosis of beta-lactam (BL) allergy is common in the pediatric population, delabeling is a critical part of antimicrobial stewardship. Undesirable consequences of inaccurate BL allergy labeling can be handled by incorporating traditional delabeling or newer risk-based strategies into antibiotic stewardship programs. Conventional assessment of BL allergy relies upon a stepwise algorithm including a clinical history with skin testing followed by drug provocation tests (DPTs). However, a growing number of studies highlighted the suboptimal diagnostic value of skin testing in children. Recently, there has been a paradigm shift in the practice of BL allergy assessment due to recent challenging data which emphasize the safety and accuracy of direct DPTs in children with a suspicion of non-immediate mild cutaneous reactions such as maculopapular eruption, delayed urticaria, and possibly also for benign immediate reactions such as urticaria/angioedema. Identifying low-risk BL allergy patients, in whom skin tests can be skipped and proceeding directly to DPTs could be safe, has become a hot topic in recent years. New risk stratification and predictive modeling studies that have the potential to better predict BL allergy risk status have recently been introduced into the field of drug allergy, particularly in adults. However, in contrast to adults, risk assessment studies in children are rare, and optimal risk definitions are controversial. In the coming years, promising potential methods to elucidate the predictors of BL allergy in children will require multidimensional approaches that may include predictive analytics, artificial intelligence techniques, and point-of-care clinical decision tools.

A combined risk modeling strategy for clinical prediction of beta-lactam allergies in children.

Background: Drug provocation test (DPT) without skin tests is increasingly recommended in the evaluation of children with low-risk beta-lactam (BL) allergies. However, risk definitions are unclear. Objective: The aim of this study was to compose a clinical predictive model that could identify the children at low risk who could safely undergo direct DPT. Methods: The clinical data of 204 children who underwent a full diagnostic algorithm for suspected BL allergy were analyzed. Clinical data were used to construct mathematical predictive model for confirmed BL allergies. A prospective new sample was used for external validation of the final model. Results: The presentations during the index reaction were anaphylaxis in 5.9% and cutaneous reactions in the majority. BL allergy was confirmed in 15.7% of suspected cases. A backward multiple logistic regression model showed that a family history of drug allergy (adjusted odds ratio [aOR], 5.52), anaphylaxis (aOR, 5.14), any atopic disease other than asthma (aOR, 4.38), and a reaction interval of 0-6 hours during the index reaction (aOR, 5.32) were significantly associated with a confirmed BL allergy. A mathematical combined model based on these factors showed a sensitivity of 77.8% and a negative predictive value (NPV) of 94.3%. The validation study replicated sensitivity and NPV values of the main cohort. Conclusion: The risk definition in BL allergies should depend on population-specific predictive models, including a combination of significant risk factors rather than empiric risk approaches. This may help to accurately determinate children at low risk who may safely proceed to direct DPT.

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

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

Three patients with glucose-6 phosphatase catalytic subunit 3 deficiency.

Objectives Severe congenital neutropenia (SCN) is a primary immunodeficiency (PID) characterized by persistent severe neutropenia, recurrent infections, and oral aphthous lesions. Severe congenital neutropenia is caused by various genetic defects such as ELANE, GFI, HAX-1, JAGN1, SRP54, and glucose-6 phosphatase catalytic subunit 3 (G6PC3) deficiency. Clinical features of the patients with G6PC3 deficiency vary from neutropenia to several systemic features in addition to developmental delay. Case presentation In this report, we presented three unrelated patients diagnosed with G6PC3 deficiency. All these patients had short stature, prominent and superficial vascular tissue, cardiac abnormalities (Atrial septal defect (secondary), mitral valve prolapse with mitral insufficiency, pulmonary hypertension) and lymphopenia. Patient 1 (P1) and 2 (P2) had urogenital abnormalities, P2 and P3 had thrombocytopenia. Conclusions We have shown that lymphopenia and CD4 lymphopenia do not rarely accompany to G6PC3 deficiency. Characteristic facial appearance, systemic manifestions, neutropenia could be the clues for the diagnosis of G6PC3 deficiency.

A novel whole blood based method for lymphocyte transformation test in drug allergies.

Drug allergies pose a great deal of danger for the patients. It hinders effective treatment procedures in hospitalized patients. Moreover, it complicates the symptoms due to the allergic reactions of the immune system. Allergic reactions may arise against any medication including antibiotics and chemotherapeutics. Therefore, it is crucial to assess the sensitization pattern of the patients to culprit drug(s) before retreatment with the same or similar drug, or in order to confirm/exclude a suspected drug hypersensitivity reaction. In vivo and in vitro tests are performed in the evaluation of patients. Current methods of in vitro drug allergy evaluations rely on time consuming and expensive methods. Ficoll separation of peripheral blood mononuclear cells, their activation with stimulants in the presence of the drug of interest, CD69 or CD25 or BrdU or radioactive thymidine analysis of the cells after a couple of days of incubation is an excessively elaborate work and also uneconomical. Moreover, it requires a great deal of expertise to interpret the results. Here, we are reporting a new whole blood based lymphocyte transformation test method that does not require ficoll separation, CD69, CD25, BrdU and radioactive thymidine analysis. Thanks to the color change in the whole blood itself one can easily determine the allergic reaction to a certain drug. This new method is less time consuming, more economical and easy to apply.

Clinical Phenotypes of Severe Cutaneous Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions are clinically heterogenous ranging from mild to severe. Most drug hypersensitivity reactions are accompanied by cutaneous manifestations. Fever, mucous membrane involvement, large blisters, facial oedema, pustulosis and visceral involvement are clinical features that lead to suspicion of severe adverse drug reactions. Severe cutaneous adverse drug reactions (SCARs) include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis. Serum sickness like reactions, drug induced vasculitis and generalized bullous fixed drug eruptions are less severe clinical entities. SCARs are uncommon but associated with significant morbidity and mortality. Physician should be aware of specific red flags and danger signs to immediately identify these reactions. Immediate drug withdrawal is mandatory. Early diagnosis and appropriate treatment significantly affect the prognosis of the disease. The purpose of our review is to discuss clinical phenotypes of severe cutaneous drug hypersensitivity reactions.

Different Presentations of Patients with Transcobalamin II Deficiency: A Single-Center Experience from Turkey

Objective: Transcobalamin II deficiency is a rare autosomal recessive disease characterized by decreased cobalamin availability, which in turn causes accumulation of homocysteine and methylmalonic acid. The presenting clinical features are failure to thrive, diarrhea, megaloblastic anemia, pancytopenia, neurologic abnormalities, and also recurrent infections due to immune abnormalities in early infancy. Materials and Methods: Here, we report the clinical and laboratory features of six children with transcobalamin II deficiency who were all molecularly confirmed. Results: The patients were admitted between 1 and 7 months of age with anemia or pancytopenia. Unexpectedly, one patient had a serum vitamin B12 level lower than the normal range and another one had nonsignificantly elevated serum homocysteine levels. Four patients had lymphopenia, four had neutropenia and three also had hypogammaglobulinemia. Suggesting the consideration of transcobalamin II deficiency in the differential diagnosis of immune deficiency. Hemophagocytic lymphohistiocytosis was also detected in one patient. Furthermore, two patients had vacuolization in the myeloid lineage in bone marrow aspiration, which may be an additional finding of transcobalamin II deficiency. The hematological abnormalities in all patients resolved after parenteral cobalamin treatment. In follow-up, two patients showed neurological impairments such as impaired speech and walking. Among our six patients who were all molecularly confirmed, two had the mutation that was reported in transcobalamin II-deficient patients of Turkish ancestry. Also, a novel TCN2 gene mutation was detected in one of the remaining patients. Conclusion: Transcobalamin II deficiency should be considered in the differential diagnosis of infants with immunological abnormalities as well as cytopenia and neurological dysfunction. Early recognition of this rare condition and initiation of adequate treatment is critical for control of the disease and better prognosis.

Seasonal variation of asthma control, lung function tests and allergic inflammation in relation to vitamin D levels: a prospective annual study.

INTRODUCTION: There are scarce data about the role of vitamin D (vitD) in asthma control related to seasons and other confounders. AIM: To investigate the seasonal relationship between vitD levels and asthma control, lung function tests (LFTs) and cytokines during a 1-year period, among 7-17-year-old asthmatic children. MATERIAL AND METHODS: Thirty patients with asthma with house dust mite monosensitization were evaluated 3 monthly about the previous month's health and vitD related lifestyle factors and asthma control test (ACT), spirometry and bronchial provocation test for a year. Serum vitD, vitD binding protein (VDBP), total IgE levels, absolute eosinophil and Treg counts and cytokine levels were simultaneously measured. The seasonal changes of vitD and other parameters and the relationship between 120 pooled data sets of vitD and major outcomes were evaluated. RESULTS: Mean vitD levels, forced expiratory volume in 1 s (FEV1%) and ACT score were lowest in winter and highest in summer. Pooled vitD levels were positively correlated with pooled ACT scores, Treg counts, FEV1% values and VDBP levels and negatively with total immunoglobulin E (IgE) and interleukin-4 (IL-4) levels and bronchodilator response. VitD levels were positively associated with ACT score, and FEV1% value and negatively with serum IgE level and bronchodilator response after adjusting for confounders. CONCLUSIONS: This study revealed that asthma control measures, LFTs and IgE levels were significantly related to serum vitD levels, independent from age, body mass index, inhaled corticosteroid use, sun exposure and season among asthmatic children. Vitamin D levels showed a positive correlation with Treg counts and a negative correlation with Th2 type cytokines.

The airway hyperresponsiveness to methacholine may be predicted by impulse oscillometry and plethysmography in children with well-controlled asthma.

OBJECTIVE: Airway hyperresponsiveness (AHR) is a hallmark of asthma. Methacholine challenge test which is mostly used to confirm AHR is not routinely available. The aim of this study was to investigate the predictive values of fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and plethysmography for the assessment of AHR in children with well-controlled asthma. METHODS: 60 children with controlled allergic asthma aged 6-18 years participated in the study. FeNO measurement, spirometry, IOS, and plethysmography were performed. Methacholine challenge test was done to assess AHR. PC20 and dose response slope (DRS) of methacholine was calculated. RESULTS: Mild to severe AHR with PC20 < 4 mg/ml was confirmed in 31 (51.7%) patients. Baseline FeNO and total specific airway resistance (SRtot)%pred and residual volume (RV)%pred levels in plethysmography were significantly higher and FEV1%pred, FEV1/FVC%pred, MMEF%pred values were lower in the group with PC20 < 4 mg/ml. FeNO, SRtot%pred, and RV%pred levels were found to be positively correlated with DRS methacholine. The higher baseline FeNO, frequency dependence of resistance (R5-R20) in IOS and SRtot%pred in plethysmography were found to be significantly related to DRS methacholine in linear regression analysis (ß: 1.35, p = 0.046, ß: 4.58, p = 0.002, and ß: 0.78, p = 0.035, respectively). The cut-off points for FeNO and SRtot% for differentiating asthmatic children with PC20 < 4 mg/ml from those with PC20 ≥ 4 mg/ml were 28 ppb (sensitivity: 67.7%, specificity: 72.4%, p < 0.001) and 294.9% (sensitivity: 35.5%, specificity: 96.6%, p = 0.013), respectively. CONCLUSION: IOS and plethysmography may serve as reliable and practical tools for prediction of mild to severe methacholine induced AHR in otherwise "seemingly well-controlled'' asthma.

Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children.

BACKGROUND: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently encountered in daily clinical practice. The aim of this study was to determine the confirmation rates, risk factors of NSAID hypersensitivity in children and to try to classify them with a standardized diagnostic protocol. METHODS: All patients with a suspicion of NSAID-induced hypersensitivity were evaluated with European Network for drug Allergy (ENDA) recommendations. The children were classified as selective responders (SRs) or cross-intolerant (CI) depending on the drug provocation test (DPT) results. RESULTS: We evaluated 106 children with a suspicion of NSAID hypersensitivity. NSAID hypersensitivity was confirmed with tests in 31 patients; 4 (12.9%) were diagnosed by skin tests and 27 (87.1%) by DPTs and two patients with a history of anaphylaxis by medical records. Eleven patients (33.3%) were classified as SRs, whereas twenty-two (66.6%) children as CIs. SRs and CIs were further classified as NSAID-induced urticaria/angioedema (n = 8), NSAID-exacerbated cutaneous disease (n = 6) and NSAID-exacerbated respiratory disease (n = 1) and single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 11). Eight (24.2%) patients could not be categorized according to ENDA/GA2LEN classification; one CI patient could not be classified based on pathomechanisms, seven CIs could not be categorized based on the underlying disease and clinical manifestations. A reaction within an hour of drug intake (aOR:3.0, 95% confidence interval: 1.18-7.67, p = 0.021), a history with multiple NSAIDs hypersensitivity (aOR:2.9, 95% confidence interval: 1.16-7.60, p = 0.022), and family history of atopy (aOR:4.0, 95% confidence interval: 1.50-10.82, p = 0.006) were found as the independent risk factors related to confirmed NSAID hypersensitivity. CONCLUSIONS: This study suggests the presence of different phenotypes which do not fit into the current classifications in children with NSAID hypersensitivity.

The characteristics of indoor and outdoor fungi and their relation with allergic respiratory diseases in the southern region of Turkey.

Indoor and outdoor fungal exposure has been shown to be associated with the development of allergic respiratory diseases. The aim of the study was to investigate the types and concentrations of airborne fungi inside and outside homes and evaluate the association between fungal levels and allergic diseases in the southern region of Turkey. A total of 61 children admitted with respiratory complaints to the pediatric allergy clinic between September 2007 and November 2008 were included in this study. The air samples were obtained using the Air IDEAL volumetric air sampler longitudinally for 1 year. A comprehensive questionnaire was used for medical history and housing conditions. Skin prick test was performed to determine fungal sensitivity and spirometric indices were employed. The predominant indoor fungal species were Cladosporium (69.3 %), Penicillium (18.9 %), Aspergillus (6.5 %), and Alternaria (3.1 %). A strong correlation between indoor and outdoor fungal levels was detected for the Cladosporium species (p < 0.001, r = 0.72) throughout the year. Living in a detached home (p = 0.036) and the presence of cockroaches (p = 0.005) were associated with total indoor fungal levels. The presence of cockroaches (aOR 3.5; 95 % CI 0.95-13.10, p = 0.059) was also associated with fungal sensitization at the edge of significance. The statistical cutoff values of indoor and outdoor Cladosporium levels to predict symptomatic asthma were found to be >176 CFU/m(3) (p = 0.003, AUC 0.696; sensitivity 65.5 %; specificity 68.7 %) and >327 CFU/m(3) (p = 0.038; AUC 0.713; sensitivity 66.6 %; specificity 76.9 %), respectively. Children with respiratory symptoms are exposed to a considerable level of fungi inside and outside their homes. The prevention of fungal exposure may provide valuable intervention for respiratory diseases.