Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. METHODS: Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' (CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' (CRU). Single-blind, placebo-controlled provocation tests (SBPCPTs) with aspirin were performed for children with CSU. RESULTS: Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P < 0.016, P = 0.024, respectively). SBPCPTs with aspirin revealed that 14 of 58 patients (24%) with CPU and one of 10 patients with CRU (10%) were aspirin hypersensitive. Aspirin hypersensitivity rate was 26.5% in patients <12 years of age. All of the 15 aspirin-hypersensitive patients (aged between 6.6 and 17.4 years), except for three, experienced an unequivocal angioedema of the lips as a positive reaction in SBPCPT. CONCLUSIONS: Nearly a quarter of children and adolescents with CSU were hypersensitive to aspirin. For children with chronic urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions.

Increased osteopontin levels in children undergoing venom immunotherapy may serve as a marker of clinical efficacy.

BACKGROUND: Venom immunotherapy (VIT) has its effect by modulating various mediators resulting in immune tolerance. The aim of this study was to measure changes in plasma osteopontin (OPN) and serum basal tryptase (sBT) levels over the course of 1 year of VIT in children with venom allergy. METHODS: Children who suffered from a large local reaction (LLR) or a systemic reaction (SR) after insect stings were included along with control subjects. Measurements were performed before the initiation of VIT and 6 and 12 months after it had been started. RESULTS: A total of 58 children (24 with SR, 18 with LLR and 16 control subjects) with a median age of 9.5 years (range 6.7-12.8) were enrolled. The plasma OPN levels of patients with LLR [median 1,477 ng/ml, interquartile range (IQR) 1,123-1,772] were significantly higher than patients with SR (882 ng/ml, 579-1,086; p < 0.001) and healthy control subjects (1,015 ng/ml, 815-1,203; p = 0.002). A significant increase in plasma OPN levels in children was determined after the 1-year VIT. The sBT levels of children with SR (4.1 ng/ml, 3.6-5.8) were significantly higher than children with LLR (3.1 ng/ml, 2.5-4.0) and control subjects (3.0 ng/ml, 2.9-3.8; p = 0.001). There was no significant change in the sBT levels of the patients after the 1-year VIT. CONCLUSIONS: The results of our study showed higher baseline levels of OPN in children with LLR compared to control subjects and children with SR. In children with SR, OPN levels were increased after the 1-year VIT. Our results may suggest a possible association between OPN and successful VIT in children.

Clinical features of children with venom allergy and risk factors for severe systemic reactions.

BACKGROUND: Severe systemic reactions (SRs) to insect venom are rare in childhood and there are few data on this study population. The aim of our study is to analyze the clinical features and to document the risk factors for severe SRs in children with insect venom allergy. METHODS: Children with SRs after Hymenoptera sting were analyzed. The diagnosis was based on medical history, skin tests and/or specific IgE testing. RESULTS: Seventy-six children were included [57 boys (75%), mean age 9.8 ± 3.4 years]. The mean age of children at the time of SR was 8.3 ± 3.4 years. Reactions were accounted for Vespula (wasp) venom in 58 (76%) and Apis mellifera (bee) venom in 18 (24%) patients. Twenty-six percent of patients had aeroallergen sensitization and 33% had atopic disease, whereas 66% had experienced previous stings. The upper limb was the most frequent area of sting (43%), and the cutaneous system (99%) was the most frequent involved system. SRs occurred in 59% of patients. Multivariate logistic regression analysis revealed eosinophilia (>5%) [odds ratio (OR) 12.6; confidence interval (CI) 1.5-109.7; p = 0.022], female sex (OR 6.4; CI 1.5-26.9; p = 0.011) and accompanying atopic disease (OR 3.4; CI 1.2-12.3; p = 0.016) as significant risk factors for severe SRs. Ninety-seven percent of patients were admitted to the emergency department; however, epinephrine was used in only 46% of patients. CONCLUSIONS: There was a high frequency of hypersensitivity to wasp venom among the study population, and severe reactions were related to mild eosinophilia, female sex and concomitant atopic diseases. A better understanding of the risk factors may lead to effective utilization of health care sources in the future.

Validation of the Turkish version of "Test for Respiratory and Asthma Control in Kids (TRACK)" questionnaire.

BACKGROUND: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire is the first to measure both the risk and impairment domains of the current guidelines in preschool children. We aimed to measure the reliability, validity and responsiveness of the Turkish version of the TRACK. METHODS: A total of 268 children (69.8% boys) were included in the study. Caregivers responded to three individual TRACK questionnaires, at each clinical visit (baseline, 1st month, and 3rd month). At each visit, physicians determined the control level and the treatment strategy based on the GINA guideline recommendations. RESULTS: The internal consistency reliability of the Turkish version of the TRACK questionnaire was found to be 0.74, 0.74, and 0.76 at each of the three visits, respectively (reliability statistics, Cronbach's alpha). There was a significant difference between the mean TRACK scores of the patients in different asthma control status categories (p < 0.001). The test-retest reliability in stable patients was 0.90. The optimal cut-off scores according to the Youden index were 80 and 60 points for uncontrolled and very poorly controlled children, respectively. CONCLUSION: The Turkish version of the TRACK is an accurate and reliable tool for evaluating asthma control status among preschool Turkish children. Its widespread use may help physicians correctly assess control levels among children and may improve the quality of life for both patients and their caregivers.

Oxidative stress in the airways of children with asthma and allergic rhinitis.

INTRODUCTION: Even though it is well known that oxidant stress plays an important role in the pathogenesis of asthma, less is known about allergic rhinitis. Moreover, it is not known whether the co-existence of the two diseases augments the level of oxidant stress within a united airway concept. AIM: To define the level of oxidative stress in children with asthma and/or allergic rhinitis in nasal and oral exhaled breath condensates (EBC) of children. METHOD: Children aged 6-18 years with asthma (n = 28), allergic rhinitis (n = 17), asthma and allergic rhinitis (n = 100), and healthy controls (n = 74) were enrolled in the study. Levels of malondialdehyde (MDA) as a marker of oxidative stress and reduced glutathione (GSH) as an antioxidant were measured by High-Performance Liquid Chromatography in the EBC. RESULTS: Malondialdehyde levels were higher, and GSH levels were lower in all patient groups compared to healthy controls in both nasal and oral EBC samples (p < 0.01) but there were no differences among the different patient groups. Interestingly, oral MDA levels were lower in patients with asthma and allergic rhinitis [17.78 nM (11.62-23.94)] compared to patients with asthma only [25.71 nM (18.81-32.61)] (p < 0.01). DISCUSSION: Both asthma and allergic rhinitis are associated with increased oxidative stress in the airways in children. However, the co-existence of the two diseases does not augment the oxidant stress further.

Phenotypes of IgE-mediated food allergy in Turkish children.

Data on food allergy-related comorbid diseases and the knowledge on factors associating specific food types with specific allergic outcomes are limited. The aim of this study was to determine the clinical spectrum of IgE-dependent food allergy and the specific food-related phenotypes in a group of children with IgE-mediated food allergy. Children diagnosed with IgE-mediated food allergy were included in a cross-sectional study. IgE-mediated food allergy was diagnosed in the presence of specific IgE or skin-prick test and a consistent and clear-cut history of food-related symptoms or positive open provocation test. Egg (57.8%), cow's milk (55.9%), hazelnut (21.9%), peanut (11.7%), walnut (7.6%), lentil (7.0%), wheat (5.7%), and beef (5.7%) were the most common food allergies in children with food allergy. The respiratory symptoms and pollen sensitization were more frequent in children with isolated tree nuts-peanut allergy compared with those with egg or milk allergy (p < 0.001); whereas atopic dermatitis was more frequent in children with isolated egg allergy compared with those with isolated cow's milk and tree nuts-peanut allergy (p < 0.001). Children with food allergy were 3.1 (p = 0.003) and 2.3 (p = 0.003) times more likely to have asthma in the presence of allergic rhinitis and tree nuts-peanut allergy, respectively. Interestingly, children with atopic dermatitis were 0.5 (p = 0.005) times less likely to have asthma. Asthma (odds ratio [OR], 2.3; p = 0.002) and having multiple food allergies (OR, 5.4; p < 0.001) were significant risk factors for anaphylaxis. The phenotypes of IgE-mediated food allergy are highly heterogeneous and some clinical phenotypes may be associated with the specific type of food and the number of food allergies.

A multi-center survey of childhood asthma in Turke--I: the cost and its determinants.

Successful management of childhood asthma requires a thorough idea of the economic impact of asthma and its determinants, as policy makers and physicians inevitably influence the outcome. The aim of this study was to define the cost of childhood asthma in Turkey and its determinants. In April 2006, a multi-center, national study was performed where data regarding cost and control levels were collected. Asthmatic children (6-18 yr) with at least a 1-yr follow-up seen during a 1-month period with scheduled or unscheduled visits were included. The survey included a questionnaire-guided interview and retrospective evaluation of files. Cost and its determinants during the last year were analyzed. A total of 618 children from 12 asthma centers were surveyed. The total annual cost of childhood asthma was US$1597.4 +/- 236.2 and there was a significant variation in costs between study centers (p < 0.05). Frequent physician visits [odds ratio (95% confidence intervals)] [2.3 (1.6-3.4)], hospitalization [1.9 (1.1-3.3)], asthma severity [1.6 (1.1-2.8)], and school absenteeism due to asthma [1.5 (1.1-2.1)] were major predictors of total annual costs (p < 0.05 for each). The comparable cost of asthma among Turkish children with that reported in developed countries suggests that interventions to decrease the economic burden of pediatric asthma should focus on the cost-effectiveness of anti-allergic household measures and on improving the control levels of asthma.

Platelet aggregation, secretion, and coagulation changes in children with asthma.

The chronic inflammation in asthma evolves by cells including eosinophils, mast cells and lymphocytes. Despite their principal function in hemostasis, platelets contribute to pathogenesis of asthma that activation of platelets occurs following antigen provocation and during asthma attack. Our aim was to evaluate the platelet functions and other hemostatic features of children with asthma, both during symptom-free period and asthma attack. We enrolled patients with asthma attack (n = 33), mild intermittent asthma (n = 18), mild persistent asthma (n = 15) and healthy children (n = 20). Demographic characteristics and disease-related features were noted. Platelet aggregation and secretion tests (expressed as ATP release) were performed by lumiaggregometer method by stimulation with collagen, epinephrine, ADP, thrombin, ristocetin and arachidonic acid. Plasma levels of D-dimer, factor VIII (FVIII) and von Willebrand factor (vWF) were assessed. There were no differences in platelet aggregation induced by agonists between study groups. ATP release from platelets of patients with asthma exacerbation induced by ADP was lower compared with mild intermittent asthma (P < 0.001). Epinephrine-stimulated ATP secretion was also lower in patients with asthma attack than mild intermittent (P = 0.039) and mild persistent asthma (P = 0.011) and controls (P = 0.018). vWF measurements were higher in children with asthma attack than other study groups (P = 0.001). However, FVIII was increased in patients with severe asthma attack. Asthma is a disease in which many immune cells play a role, one of which is the platelet. Distinctions in platelet secretion profiles and plasma levels of vWF and FVIII provide evidence that coagulation mechanisms might be critical for asthma pathogenesis.

Mechanisms of subcutaneous allergen immunotherapy.

Allergen-specific immunotherapy (SIT) is the only curative approach in the treatment of allergic diseases defined up-to-date. Peripheral T-cell tolerance to allergens, the goal of successful allergen-SIT, is the primary mechanism in healthy immune responses to allergens. By repeated administration of increased doses of the causative allergen, allergen-SIT induces a state of immune tolerance to allergens through the constitution of T regulatory (Treg) cells, including allergen-specific interleukin (IL)-10-secreting Treg type 1 cells and CD4(+)CD25(+)Treg cells; induction of suppressive cytokines, such as IL-10 and transforming growth factor ß; suppression of allergen-specific IgE and induction of IgG4 and IgA; and suppression of mast cells, basophils, eosinophils, and inflammatory dendritic cells. This review summarizes the current knowledge on the mechanisms of allergen-SIT with emphasis on the roles of Treg cells in allergen-SIT.

Parental perspectives on influenza vaccination in children with asthma.

BACKGROUND: Influenza is an important cause of epidemic and pandemic disease leading to mortality and morbidity in children. Despite great efforts to increase influenza vaccination, many children with chronic medical conditions do not receive influenza vaccine. Our aim was to identify the demographic factors and asthma-associated characteristics related to vaccination, caregivers' attitudes and knowledge about influenza disease during the 2007-2008 influenza season. METHODS: Caregivers of children with asthma were surveyed via a self-administered questionnaire to document their knowledge about influenza disease and vaccine and factors influencing vaccination. RESULTS: We enrolled 311 children with asthma. The rate of lifetime influenza vaccination was 69.5%, whereas 51.8% of the patients had been vaccinated in the current season. There were no significant differences in demographic factors and asthma control parameters between the groups who received or did not receive influenza vaccine. Most of the parents whose children were vaccinated believed that influenza vaccination would decrease the prevalence and severity of asthma attacks (P < 0.05). The most important reason cited by parents for deciding on the influenza vaccine for their child was physician recommendation (80.1%). The major reasons for declining the vaccination were unawareness that the influenza vaccine was a requirement for their child (29.3%) and illness at the time of vaccination (20%). CONCLUSION: Physician recommendation is important in the influenza vaccination decision. Demographic factors and asthma control parameters had no influence on immunization uptake but parental beliefs and attitudes could be determinant. Greater effort is needed to increase influenza vaccination rates, in children with asthma.

The effect of CD14-c159T genotypes on the cytokine response to endotoxin by peripheral blood mononuclear cells from asthmatic children.

BACKGROUND: A C-T polymorphism at position 159 in the promoter of CD14 (C-159T) modulates the cellular response to endotoxin and significantly influences total IgE levels. The effect of this genetic variant on the cytokine response of the inflammatory cells is incompletely understood. OBJECTIVE: To investigate the effects of CD14-C159T genotypes on the response to endotoxin by peripheral blood mononuclear cells (PBMCs) in children with asthma. METHODS: The PBMCs from asthmatic children with the TT (n = 11) and CC (n = 11) genotypes at the CD14 promoter were cultured in the presence of endotoxin, 100 ng/mL; concanavalin A, 10 microg/mL; or medium alone. Concentrations of soluble CD14 (sCD14), interleukin (IL) 1beta, IL-4, IL-10, IL-12, IL-13, interferon-gamma, and transforming growth factor beta were determined in culture supernatants by enzyme-linked immunosorbent assay, and the transcriptional differences were evaluated using reverse-transcriptase polymerase chain reaction. RESULTS: Under unstimulated conditions, children with the TT genotype produced higher levels of sCD14 into the culture supernatant compared with children with the CC genotype (P = .03, Mann Whitney U test). Both IL-10 and IL-1beta concentrations were significantly higher in culture supernatants of children with the TT genotype after endotoxin stimulation (P = .02 and P = .009, respectively, by analysis of covariance [ANCOVA]). Messenger RNA expression was consistent with the results of protein concentration for IL-10 and sCD14. Concanavalin A stimulation resulted in lower levels of IL-4 in children with the TT genotype (P = .02, ANCOVA). CONCLUSION: The genotype at the CD14 promoter C159T locus may significantly influence the cytokine response of PBMCs obtained from asthmatic children. Differences in IL-10 and IL-4 production by alternative genotypes may contribute to the observed genotype effect on total IgE.

Oxidative stress and genetic and epidemiologic determinants of oxidant injury in childhood asthma.

BACKGROUND: The factors contributing to the oxidant/antioxidant imbalance in asthma are incompletely understood. OBJECTIVE: To determine the factors associated with oxidative stress including asthma severity and the genotype of the antioxidant enzymes. METHODS: A total of 196 children with mild asthma, 116 children with moderate-severe asthma, and 2 healthy control groups (187 and 68 children) were included in the study. Plasma levels of malondialdehyde were measured as the indicator of oxidative stress, and reduced glutathione levels as the indicator of antioxidant defense. Children were genotyped for null variants of glutathione S transferase (GST) T1 and GSTM1, and ile105val variant of GSTP1. Risk factors were analyzed with multivariate logistic regression. RESULTS: Systemic levels of malondialdehyde increased and reduced glutathione levels decreased significantly from healthy controls to patients with mild asthma and then to patients with moderate-severe asthma (P < .001 for each). Multivariate logistic regression identified asthma and asthma severity as independent factors associated with oxidative stress (odds ratio between 17 and 56; P < .001). Children with asthma with GSTP1 val/val genotype had higher malondialdehyde and lower glutathione levels compared with other genotypes (P = .023 and P = .014, respectively). GSTP1 val/val genotype was independently associated with asthma severity (odds ratio, 4.210; 95% CI, 1.581-11.214; P = .004). CONCLUSION: Our study indicates the presence of a strong oxidative stress in children with asthma that increases with the severity of the disease. In this population, val/val genotype at GSTP1 ile105val locus may be an important factor in determining the degree of oxidant injury. CLINICAL IMPLICATIONS: Children with asthma with val/val genotype at GSTP1 ile105val locus may be good candidates for supplemental antioxidant therapy.