MicroRNA Levels in Exhaled Breath Condensate of Patients with Esophageal Atresia.

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

Omalizumab treatment in adolescents with chronic spontaneous urticaria: Efficacy and safety

BACKGROUND: Omalizumab is useful as an add-on treatment in patients unresponsive to high doses of second-generation antihistamines. This study aimed to evaluate the efficacy and safety of omalizumab treatment in adolescents with refractory chronic spontaneous urticaria (CSU). METHODS: CSU patients aged 12-18 years old with the diagnosis of symptomatic CSU and unresponsive to classical treatment were included in the study. All patients had an urticaria-activity-score (UAS7) of ≥ 16 or and were treated with 300 mg omalizumab every four weeks. The degree of response was classified into complete, partial and non-responders due to UAS7. RESULTS: A total of 29 patients were evaluated. The median age and symptom onset age of the patients was 15.2 (IQR, 12.8-16.5) years and 14.0 (IQR, 11.8-15.9) years, respectively. The median duration of urticaria was eight (IQR, 4-24) months at admission. Eleven (37.9%) patients had angioedema and ten (34.5%) patients had concomitant allergic diseases. The median age at the beginning of treatment with omalizumab was 15.4 (IQR, 12.9-16.9) years. The median symptom duration was 12 (IQR, 6.5-27.5) months before the omalizumab treatment. Twenty-eight (96.5%) of the patients (89.6% complete, 6.9% partial) achieved response; however, one patient was a non-responder (3.5%). The adverse effect was observed in one (3.4%) patient as angioedema after the third dose. Twenty-three patients were followed up for a median of 18 (IQR, 13-27) months. Relapse was observed in three (13%) patients. CONCLUSIONS: Omalizumab is considered as an effective and safe treatment for CSU in adolescents. Relapses mostly occur within the first year after the cessation of treatment

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Omalizumab treatment in adolescents with chronic spontaneous urticaria: Efficacy and safety.

BACKGROUND: Omalizumab is useful as an add-on treatment in patients unresponsive to high doses of second-generation antihistamines. This study aimed to evaluate the efficacy and safety of omalizumab treatment in adolescents with refractory chronic spontaneous urticaria (CSU). METHODS: CSU patients aged 12-18 years old with the diagnosis of symptomatic CSU and unresponsive to classical treatment were included in the study. All patients had an urticaria-activity-score (UAS7) of ≥16 or and were treated with 300mg omalizumab every four weeks. The degree of response was classified into complete, partial and non-responders due to UAS7. RESULTS: A total of 29 patients were evaluated. The median age and symptom onset age of the patients was 15.2 (IQR, 12.8-16.5) years and 14.0 (IQR, 11.8-15.9) years, respectively. The median duration of urticaria was eight (IQR, 4-24) months at admission. Eleven (37.9%) patients had angioedema and ten (34.5%) patients had concomitant allergic diseases. The median age at the beginning of treatment with omalizumab was 15.4 (IQR, 12.9-16.9) years. The median symptom duration was 12 (IQR, 6.5-27.5) months before the omalizumab treatment. Twenty-eight (96.5%) of the patients (89.6% complete, 6.9% partial) achieved response; however, one patient was a non-responder (3.5%). The adverse effect was observed in one (3.4%) patient as angioedema after the third dose. Twenty-three patients were followed up for a median of 18 (IQR, 13-27) months. Relapse was observed in three (13%) patients. CONCLUSIONS: Omalizumab is considered as an effective and safe treatment for CSU in adolescents. Relapses mostly occur within the first year after the cessation of treatment.

Physicians prescribe adrenaline autoinjectors, do parents use them when needed?

Background: Anaphylaxis is a sudden, severe, and potentially life-threatening allergic reaction, affecting a portion of allergic patients. Adrenaline is the first-line medication for anaphylaxis and available in many parts of the world as adrenaline autoinjectors (AAIs). Objective: Aim of this study was to determine attitudes and knowledge levels of patients/parents regarding the use of AAIs, frequency, and rate of appropriate AAI use and to give a standardized and better education by improving on mistakes during administration. Method: 190 patients aged 1-18 years who were prescribed AAIs for any reason between 2012 and 2017 in Hacettepe University Pediatric Allergy Unit. Demographic data were collected during face-to-face interview or by telephone. Parents completed a mini-survey regarding use, carriage, and storage of AAI. Results: Some 190 patients (64.7% male) aged 7.83 (4.99-12.08) years, median (inter-quartile), were included in the study. The indications for AAI prescription were food allergy (78.9%); venom allergy (14.2%); idiopathic anaphylaxis (3.7%); mastocytosis (2.1%); and drug allergy (1.0%). One-fourth of AAI-prescribed patients experienced anaphylaxis requiring the use of AAI within the past five years. However, only 30% of the patients dared to use AAI; only three-quarters of whom had managed to use it correctly. Conclusion: After prescription of AAI and initial training, patients and parents' concerns and fears should be taken into consideration and necessary support should be provided. At every opportunity and each clinical visit, not only should training sessions be repeated but also the patients and parents should be psychologically supported

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Physicians prescribe adrenaline autoinjectors, do parents use them when needed?

BACKGROUND: Anaphylaxis is a sudden, severe, and potentially life-threatening allergic reaction, affecting a portion of allergic patients. Adrenaline is the first-line medication for anaphylaxis and available in many parts of the world as adrenaline autoinjectors (AAIs). OBJECTIVE: Aim of this study was to determine attitudes and knowledge levels of patients/parents regarding the use of AAIs, frequency, and rate of appropriate AAI use and to give a standardized and better education by improving on mistakes during administration. METHOD: 190 patients aged 1-18 years who were prescribed AAIs for any reason between 2012 and 2017 in Hacettepe University Pediatric Allergy Unit. Demographic data were collected during face-to-face interview or by telephone. Parents completed a mini-survey regarding use, carriage, and storage of AAI. RESULTS: Some 190 patients (64.7% male) aged 7.83 (4.99-12.08) years, median (inter-quartile), were included in the study. The indications for AAI prescription were food allergy (78.9%); venom allergy (14.2%); idiopathic anaphylaxis (3.7%); mastocytosis (2.1%); and drug allergy (1.0%). One-fourth of AAI-prescribed patients experienced anaphylaxis requiring the use of AAI within the past five years. However, only 30% of the patients dared to use AAI; only three-quarters of whom had managed to use it correctly. CONCLUSION: After prescription of AAI and initial training, patients and parents' concerns and fears should be taken into consideration and necessary support should be provided. At every opportunity and each clinical visit, not only should training sessions be repeated but also the patients and parents should be psychologically supported.

Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism?

Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis.

Steroid-refractory inflammatory bowel disease is a risk factor for CMV infection.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) show increased the prevalence of cytomegalovirus (CMV) infection due to the severity of the disease and the immunosuppressive treatments they receive. The aim of this study was to determine the prevalence of CMV infection in IBD patients and identify the risk factors for CMV infection with different demographic characteristics in IBD patients. PATIENTS AND METHODS: We enrolled 85 patients diagnosed with IBD (43 with ulcerative colitis (UC) and 42 with Crohn's disease (CD)) in this prospective study. The clinical disease activities of UC and CD were assessed using Truelove-Witts and Crohn's disease activity index (CDAI). CMV infection was assessed by detection of DNA using real-time polymerase chain reaction (PCR) in blood samples and quantitative PCR in colonic biopsy specimens and by detection of inclusion bodies using hematoxylin-eosin staining. RESULTS: Thirteen patients with IBD exhibited concomitant CMV infection. CMV infection was not detected in any of the patients in remission. Viral loads measured in the colonic mucosa of infected patients ranged from 800-7000 genome copies/mL total extracted DNA. The mean serum CMV DNA level was 1694 ± 910 copies/mL (range: 800-3800). The rate of steroid resistance in CMV-positive cases was significantly higher than that in CMV-negative cases (p = 0.001). CD with acute exacerbation was a risk factor for CMV disease (p = 0.04). All of the CMV-positive patients received immunosuppressive treatments. CONCLUSIONS: CMV infection should be suspected in steroid-resistant UC and CD. Antiviral treatment improved the clinical outcome in steroid-resistant IBD cases with serum CMV DNA levels above 1000 copies/mL.

Effect of cytochrome P450 2C19 polymorphisms on the Helicobacter pylori eradication rate following two-week triple therapy with pantoprazole or rabeprazole.

OBJECTIVE: Cytochrome P450 2C19 (CYP2C19) polymorphisms play an important role in the metabolism of proton pump inhibitors. Rabeprazole is primarily metabolized via non-enzymatic pathways. In this study, we determined whether rabeprazole- and pantoprazole-based eradication treatments were influenced by CYP2C19 polymorphisms. PATIENTS AND METHODS: A total of 200 patients infected with Helicobacter pylori were treated with either 40 mg of pantoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin, 1000 mg of amoxicillin twice daily for 2 weeks. CYP2C19 genotype status was determined by Polymerase Chain Reaction (PCR)-restriction-fragment-length polymorphism. The genotypes of cytochrome P450 2C19 were classified as homozigote extensive metabolizer (HomEM), heterozigote metabolizer (HetEM) and poor metabolizer (PM). The CYP2C19 genotype of all patients, the effectiveness of the treatment, the effect of the genotypic polymorphism on the treatment were assessed. RESULTS: The frequencies of HotEM, HetEM, PM were 78%, 19.5% and 2.5%, respectively. 48% (n = 96) of the patients received treatment with rabeprazole and 52% (n = 104) with pantoprazole. The eradication rate was 64.7% for HomEM, 79.4% for HetEM, 100% for PM (p = 0.06). In HetEM, PM, are considered as a single group, the eradication rates were higher in patients with the HetEM and PM (HetEM+PM) genotypes than in those with the wild-type genotype (81.8 vs. 64.7% p = 0.031). Among the patients treated with rabeprazole, the eradication rates were significantly lower in those with the HomEM genotype than in those with the HetEM+PM genotypes (60% vs. 85.7% p = 0.023). CONCLUSIONS: The genotypic polymorphism is effective on the rate of eradication. Eradication treatment rate with rabeprazole is influenced by CYP2C19 genotype.

Low indoleamine 2,3-dioxygenase activity in persistent food allergy in children.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in food allergy has not yet been elucidated. METHODS: Serum Trp and Kyn concentrations were analyzed by high-pressure liquid chromatography. Expression of IDO gene was measured by real-time PCR. The levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ in cell culture supernatants were measured by ELISA. RESULTS: Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged-matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones [LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 µM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04] (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food-allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL-4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL-10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN-γ synthesis, when stimulated with IL-2 and ß-lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively). CONCLUSION: Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization.

Actual drug allergy during childhood: Five years’ experience at a tertiary referral centre

BACKGROUND: Drug hypersensitivity reactions (DHR) are common in the paediatric population, representing a public health problem. Recent studies have confirmed that the frequency of drug allergy is overestimated by both parents and physicians. The aim of this study is to determine the prevalence and risk factors of actual drug allergies in children admitted to a tertiary referral allergy centre. METHODS: Medical records covering the period of 2005-2010 of children with a history of DHR were reviewed. Demographic features of the patients and results of skin and drug provocation tests were noted. The European Network for Drug Allergy (ENDA) questionnaire was filled by using medical records and making phone calls with parents. RESULTS: Ninety-six patients with 140 DHRs were evaluated. Seventeen children had confirmed drug allergy by positive skin tests (n = 11) and drug provocation tests (n = 5). One patient underwent severe anaphylaxis and subsequent cardiac arrest during infusion of the drug, and therefore diagnostic tests were not performed. Actual drug allergy was more frequent in children with chronic diseases (58.8% vs. 26.5%,p = 0.018) and histories of anaphylaxis during DHR (58.8% vs. 24%, p = 0.001). The patients' history of anaphylaxis [OR: 5.789, 95%CI: 1.880-17.554, p = 0.002], sweating [OR: 7.8, 95%CI: 1.041-58.443,p = 0.046] and dyspnoea [OR: 5.230, 95%CI: 1.836-14.894, p = 0.002] during suspicious DHRs increased the risk for actual drug allergy. CONCLUSION: Actual drug allergy was determined in 17.7% of the patients with a suspicious DHR. Having a history of anaphylaxis during suspected drug reactions as well as symptoms of sweating and dyspnoea increased the risk for actual drug allergy

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Actual drug allergy during childhood: Five years' experience at a tertiary referral centre.

BACKGROUND: Drug hypersensitivity reactions (DHR) are common in the paediatric population, representing a public health problem. Recent studies have confirmed that the frequency of drug allergy is overestimated by both parents and physicians. The aim of this study is to determine the prevalence and risk factors of actual drug allergies in children admitted to a tertiary referral allergy centre. METHODS: Medical records covering the period of 2005-2010 of children with a history of DHR were reviewed. Demographic features of the patients and results of skin and drug provocation tests were noted. The European Network for Drug Allergy (ENDA) questionnaire was filled by using medical records and making phone calls with parents. RESULTS: Ninety-six patients with 140 DHRs were evaluated. Seventeen children had confirmed drug allergy by positive skin tests (n=11) and drug provocation tests (n=5). One patient underwent severe anaphylaxis and subsequent cardiac arrest during infusion of the drug, and therefore diagnostic tests were not performed. Actual drug allergy was more frequent in children with chronic diseases (58.8% vs. 26.5%, p=0.018) and histories of anaphylaxis during DHR (58.8% vs. 24%, p=0.001). The patients' history of anaphylaxis [OR: 5.789, 95%CI: 1.880-17.554, p=0.002], sweating [OR: 7.8, 95%CI: 1.041-58.443, p=0.046] and dyspnoea [OR: 5.230, 95%CI: 1.836-14.894, p=0.002] during suspicious DHRs increased the risk for actual drug allergy. CONCLUSION: Actual drug allergy was determined in 17.7% of the patients with a suspicious DHR. Having a history of anaphylaxis during suspected drug reactions as well as symptoms of sweating and dyspnoea increased the risk for actual drug allergy.

Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine.

BACKGROUND: Allergen-specific immunotherapy (SIT) faces problems related to side effects and limited efficacy. Direct administration of allergen extracts into lymph nodes induces increased specific IgG production and T-cell responses using significantly lower allergen doses. METHODS: In this study, mechanisms of immune regulation by MAT vaccines in vitro and in allergen-SIT of cat-allergic rhinitis patients, who received 3 inguinal intra-lymph node injections of MAT-Fel d 1 vaccine, were investigated in PBMC and cell cultures for specific T-cell proliferation, Fel d 1-tetramer-specific responses, and multiple immune regulatory molecules. RESULTS: MAT-Fel d 1 vaccine was efficiently internalized by antigen-presenting cells. This was followed by precaspase 1 cleavage to caspase 1 and secretion of IL-1ß, indicating inflammasome activation. Mat-Fel d 1 induced specific T-cell proliferation and an IL-10- and IFN-γ-dominated T-cell responses with decreased Th2 cytokines at 100 times lower doses than Fel d 1. Induction of immune tolerance by MAT-Fel d 1-ILIT involved multiple mechanisms of immune suppression. Early Fel d 1-specific T-cell activation was followed by full T-cell unresponsiveness to allergen after 1 year in the MAT-Fel d 1 group, characterized by increased allergen-specific T regulatory cells, decreased circulating Fel d 1 tetramer-positive cells, increased IL-10 and FOXP3 expression, and change in the HR2/HR1 ratio toward HR2. CONCLUSIONS: This study demonstrates the induction of allergen tolerance after 3 intra-lymph node injections of MAT-Fel d 1 vaccine, mediated by increased cellular internalization of the allergen, activation of inflammasome, and generation of allergen-specific peripheral T-cell tolerance.

Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C.

Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon-based therapy. We aimed to investigate long-term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty-three patients had TF, and 62 patients were treatment-naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥ 2 stage increase in fibrosis during follow-up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma-glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01-1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81-19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon-based CHC treatment may lead to accelerated FPR in the long-term compared with the natural course.

Suppression of B-cell activation and IgE, IgA, IgG1 and IgG4 production by mammalian telomeric oligonucleotides.

BACKGROUND: The fine balance of immunoglobulins (Ig) E, IgG1, IgG4 and IgA in healthy production is maintained by the interaction of B cells with adaptive and innate immune response. The regulation of toll-like receptors (TLRs)-driven innate and adaptive immune effector B-cell response and the role of mammalian telomeric TTAGGG repeat elements represent an important research area. METHODS: Human PBMC and purified naive and memory B cells were stimulated with specific ligands for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9 in the presence or absence of telomeric oligonucleotides. B-cell proliferation, differentiation and antibody production were determined. RESULTS: TLR9 ligand directly activates naive and memory B cells, whereas TLR7 can stimulate them in the presence of plasmacytoid dendritic cells. Human B cells proliferate and turn into antibody-secreting cells in response to TLR3, TLR7 and TLR9, but not to TLR2, TLR4, TLR5 and TLR8 ligands. Stimulation of B cells with intracellular TLR3, TLR7 and TLR9 induced an activation cascade leading to memory B-cell generation and particularly IgG1, but also IgA, IgG4 and very low levels of IgE production. Mammalian telomeric oligodeoxynucleotide (ODN) significantly inhibited all features of TLR ligand-induced events in B cells including B-cell proliferation, IgE, IgG1, IgG4, IgA production, class switch recombination, plasma cell differentiation induced by TLR3, TLR7 and TLR9 ligands. CONCLUSION: B cells require specific TLR stimulation, T-cell and plasmacytoid dendritic cell help for distinct activation and Ig production profiles. Host-derived telomeric ODN suppress B-cell activation and antibody production demonstrating a natural mechanism for the control of overexuberant B-cell activation, antibody production and generation of memory.

Importance of serum basal tryptase levels in children with insect venom allergy.

BACKGROUND: The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). METHODS: Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. RESULTS: A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 µg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 µg/l (2.5-4.0)] and healthy control subjects [2.9 µg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 µg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. CONCLUSIONS: Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy.

Mechanisms of peripheral tolerance to allergens.

The immune system is regulated to protect the host from exaggerated stimulatory signals establishing a state of tolerance in healthy individuals. The disequilibrium in immune regulatory vs effector mechanisms results in allergic or autoimmune disorders in genetically predisposed subjects under certain environmental conditions. As demonstrated in allergen-specific immunotherapy and in the healthy immune response to high-dose allergen exposure models in humans, T regulatory cells are essential in the suppression of Th2-mediated inflammation, maintenance of immune tolerance, induction of the two suppressive cytokines interleukin-10 and transforming growth factor-ß, inhibition of allergen-specific IgE, and enhancement of IgG4 and IgA. Also, suppression of dendritic cells, mast cells, and eosinophils contributes to the construction of peripheral tolerance to allergens. This review focuses on mechanisms of peripheral tolerance to allergens with special emphasis on recent developments in the area of immune regulation.

The reliability and validity of Turkish version of Childhood Asthma Control Test.

INTRODUCTION: The reliability and validity of Turkish version of Childhood Asthma Control Test (C-ACT). PURPOSE: The management of asthma is an important as well as difficult issue of physician's daily practice particularly in busy clinical settings. C-ACT was created to identify asthma control levels in children aged 4-11 years. Our aim was to evaluate the reliability, validity and responsiveness of C-ACT in a Turkish sample of children with asthma. METHOD: In this multicenter study, 368 children were enrolled. C-ACT was completed every month by parents and patients who were evaluated in 3 visits within 2 month intervals. At each visit, physicians interpret the control level and decided for the treatment step as established in GINA guidelines. RESULTS: The internal consistency reliability of the Turkish version of C-ACT (C-ACT1 to C-ACT5) was found to be 0.82, 0.83, 0.82, 0.82 and 0.80, respectively (reliability statistics, Cronbach's alpha). Test-retest reliability was 0.71. There was significant correlation between C-ACT and physician's assessment of asthma control at visit 1 (r = 0.65, P < 0.001). CONCLUSIONS: Turkish version of C-ACT is an accurate and reliable tool to evaluate asthma control in children aged 4-11 years. Its widespread use may facilitate appropriate assessment of asthma control and may lead to decrease the number of uncontrolled patients.

The effect of CD14 C159T polymorphism on in vitro IgE synthesis and cytokine production by PBMC from children with asthma.

BACKGROUND: Even though the genotype at the promoter region of the CD14 molecule is known to affect the atopic phenotypes, the cellular and molecular basis of this association is largely unknown. OBJECTIVE: To investigate the effect of lipopolysaccharide (LPS) on IgE production and cytokine profile by peripheral blood mononuclear cells (PBMC) obtained from asthmatic children with the TT and the CC genotypes at position -159 of the CD14 gene. METHODS: Peripheral blood mononuclear cells from asthmatic children with alternative genotypes at CD14 C159T locus were stimulated with 2 and 200 ng/ml LPS in vitro. The IgE, IgG and, IgM response was determined by ELISA and Ig έ-germline, IgG, and IgM transcription by real-time PCR. A cluster of cytokines was measured by cytometric bead array. RESULTS: Asthmatic children with the TT genotype but not those with the CC genotype responded with increased IgE synthesis and germline transcription to LPS stimulation. There were no genotype-related differences in IgG and IgM. TT but not the CC genotype was associated with significantly increased interleukin (IL)-4/IL-12 and IL-4/interferon-gamma (IFN-γ) ratios in the culture supernatant. There were no genotype-related differences in IL-1ß, IL-7, IL-10, IL-13, IL-17A, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein, and tumor necrosis factor alpha. CONCLUSION: Peripheral blood mononuclear cells from asthmatic children with the TT genotype at position -159 of the CD14 gene make more IgE than those with the CC genotype following LPS stimulation because of increased germline transcription and have an augmented Th2 cytokine profile.