Omer Kalayci

A comprehensive evaluation of the enzymatic and nonenzymatic antioxidant systems in childhood asthma

BACKGROUND Even though there is ample evidence on the oxidative stress in asthma, there is limited information on the antioxidant defense systems. OBJECTIVES To conduct a comprehensive evaluation of various components of both enzymatic and nonenzymatic antioxidants in a large group of children with asthma. METHODS A total of 164 children with mild asthma and 173 healthy children were included in the study. Levels of the enzymes glutathione peroxidase and superoxide dismutase were measured by using ELISA, whereas reduced glutathione, ascorbic acid, alpha-tocopherol, lycopene, beta-carotene, amino acids participating in glutathione synthesis, and amino acids susceptible to oxidation were measured by HPLC. All comparisons were adjusted for atopy, body mass index, smoke exposure, and pet ownership. RESULTS Levels of the enzymes glutathione peroxidase and superoxide dismutase and of the nonenzymatic components of the antioxidant system including reduced glutathione, ascorbic acid, alpha-tocopherol, lycopene, and beta-carotene were significantly lower in children with asthma compared with healthy controls (P < .001 for each). Of the amino acids contributing to glutathione synthesis, glycine and glutamine were significantly lower in children with asthma (P < .001). The majority of the amino acid susceptible to oxidative stress displayed lower levels in children with asthma (P < .05). CONCLUSION Childhood asthma is associated with significant decreases in various components of both enzymatic and nonenzymatic antioxidant defenses.

Oxidative Stress in Asthma

Asthma is a chronic inflammatory lung disease that results in airflow limitation, hyperreactivity, and airway remodeling. There is strong evidence that an imbalance between the reducing and oxidizing systems favoring a more oxidative state is present in asthma. Endogenous and exogenous reactive oxygen species, such as superoxide anion, hydroxyl radical, hypohalite radical, and hydrogen peroxide, and reactive nitrogen species, such as nitric oxide, peroxynitrite, and nitrite, play a major role in the airway inflammation and are determinants of asthma severity. Asthma is also associated with decreased antioxidant defenses, such as superoxide dismutase, catalase, and glutathione. In this review, we will summarize the current knowledge and discuss the current and future strategies for the modulation of oxidative stress in asthma.

Oxidative stress and its determinants in the airways of children with asthma

Background:  There is ample evidence for the existence of a systemic oxidative stress in childhood asthma but relatively little information on the oxidant stress in the airways.

The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom‐medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass‐specific IgG, IgG1 and IgG4 increased significantly already at the end of the seven‐injection build‐up therapy (p < 0.001, for all). Interleukin (IL)‐4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen‐induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper‐reactivity. Changes in specific IgE and IgG levels and decreased IL‐4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.

Evaluation of the utility of atopy patch testing, skin prick testing, and total and specific IgE assays in the diagnosis of cow's milk allergy

BACKGROUND Information on the utility of atopy patch testing (APT) in the diagnosis of food allergy is derived from studies of children with atopic dermatitis. OBJECTIVE To evaluate the usefulness of APT in the diagnosis of cows milk allergy (CMA) and to determine interleukin 4 and interferon-gamma production by peripheral blood mononuclear cells. METHODS Thirty-seven children (median age, 11 months) with suspected CMA who had a variety of symptoms that involved many organ systems were evaluated using double-blind placebo-controlled food challenges (DBPCFCs), and the performances of milk specific IgE, skin prick testing (SPT), and APT were determined. To search for a possible relationship between the diagnostic tests and the TH1/TH2 immune response, we measured interferon-gamma and interleukin 4 levels in the supernatants of peripheral blood mononuclear cell cultures. RESULTS Seventeen children with positive DBPCFC results and 6 with a history of anaphylaxis were diagnosed as having CMA. The combined use of APT and SPT had a sensitivity of 100% and a negative predictive value of 100% but a specificity of 50% and a positive predictive value of 76%. The addition of milk specific IgE assays to APT and SPT did not improve these values. Pattern of cytokine secretion was not associated with APT positivity or a specific response to DBPCFC. CONCLUSIONS Atopy patch testing may be a useful adjunct to SPT in excluding CMA in children who have allergic manifestations other than atopic dermatitis. However, DBPCFCs are still necessary in the presence of positive test results.

Cow's milk allergy as a global challenge

Purpose of reviewCows milk is a leading cause of food allergy especially in infants and children. ‘Diagnosis and Rationale for Action against Cows Milk Allergy’ published by the World Allergy Organization has underlined that there is not enough information concerning geographical trends in cows milk allergy (CMA) in children or adults. Experts from Australia, Asia, North America, Latin America, the Middle East and Europe have gathered together in a 2-day meeting in order to present various regional approaches to CMA. This report is a summary of the information that was presented at this meeting. Recent findingsEven though there seems to be uniformity concerning the diagnosis and treatment of CMA, the diagnostic approach to CMA shows variations among different regions. Common concerns were inadequate applications of challenge tests for the diagnosis and inadequate supply of the cows milk substitute formulas. SummaryCMA is a global challenge and collaboration of the national and international scientific communities is essential to produce and update practical guidelines for CMA.

Challenges in identifying asthma subgroups using unsupervised statistical learning techniques.

RATIONALE Unsupervised statistical learning techniques, such as exploratory factor analysis (EFA) and hierarchical clustering (HC), have been used to identify asthma phenotypes, with partly consistent results. Some of the inconsistency is caused by the variable selection and demographic and clinical differences among study populations. OBJECTIVES To investigate the effects of the choice of statistical method and different preparations of data on the clustering results; and to relate these to disease severity. METHODS Several variants of EFA and HC were applied and compared using various sets of variables and different encodings and transformations within a dataset of 383 children with asthma. Variables included lung function, inflammatory and allergy markers, family history, environmental exposures, and medications. Clusters and original variables were related to asthma severity (logistic regression and Bayesian network analysis). MEASUREMENTS AND MAIN RESULTS EFA identified five components (eigenvalues ≥ 1) explaining 35% of the overall variance. Variations of the HC (as linkage-distance functions) did not affect the cluster inference; however, using different variable encodings and transformations did. The derived clusters predicted asthma severity less than the original variables. Prognostic factors of severity were medication usage, current symptoms, lung function, paternal asthma, body mass index, and age of asthma onset. Bayesian networks indicated conditional dependence among variables. CONCLUSIONS The use of different unsupervised statistical learning methods and different variable sets and encodings can lead to multiple and inconsistent subgroupings of asthma, not necessarily correlated with severity. The search for asthma phenotypes needs more careful selection of markers, consistent across different study populations, and more cautious interpretation of results from unsupervised learning.

The prevalence of self-reported asthma and respiratory symptoms in Ankara, Turkey.

The prevalence of self-reported asthma was studied in a group of Turkish adults using the European Community Respiratory Health Survey (ECRHS) questionnaire distributed during 1994 local elections in Ankara, Turkey. A total of 2020 questionnaires were issued and 1820(90%) were returned. The mean age of the subjects was 34.5 +/- 10.2 years. The prevalence of wheezing at any time in the past was 39.1% which is much higher than has been reported in the literature. However, only 21.7% of the study population had wheezing in the year preceding the survey and 2.9% of them had severe asthma attacks. The prevlaences of nocturnal wheeze, nocturnal cough and morning tightness were higher in females (P = 0.05 for each). The results of this study showed a high rate of reported symptoms but a low rate of diagnosis and treatment of asthma among the adult population in Ankara.

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.

Increased Interleukin-4 and Decreased Interferon Gamma Production in Children with Asthma: Function of Atopy or Asthma?

Both atopy and asthma are claimed to be associated with a Th-2 cytokine pattern. We sought to determine the contribution of atopy and asthma to the observed Th-2/Th-1 imbalance in these conditions. Of 60 children aged 6–16 years that were included in the study, 13 were nonatopic nonasthmatic, 15 atopic nonasthmatic, 14 nonatopic asthmatic, and 18 atopic asthmatic. Atopic children had positive skin prick tests to grass pollens only. All children were studied after an asymptomatic and drug-free period of at least three months. Total IgE was measured in serum. Peripheral blood mononuclear cells were cultured and stimulated in vitro with phytohemagglutinin and interferongamma (IFN-γ) and interleukin-4 (IL-4) measured in the supernatants. Total IgE was significantly higher in atopic asthmatics compared to nonatopic asthmatics (p = 0.004), and nonatopic nonasthmatics (p = 0.001), but was not different from atopic nonasthmatics (p > 0.05). On the other hand, IL-4 was significantly elevated in atopic asthmatics and in nonatopic asthmatics compared to nonatopic nonasthmatics (p = 0.037 and p = 0.009, respectively). Although atopic asthmatics had lower IFN-γ values than nonatopic asthmatics, the difference did not reach statistical significance. No correlation was detected between any two parameters. Our results suggest that both atopy and asthma contribute to the increased levels of IL-4 and that, whereas nonatopic asthma is associated with increases in both IL-4 and IFN-γ release by mononuclear cells, only atopic asthma is characterized by a Th-2 type cytokine dominance.