Ahmet Akkaya

Apoptosis and Loss of Adhesion of Bronchial Epithelial Cells in Asthma

Background: Asthma is an inflammatory airway disease associated with infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (EC). We have recently shown that T cells and eosinophils cooperate in inducing bronchial EC apoptosis in asthma through secretion of IFN-γ and TNF-α. Since EC shedding is a histologic hallmark of asthma, the intercellular junction of EC may be a target of pro-inflammatory cytokines. Methods: Bronchial EC, cultured and exposed to IFN-γ and TNF-α, were studied for the expression of adhesion molecules and apoptosis. In addition, the epithelial layer of bronchial biopsies from asthma patients was evaluated for apoptosis, shedding, and expression of adhesion molecules. Results: We demonstrate that the induction of EC apoptosis is accompanied by loss of E-cadherin. In situ examination of E-cadherin in asthma revealed a reduction in its expression on EC membranes. In contrast, the in vitro and in vivo expression of β1-integrins and intercellular adhesion molecule-1 (ICAM-1) increased on EC during asthmatic airway inflammation. Conclusions: Loss of cadherin-mediated intercellular adhesion and apoptosis could account for fragility and shedding of EC in asthma, especially since this occurs between columnar and basal EC.

Mean platelet volume is increased in patients with severe obstructive sleep apnea

Abstract Increased platelet activation and aggregation which are closely related to cardiovascular complications have been reported in patients with obstructive sleep apnea (OSA). The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation in patients with OSA. The 95 subjects referred for evaluation of OSA underwent overnight polysomnography. Blood samples were taken for MPV determination. According to the apnea-hypopnea index (AHI), subjects were divided into three groups; group 1: control subjects without OSA (AHI < 5, n = 24), group 2: patients with mild to moderate OSA (AHI: 5–30, n = 42), and group 3: severe OSA (AHI > 30, n = 29). Body mass index (BMI) of patients with severe OSA was significantly higher than control subjects (31.5 ± 4.0 vs. 28.2 ± 5.0; p = 0.02). The MPV was significantly higher in patients with severe OSA than in the control group (8.9 ± 1.0 vs. 8.2 ± 0.7 fl; p = 0.01). Correlation analysis within 71 patients with OSA indicated that MPV was correlated with AHI (p < 0.001, r = 0.44) and DI (p = 0.001, r = 0.37). In multivariate regression analysis, when MPV was taken as independent with other study variables which are potential confounders such as age, gender and BMI, MPV was independently correlated with both AHI (β = 0.44, p < 0.001) and DI (β = 0.38, p < 0.001). We have shown that MPV was significantly higher in patients with severe OSA when compared with control subjects and MPV was correlated with AHI and DI.

Antioxidant enzymes and melatonin levels in patients with bronchial asthma and chronic obstructive pulmonary disease during stable and exacerbation periods.

An imbalance between oxidative stress and antioxidative capacity may play an important role in the development and progression of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). We carried out a study to assess the systemic oxidant–antioxidant status during the exacerbation and the stable period in patients with BA and COPD. A total of 33 patients, 16 with BA and 17 with COPD were included in the study. During the exacerbation and the stable periods, levels of malondialdehyde (MDA), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), glutathione reductase (GRd), and catalase (CAT) in erythrocytes and serum melatonin concentrations were investigated. Blood counts, respiratory functions, and blood gases of the patients were also performed. During an exacerbation period of BA, despite the decreases in GSH‐Px, GRd and melatonin levels, MDA and CAT levels, and the white blood cell count, the percentage of eosinophils were significantly higher than in the stable period. Also, it was found that FEV1/L (where FEV1 is the forced expiratory volume in 1 s), FVC/L (where FVC is forced vital capacity), PEF/L/s (where PEF is peak expiratory flow), pO2 (where pO2 is oxygen pressure) levels increased during the stable period in patients with BA. MDA and SOD values were higher in the exacerbation period than in the stable period although GSH‐Px, GRd, melatonin, pH, and pO2 values were lower in the exacerbation period than in the stable period. The blood counts and the respiratory function tests did not change between the exacerbation and the stable period of patients with COPD significantly. In conclusion, we observed that oxidative stress in the exacerbation period of patients with BA and COPD increased whereas the antioxidant enzymes and melatonin values reduced. The episodes of BA or COPD might be associated with elevated levels of oxidative stress. Copyright

Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects

BACKGROUND Increased airway smooth muscle (ASM) mass is an essential component of airway remodeling and asthma development, and there is no medication specifically against it. Tight junction (TJ) proteins, which are expressed in endothelial and epithelial cells and affect tissue integrity, might exist in other types of cells and display additional functions in the asthmatic lung. OBJECTIVE The aim of this study was to investigate the existence, regulation, and function of TJ proteins in ASM in asthmatic patients. METHODS The expression and function of TJ proteins in primary ASM cell lines, human bronchial biopsy specimens, and a murine model of asthma were analyzed by means of RT-PCR, multispectral imaging flow cytometry, immunohistochemistry, Western blotting, 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester staining, tritiated thymidine incorporation, wound-healing assay, and luminometric bead array. RESULTS Increased claudin-1 expression was observed in ASM of asthmatic patients, as well as in a murine model of asthma-like airway inflammation. Whereas IL-1β and TNF-α upregulated claudin-1 expression, it was downregulated by the T(H)2 cytokines IL-4 and IL-13 in primary human ASM cells. Claudin-1 was localized to the nucleus and cytoplasm but not to the cell surface in ASM cells. Claudin-1 played a central role in ASM cell proliferation, as demonstrated by increased ASM cell proliferation seen with overexpression and decreased proliferation seen with small interfering RNA knockdown of claudin-1. Overexpression of claudin-1 induced vascular endothelial growth factor and downregulated IL-6, IL-8, and IFN-γ-induced protein 10 production by ASM cells. Claudin-1 upregulation by IL-1β or TNF-α was suppressed by dexamethasone but not by rapamycin, FK506, or salbutamol. CONCLUSION These results demonstrate that claudin-1 might play a role in airway remodeling in asthmatic patients by means of regulation of ASM cell proliferation, angiogenesis, and inflammation.

Habitual Snoring in Primary School Children: Prevalence and Association with Sleep-Related Disorders and School Performance

Objectives: To determine the prevalence of habitual snoring (HS) and its association with both day- and nighttime symptoms, school performance and behavioral disturbances in a sample of primary school children. Subjects and Methods: A cross-sectional study was performed on 1,605 children (819 boys and 786 girls) aged 7–13 years from 9 randomly selected primary schools located within the city limits of Isparta, Turkey. HS and sleep problems were assessed using a 55-item multiple-choice questionnaire. Results: Of the 1,605 questionnaires, 1,164 were fully completed and returned, giving a response rate of 72.5%. The overall prevalence of snoring was 38.9%, while HS accounted for 3.5%. The prevalence of HS among boys (25, 3.0%) was higher than among girls (16, 2.0%; χ2 for trend: p < 0.001, OR: 1.92, 95% CI: 1.01–3.66). There was an association between younger age and HS, as children aged 7–8 years had the highest prevalence (χ2 for trend: 0.054, OR: 1.85, 95% CI: 0.81–4.22). Habitual snorers had more daytime and nighttime symptoms. Allergic symptoms, daytime mouth breathing, shaking the child for apnea, restless sleep and hyperactivity were significant and independent risk factors and sleep-related symptoms for HS. A significant and independent association was found between poor school performance and hyperactivity, nocturnal enuresis, tooth grinding and low parental/maternal education in multivariate analysis. Conclusion: Children with HS were more likely to have sleep-related daytime and nighttime symptoms. No significant associ- ation was determined between HS and poor school performance.

T cells and eosinophils in bronchial smooth muscle cell death in asthma

Background Bronchial smooth muscle cells (SMC) proliferate, express adhesion molecules, secrete cytokines and thus efficiently contribute to the pathogenesis of asthma.

The effects of continuous positive airway pressure therapy on mean platelet volume in patients with obstructive sleep apnea

Previous studies have reported increased platelet activation and aggregation in patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) treatment has been shown to decrease platelet activation. We aimed to study the effects of nasal CPAP therapy has on MPV values in patients with severe OSA. Thirty-one patients (21 men; mean age 53.8 ± 9.2 years) with severe OSA (AHI > 30 events/hour) constituted the study group. An age, gender and body mass index (BMI) matched control group was composed 25 subjects (14 men; mean age 49.6 ± 8.5 years) without OSA (AHI < 5 events/hour). We measured MPV values in patients with severe OSA and control subjects and we measured MPV values after 6 months of CPAP therapy in severe OS patients. The median (IQR) MPV values were significantly higher in patients with severe OSA than in control group (8.5 [8.3–9.1] vs. 8.3 [7.5–8.8] fL; p = 0.03). The platelet counts were significantly lower in patients with severe OSA than in control group (217.8 ± 45.9 vs. 265.4 ± 64.0 × 109/L; p = 0.002). The six months of CPAP therapy caused significant reductions in median (IQR) MPV values in patients with severe OSA (8.5 [8.3–9.1] to 7.9 [7.4–8.2] fL; p < 0.001). Six months of CPAP therapy caused significant increase in platelet counts when compared with baseline values (217.8 ± 45.9 to 233.7 ± 60.6 × 109/L; p < 0.001). We have found that the MPV values of patients with severe OSA were significantly higher than those of the control subjects and 6 months CPAP therapy caused significant reductions in the MPV values in patients with severe OSA.

C-Reactive Protein Levels in Patients with Chronic Obstructive Pulmonary Disease: Role of Infection

Objective: To investigate the value of C-reactive protein (CRP) as a marker of chronic obstructive pulmonary disease (COPD) exacerbations or specifically bacterial exacerbations and to evaluate a correlation between raised CRP levels and other markers of inflammation in patients with an acute exacerbation (AECOPD). Subjects and Methods: The medical records of patients with AECOPD were retrospectively analyzed. They were categorized according to the nature of sputum as mucoid or purulent and to the findings on chest radiographs as with pneumonia (PCOPD) or without pneumonia. Stable COPD (SCOPD) patients and a group of asymptomatic nonsmokers were also included in the study. Results: All COPD patients (SCOPD: 30; AECOPD: 51; PCOPD: 32) and control subjects (30) were male. The mean CRP levels and WBC counts of the groups were PCOPD: 108.1 ± 61.8 mg/l and 13.7 ± 6.8 × 109/l; AECOPD: 36.8 ± 43.9 mg/l and 11.4 ± 4.8 × 109/l; SCOPD: 3.9 ± 1.4 mg/l and 7.9 ± 1.9 × 109/l; control: 2.1 ± 0.9 mg/l and 7.7 ± 1.1 × 109/l. The mean CRP level of AECOPD was statistically different from those of PCOPD and SCOPD (p = 0.0001, p = 0.002, respectively). The sensitivity and specificity of CRP to determine an acute exacerbation were 72.5 and 100%, respectively. Among the patients with AECOPD, 25 had purulent sputum and a mean CRP level of 46.4 ± 48.6 mg/l, which is significantly higher than the CRP level (28.0 ± 44.5 mg/l) of the 18 patients with mucoid expectoration (p = 0.015). Among the mucoid-expectorating subgroup, the patients with leukocytosis had significantly higher CRP levels than the patients without leukocytosis (p = 0.034). Conclusion: A high serum CRP value may indicate an infectious exacerbation in COPD patients and it correlates with sputum purulence and increased serum WBC counts.

POLLEN CALENDAR OF ISPARTA, TURKEY

Pollen grains were identified using a Durham sampler in the atmosphere of Is parta during 1995 and 1996. During two years, a total of 15,660 pollen grains belonging to41 taxa, as well as unidentified pollen grains, were recorded. In 1995, 7357 pollen grains were identified and in 1996, 8303. Total pollen grains were 71% arboreal,25% non-arboreal plants, and 4% unidentified. In the region investigated, Pinus L., Cupressaceae, Gramineae, Platanus L., Quercus L., Artemisia L., Chenopodiaceae/Amaranthaceae, and Urticaceae were responsible for the greatest amounts of pollen. The pollen concentration reached its highest level in May.

The attitude toward tobacco dependence and barriers to discussing smoking cessation: a survey among Turkish general practitioners

ObjectivesTo evaluate the general attitude of a sample of Turkish general practitioners (GPs) toward tobacco dependence and to assess their knowledge and behavior regarding smoking cessation (SC).MethodsA self-administered questionnaire modified from WHO, Global Health Professional Survey was distributed to GPs, working in our district, Isparta.ResultsAs much as 41% of GPs were current smokers. Ever smokers were generally less likely to agree with statements that would change their freedom to smoke in certain places. While 46% of GPs frequently inquired about tobacco use in their patients, 13.5% did not advise any of their patients to quit smoking during the month preceding the questionnaire. The most common barriers reported by GPs to discussing SC with their patients were as follows: considering the discussion not to be effective (57.8%), having low confidence in knowledge (48.1%), having unpleasant personal experience or considering it a thankless task (46.1%).ConclusionsIt appears essential to reduce the number of GPs who smoke and to improve GP training on SC procedures for integrating SC treatment into primary care in Turkey.