Fusun Yildiz

The Effect of Clarithromycin on Inflammatory Markers in Chronic Obstructive Pulmonary Disease: Preliminary Data

BACKGROUND: Clarithromycin is an antimicrobial agent that can be used for treatment of chronic obstructive pulmonary disease (COPD) exacerbations with bronchodilator therapy. However, it has also been shown that clarithromycin has antiinflammatory effects by the inhibition of cytokine production. OBJECTIVE: To evaluate the antiinflammatory effect of clarithromycin on serum and sputum interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and leukotriene B4 levels in patients with COPD. METHODS: Thirty men with mild to moderate COPD were enrolled in this prospective, single-center, double-blind, placebo-controlled study. None of the patients was receiving systemic or inhaled corticosteroids during the study. Subjects received either clarithromycin or placebo for 14 days. Before and after this treatment period, spirometric tests and arterial blood gas analysis were performed, blood was drawn for measurement of serum inflammatory markers, and sputum was induced. RESULTS: There were no statistically significant differences in baseline clinical or laboratory parameters between the groups. After the treatment, the induced sputum total cell counts, and IL-8 and TNF-α levels decreased significantly in the clarithromycin group compared with pretreatment levels (mean ± SD IL-8 1606 ± 367.3 vs 882 ± 143.6 pg/mL, p = 0.001; TNF-α 638.2 ± 287.5 vs 390 ± 235 pg/mL, p = 0.001). Similarly, decreases in serum inflammatory markers were found in the clarithromycin group while there was no significant change in the placebo group. CONCLUSIONS: This study demonstrated that the decrease in IL-8 and TNF-α levels might be related to the antiinflammatory effect of clarithromycin. Thus, we suggest that the use of clarithromycin in COPD exacerbations may either treat the infection or help control the inflammation. Future studies are needed to determine the clinical significance of these findings.

Inhaled Corticosteroids May Reduce Neutrophilic Inflammation in Patients with Stable Chronic Obstructive Pulmonary Disease

Background: Although both inhaled and oral corticosteroids have anti-inflammatory effects causing improvement in clinical symptoms and spirometry in the treatment of asthma, the role of corticosteroids in the management of chronic obstructive pulmonary disease (COPD) is controversial. Objective: To evaluate the effects of inhaled corticosteroids on sputum neutrophilia in clinically stable COPD patients. Methods: In total, 18 patients were enrolled in the study. During 2 months, 9 patients in group A inhaled fluticasone propionate (FP) 500 μg 3 times daily. In group B 9 patients received placebo. All of the patients continued to inhale both salbutamol and ipratropium bromide. In 9 patients, sustained-released theophylline was also administered. Blood samples, spirometric tests, blood gas analyses, and either spontaneous or induced sputum cultures were evaluated on entry into the study, after a 2 months of treatment and following the 6-week washout period. Results: After the 2-month FP treatment, no significant changes in the number of peripheral blood neutrophils, blood gas and spirometry data were observed in both groups. In group A, the total cell number and the number of neutrophils decreased from a mean of 3.4 ± 1.3 × 106 cells/g and 0.6 ± 0.3 × 106 neutrophils/g on entry into study to 1.9 ± 0.6 × 106 cells/g and 0.02 ± 0.01 × 106 neutrophils/g after 8-week treatment with FP, returning to 3.3 ± 1.1 × 106 cells/g and 0.5 ± 0.3 × 106 neutrophils/g following the washout period. The percentages of neutrophils were 55.6 and 77.9% in groups A and B after 2 months of FP treatment. There was no significant change in group B values during the study. Conclusion: These data suggest that neutrophilic inflammation in sputum may be decreased by inhaled corticosteroids in clinically stable COPD patients.

Prevalence and risk factors of allergies in Turkey: Results of a multicentric cross-sectional study in children

The Prevalence And Risk Factors of Allergies in Turkey (PARFAIT) study was planned to evaluate prevalence and risk factors of asthma and allergic diseases and also to find out which geographical variables and/or climatic conditions play a role determining the prevalence of allergic diseases in Turkish school children. Study was planned as cross‐sectional questionnaire‐based. About 25,843 questionnaires from 14 centers were appropriate for analysis. Parental history of allergy, having an atopic sibling and other atopic disease in index case was significant risk factors for all allergic diseases. Breast feeding decreased the risk of current asthma (OR: 0.92, CI: 0.86–0.99) and wheezing (OR: 0.93, CI: 0.87–0.99) but not allergic rhinitis and eczema. Respiratory infection in the past was an important risk factor for the occurrence of allergic diseases especially for asthma which was increased 4.53‐fold. Children exposed to household smoke were significantly at higher risk of asthma, wheezing, and allergic rhinitis (OR: 1.20, CI: 1.08–1.33; OR: 1.21, CI: 1.09–1.34; and OR: 1.32, CI: 1.21–1.43, respectively). All allergic diseases were increased in those children living in areas which have altitude of below 1000 m and mean yearly atmospheric pressure above 1000 mb. The study has suggested that household and country‐specific environmental factors are associated with asthma, wheezing, allergic rhinitis, and eczema risk during childhood in Turkey.

Effects of erdosteine on bleomycin-induced lung fibrosis in rats

This study was designed to examine the effects of erdosteine on bleomycin (BLM)-induced lung fibrosis in rats. Thirty-three Sprague–Dawley rats were divided randomly into three groups, bleomycin alone (BLM), bleomycin + erdosteine (BLM + ERD), and saline alone (control). The BLM and BLM + ERD groups, were given 2.5 mg/kg BLM intratracheally. The first dose of oral erdosteine (10 mg/kg/day) in the BLM + ERD group was started 2 days before BLM administration and continued until animals were sacrificed. Animals were sacrificed 14 days after intratracheal instillation of BLM. The effect of erdosteine on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and biochemical measurements of lung tissue superoxide dismutase (SOD) and glutathione (GSH) as antioxidants, malondialdehyde (MDA) as an index for lipid peroxidation, and nitrite/nitrate levels. Bleomycin-induced lung fibrosis as determined by lung histology was prevented with erdosteine (grades of fibrosis were 4.9, 2.3, and 0.2 in BLM, BLM + ERD, and control groups, respectively). Erdosteine also prevented bleomycin-induced increase in MDA (MDA levels were 0.50 ± 0.15, 0.11 ± 0.02, and 0.087± 0.03 nmol/mg protein in BLM, BLM + ERD, and control groups, respectively) and nitrite/nitrate (nitrite/nitrate levels were 0.92 ± 0.06, 0.60 ± 0.09, and 0.56± 0.1 μmol/mg protein in BLM, BLM + ERD, and control groups respectively) levels. Bleomycin-induced decrease in GSH and SOD levels in the lung tissue also prevented by erdosteine [(GSH levels were 213.5 ± 12.4, 253.2± 25.2, and 287.9± 34.4 nmol/mg protein) (SOD levels were 1.42± 0.12, 1.75± 0.17, and 1.89± 0.09 U/mg protein) in BLM, BLM + ERD, and control groups respectively]. Erdosteine prevented bleomycin-induced increases in total cell number and neutrophil content of the BAL fluid. In conclusion, oral erdosteine is effective in prevention of BLM-induced lung fibrosis in rats possibly via the repression of neutrophil accumulation, inhibition of lipid peroxidation, and maintenance of antioxidant and free radical scavenger properties.

Prevalence and Risk Factors of Allergies in Turkey (PARFAIT): results of a multicentre cross-sectional study in adults

The Prevalence and Risk Factors of Allergies in Turkey (PARFAIT) study was planned to evaluate the prevalence of and risk factors for asthma and allergic diseases in Turkey. The present analysis used data from 25,843 parents of primary school children, obtained from a cross-sectional questionnaire-based study. A total of 25,843 questionnaires from 14 centres were evaluated. In rural areas, the prevalences asthma, wheezing, allergic rhinitis and eczema in males were: 8.5% (95% confidence interval (CI) 7.9–9.1%), 13.5% (95% CI 12.8–14.2%), 17.5% (95% CI 16.7–18.2%) and 10.8% (95% CI 10.2–11.4%), respectively; and in females were: 11.2% (95% CI 10.9–11.8%), 14.7% (95% CI 14.3–15.1%), 21.2% (95% CI 20.4–22.0%) and 13.1% (95% CI 12.4–13.8%), respectively. In urban areas, the corresponding prevalences in males were: 6.2% (95% CI 5.8–6.6%), 10.8% (95% CI 10.3–11.3%), 11.7% (95% CI 11.4–12.0%) and 6.6% (95% CI 6.2–7.0%), respectively; and in females were: 7.5 % (95% CI 7.9–7.1%), 12.0% (95% CI 11.7–12.3%), 17.0% (95% CI 16.4–17.6%) and 7.3% (95% CI 6.9–7.7%), respectively. Having an atopic first-degree relative or any other atopic diseases had significant effects on the prevalence of allergic diseases. Housing conditions, such as living in a shanty-type house, visible moulds at home and use of wood or biomass as heating or cooking material were associated with one or more allergic diseases. Although genetic susceptibility is strongly associated, country- and population-based environmental factors may contribute to increased prevalence rates of allergic diseases.

The effects of antioxidants on exercise‐induced lipid peroxidation in patients with COPD

Objective:  The oxidant–antioxidant balance plays an important role in the pathogenesis of COPD. The aim of the present study was to evaluate the effects of exercise, as an oxidative stress factor on the oxidant–antioxidant balance and to investigate whether short‐term antioxidant treatment affects lipid peroxidation products.

Inhaled corticosteroid effects both eosinophilic and non-eosinophilic inflammation in asthmatic patients.

AIM: To determine induced sputum cell counts and interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and leukotriene B4 (LTB4) levels as markers of neutrophilic inflammation in moderate persistent asthma, and to evaluate the response to inhaled steroid therapy. METHODS: Forty-five moderate asthmatic patients and 10 non-smoker controls were included in this study. All patients received inhaled corticosteroid (800 microg of budesonide) for 12 weeks. Before and after treatment pulmonary function tests were performed, and symptom scores were determined. Blood was drawn for analysis of serum inflammatory markers, and sputum was induced. RESULTS: Induced sputum cell counts and inflammatory markers were significantly higher in patients with asthma than in the control group. The induced sputum eosinophil counts of 12 patients (26%) were found to be less than 5%, the non-eosinophilic group, and sputum neutrophil counts, IL-8 and TNF-alpha levels were significantly higher than the eosinophilic group (neutrophil, 50+/-14% versus 19+/-10%, p<0.01). In both groups, there was a significant decrease in sputum total cell counts and serum and sputum IL-8, TNF-alpha and LTB4 levels after the treatment. There was no change in sputum neutrophil counts. Although the sputum eosinophil count decreased only in the eosinophilic subjects, there was no significant difference in inflammatory markers between the groups. The symptom scores were significantly improved after treatment, while the improvement did not reach statistical significance on pulmonary function test parameters. CONCLUSION: Notably, in chronic asthma there is a subgroup of patients whose predominant inflammatory cells are not eosinophils. Sputum neutrophil counts and neutrophilic inflammatory markers are significantly higher in these patients. In the non-eosinophilic group, inhaled steroid caused an important decrease in inflammatory markers; however, there was no change in the sputum eosinophil and neutrophil counts.

Importance of Inhaler Device Use Status in the Control of Asthma in Adults: The Asthma Inhaler Treatment Study

BACKGROUND: Proper education and training in correct inhalation technique has been reported to have a substantial role in the achievement of optimal therapeutic benefit and asthma control. The present study was designed to evaluate inhaler technique and the role of education in relation to asthma control among patients with persistent asthma in Turkey. METHODS: A total of 572 patients with persistent asthma (mean ± SD age 42.7 ± 12.2 y, 76% females) were included in this non-interventional, observational, registry study conducted across Turkey. Data on the effective and correct use of inhaler devices were collected via the Ease of Use for the Inhaler Device Questionnaire to patients and physicians. RESULTS: Asthma control (overall 61.5% at baseline, and increased to 87.3% during follow-up) was better, with significant improvement in technique and decrease in basic errors to the range 0–1, regardless of the inhaler type. Overall, the most common basic error associated with inhalation maneuvers was failure to exhale before inhaling through the device (18.9%). There was concordance between the patients and physicians in the ratio of correct inhaler technique only for spray-type inhalers. CONCLUSIONS: Close follow-up with repeated checking of the patients inhaler technique and correction of errors each time by a physician seem to be associated with a significant decrease in the percent of patients who make basic errors in inhalation maneuvers and device-independent errors, and with better control of persistent asthma.

Effects of Erdosteine on Smoking-Induced Lipid Peroxidation in Healthy Smokers

AbstractAim: Oxidative stress caused by smoking has been implicated in many pulmonary diseases. Smoking causes reductions in plasma nitrate plus nitrite (NOx) concentrations and increases in plasma malondialdehyde (MDA) concentrations, which indicate oxidative stress and lipid peroxidation, respectively. In this study, we investigated the acute effects of smoking a single cigarette on the plasma concentrations of NOx and thiobarbituric acid reactive substances (TBARS) including MDA, and whether administration of erdosteine, a mucolytic and antioxidant agent, affects these parameters. Methods: Thirty healthy smokers were included in the study. Subjects smoked a single cigarette in 10 minutes on the study day. For analysis of NOx, TBARS and cotinine, blood was drawn from each subject before and 5 and 30 minutes after smoking. The subjects were then randomly divided into two groups, one receiving placebo and the other erdosteine suspension 175mg/5mL twice daily for 1 month. After this treatment period, the same study protocol was carried out. Two subjects in the placebo and five subjects in the study group were excluded because of noncompliance. Results: Twenty-three (14 female, 9 male) subjects completed the study. Their mean age was 32 ± 8 years and their smoking history was 14 ± 9 pack-years. Baseline NOx, TBARS and cotinine concentrations were similar between the groups. NOx concentrations decreased significantly after smoke exposure. At the end of the treatment period there were no significant differences in NOx, TBARS or cotinine concentrations between the groups. The concentration of TBARS after smoking decreased significantly in the erdosteine-treated group (at 5 minutes: 2.8 ± 0.5 μmol/L before treatment and 2.3 ± 0.3 μmol/L after treatment, p < 0.05; at 30 minutes: 2.8 ± 0.5 μmol/L before treatment and 1.8 ± 0.7 μmol/L after treatment, p < 0.05). Smoking history was significantly correlated with cotinine concentrations. Conclusion: Acute smoke exposure decreased plasma NOx concentrations in healthy smokers, and this was not changed with erdosteine treatment. However, significant decreases were noted in TBARS concentrations after smoke exposure in the group that received erdosteine, suggesting that short-term erdosteine administration might help prevent smoking-induced lipid peroxidation.

Protective effects of N-acetylcysteine on peroxidative changes of the fetal rat lungs whose mothers were exposed to cigarette smoke:

Background: This experimental study investigated the protective effects of N-acetylcysteine (NAC) on peroxidative changes in fetal lungs in the offspring of rats exposed to cigarette smoke. Methods: Thirty fetal rats used for analysis, were divided into three groups as follows: control group (n = 10), whose mothers were exposed to fresh air; group I (n=10), whose mothers were exposed to cigarette smoke; and group II (n=10), whose mothers were exposed to cigarette smoke and given 10 mg/kg per day NAC. In groups I and II, smoke exposure was started 4 weeks before the pregnancy, and continued to the 14th day of pregnancy, and in Group II, NAC was administered intraperitoneally for 14 days. The mothers and their fetuses were decapitated on the 14th day of pregnancy. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the lung tissues of fetuses to determine the oxidant-antioxidant balance. Results: While tissue MDA levels in Group I were found significantly higher than the control group (129.7±65.4 versus 63.4±15.4 nmol/100 mg protein, P <0.05), GSH levels were significantly lower (17.1±7.3 versus 45.4±8.1 nmol/mg protein, P <0.01). Furthermore, in Group II, MDA levels were significantly lower (56.9± 20.6 versus 129.7±65.4 nmol/100 mg protein, P <0.05), and GSH levels were significantly higher (34.57±10.7 versus 17.1±7.3 nmol/mg protein, P <0.0001) when compared with Group I. No statistically significant difference was found in tissue MDA and GSH levels between Group II and the control group (P >0.05). Conclusions: These results suggest that smoke exposure during pregnancy causes oxidative damage in fetal lungs. This smoke-induced damage might be prevented by NAC. Human & Experimental Toxicology (2007) 26, 99-103