Ahmet Ilgazli

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.

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.

Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD

Objective:  Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.

Effects of different anti-asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics

Objectives:  Inhaled corticosteroids, leukotriene receptor antagonists, and theophylline are recommended for the treatment of mild persistent asthma. The aim of this study was to compare the changes in sputum total cell and eosinophil counts, and eosinophil cationic protein (ECP) levels in serum and sputum following treatment with leukotriene receptor antagonists, inhaled corticosteroids, and theophylline in patients with mild persistent asthma.

Protective effects of N‐acetylcysteine on the peroxidative changes of rat lungs exposed to inhalation of thinners

Objective:  Long‐term inhalation of thinners may cause damage, both to the lungs and to other organ systems. It causes cellular damage via formation of reactive oxygen species. The lung is protected from oxidative stress by the glutathione (GSH) antioxidant system which can be augmented by the thiol drug, N‐acetylcysteine (NAC). This study investigated the protective effect of NAC on peroxidative changes in rat lungs exposed to inhalation of thinners for 8 weeks.

The Effects of Levofloxacin on Ecg Parameters and Late Potentials

In this study, our aim was to investigate the proarrhythmic effects of levofloxacin. Twenty-six patients who were diagnosed as having community-acquired pneumonia were enrolled in the study. Intravenous levofloxacin, 500 mg daily, was given, and 12-lead ECG measurements were obtained before the infusion, at 30 and 60 minutes during infusion, and 10 minutes after its cessation. Resting late potentials were recorded before and after infusion. Twelve female and 14 male patients were participated the study. Mean age was 51.3 ± 22.3 years. Levofloxacin infusion increased the heart rate (HR) and prolonged the corrected QT (QTc) intervals significantly (baseline HR: 84.6 ± 18.8 vs. HR at 60 minutes: 88.6 ± 18, P = 0.02; baseline QTc: 413.5 ± 36.9 milliseconds vs. QTc at 60 minutes: 426.1 ± 34.7, P = 0,006). There was no significant difference between the late potential values obtained before and after infusion. None of our patients experienced severe arrhythmia that required stopping the treatment. A single dose of IV levofloxacin prolongs the QTc interval without significant change in late potentials. Monitoring ECG during levofloxacin infusion might be necessary in patients who have a condition that could affect the QTc interval.

The Effects of Inhaled Steroid and Theophylline on Systemic Inflammation in Copd

Chronic obstructive pulmonary disease (COPD) is a systemic disease characterized by chronic, progressive airflow limitation and airway inflammation. In this study, our aim is to compare the effects of inhaled corticosteroids and theophylline on systemic inflammatory markers in COPD. Twenty-nine moderate to severe COPD patients were randomly separated into two groups. In Group 1, inhaled corticosteroids (fluticasone propionate, 1000 meg/day) were added to regular bronchodilator therapy for 8 weeks, and theophylline (400mg/day) was added in Group 2. Pulmonary function tests were performed and serum CRP, TNF-α, and IL-6 levels were measured before and after treatment. There was a statistically significant decrease in serum CRP levels in both groups following treatment (ICS group 1.06±1.2 vs 0.49±0.22 mg/dl p< 0.05; THEO group 1.66±2.23 vs 0.59±0.35 mg/dl p< 0.05). There was a significant reduction in serum TNF-α levels in the THEO group (3.82±3.44 vs 1.89±1.33 pg/ml p< 0.05). There was no significant change in IL-6 level following treatment in either group. There was a significant increase in FEV1 in the ICS group while a non-significant increase was noted in the THEO group following treatment. It has been suggested that both ICS and THEO could be used as an anti-inflammatory agent in the treatment of COPD. Furthermore, the measurement of serum inflammatory markers is an easy and non-invasive method for the determination and follow-up of systemic inflammation in COPD. Further studies including larger patient population are needed.

Effects of Different Combined Bronchodilator Therapies on Airway Inflammation in COPD

AbstractBackground: Chronic obstructive pulmonary disease (COPD) is characterised by chronic progressive airway obstruction and inflammation. Only a few studies have evaluated the effects of bronchodilator therapy on airway inflammation in patients with COPD. Objective: The aim of this study was to investigate the effects of different combinations of bronchodilator therapies on airway inflammation in COPD. Methods: Thirty patients with COPD and ten healthy nonsmoker subjects were included in the study. COPD patients were randomly classified into three groups. Groups 1, 2 and 3 were treated with ipratropium bromide plus formoterol (IP + FOR), theophylline plus ipratropium bromide (IP + THEO), and formoterol plus theophylline (FOR + THEO), respectively, for 12 weeks. Pulmonary function tests were performed, blood was drawn for arterial blood gas analyses, and sputum was induced before and after treatment. The induced sputum total and differential cell counts, serum and sputum inflammatory markers including interleukin (IL)-8, tumour necrosis factor (TNF)-α and leukotriene (LT)-B4 were measured. Results: When compared with the control group, total sputum cell counts, number of neutrophils, and sputum and serum inflammatory marker levels were significantly higher in COPD patients. Although there were no statistically significant differences among the groups, inflammatory parameters were found to be significantly reduced in all three treatment groups at the end of treatment. Total cell counts were: 2.4 ± 0.9 versus 1.28 ± 0.5 × 106 cells/g in the IP + FOR group (p < 0.05), 2.32 ± 0.4 versus 1.37 ± 0.6 × 106 cells/g in the IP + THEO group (p < 0.05), and 3.05 ± 1.3 versus 1.6 ± 0.8 × 106 cells/g in the FOR + THEO group (p < 0.05). Sputum IL-8 levels were: 1738.5 ± 292 versus 848 ± 262 ng/L in the IP + FOR group (p < 0.05), 1543.2 ± 378 versus 800.2 ± 224 ng/L in the IP + THEO group (p < 0.05), and 1561.2 ± 412 versus 815.7 ± 259 ng/L in the FOR + THEO group (p < 0.05). Conclusion: Different combinations of bronchodilator therapies caused significant changes in sputum and blood IL-8, TNF-α and LTB4 levels of COPD patients without significantly improving pulmonary function tests or arterial blood gas parameters.