Glutathione and nitrite levels in induced sputum at COPD patients and healthy smokers.

OBJECTIVES: The role of oxidative stress at the pathogenesis of chronic obstructive pulmonary disease (COPD) is known. The aim of this study is to investigate the oxidative stress with sputum induction that is a simple method in COPD patients and healthy smokers. METHODS: Sputum induction was performed in 21 COPD patients (10 stable, 11 acute exacerbations), nine healthy smokers, and ten healthy non-smokers. Glutathione, NO2 (-) levels, and cell counts at sputum, and plasma NO2 (-) contents were evaluated in all subjects. RESULTS: Mean sputum glutathione and NO2 (-) levels were significantly higher in acute exacerbations with COPD patients than healthy smokers (P=0.007 and P<0.001 respectively), and non-smokers (P<0.001 and P<0.001 respectively). On the other hand, sputum glutathione and NO2 (-) levels did not show significant differences between stable and acute exacerbations with COPD patients. Although, sputum glutathione levels were higher in stable COPD patients than healthy smokers', no statistically significant difference was established. In addition, sputum glutathione levels were significantly higher in healthy smokers than non-smokers (P<0.001). CONCLUSIONS: As a result, we can say that oxidative stress increases not only in COPD patients but also in healthy smokers. In addition, sputum induction that is a simple method can be used to demonstrate to show oxidative stress.

The prevalence of chronic obstructive pulmonary disease in Elazig, Eastern Turkey.

BACKGROUND: To investigate the prevalence of Chronic Obstructive Pulmonary Disease (COPD) in the urban and rural areas of the Elazig Region of Turkey. METHODS: A questionnaire was conducted and spirometric measurements were made, based on the BOLD protocol. A total of 1270 individuals, over 18 years of age, were included in the study, comprising 610 individuals from the city center and 660 from the rural area. The questionnaire included demographics, symptoms and possible risk factors. The description and staging of COPD were in accordance with GOLD (Global Initiative for Chronic Obstructive Lung Disease). RESULTS: Of the 1270 cases, 1206 (94.9%) were able to complete the questionnaire and undergo spirometric analysis. Of these 1206 cases, 1188 (98.5%) were used in the final assessment; the remainder were excluded due to errors in the spirometric analysis. Of the cases included in the study, 43.2% (25.9% female; 56.7% male) were current smokers. The prevalence of COPD at ≥ 18 years old was 4.5% (female 2.5%; male 6%); the prevalence at ≥ 45 years old was 11.5% (female 5.9%; male 15.1%). The majority of the COPD cases were at stages I and II (22.6% and 66%, respectively). The prevalence of COPD was higher among current and former smokers (5.8%) than non-smokers (2.8%). In general, the risk factors for COPD were found to be age, male gender, smoking, living in a rural area, and low income. CONCLUSIONS: The prevalence of COPD in Elazig, Turkey was highest among the elderly and smokers, and constituted primarily stages I and II of the disease.

Evaluation of the anti-inflammatory effect of infliximab in a mouse model of acute asthma.

BACKGROUND AND OBJECTIVE: To evaluate the potential role of anti-tumour necrosis factor (TNF)-alpha mAb (infliximab) on the inflammatory response in a mouse model of acute asthma. METHODS: BALB/c mice received intraperitoneal (i.p.) ovalbumin (OVA) on days 0 and 14, 100 microg of OVA intranasally on day 14 and 50 microg of OVA intranasally on days 25, 26 and 27. The low-dose (2.5 mg/kg) and high-dose (6.25 mg/kg) infliximab groups received i.p. infliximab before each i.p. sensitization and on challenge days 1, 6, 13, 20 and 27. The control group received i.p. injections of normal saline with alum on days 0 and 14 and normal saline without alum on days 14, 25, 26 and 27. RESULTS: There were statistically significant decreases in the numbers of BAL fluid (BALF) neutrophils, eosinophils, as well as lung eosinophils in both the low- and high-dose infliximab groups when compared with the control OVA sensitized/challenged group. The lower dose of infliximab did not alter lung neutrophil counts, but a marked decrease was seen with the high dose of infliximab. After treatment with low and high doses of infliximab, BALF levels of regulated on activation normal T cell expressed and secreted (RANTES), granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, IL-6, macrophage inflammatory protein (MIP)-2, and levels of RANTES, IL-4, GM-CSF, TNF-alpha, IL-6 and MIP-2 in lung tissue were significantly decreased when compared with the control OVA sensitized/challenged group. There was a significant decrease in BALF IL-4 only in the high-dose infliximab group. CONCLUSIONS: These results show that an anti-TNF-alpha mAb has a considerable anti-inflammatory effect on allergen-induced lung inflammation in an animal model of acute asthma.

Lymphocyte subpopulations in pulmonary tuberculosis patients.

Protection against Mycobacterium tuberculosis is based on cell-mediated immunity, most importantly involving CD4(+) and CD8(+) T-cell subsets. The aim of this study was to evaluate CD4(+) and CD8(+) T-cell profiles and CD19(+) and CD3(+)CD(16 + 56)(+) populations in patients with pulmonary tuberculosis. CD4(+) and CD8(+) T cells, B-lymphocytes, and natural killer (NK) cells were evaluated in 75 active (APTB) and 25 inactive (IPTB) pulmonary tuberculosis cases and 20 healthy subjects (HCs). The results were compared at different stages of antituberculosis treatment in the APTB patients and also according to X-ray findings in the newly diagnosed APTB patients. The percentages of CD4(+) T cells were significantly lower (P < .01) and those of CD3(+)CD(16+56)(+) cells were significantly higher (P < .01) in APTB patients than in HCs. CD8(+) T cells were significantly decreased (P < .05), and CD3(-)CD(16+56)(+) cells were significantly increased (P < .01), in IPTB patients compared to HCs. The percentages of CD4(+), CD8(+), CD3(-)CD19(+), and CD3(-)CD(16+56)(+) cells showed no differences at different times of the antituberculosis regimen, and different stages of newly diagnosed APTB patients. APTB patients have a reduced percentage of circulating CD4(+) T cells and an increased percentage of NK cells compared with healthy individuals. These cells could play important roles in the immune response to M tuberculosis infection.

Serum interleukin-2 and neopterin levels as useful markers for treatment of active pulmonary tuberculosis.

Macrophages and T cells are responsible for the main immune response to tuberculosis by secreting many cytokines and other substances. The aim of this study was to determine the effects of multidrug treatment on serum levels of interleukin-2 (IL-2), secreted by activated T cells, and of neopterin, secreted by macrophages and monocytes, in patients with pulmonary tuberculosis. The study included 30 patients with active pulmonary tuberculosis, confirmed by the detection of acid-fast bacilli in direct sputum smears and/or sputum cultures. The serum levels of IL-2 and neopterin were measured before and during the treatment and compared with 15 patients with inactive pulmonary tuberculosis and 15 healthy controls. Serum IL-2 and neopterin levels were higher in patients with active tuberculosis (164.53 +/- 58.91 pg/ml and 69.54 +/- 29.42 nmol/l, respectively) than those in inactive tuberculosis (95.43 +/- 31.17 pg/ml and 10.71 +/- 1.78 nmol/l) or controls (79.20 +/- 14.81 pg/ml and 9.50 +/- 2.27 nmol/l) (p < 0.001 for each parameter). No significant differences were found in IL-2 and neopterin levels between inactive tuberculosis and control subjects. The IL-2 levels remained elevated in active tuberculosis at 2nd month of treatment (p < 0.001) and decreased to the control levels after 4th month. Neopterin levels were significantly higher in active tuberculosis than those in inactive tuberculosis or controls at the 2nd and 4th months of treatment. These findings indicate that measurements of serum IL-2 and neopterin levels are useful in following up the treatment and immune response to tuberculosis.

The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model.

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC(4), D(4) and E(4)) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

Changes in serum cytokine levels in active tuberculosis with treatment.

It has been reported that IFN-gamma, TNF-alpha, and IL-12 stimulate, and that IL-10, TGF-beta, and IL-4 suppress the protective immune response against tuberculosis. We aim to evaluate changes in the serum levels of pro and antiinflammatory cytokines in active pulmonary tuberculosis (APTB) and the possible effects of treatment on these changes. Serum IL-12p40, IL-4, IL-10, TNF-alpha, IFN-gamma, and TGF-beta1 levels were determined in 20 APTB cases (group 1) before and 2, 4, and 6 months after therapy. The same parameters were also determined in 9 inactive pulmonary tuberculosis (IPTB) cases (group 2) and 9 healthy controls (HC, group 3). Before treatment, the mean serum IFN-gamma, TNF-alpha, and IL-10 levels in group 1 were statistically higher than those in group 2 (P=.001, P=.024, P=.016, resp) or group 3 (P=.003, P=.002, P=.011, resp). The levels in group 1 decreased significantly after treatment (P=.001 for IFN-gamma, P=.004 for TNF-alpha, P=.000 for IL-10). The serum levels of IL-12p40 were significantly higher in group 1 than in group 3 (P=.012) and decreased insignificantly after treatment. There was no difference in serum IL-4 and TGF-beta1 levels among the groups (P>.05). Because the serum IL-12p40, IL-10, TNF-alpha, and IFN-gamma levels were high in APTB, we believe that these cytokines have important roles in the immune response to Mycobacterium tuberculosis (M tuberculosis). These parameters could be used in follow-up as indicators of the success of APTB therapy.

[Investigating the anti-inflammatory effect of dexamethasone in an asthma mouse model]. / Astim fare modelinde deksametazonun antiinflamatuvar etkisinin arastirilmasi.

We performed an asthma mice model in this study and aimed to investigate the levels of mediators in bronchoalveolar lavage fluid (BALF), and lung tissue, and the pathological changes response to the steroid treatment. BALB/c mice divided into three groups. PBS was applied to group 1 (control group). Asthma model was performed by exposing to ovalbumin in group 2 and 3. DEX was injected to group 3. After the last DEX dose all of the mice were killed by cervical dislocation. The samples of BALF and lung tissue were obtained. IL-4 and IL-5 levels of all samples were measured and inflammatory cells were counted in BALF. Evident eosinophilia was determined in BALF of group 2. Eosinophil numbers were lower in group 3 when compared with group 2 and this was statistically significant (p< 0.001). Inflammatory cell infiltration, eodema and hyperemia observed around the walls of bronchus and bronchiols in group 2. The lungs of group 3 had normal histological appearance. Both two cytokin levels of lung tissue were higher in group 2 than group 1, and this was statistically significant (for IL-4 p< 0.003, and for IL-5 p< 0.002). In group 3, both two cytokin levels were statistically lower than group 2 (for IL-4 p< 0.001, and for IL-5 p< 0.026). In BALF samples both two cytokin levels were higher in group 2 than group 1, and this was statistically significant (for IL-4 p< 0.004, and for IL-5 p< 0.001). In group 3, both two cytokin levels were lower than group 2, but it was not statistically significant (p> 0.05). In conclusion, it is thought that antiinflammatory effect of glucocorticoids occur by inhibiting the formation of IL-4, IL-5 and eosinophils.

[Nutritional status, pulmonary functions, and exercise performance in COPD cases]. / KOAH olgularinda beslenme durumu, solunum fonksiyonlari ve egzersiz performansi.

The aim of this study was evaluation of nutritional status in attack and stable chronic obstructive pulmonary disease (COPD) cases, and investigating the relation between nutrition parameters and pulmonary functions, exercise performance and general healthy status. Anthropometric measures of 10 cases with attack (group 1), 14 stabilized COPD cases (group 2) and 10 control cases (group 3) were evaluated by measuring serum albumin, transferrin, tumor necrosis factor-alpha (TNF-alpha) levels, and fat-free mass (FFM) levels. Six minutes walking test (mwt) and SGRQ questionnaire were performed. Body mass index (BMI) of group 1 and 2 were significantly lower than group 3 (p= 0.023, p= 0.008, respectively). Albumin levels were significantly lower in group 1 than group 2 (p< 0.001) and 3 (p= 0.001). Levels of transferrin were significantly lower in group 1 compared with group 3 (p= 0.015). TNF-alpha levels were significantly high in group 1 compared with group 2 (p= 0.002), and high in group 2 compared with group 3 (p= 0.001). FFM was significantly low in group 1 compared with group 2 (p= 0.003), and low in group 2 compared with group 3 (p< 0.001). Mean distance of 6 mwt was 225.80 +/- 40.35 m in group 1, it was 405.16 +/- 95.51 m in group 2 (p< 0.001). A positive relation was seen between FFM and BMI, 6 mwt (p= 0.006, r= 0.481 ve p< 0.001, r= 0.830, respectively), between albumin levels and 6 mwt (p< 0.001, r= 0.850). A negative correlation was observed between TNF-alpha and 6 mwt (p< 0.001, r= -0.745). There was no statistical difference in antropometric measures between groups. Total score and daily life were statistically high in group 1 than group 2 (p= 0.009, p= 0.013). Although no changes was seen in antropometric measures of COPD cases, a nutritional defect was seen and a significant relation was observed between nutrition parameters and effort capacity.

[The prevalence of occupational asthma in auto and furniture dye workers in downtown Elazig]. / Elazig merkezinde oto ve mobilya atölyelerinde çalisan boya isçilerinde mesleki astim sikligi.

Occupational asthma (OA) is characterized by reversible airway obstruction and/or bronchial hyperresponsiveness occurred after exposition to dust, vapor, gas or smoke which are present in the workplace. We aimed to determine the frequency of OA in auto and furniture dye workers in our city center. One-hundred-forty-two workers in Elazig Central Industrial Centre (86 auto, 56 furniture dyes) were included in the study. The workers were questioned with "Turkish Thorax Association Occupational and Environmental Pulmonary Diseases Evaluation Form", and physical examination and pulmonary function tests (PFT) were performed. Follow of peak expiratory flow rate (PEFR) and reversibility tests were performed to patients who had complaints or abnormality in PFT. The workers who had reversibility and positive daily PEFR variability were taken away from work and PEFR variables were followed. The workers had no symptoms when they were taken away from work and daily PEFR were below than 20%, accepted as OA. Twenty-one workers of 22 workers who have abnormal questionnaire, symptoms and abnormality in PFT, accepted daily PEFR measurements. Daily PEFR variability and reversibility test were positive in 5 (3.52%) workers who were accepted as OA. We detected the prevalence of OA, an important worker health problem, was 3.52% in auto and furniture dyes in industrial centre of our city. We think that the prevalence of OA can be determined with detailed history, serial PEFR follow and using PFT, in the absence of specific bronchial provocative tests. Thus, it is important to be become conscious about OA the groups who are under risk.

Glutathione and nitrite in induced sputum from patients with stable and acute asthma compared with controls.

BACKGROUND: Oxidative stress is believed to play an important role in the pathogenesis of asthma. Determining the reduced glutathione (GSH) and nitric oxide (NO) contents of the airway is useful when investigating oxidative stress in the lung. OBJECTIVE: To explore antioxidant defenses by measuring sputum GSH levels and to evaluate oxidant stress by measuring sputum nitrite (NO2-) levels in asthma patients. METHODS: Sputum GSH, NO2-, cell counts, and plasma NO2- contents were evaluated in 11 patients with stable asthma, 10 patients with acute asthma attacks, and 11 controls. RESULTS: The highest GSH content in sputum samples was in stable asthma patients compared with the other groups (P < .001), and patients with exacerbations of asthma had a greater GSH content than controls (P < .001). Mean sputum NO2- content was significantly lower in controls than in acute (P = .001) and stable (P < .001) asthma patients. There was no significant difference in sputum NO2- contents between acute and stable asthma patients, although there was a trend toward higher levels in acute asthma patients (P = .38). CONCLUSIONS: Sputum induction can be used to obtain bronchial secretions for the evaluation of GSH and NO2- contents. Oxidative stress is chronic and probably less severe in patients with stable asthma. Glutathione and NO2- may serve as markers for determining the extent of the oxidative processes in asthma, which is characterized by chronic airway inflammation.

Airway wall thickness in patients with COPD and healthy current smokers and healthy non-smokers: assessment with high resolution computed tomographic scanning.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction caused by emphysema or airway narrowing, or both. Recently airway dimensions have been measured using high-resolution computed tomography (HRCT). To evaluate large and small airway dimensions by HRCT and compare them with pulmonary function tests in patients with COPD and in smokers with or without airflow obstruction. METHODS: We used HRCT scanning to measure airway wall thickness at the segmental and sub-segmental levels in COPD patients (group II, stage II, n = 17, and group III, stage III, n = 5), healthy current smokers (group I, n = 10) and healthy non-smokers (group 0, n = 10). RESULTS: FEV1 was lower in patients with severe or moderate COPD than in healthy current smokers and non-smokers. FEV1 was lower in group I than group 0 (p < 0.005). There was no statistically significant difference between patients with moderate COPD and severe COPD in the ratio of airway wall thickness to outer diameter (T/D ratio) or the percentage wall area (WA%). Both groups II and III had higher T/D ratios than group I (p < 0.01), and group I had a higher T/D ratio than group 0 (p < 0.001). Both groups II and III had higher WA% than group I (p < 0.01 and p < 0.05, respectively), and group I had a higher WA% than group 0 (p < 0.001). A negative correlation was found between airway wall thickness and FEV1. CONCLUSIONS: Computed tomography measurements of large and small airway dimensions are useful for evaluating lung function in patients with COPD and healthy current smokers. Airway wall thickening is inversely related to the degree of airflow obstruction and positively related to cumulative smoking history.

[The knowledge, attitude and behavior related to the tuberculosis and approaches of tuberculosis therapy by the physicians providing first step service]. / Birinci Basamak Hekimlerinin Akciger Tüberkülozu Konusunda Bilgi, Tutum ve Davranislari ile Tedavi Yaklasimlari.

Before a performed education of tuberculosis for physicians who give first step treatment in our city center, a questionnaire was applied to the participants to evaluate the knowledge, attitude, behavior and approach to the treatment. The 66 practicing physician having an employment period of 64.88 +/- 39.42 months were coming from tuberculosis eradication dispensers at the rate of 3%, and from heath center at the rate 97%. The percentage of facing with tuberculosis patients in physicians, exclude who work in tuberculosis eradication dispensers, per year was median 7.30 +/- 9.77 (0-50). 21.2%, of the physicians determine that disease could be spread by only with respiratory tract, 77.3% of them consider that other than respiratory tract and 59.1% of them deemed that the most important factor is living in the same place with a tuberculosis patient and 75.8% of them determine that for a certain diagnosis the sputum examination is enough. 80.3% of the participants said that in our country conditions PPD must be done for the diagnosis. When the most important 4 tuberculosis drugs are asked only 16.7% of the physicians include morphozinamide as a first choice tuberculosis therapy. 48.5% of the physicians deemed that the therapy duration must be at least 6 months. 74.2% of them determine that follow up the disease must be made by sputum plus another examination, 93.9% of them indicated that the tuberculosis patients must be reported to tuberculosis eradication dispensers. When the hepatotoxicity is occurred, only 27.3% of the physicians could interfere the necessary implementation. 74.2% of them determine that the most important problem in control of tuberculosis is about diagnosis, therapy and follow up. When the directly observed treatment short course (DOTS) strategy is asked 16.7% of them gave correct answer. 34.9% of the first step physicians think that tuberculosis eradication dispensers is the primary responsible center in the control of tuberculosis but 53% of them think that tuberculosis eradication dispensers is inadequate in this subject. In conclusion, the first step practice physicians who work in Elazig city center have insufficient knowledge and it is needed periodically postgraduate education.