Figen Deveci

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 (LTC4, D4 and E4) 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-γ, TNF-α, and IL-12 stimulate, and that IL-10, TGF-β, 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-α, IFN-γ, and TGF-β1 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-γ, TNF-α, 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-γ, P = .004 for TNF-α, 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-β1 levels among the groups (P > .05). Because the serum IL-12p40, IL-10, TNF-α, and IFN-γ 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.

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.

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)‐α mAb (infliximab) on the inflammatory response in a mouse model of acute asthma.

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.

Plasma malondialdehyde and serum trace element concentrations in patients with active pulmonary tuberculosis.

Increased amounts of reactive oxygen species (ROS) are produced as a consequence of a phagocyte respiratory burst during pulmonary inflammation. The aim of our study was to assess the concentration of malondialdehyde (MDA) and trace metals in patients with active pulmonary tuberculosis (TB).Eighty-three subjects were enrolled into the study and prospectively divided into three groups: 22 subjects with healthy controls (group I), 21 patients with inactive pulmonary TB (group II), and 40 patients with active pulmonary TB (group III). Before beginning the therapy, plasma MDA and serum concentrations of zinc (Zn), copper (Cu), albumin, and iron (Fe) were measured. The concentration of MDA and Cu in group III were higher than in the other groups (p<0.0001). The serum Zn and albumin levels were significantly lower in group III compared with healthy controls (p<0.05). There was a positive correlation between MDA and erythrocyte sedimentation rate (r=+0.647, p<0.0001; Spearman’s test).Our data indicated increased circulating levels of MDA and changed serum trace metal levels in active pulmonary TB. Trace metal levels must be closely followed during the diseases process and further studies are needed to assess the role of antioxidants as adjuvant therapy in patients with active pulmonary TB.

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.

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.

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.

Asthma phenotypes in Turkey: a multicenter cross-sectional study in adult asthmatics; PHENOTURK study.

To evaluate asthma phenotypes in patients with asthma from different regions of Turkey.