M. Hamdi Muz

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.

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.

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.

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.