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1.
Front Med (Lausanne) ; 9: 894126, 2022.
Article in English | MEDLINE | ID: mdl-36117966

ABSTRACT

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

2.
Tuberk Toraks ; 69(2): 187-195, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34256509

ABSTRACT

INTRODUCTION: The aim of the study was to investigate the effects of radiological distribution on COVID-19 clinic and prognosis and to determine the relationship between laboratory parameters and thorax CT findings. MATERIALS AND METHODS: Patients with COVID-19 were evaluated retrospectively. Laboratory parameters were obtained from medical records. Ground-glass opacities (GGO) and consolidation were evaluated on thorax CT. The presence of a single lobe lesion was considered as limited while multiple lobe lesions were considered as diffuse involvement for both GGO and consolidation. RESULT: A total 200 patients with COVID-19 were evaluated. 178 of them (89%) were discharged, 17 patients (8.5%) were transferred to the ICU and five patients died (2.5%). The ratios of mortality and transfer to the ICU in patients with diffused GGO were significantly higher compared to patients with limited GGOs. It was observed that troponin ≥0.06 µg/L, platelet <140 and fibrinogen ≥350 mg/dl were independent predictors of the presences of diffused GGOs in thorax CT. CONCLUSIONS: Diffused GGOs on thorax CT are correlated with the rate of mortality and transfer to the ICU in patients with COVID-19. Also, troponin, fibrinogen, and platelet levels can be used while predicting extensive parenchymal disease on thorax CT.


Subject(s)
COVID-19/diagnosis , Lung/diagnostic imaging , Tomography, X-Ray Computed/methods , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Prognosis , Retrospective Studies , SARS-CoV-2
3.
Diagn Cytopathol ; 49(9): 1012-1021, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34078002

ABSTRACT

INTRODUCTION: Isolated mediastinal and/or hilar lymphadenopathy (IMHL) has become an increasingly common finding as a result of the increased use of thoracic imaging modalities. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is accepted as the first step diagnostic method in the differential diagnosis of IMHL. OBJECTIVE: To determine the diagnostic yield of the procedure and to analyze clinical and sonographic findings that can be used to differentiate the etiology of lymph node pathologies. METHODS: Patients who underwent EBUS-TBNA procedure between March 2017 and March 2020 were included in this retrospective study. Demographic data, symptoms, comorbid diseases, and EBUS findings were obtained from the records of the patients. RESULTS: EBUS-TBNA provided a diagnosis in 88 patients out of 120 patients (granulomatous diseases n = 54, malignant diseases n = 21, and anthracotic lymph nodes n = 13), and 32 patients had a negative EBUS-TBNA. 22/32 negative EBUS-TBNA samples were true negatives (reactive lymphadenopathy). The sensitivity of the procedure was 89.8% while negative predict value was 68.7%, diagnostic yield of 91.6%. Patients with reactive lymph nodes had significantly more comorbidities (77.3%-19.4%, p < .001) and a lower number of lymph node stations (1.6 ± 0.8-2.7 ± 0.9, p < .001). Patients with anthracotic lymph nodes were older and mostly consisted of females (11/13, p < .001). CONCLUSION: EBUS-TBNA has high-diagnostic efficiency in the differential diagnosis of IMHL. The number and size of lymph node stations can provide useful information for differential diagnosis. Clinical follow-up can be a more beneficial approach in patients with reactive and anthracotic lymph nodes before invasive sampling.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/standards , Lymphadenopathy/pathology , Adult , Aged , Comorbidity , Diagnosis, Differential , Female , Humans , Lymph Nodes/pathology , Lymphadenopathy/epidemiology , Male , Mediastinum/pathology , Middle Aged , Sensitivity and Specificity
4.
Respir Med ; 183: 106433, 2021 07.
Article in English | MEDLINE | ID: mdl-33957434

ABSTRACT

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.


Subject(s)
COVID-19/mortality , Pandemics , Population Surveillance , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate/trends , Turkey/epidemiology
5.
Expert Rev Respir Med ; 15(8): 1061-1068, 2021 08.
Article in English | MEDLINE | ID: mdl-33905286

ABSTRACT

Aim: This study aims to determine the prognostic value of the Glasgow Prognostic Score (GPS) and fibrinogen to albumin ratio (FAR) in patients with COVID-19.Methods: Electronic database records of 400 patients with COVID-19 were retrospectively analyzed and the initial levels of CRP, albumin, fibrinogen values were recorded. The ground-glass opacities (GGO) and consolidations were evaluated on thorax CT. Hospital mortality and the need for intensive care unit (ICU) transfer were determined as adverse outcomes.Results: It was determined that 345 patients (86.25%) were discharged while 31 patients (7.75%) were transferred to ICU in addition to 24 patients who died (6%). The rates of deaths and transfers to ICU were significantly increased in GPS 2 group compared to both GPS 0 and 1 groups. Additionally, increased FAR was observed in patients who died and transferred to ICU compared to the discharged patients. The FAR was significantly increased in patients with diffuse GGO. Logistic regression analysis indicated that FAR ≥144.59 and the presence of GPS 2 were independent predictors of the adverse outcomes in COVID-19 patients.Conclusion: Our results demonstrated that the GPS and FAR could possess a predictive value for adverse outcomes in patients with COVID-19.


Subject(s)
COVID-19 , Albumins , Fibrinogen , Humans , Prognosis , Retrospective Studies , SARS-CoV-2
6.
Clin Respir J ; 15(4): 445-453, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33319462

ABSTRACT

INTRODUCTION: Endocan is a proteoglycan that is regarded as a novel marker of endothelial dysfunction. Endothelial dysfunction in pulmonary vascular bed is known to play an important role for the pathogenesis of COPD. OBJECTIVE: This study aimed to determine serum endocan levels in patients with stable COPD and acute exacerbation of COPD (AECOPD) and to test the relationship between serum endocan levels and exacerbations. METHODS: This study enrolled a total of 55 COPD patients, 24 of which had AECOPD and 31 had stable COPD. All patients' basic demographic and clinical data were recorded and blood samples were collected. RESULTS: Serum endocan levels were significantly higher in the AECOPD group compared to the stable COPD and control groups (for both p < 0.001) and stable COPD group had higher levels than the control group (p < 0.005). Additionally, serum endocan levels were negatively correlated with FVC, FEV1, partial oxygen pressure and oxygen saturation (r = -0.30, p = 0.03; r = -0.34, p = 0.01; r = -0.34, p = 0.01 and r = -0.36, p = 0.007 respectively), and positively correlated with disease duration and systolic pulmonary artery pressure (r = 0.47, p < 0.001; r = 0.31, p = 0.02 respectively). A cut-off value of 434.29 pg/ml for endocan predicted exacerbation with a sensitivity of 79% and a specificity of 84% (AUC: 0.778, 95% Cl 0.648-0.909; p < 0.001). Logistic regression analysis revealed that increased endocan levels was independent predictor of COPD exacerbation (OR = 9.32, 95%CI, 1.64-52.95; p = 0.01). CONCLUSION: Endocan may be a novel biomarker for detection of endothelial dysfunction and prediction of exacerbations in patients with COPD.


Subject(s)
Neoplasm Proteins , Proteoglycans , Pulmonary Disease, Chronic Obstructive , Biomarkers , Humans , Lung , Neoplasm Proteins/blood , Proteoglycans/blood , Pulmonary Disease, Chronic Obstructive/diagnosis , Severity of Illness Index
7.
J Clin Rheumatol ; 22(5): 248-52, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27464768

ABSTRACT

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease that is associated with poor sleep quality. OBJECTIVES: The present study aimed to investigate the relationship between disease activity and sleep quality in patients with AS and to evaluate the potential effect of anti-tumor necrosis factor (TNF) treatment on sleep quality and pattern. METHODS: Fifty-nine patients with AS were consecutively included in the study. Twenty-eight patients (47.5%) were receiving anti-TNF, and 31 (52.5%) patients were receiving only nonsteroidal anti-inflammatory drugs (NSAIDs). Demographic and treatment characteristics, spinal mobility measurements, disease activity measurements, and sleep questionnaire results of each patient were recorded. Each patient underwent a polysomnography examination for the evaluation of sleep patterns. RESULTS: When compared with the patients on NSAID treatment, patients receiving anti-TNF treatment had significantly greater total sleep time and sleep efficiency (P = 0.003 and P < 0.001, respectively). They had a significantly lower (better) Pittsburgh Sleep Quality Index, sleep onset latency, number of awakenings, and arousal index (P < 0.001, for all). Moreover, they had a significantly shorter superficial sleep period (stage 1) and a significantly longer rapid eye movement sleep period (P < 0.001 and P = 0.02, respectively). Higher indexes of disease activity (Bath AS Disease Activity Index, Bath AS Functional Index, and visual analog scale) were reflecting poorer sleep quality. CONCLUSIONS: Sleep quality and pattern was markedly better in patients with AS on anti-TNF compared with the patients on NSAID treatments. Increased disease activity can impair the quality of sleep in AS. Improved sleep quality and pattern in patients on anti-TNF treatment may be related to improved disease activity.


Subject(s)
Polysomnography/methods , Quality of Life , Sleep Wake Disorders , Sleep/drug effects , Spondylitis, Ankylosing , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/therapeutic use , Female , Humans , Male , Middle Aged , Pain Measurement , Patient Acuity , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/physiopathology , Spondylitis, Ankylosing/diagnosis , Spondylitis, Ankylosing/drug therapy , Spondylitis, Ankylosing/psychology , Statistics as Topic , Surveys and Questionnaires , Turkey
8.
Arch Iran Med ; 17(8): 589-90, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25065285

ABSTRACT

Plastic bronchitis, causing airway obstruction, is a rare condition, especially in adults. In this paper, an adult male patient with heart failure, viral hepatitis, and a history of previous pneumonia, and expectorating white, plaque-like secretions for the last 6 months is presented along with the review of the relevant literature. The material expectorated by the patient was evaluated; macroscopically, this material was observed to be identical to the shape of bronchial branching. Steroid treatment was commenced after the diagnosis was established, resulting in the nearly total disappearance of the expectorated material.


Subject(s)
Airway Obstruction/diagnosis , Bronchitis/diagnosis , Airway Obstruction/complications , Bronchitis/complications , Heart Failure/complications , Humans , Male , Middle Aged , Rare Diseases
9.
J Thorac Dis ; 6(6): 765-71, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24977001

ABSTRACT

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.

10.
Eur J Intern Med ; 22(2): 172-6, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21402248

ABSTRACT

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.


Subject(s)
Pulmonary Disease, Chronic Obstructive/epidemiology , Adolescent , Adult , Age Factors , Female , Humans , Logistic Models , Male , Middle Aged , Poverty , Prevalence , Pulmonary Disease, Chronic Obstructive/etiology , Risk Factors , Rural Population/statistics & numerical data , Sex Factors , Smoking/adverse effects , Spirometry , Surveys and Questionnaires , Turkey/epidemiology , Urban Population/statistics & numerical data , Young Adult
11.
Tuberk Toraks ; 58(2): 162-72, 2010.
Article in Turkish | MEDLINE | ID: mdl-20865569

ABSTRACT

It is determined that endocrine factors can play role on cachexia in chronic obstructive pulmonary disease (COPD). High levels of ghrelin is reported in cachectic COPD cases but its' relation couldn't shown statistically. In our study, it is aimed to detect serum ghrelin levels in COPD, its' relation with proinflammatory cytokines and whether serum ghrelin is associated with cachexia. Sixty stable COPD patients and 15 healthy volunteers were included in the study. COPD patients were divided into two groups, cachectic and normal weight, according to their body mass index. Spirometric assessments were performed and serum tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) and ghrelin levels were measured in all cases. When COPD patients were compared with control group; serum ghrelin levels were statistically lower, TNF-a and IL-6 levels were statistically higher in COPD group. For cachectic COPD patients; serum ghrelin levels were statistically lower and IL-6 levels were statistically higher, compared with normal weight COPD patients. Although, serum TNF-a levels were higher for cachectic COPD patients; these levels were not significant. Positive correlation between serum ghrelin levels and body mass index was detected in patients with COPD. As a result; it is thought that increased proinflammatory cytokines and decreased serum active ghrelin levels may contribute to the development of weight loss.


Subject(s)
Cachexia/blood , Ghrelin/blood , Interleukin-6/blood , Pulmonary Disease, Chronic Obstructive/blood , Tumor Necrosis Factor-alpha/blood , Aged , Body Mass Index , Cachexia/etiology , Case-Control Studies , Female , Humans , Male , Pulmonary Disease, Chronic Obstructive/complications , Spirometry , Weight Loss
12.
Tuberk Toraks ; 56(2): 127-38, 2008.
Article in Turkish | MEDLINE | ID: mdl-18701972

ABSTRACT

We aimed to investigate the levels of some chemokines, inflammatory cell counts in bronchoalveolar lavage (BAL) fluid, histopathological changes in lung tissue, to determine the effect of erdosteine on acute inflammatory changes and fibrosis in a rat fibrosis model induced by bleomycine (BLM). Forty-five Wistar male rats were taken into the study. On day 0, intratracheal saline to control group (group 1, n= 15), intratracheal BLM 7.5 U/kg to BLM (group 2, n= 15) and erdosteine group (group 3, n= 15) was administered. In group 3, oral erdosteine (10 mg/kg/day) was applied two days before BLM. On day 0, 14, and 29th five rats in each groups were sacrificed, BAL fluid was performed. Malonyldialdehyde (MDA), macrophage inflammatory protein (MIP)-1alpha, MIP-2 levels in BAL fluid, hydroxyproline levels in lung tissue were measured. Histopathological examination was performed. When BLM group compared to erdosteine group, the levels of MDA, MIP-1alpha, MIP-2, and neutrophil counts, the hydroxyproline (OH-P) level of lung tissue were decreased in erdosteine group on acute inflammatory phase (day 14) (p< 0.001, p= 0.017, p= 0.009, p< 0.001, p= 0.009, respectively), and late fibrosis phase (day 29) except BAL MIP-2 (p= 0.022, p= 0.025, p= 0.01, p< 0.001, respectively). Fibrosis level was significantly lower in erdosteine group than BLM group on day 29 (p= 0.01). We conclude that erdosteine may prevent the acute lung inflammation and fibrosis by suppressing the accumulation of neutrophils, inhibition of lipid peroxydation, chemokine production, and release.


Subject(s)
Expectorants/therapeutic use , Pulmonary Fibrosis/prevention & control , Thioglycolates/therapeutic use , Thiophenes/therapeutic use , Animals , Bleomycin/toxicity , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Chemokines/analysis , Humans , Male , Pulmonary Fibrosis/chemically induced , Random Allocation , Rats , Rats, Wistar
13.
Respirology ; 13(4): 488-97, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18410261

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Asthma/drug therapy , Animals , Anti-Inflammatory Agents/administration & dosage , Antibodies, Monoclonal/administration & dosage , Bronchoalveolar Lavage , Cytokines/metabolism , Disease Models, Animal , Immunization , Immunohistochemistry , Infliximab , Leukocyte Count , Lung/metabolism , Lung/pathology , Male , Mice , Mice, Inbred BALB C , Ovalbumin/administration & dosage , Ovalbumin/immunology , Tumor Necrosis Factor-alpha/metabolism
14.
Exp Mol Med ; 39(5): 614-20, 2007 Oct 31.
Article in English | MEDLINE | ID: mdl-18059137

ABSTRACT

Endothelin (ET) receptor antagonists have been developed to produce a reduction of ET related effects in various diseases, as well as in animal models of airway inflammation. We aimed to investigate the anti-inflammatory potential of bosentan on a rat model of emphysema. Thirty Wistar male rats were classified as control group (group 1), intratracheally (i.t.) instilled with saline, treated with vehicle solution; elastase group (group 2), i.t. instilled with porcine pancreatic elastase (PPE), treated with vehicle solution; and PPE+bosentan group (group 3), i.t. instilled with PPE, treated with bosentan. The levels of TNF-alpha, IL-1beta, IL-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and lung tissue, cell counts in BALF, and histologic analysis of all groups were evaluated. Neutrophile granulocytes (NG) and alveolar macrophages (AM) were increased more in group 2 than in group 1 (P<0.001, P=0.04, respectively). Compared with group 2, neutrophil granulocyte (NG) and alveolar macrophages (AM) counts were decreased in group 3 (P<0.001). Histological examination confirmed a diffuse neutrophilic inflammation and irregular alveolar air space enlargement in group 2. Treatment with bosentan partially reduced the enlarged lung volumes. Compared with group 1, the BALF levels of TNF-alpha and IL-6, and the lung tissue levels of IL-1beta, IL-6, and IL-8 were increased in group 2 (P=0.028, P=0.005, P=0.001, P=0.019, P<0.001, respectively). The TNF-alpha and IL-8 levels of BALF (P=0.007, P=0.001, respectively), and the TNF-alpha, IL-1beta, IL-6, and the IL-8 levels of lung tissue (P=0.031, P=0.017, P=0.007, P<0.001) were decreased in group 3 compared to group 2. In conclusion, bosentan decreased the inflammatory response by reducing numbers of inflammatory cells and proinflammatory cytokines.


Subject(s)
Cytokines/biosynthesis , Emphysema/drug therapy , Endothelin Receptor Antagonists , Sulfonamides/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Bosentan , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Emphysema/etiology , Emphysema/immunology , Emphysema/pathology , Inflammation Mediators/metabolism , Lung/drug effects , Lung/immunology , Lung/pathology , Male , Pancreatic Elastase/administration & dosage , Pancreatic Elastase/toxicity , Rats , Rats, Wistar
15.
Tohoku J Exp Med ; 209(4): 321-8, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16864954

ABSTRACT

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.


Subject(s)
Interleukin-2/blood , Neopterin/blood , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Aged , Biomarkers/blood , Female , Humans , Immunity, Cellular/physiology , Male , Middle Aged , Tuberculosis, Pulmonary/immunology
16.
Exp Mol Med ; 38(2): 109-18, 2006 Apr 30.
Article in English | MEDLINE | ID: mdl-16672764

ABSTRACT

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.


Subject(s)
Acetates/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Cysteine/biosynthesis , Leukotriene Antagonists/therapeutic use , Leukotrienes/biosynthesis , Quinolines/therapeutic use , Airway Obstruction/drug therapy , Airway Obstruction/pathology , Animals , Asthma/metabolism , Asthma/pathology , Collagen/metabolism , Cyclopropanes , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Goblet Cells/pathology , Hyperplasia , Hypertrophy , Lung/pathology , Mice , Mice, Inbred BALB C , Mucus/metabolism , Muscle, Smooth/pathology , Pulmonary Fibrosis/pathology , Receptors, Leukotriene/metabolism , Respiratory Mucosa/pathology , Sulfides
17.
Mediators Inflamm ; 2005(5): 256-62, 2005 Oct 24.
Article in English | MEDLINE | ID: mdl-16258192

ABSTRACT

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.


Subject(s)
Cytokines/blood , Tuberculosis, Pulmonary/blood , Adult , Female , Humans , Male , Mycobacterium tuberculosis/isolation & purification , Tuberculin Test , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
18.
Tuberk Toraks ; 53(3): 245-51, 2005.
Article in Turkish | MEDLINE | ID: mdl-16258883

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Bronchoalveolar Lavage Fluid/cytology , Dexamethasone/therapeutic use , Lung/pathology , Animals , Anti-Inflammatory Agents/pharmacology , Asthma/pathology , Bronchoalveolar Lavage Fluid/immunology , Dexamethasone/pharmacology , Disease Models, Animal , Female , Immunohistochemistry/veterinary , Interleukin-4/immunology , Interleukin-5/immunology , Lung/cytology , Lung/immunology , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Random Allocation
19.
Tuberk Toraks ; 53(4): 330-9, 2005.
Article in Turkish | MEDLINE | ID: mdl-16456731

ABSTRACT

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.


Subject(s)
Exercise/physiology , Lung/physiopathology , Nutritional Status , Pulmonary Disease, Chronic Obstructive/physiopathology , Anthropometry , Biomarkers/blood , Body Composition , Body Mass Index , Case-Control Studies , Exercise Test , Female , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/metabolism , Respiratory Function Tests , Serum Albumin/analysis , Serum Albumin/metabolism , Severity of Illness Index , Transferrin/analysis , Transferrin/metabolism , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism
20.
Tuberk Toraks ; 53(4): 371-8, 2005.
Article in Turkish | MEDLINE | ID: mdl-16456736

ABSTRACT

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.


Subject(s)
Asthma/epidemiology , Hypersensitivity, Immediate/epidemiology , Occupational Diseases/epidemiology , Paint/adverse effects , Adult , Asthma/diagnosis , Asthma/etiology , Bronchial Provocation Tests , Coloring Agents/adverse effects , Humans , Hypersensitivity, Immediate/diagnosis , Hypersensitivity, Immediate/etiology , Male , Occupational Diseases/diagnosis , Occupational Diseases/etiology , Prevalence , Respiratory Function Tests , Risk Factors , Turkey/epidemiology
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