Chronic obstructive pulmonary disease phenotypes in Turkey: the COPET study-a national, multicenter cross-sectional observational study.

BACKGROUND: While mortality rates decrease in many chronic diseases, it continues to increase in COPD. This situation has led to the need to develop new approaches such as phenotypes in the management of COPD. We aimed to investigate the distribution, characteristics and treatment preference of COPD phenotypes in Turkey. METHODS: The study was designed as a national, multicenter, observational and cross-sectional. A total of 1141 stable COPD patients were included in the analysis. RESULTS: The phenotype distribution was as follows: 55.7% nonexacerbators (NON-AE), 25.6% frequent exacerbators without chronic bronchitis (AE NON-CB), 13.9% frequent exacerbators with chronic bronchitis (AE-CB), and 4.8% with asthma and COPD overlap (ACO). The FEV1 values were significantly higher in the ACO and NON-AE than in the AE-CB and AE NON-CB (p < 0.001). The symptom scores, ADO (age, dyspnoea and FEV1 ) index and the rates of exacerbations were significantly higher in the AE-CB and AE NON-CB phenotypes than in the ACO and NON-AE phenotypes (p < 0.001). Treatment preference in patients with COPD was statistically different among the phenotypes (p < 0.001). Subgroup analysis was performed in terms of emphysema, chronic bronchitis and ACO phenotypes of 1107 patients who had thoracic computed tomography. A total of 202 patients had more than one phenotypic trait, and 149 patients showed no features of a specific phenotype. DISCUSSION: Most of the phenotype models have tried to classify the patient into a certain phenotype so far. However, we observed that some of the patients with COPD had two or more phenotypes together. Therefore, rather than determining which phenotype the patients are classified in, searching for the phenotypic traits of each patient may enable more effective and individualized treatment.

Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study.

Background: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilic asthma. Objective: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to compare the superiority of one over the other, especially in asthma with an eosinophilic phenotype. Methods: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants, and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E values were examined. Results: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups (p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group (p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis. The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. The present study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore, when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostin in serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Conclusion: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study.

BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilicasthma. OBJECTIVE: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to comparethe superiority of one over the other, especially in asthma with an eosinophilic phenotype. METHODS: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants,and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E valueswere examined. RESULTS: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups(p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group(p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis.The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. Thepresent study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore,when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostinin serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. CONCLUSION: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Demographic, Clinical and Management Characteristics of Newly Diagnosed COPD Patients in Turkey: A Real-Life Study.

Purpose: In order to determine the clinical and sociodemographic characteristics of newly diagnosed treatment-naïve asthma and COPD patients in Turkey, a multicenter study in 2012 was initiated . We aimed to investigate the characteristics and therapies of COPD patients in the original study in more detail. Patients and Methods: This nation-wide, multicentric, non-interventional, prospective, real-life observational cohort study was conducted in 122 centers. The newly diagnosed patients were not receiving any treatment before the recruitment. Their general characteristics, the combined GOLD 2011 COPD categories and exacerbation histories were noted. The patients were followed up with 3 voluntary visits for 1 year. Their adherence to the inhaled treatment according to GOLD 2011 was evaluated during follow-up visits. Results: The study included 776 COPD patients. Their mean age was 59.4±9.1 years, and 11.9% of the patients were female. 35.1% of the patients were in the GOLD 2011 C and D category. 12.6% are frequent exacerbators, and 52.8% had at least one comorbid condition. 71.8% overtreatment rate was detected. Their attendance rates for three follow-up visits became 55.9%, 32.9% and 18.7%, respectively. The adherence rate to the treatment was measured as 81.9%. Conclusion: Although these patients were diagnosed for the first time, the GOLD C and D categories and frequent exacerbator phenotype were found at a high rate. They were usually prescribed an overtreatment regimen. We think that newly diagnosed COPD patients should be evaluated carefully, and best effort should be made to treat these patients in accordance with the recommendations of the major COPD guidelines.

Bone mineral density in emphysema and chronic bronchitis phenotypes in hospitalized male chronic obstructive pulmonary disease patients.

INTRODUCTION: Risk of osteoporosis known to increase in chronic obstructive pulmonary disease (COPD), but is usually overlooked, especially in male patients. OBJECTIVES: The present study compares the bone mineral density (BMD) measurements of male COPD patients with emphysema and the chronic bronchitis phenotype, and evaluates the association between density of emphysema and osteoporosis. METHODS: Ninety-four patients with COPD, and with emphysema and the chronic bronchitis phenotype, were included in the prospective study. A high-resolution computed tomography (HRCT) was used for the diagnosis of emphysema, and a dual X-ray absorptiometry was used to measure the BMD of the lumbar vertebrae and neck of the femur. RESULTS: Emphysema phenotype 45.75% and chronic bronchitis phenotype 54.25%, based on their clinical findings and a quantitative volumetric analysis by HRCT. Osteoporosis was found 60.47% and 17.65% of patients with emphysema and bronchitis, while osteopenia was detected 27.91% and 41.18% of patients with emphysema and bronchitis, respectively. A negative correlation was found between HRCT emphysema density and the bone densitometer t-score in patients with osteoporosis. Among the patients with osteoporosis, a positive correlation was found between Body Mass Index (BMI) and the bone densitometer t-score. Only BMI and emphysema score were found to be independent risk factors for a low BMD. One unit drop in BMI increased the risk of osteoporosis by 28% (OR = 1.28, 95% CI 1.14-1.45) (P < 0.001). One unit increase in emphysema score increased the risk of osteoporosis by 6% (OR = 1.06, 95% CI 1.03-1.09) (P < 0.001). CONCLUSION: Especially male patients with emphysema, high dyspnea score, low BMI and frequent exacerbations should be evaluated for osteoporosis.

Differences of viral panel positive versus negative by real-time PCR in COPD exacerbated patients.

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) are often caused by respiratory tract infections. The aim of this study was to investigate the clinical, laboratory and computed tomography features of patients with hospitalized COPD exacerbations in which respiratory viruses were detected using a real-time polymerase chain reaction (PCR) technique. MATERIALS AND METHODS: This retrospectively planned study included patients hospitalized in the chest diseases clinic due to exacerbation of COPD between November 2018-February 2019. The study included patients who had virus-specific real-time PCR, and computed tomography scans of the chest. RESULT: A total of 110 patients were included in the study. Respiratory viruses were identified in the nasopharyngeal swabs of 50 patients (45.5%) using the real-time PCR method, with rhinovirus (25%), influenza A (13.1%) and coronavirus (11.8%) being the most commonly isolated agents. The mean age of the patients was 68.28 ± 9.59 years in the virus-positive group and 68.20 ± 8.27 years in the virus-negative group (p= 0.963). Gender distribution, rate of smokers, exposure to biofuels, blood leukocyte count, neutrophil percentage, C-reactive protein (CRP) level, FEV1/FVC ratio did not significantly differ between the two groups (p> 0.05). Procalcitonin (PCT) and FEV1 values were significantly lower (p= 0.001 and p= 0.028, respectively) and the number of exacerbations was significantly higher in the virus-positive group (p= 0.001). The length of hospital stay was longer in the virus-positive group than in the virus-negative group (p= 0.012). Among the findings of computed tomography (CT) of the chest, bronchial wall thickening, cystic bronchiectasis, and emphysema did not differ significantly (p> 0.05). The rate of infiltrative lesions (tree-in-bud opacity, ground-glass opacity, atypical pneumonia) was significantly higher in the virus-positive group (p= 0.020). CONCLUSIONS: Viral respiratory tract infections should be considered in hospitalized patients with an exacerbation of COPD who have a history of frequent exacerbations, normal PCT value, and the absence of consolidation in CT scan of the chest. The use of broadspectrum antibiotic therapy should be avoided in patients with these features.

Carotid intima-media thickness in chronic obstructive pulmonary disease and survival: A multicenter prospective study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Carotid intima-media thickness (CIMT) is a noninvasive method assessing atherosclerosis. OBJECTIVE: It was aimed to determine relationship and survival between COPD and CIMT. METHODS: CIMT was measured using Doppler ultrasound (USG) in 668 stable COPD patients at 24 centers. Patients were followed-up for 2 years. RESULTS: There were 610 patients who completed the study. There were 200 patients CIMT with <0.78 mm (group 1), and 410 with CIMT ≥ 0.78 mm (group 2). There was a significant difference at the parameters of age, gender, smoking load, biomass exposure, GOLD groups and degree of airway obstruction (FEV1) between groups 1 and 2. Our results revealed positive correlations between mean CIMT and age, smoking load (pack-years), biomass exposure (years), exacerbation rate (last year), duration of hypertension (years) and cholesterol level; negative correlations between CIMT and FEV1 (P < 0.05). According to logistic regression model, compared with group A, risk of CIMT increase was 2.2-fold in group B, 9.7-fold in group C and 4.4-fold in group D (P < 0.05). Risk of CIMT increase was also related with cholesterol level (P < 0.05). Compared with infrequent exacerbation, it was 2.8-fold in the patients with frequent exacerbation (P < 0.05). The mean survival time was slightly higher in group 1, but not significant (23.9 vs 21.8 months) (P > 0.05). CONCLUSION: This study is the first regarding CIMT with combined GOLD assessment groups. It has revealed important findings supporting the increase in atherosclerosis risk in COPD patients. We recommend Doppler USG of the carotid artery in COPD patients at severe stages.

Asthma control and adherence in newly diagnosed young and elderly adult patients with asthma in Turkey.

OBJECTIVE: This study aimed to evaluate the factors that affect asthma control and adherence to treatment in newly diagnosed elderly asthmatics in Turkey compared with younger patients. METHODS: This real-life prospective observational cohort study was conducted at 136 centers. A web-based questionnaire was administered to the patients who were followed up for 12 months. RESULTS: Analysis included 1037 young adult asthma patients (age <65 years) and 79 elderly asthma patients (age ≥65 years). The percentage of patients with total control in the elderly and young groups were 33.9% and 37.1% at visit 1, 20.0% and 42.1% (p = 0.012) at visit 2, and 50.0% and 49.8% at visit 3, respectively. Adherence to treatment was similar for both groups. Visit compliance was better in the elderly group than in the young group at visit 1 (72.2% vs. 60.8%, p = 0.045), visit 2 (51.9% vs. 34.9%, p = 0.002), and visit 3 (32.9% vs. 19.4%, p = 0.004). Adherence to treatment increased with asthma control in both groups (both p < 0.001) but decreased with the presence of gastritis/ulcer, gastroesophageal reflux, and coronary artery disease in the elderly. CONCLUSIONS: Asthma control and adherence to treatment were similar for the elderly and young asthma patients, though the follow-up rate was lower in young patients. The presence of gastritis/ulcer, gastroesophageal reflux and coronary artery disease had negative impacts on the adherence to treatment in elderly adult patients.

Real life profile of asthma and chronic obstructive pulmonary disease patients in Turkey.

INTRODUCTION: Despite the presentation of similar symptoms, the airway diseases have different underlying pathophysiological processes and must be distinguished to enable the administration of appropriate treatment. In several studies the clinician- and patient-related causes of poor compliance to treatment in asthma/chronic obstructive pulmonary disease (COPD) patients have been evaluated. This study aimed to determine the clinical and sociodemographic characteristics of newly diagnosed treatment-naïve asthma and COPD patients in Turkey. MATERIALS AND METHODS: This national, multicentre, prospective, observational study was conducted in 122 centres. A questionnaire including items related to demographic, clinical, laboratory parameters was applied. All patients were intended to be followed-up for 12 months. RESULT: 1892 adult patients (1116 asthma and 776 COPD) from 122 centres were enrolled. Overall 95%, 86% and 65% of intermittent, mild persistent and moderate persistent asthma patients were over-treated. Among COPD patients, the percentages of over-treated patients were 66%, 79% and 82% for those with GOLD stage A, B and C. Physicians' adherence to guidelines was appropriate in 93% of severe persistent asthma patients and 89% of GOLD stage D COPD patients. Among patients with high compliance to treatment, proportion of asthma patients with total control was 44% and that of COPD patients at GOLD stage A was 41%. In consecutive two visits, this figure increased to 52% and 63% in asthma patients and 54% and 50% in COPD patients. CONCLUSIONS: The main findings are: (a) patients are frequently over-treated and (b) patients do not adhere to visits as expected, in both asthma and COPD.

Cognitive function in chronic obstructive pulmonary disease: relationship to global initiative for chronic obstructive lung disease 2011 categories.

BACKGROUND AND OBJECTIVE: Recently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD. METHODS: We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language. RESULTS: Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. CONCLUSIONS: The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD.

Phenotyping of chronic obstructive pulmonary disease using the modified Bhalla scoring system for high-resolution computed tomography.

BACKGROUND: Identifying different phenotypes of chronic obstructive pulmonary disease (COPD) is important for both therapeutic options and clinical outcome of the disease. OBJECTIVE: To characterize the phenotypes of COPD according to high-resolution computed tomography (HRCT) findings; and to correlate HRCT scores obtained using the modified Bhalla scoring system with clinical and physiological indicators of systemic inflammation. METHODS: The present study included 80 consecutive patients with stable COPD. HRCT scans were evaluated by two independent radiologists according to the modified Bhalla scoring system. RESULTS: Fifty-four patients exhibited morphological changes on HRCT examination while 26 had no pathological findings. Patients with HRCT findings had lower spirometric measurements and higher levels of inflammation, and reported more exacerbations in the previous year compared with patients with no findings on HRCT. Patients with morphological changes were classified into one of three groups according to their HRCT phenotype(s): emphysema (E) only, E + bronchiectasis (B)/peribronchial thickening (PBT) or B/PBT only. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, C-reactive protein (CRP) levels and the number of exacerbations among the groups were significantly different. Pairwise comparisons between the E only and E+B/PBT groups showed significantly lower FVC, FEV1 and FEV1/FVC values, and higher CRP levels and number of exacerbations compared with the B/PBT group. No significant differences were found between the E+B/PBT and the B/PBT groups. An inverse correlation was found between the total HRCT score and FVC, FEV1 and FEV1/FVC; the correlation was positive with CRP level, erythrocyte sedimentation rate and number of exacerbations. CONCLUSION: The present study exposed the intimate relationship between phenotype(s) characterized by HRCT and scoring for morphological abnormalities; and clinical and functional parameters and inflammatory markers. The inclusion of HRCT among routine examinations for COPD may provide significant benefits both in the management and prognosis of COPD patients.

Attentional control is partially impaired in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome is associated with executive cognitive impairment. An important question is whether impairment in executive functioning in obstructive sleep apnea syndrome is independent of dysfunction in attention. Attentional control is a subcomponent of executive functioning that is mediated by frontal lobe processing. In the current study, we investigated whether attentional control is deficient in obstructive sleep apnea syndrome. Attentional control processes were investigated through conflict adaptation and conflict frequency paradigms. These neuropsychological paradigms were assessed by using the Simon, Flanker and Stroop tasks. We additionally analysed post-error slowing data within these tasks. Error processing is another index of cognitive control that is mediated by frontal lobe functioning. Our sample consisted of 14 healthy adults and 24 patients with untreated moderate-severe obstructive sleep apnea syndrome. Results indicated that attentional control is partially dysfunctional among patients with obstructive sleep apnea syndrome. Attentional control processes were deficient when focal attention (Flanker task) processes were involved, but were intact when observed using the Simon and Stroop tasks. A non-significant trend in post-error slowing data suggested that error processing, assessed with the Flanker task, was diminished among patients with obstructive sleep apnea syndrome. These results support the view that obstructive sleep apnea syndrome leads to some amount of frontal lobe dysfunction, and that attentional control and error processing might be particularly affected by obstructive sleep apnea syndrome.

Flexible bronchoscopy may decrease respiratory muscle strength: premedicational midazolam in focus.

BACKGROUND: Flexible bronchoscopy (FB) is a procedure accepted to be safe in general, with low complication rates reported. On the other hand, it is known that patients with pre-existing respiratory failure have developed hypoventilation following FB. In this study the effects of FB on respiratory muscle strength were investigated by measuring maximum respiratory pressures. METHODS: One hundred and forty patients, aged between 25 and 90 years, who had undergone diagnostic bronchoscopy between February 2012 and May 2012, were recruited to the study. Pre- and post-procedure maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured. A correlation between the MIP and MEP changes and patient characteristics and FB variables were investigated. RESULTS: Significant decreases in both MIP and MEP values were observed following FB (p < 0.001 for both). Decreases were attributed to the midazolam used for sedation. Significant decreases in respiratory muscle strengths were observed especially in the high-dose midazolam group, compared to both low-dose and non-midazolam groups. CONCLUSIONS: It was determined that respiratory muscle weakness may arise post-procedure in patients who have undergone FB, and this is constitutively related to midazolam premedication. Respiratory muscle weakness might play a role in potential hypoventilation in critical patients who undergo FB.

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats.

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-ß1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-β1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.

Anti-inflammatory and anti-fibrotic effects of sirolimus on bleomycin-induced pulmonary fibrosis in rats.

PURPOSE: Pulmonary fibrosis is a devastating disease with a poor prognosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. The aim of this study was to evaluate the anti-inflammatory and anti-fibrotic effects of sirolimus (SRL), which is a potential anti-fibrotic agent, by using bleomycin (BLM)-induced pulmonary fibrosis model in rats. METHODS: A single intra-tracheal injection of BLM (2.5 U/kg) was administered and sirolimus (2.5 mg/kg/day) was given orally, beginning either one day before (early SRL) or nine days after (late SRL) the BLM administration. The effect of SRL on fibrosis was studied by analysis of cytokine levels in BAL fluid, measurement of lung tissue hydroxyproline (HPL) content and histopathological examination. RESULTS: Both early and late SRL administrations caused a decrease in the levels of IL-13, PDGF-A and TGF-ß1 (p=0.001) and an increase in IFN-γ levels (p=0.001) in BAL fluid. Early and late SRL also caused a decrease in HPL content (p=0.001). Early sirolimus caused a significant decrease in fibrosis score (p=0.001), while late SRL did not. CONCLUSION: Sirolimus was effective in BLM-induced pulmonary fibrosis model, especially in the early phases of the disease.

Pneumothorax as an initial manifestation of obstructive sleep apnea syndrome.

CASE REPORT: A sixty-five-year-old man with bullous lung disease was admitted to emergency service with chest pain and dyspnea that developed during sleep. Pneumothorax was diagnosed both clinically and radiologically. After the chest drainage, the patient presented with a prolonged air leak that required thoracotomy. Further history and occurrence of pneumothorax during sleep suggested that obstructive sleep apnea might play a role in the development of pneumothorax. Nocturnal polysomnography later confirmed the diagnosis of severe obstructive sleep apnea syndrome. DISCUSSION: We hypothesized that obstructive sleep apnea may be a risk factor for pneumothorax especially in patients with bullous lung disease, and pneumothorax may be listed in the complications of obstructive sleep apnea syndrome.

Respiratory failure caused by giant thymolipoma.

The authors present the case of a 31-year-old woman with a massive anterior mediastinal tumor who presented with respiratory failure. A thoracic computed tomographic scan suggested a mediastinal lipomatous mass, and an operation was performed. Resection of the tumor resulted in immediate improvement in the patient's pulmonary status, and the histopathologic examination revealed thymolipoma. Because thymolipoma can attain enormous dimensions and compress adjacent structures, it should be immediately resected.

Single dose of tiotropium improves the 6-minute walk distance in chronic obstructive pulmonary disease.

The aim of this study was to evaluate the effect of a single dose of tiotropium on the exercise capacity of stable chronic obstructive pulmonary disease (COPD) patients. The study was a randomized, placebo-controlled, double-blind, cross-over study. Forty-four stable COPD patients with moderate to severe airway obstruction were selected according to the GOLD criteria. The regular anticholinergic therapies of the patients were interrupted one week before the test. In the morning hours of the first day, half the group was given one capsule (18 mcg) of tiotropium and the other half was given placebo as inhalation using the HandiHaler device. Before and 120 min after the medication, the 6-min walk test was performed. Oxygen saturation, modified Borg dyspnea ratings, blood pressure, and heart rate were recorded before and after the test. The same procedure was repeated at the same time on the third day but this time the patients were given placebo if they used tiotropium on the first day and vice versa. Before using tiotropium or placebo there was no difference between 6-min walk distances. The 6-min walk distance after the use of tiotropium (429.3 +/- 70.6 m) was significantly longer than that after the use of placebo (414.7 +/- 74.6 m). The changes in Borg dyspnea ratings and arterial oxygen saturation values with tiotropium and placebo use were not significant. We conclude that exercise capacity might be improved by using a single-dose tiotropium inhalation in moderate to severe COPD patients.