Research Burden of Interstitial Lung Diseases in Turkey - RBILD.

Introduction: The aim of our study is to investigate the etiological distribution of ILD in Turkey by stratifying the epidemiological characteristics of ILD cases, and the direct cost of initial diagnosis of the diagnosed patients. Material-Method: The study was conducted as a multicenter, prospective, cross-sectional, clinical observation study. Patients over the age of 18 and who accepted to participate to the study were included and evaluated as considered to be ILD. The findings of diagnosis, examination and treatment carried out by the centers in accordance with routine diagnostic procedures were recorded observationally. Results: In total,1070 patients were included in this study. 567 (53%) of the patients were male and 503 (47%) were female. The most frequently diagnosed disease was IPF (30.5%). Dyspnea (75.9%) was the highest incidence among the presenting symptoms. Physical examination found bibasilar inspiratory crackles in 56.2 % and radiological findings included reticular opacities and interlobular septal thickenings in 55.9 % of the cases. It was observed that clinical and radiological findings were used most frequently (74.9%) as a diagnostic tool. While the most common treatment approaches were the use of systemic steroids and antifibrotic drugs with a rate of 30.7% and 85.6%, respectively. The total median cost from the patient's admission to diagnosis was 540 Turkish Lira. Conclusion: We believe that our findings compared with data from other countries will be useful in showing the current situation of ILD in our country to discuss this problem and making plans for a solution.

Serum biomarkers in patients with stable and exacerbated COPD-bronchiectasis overlap syndrome.

INTRODUCTION: Bronchiectasis (B), commonly seen in patients with chronic obstructive pulmonary disease (COPD), is associated with exacerbations and predicts mortality. OBJECTIVES: To differentiate patient groups with COPD-(B+) or COPD-(B-) and their exacerbations by using inflammatory markers. METHODS: Consecutive COPD patients were divided into two groups according to findings on high resolution thorax CT (HRCT) images using Smith and modified Reiff scores. Patients were prospectively followed for possible future exacerbations. Serum fibrinogen, C-reactive protein (CRP), soluble urokinase-type plasminogen activator receptor (suPAR) and Plasminogen activator inhibitor-1 (PAI-1) levels were studied during exacerbation and stable periods. RESULTS: Eighty-seven patients were included and (85 M, 2 F), mean aged was 68.1 ± 9 (46-87). HRCT confirmed bronchiectasis in 38 (43.7%) patients, most commonly in tubular form (89.4%) and in lower lobes. COPD-B(+) group had lower body mass index (P = 0.036), more advanced stage of disease (P = 0.004) and more frequent exacerbation (P = 0.01). The HRCT scores were correlated with exacerbation rate (r = 0.356, P < 0.05). Fibrinogen and CRP values were higher in exacerbation (P = 0.01, P = 0.013, respectively) especially in COPD-B(+) patients. suPAR and PAI-1 levels were also higher in COPD-B(+) patients although it was not statistically significant. CONCLUSION: Bronchiectasis is common and causes frequent exacerbations in COPD. Identifying of COPD-B(+) phenotype by HRCT scoring systems has considerable importance for both therapeutic options and clinical outcome of the disease. In addition to fibrinogen and CRP, high serum levels of suPAR and PAI-1 suggest us their significant roles in increased systemic inflammation associated with coexisting of COPD and bronchiectasis.

The usefulness and prognostic value of Memorial Symptom Assessment-Short Form and Condensed Memorial Symptom Assessment Scale in assessment of lung cancer patients.

PURPOSE: Lung cancer is associated with high level of symptoms and patient-reported symptoms have been rarely used as a prognostic score to predict patients survival. METHODS: Frequency and burden of symptoms in lung cancer patients were evaluated before the diagnosis with the Memorial Symptom Assessment-Short Form (MSAS-SF) and Condensed Memorial Symptom Assessment Scale (CMSAS) questionnaires. Performance status, stage of disease, serum albumin, and C-reactive protein (CRP) levels were recorded. Patients were staged according to 8th TNM classification. A survival analysis was applied. RESULTS: The mean age of 116 patients (adenocarcinoma 51, squamous cell 43, non-small cell 5, small cell 17) was 65.2 ± 10.1 (28-87) years. The most common seen physical and psychological symptoms were cough (86.3%), lack of energy (74.3%), dyspnea (70.1%), and feeling sad (61.5%), feeling nervous (61.5%), and worrying (53.8%). Total and subscores of MSAS and CMSAS are significantly higher in M1 disease than M0 disease. All MSAS-SF and CMSAS scores, but not MSAS-PSYCH and CMSAS-PSYCH, positively correlated with age, high serum CRP, white blood cells/neutrophils counts, and TNM stage, and negatively correlated with albumin levels, performance status, and overall survival (OS). Median survival was 77, 195, 370, and 579 days for the four prognostic interquartile groups according to CMSAS-SUM score (p < 0.0001). CONCLUSION: MSAS-SF and CMSAS questionnaires can be useful tool for discriminating metastatic from non-metastatic disease in treatment-naïve patients with lung cancer. Since both questionnaires well correlated with OS and important prognostic factors, they can use to plan palliative care and to help for predicting survival of lung cancer patients.

A New Promising Treatment Strategy for Carbon Monoxide Poisoning: High Flow Nasal Cannula Oxygen Therapy.

BACKGROUND High-flow nasal cannula (HFNC) is an alternative to conventional normobaric oxygen therapy (NBO) for hypoxemic patients. Since nothing is known about its effect on carbon monoxide (CO) poisoning, we hypothesized that HFNC might be a useful device in the treatment of CO poisoning victims. MATERIAL AND METHODS We retrospectively reviewed the medical records of patients who were admitted consecutively to the emergency department with CO intoxication. Patients were divided into 2 groups: patients treated with HFNC and patients treated with conventional face mask (CFM). Demographic data, pretreatment, and control (after 1 hour) arterial blood gas analyses values of the patients were evaluated. RESULTS Sixty-eight patients (mean age 35.8±18.7 years) were included in this study. NBO was given via HFNC to 38 patients (55.9%), and via CFM to 30 patients (44.1%). The demographic characteristics and pretreatment values of carboxy-hemoglobin (COHb) were similar in the 2 groups. The mean COHb value of the HFNC group at the first hour was found significantly lower than the CFM group: 9.5±4.7 and 12.0±5.1, respectively (P=0.041). Improvement of COHb level was significantly higher in the HFNC group compared to the CFM group: 12.5±4.5 versus 6.7±3.7, respectively (P=0.001). CONCLUSIONS HFNC was superior than CFM in alleviating COHb levels in the victims of CO poisoning. We believe that using HFNC will increase patient comfort by shortening the duration of treatment in emergency department settings, especially in patients who have mild clinical findings of CO poisoning.

Elongation factor-2 kinase (eEF-2K) expression is associated with poor patient survival and promotes proliferation, invasion and tumor growth of lung cancer.

OBJECTIVES: Lung cancer is the leading cause of cancer related deaths in worldwide. Despite recent advances in treatment options, patient survival has not improved substantially due to lack of commonly expressed molecular targets and effective targeted therapeutics. Thus, better understanding of the biology of lung cancer and identification of novel therapeutic targets are urgently needed for development of highly effective molecularly targeted therapies. MATERIALS AND METHODS: Viability, proliferation and metastatic ability of lung cancer cells were evaluated using methylthiazoltetrazolium (MTT), colony formation and matrigel invasion assays, respectively. Western blotting, RT-PCR, and gene knockdown by siRNA transfections were carried out to investigate the effects of eEF-2K on lung cancer cells. Athymic Nu/Nu mice were treated with liposomal eEF-2KeEF-2K or control siRNA and tumor growth was evaluated in tumor xenograft models of lung cancer. RESULTS AND DISCUSSION: Here, we report that Eukaryotic Elongation Factor-2 kinase (eEF-2K), a member of an atypical alpha kinases family, is significantly upregulated in lung cancer cell lines and its expression is associated with shorter overall patient survival in lung cancer. Inhibition eEF-2K expression by siRNA or a chemical inhibitorsignificantly suppressed lung cancer cell proliferation, colony formation, survival, migration/invasion and tumorigenesis by inhibiting cyclin D1, Src and Mitogen-Activated Protein Kinases/Extracellular Signal-Regulated Kinase (MAPK/ERK) signaling. In vivo targeting of eEF-2K by systemically injected nanoliposomal eEF-2K siRNA resulted in a significant inhibition of lung cancer tumor xenografts in nude mice. Our results suggest, for the first time, that expression of eEF-2K is associated with poor patient prognosis and involved in regulation of critical pathways, including Src and MAPK/ERK and cyclin D1, promoting tumor growth and progression, and thus may be a novel potential therapeutic target in lung cancer.

Massive Pulmonary Embolism in a Patient with Heparin Induced Thrombocytopenia: Successful Treatment with Dabigatran.

Heparin induced thrombocytopenia (HIT) is a rare, potentially fatal, immune-mediated complication of heparin therapy, associated with thrombosis and thrombocytopenia. In this study, a successful dabigatran administration in a case with massive pulmonary thromboembolism (mPTE) and HIT is presented. 57 years-old female, who was receiving low molecular weight heparin (LMWH) (0.4 mL once a daily, S.C. for 11 days) due to total knee replacement, was referred to our clinic with the hypotension and syncope attacks. Her echocardiography and pulmonary CT angiography findings were consistent with mPTE. We detected a serious decrease in her platelet count highly suggestive for HIT (plt: 54×10(3)/µL). LMWH was discontinued and dabigatran was started (150 mg twice daily). After platelet count increased over 150×10(3)/µL, dabigatran was switched to warfarin. Since heparin is widely used in medicine, all physicians need to be aware of this life threatening complication of heparin. Replacing heparin with an alternative anticoagulant such as dabigatran may become a life-saving strategy especially in case of HIT complicated with mPTE.

Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer?

BACKGROUND: The aim of this study was to investigate oxidative stress and thiol/disulfide status with a novel automated homeostasis assay in advanced non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with advanced NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy subjects were chosen for the study. We measured plasma total thiol (-SH+-S-S-), native thiol (thiol) (-SH), and disulfide (-S-S-) levels in the patients with NSCLC and the healthy subjects. The thiol/disulfide (-SH/-S-S-) ratio was also calculated. RESULTS: Statistically significant differences between the patient group and the control group were detected for the thiol/disulfide parameters. The mean native thiol, total thiol, and disulfide levels were significantly lower in the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for native thiol and disulfide, respectively. Median overall survival (OS) was significantly shorter in patients with low native thiol and disulfide levels according to the cut-off value (respectively, P = 0.001; P = 0.006). Native thiol, total thiol, and disulfide levels were correlated with Karnofsky performance status (KPS), OS, and age. Additionally, hierarchical regression analyses showed gender, KPS, lung metastases, and plasma native thiol levels were the determinants of OS in the final model. CONCLUSION: These results suggest that in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels decrease, while the native thiol/disulfide ratio does not change. Low levels of thiol/disulfide parameters are related to tumor aggressiveness and may predict a poor outcome for patients with NSCLC.

The clinical significance of hematologic parameters in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystemic inflammatory granulomatous disease of unknown etiology. No suitable biomarkers are available to evaluate the prognosis of this disease, which still has an unpredictable clinical course. The aim of this study was to evaluate the potential clinical usefulness of hematologic markers. MATERIALS AND METHODS: We investigated 172 subjects: 116 patients with sarcoidosis and 56 healthy individuals at Suleyman Demirel University and Dr. Suat Seren Chest Diseases and Thoracic Surgery Training Hospital. Complete blood count, demographics and pulmonary function test data from sarcoidosis patients between 2008 and 2013 were evaluated and collated retrospectively. The cut-off values were determined by calculating the neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) of the patients. RESULTS: The cut-off values were determined as 2 and 8.95 for NLR and MPV, respectively. NLRs were significantly higher in sarcoidosis patients than in healthy controls (P < 0.001) and were directly correlated with erythrocyte sedimentation rate (ESR) levels (R = 0.183, P = 0.017). Receiver operator characteristic (ROC) curve analysis revealed a 0.83 [confidence interval (CI) 68.8%-88.4%] area under the curve, 80% sensitivity and 59% specificity at the cut-off of NLR. Higher NLRs (≥2) were detected in patients with sarcoidosis than in the control group (P < 0.001). Also, high NLRs were more frequent in patients with extrapulmonary involvement (P = 0.031). MPV values were not different between control and patient groups. CONCLUSIONS: NLR may be a biomarker with good sensitivity that is easily detected in serum. It can be proposed in clinical practice to identify a patient's prognosis. However, large prospective studies are required to further demonstrate the prognostic significance of these values.

Elevated serum matrix metalloproteinase-2 and -9 and their correlations with severity of disease in patients with community-acquired pneumonia.

BACKGROUND/AIM: To determine the role of matrix metalloproteinases (MMPs) and their relationship with the clinical course of community-acquired pneumonia (CAP). MATERIALS AND METHODS: Sixty-two consecutively hospitalized patients with CAP were enrolled and their pneumonia severity index (PSI), time to clinical stability (TCS), treatment response, and complications were recorded. The pre- and posttreatment serum concentrations of MMPs and their inhibitors were analyzed by ELISA. The activities of MMPs were evaluated by gelatin zymography. RESULTS: MMP-2 and -9 serum levels and their activities were higher in CAP patients than controls (P < 0.001 and P < 0.001, respectively). Low-risk patients had lower levels of MMP-2 and TIMP-1 than high-risk patients (P = 0.044, P = 0.001, respectively). Pretreatment serum TIMP-1 level was higher in patients with TCS of >3 days (P = 0.004) and was correlated with oxygenation and PSI scores. Posttreatment serum levels of MMP-9 and TIMP-1 were decreased after antibiotics (P = 0.000 1 and P = 0.0 17, respectively). CONCLUSION: Although MMP-2, MMP-9, and TIMP-1 correlate with many poor prognostic factors, more studies are required to prove their possible role in predicting the severity of CAP.

Evaluation of patients followed up in a cigarette cessation clinic.

OBJECTIVES: The aim of this study was to evaluate the demographic characteristics and factors determining success in a smoking cessation clinic in smokers who completed a 1-year follow up. METHOD: A total of 349 patients were assessed retrospectively. RESULTS: There were 238 men (mean age: 41+/-13.5 years) and 111 women (mean age: 37+/-11.9 years) (t-test P=0.004). The average age at which they began to smoke, number of years of smoking and the number of cigarettes/day were 17.5+/-5.2 years (median 17), 22.1+/-13.3 years, 23.5+/-12.0, respectively. Cigarette smoking was mostly observed in university graduates (56.8%) and a moderate negative correlation existed between education status and smoking duration (r=-0.27, P=0.000). Patients with a Fagerström Tolerance Questionnaire score of >or=6 and those exposed to cigarette smoke in childhood tended to commence and become committed smokers later in life (chi2=4.915, P=0.027). In all, 151 patients (43.26%) were successful in quitting (chi2=36.4, P=0.000). Of these, 87 (24.93%) used medication such as nicotine patches (13.5%), bupropion (7.2%), nicotine patches+bupropion (4.3%) and 64 (18.33%) refused medication, but came for professional support. CONCLUSION: Increased education level, behavioural therapy and intensive motivational support, follow-up visits and phone calls all appear to play important roles in smoking cessation. Families also play a major role.