Can serum progranulin level be used as a prognostic biomarker in non-small cell lung cancer?

Progranulin has been considered to be a poor prognostic biomarker for some types of malignancies. However, the clinical significance of serum progranulin level and the prognostic value are still not explored in advanced stages of lung cancer.  The current study investigates the prognostic significance of progranulin serum levels in advanced-stage non-small cell lung cancer (NSCLC) patients. This study involved 94 subjects (70 advanced-stage NSCLC patients and 24 healthy controls). Serum progranulin level was measured by enzyme-linked immunosorbent assay (ELISA) and was correlated with patient outcome. The association between circulating progranulin level and clinicopathological parameters was detected. Serum progranulin cut-off level predicting six-month survival was determined. Serum progranulin level was found significantly elevated in NSCLC patients than in the control group (p<0.001). We did not determine a significant difference between stage IIIB and stage IV NSCLC patients for serum progranulin levels (p=0.166). When we evaluated the laboratory parameters, only serum LDH level was found significantly correlated with serum progranulin level (p=0.043), also bone and liver metastasis showed a significant correlation with progranulin level (p=0.008 and p = 0.024, respectively). The cut-off level of serum progranulin in predicting six months of survival was determined as 16.03 ng/ml (AUC = 0.973, 95%Cl: 0.903-0.997, p<0.001) with 97.06% sensitivity and 88.89% specificity. Overall survival was determined shorter in patients with progranulin level ≥16 ng/ml than those with <16 ng/ml (p<0.001). Also, in the multivariate analysis using the Cox regression model serum progranulin level was found as an independent prognostic factor for NSCLC (p=0.001). Serum progranulin level may be a useful biomarker for predicting poor survival in advanced-stage NSCLC patients.

Dietary intake of patients with moderate to severe COPD in relation to fat-free mass index: a cross-sectional study.

BACKGROUND: Fat-free mass (FFM) depletion has been shown to be a better predictor of mortality than BMI in chronic obstructive pulmonary disease (COPD) patients. The specific aim of the current study was to assess the nutritional status of stable COPD patients in relation to fat free mass index profiles. METHODS: We investigated 65 male moderate-to-severe stable COPD patients. A self-reported questionnaire was applied about general characteristics and smoking history. Nutritional intake was assessed by using a 54-item quantitative food frequency questionnaire. Weight, height, mid-upper arm circumference (MUAC), waist circumference (WC), handgrip strength and body composition measurements were taken by a trained dietitian. The data were analyzed with SPSS 15.0 software. RESULTS: The mean age of the patients was 62.1 ± 8.9 years. Among all of the patients 13.8% was underweight (BMI < 21 kg/m(2)) and 18.5% had a low fat-free mass index (FFMI < 16 kg/m(2)). The percentages of the patients who did not meet the daily recommended intakes (RNI) were highest for magnesium (93.8%) and calcium (92.3%). Mean daily consumptions of milk-yogurt, red meat and fruits were significantly low in the low FFMI group compared to normal FFMI group (for all; p < 0.05). Patients with normal FFMI had significantly higher weight, height, WC, MUAC, handgrip strength, fat and fat-free mass than the patients with low FFMI (for all; p < 0.05). CONCLUSIONS: Dieticians should be aware of COPD patients with low FFMI in order to evaluate the nutritional intake and therefore plan nutritional strategies to improve prognosis of the disease.

Pulmonary lymphangioleiomyomatosis: a rare case.

Lymphangioleiomyomatosis is an uncommon lung disease primarily affecting women of childbearing age. It is characterized by the progressive proliferation and infiltration of smooth muscle-like cells, which lead to cystic destruction of the lung parenchyma; obstruction of airways, blood vessels, and lymphatics; and loss of pulmonary function. We present the case of a 46-year-old female patient with chest pain, cough, sputum, and dyspnea on exertion for three weeks. Minimal pneumothorax was noted, and the patient was referred to our center for further investigation and treatment. High-resolution computed tomography revealed numerous bilateral thin-walled air cysts and interstitial thickening affecting the central and peripheral part of the upper zone of the lung. We performed an open-lung biopsy to confirm lymphangioleiomyomatosis. Our aim is to discuss the pathogenesis and other lesions noted in the differential diagnosis of this rare disease.

C-reactive protein levels are raised in stable Chronic obstructive pulmonary disease patients independent of smoking behavior and biomass exposure.

BACKGROUND: The aim of this case control study is to assess the relationship between serum C-reactive protein (CRP) levels and well-known clinical parameters in Chronic obstructive pulmonary disease (COPD) considering the impact of smoking behavior, biomass exposure and accompanying clinical entities, namely pulmonary hypertension, systemic hypertension and diabetes mellitus. METHODS: Spirometry, echocardiography, arterial oxygen saturation (SpO2) measurements, BODE scores and serum CRP levels were investigated in stable COPD patients. Associations between CRP levels and clinical parameters were evaluated. RESULTS: CRP levels are significantly higher in COPD patients than in healthy controls. CRP levels were not significantly different between COPD patients treated with inhaled corticosteroids and those not treated. CRP levels significantly correlated with age, FEV1% predicted, FVC% predicted, SpO2, MMRC, 6 minute walk distance, BODE scores and haemoglobin levels. In multivariate analysis BODE scores and concomitant systemic hypertension manifested the strongest association with CRP levels. CRP levels in COPD patients with and without pulmonary hypertension were significantly different. CRP levels did not differ significantly according to smoking status or biomass exposure, moreover COPD cases due to biomass exposure who never smoked also had higher CRP levels compared to healthy controls. CONCLUSIONS: Systemic inflammation is inherent to COPD independent of ever-smoking status and correlates with disease severity, concomitant systemic hypertension and pulmonary hypertension.

Factors associated with treatment outcome in 64 HIV negative patients with multidrug resistant tuberculosis.

OBJECTIVES: In this study we aimed to determine the factors associated with treatment outcome in HIV negative patients with multidrug resistant tuberculosis (MDR TB). MATERIALS AND METHODS: The study comprised 64 (43 female and 21 male) patients in whom second line TB drugs were administered in directly observed treatment (DOT) programme. Achievement of sputum AFB (acid fast bacilli) negativity in the 3rd month of the treatment was accepted as the bacteriologic response. Treatment outcome of the patients and the factors influencing the bacteriologic response were evaluated. RESULTS: The mean time of sputum smear negativity was determined as 3±2.2 months. Bacteriologic response was determined in 73.4% of the patients. The mean duration time of the treatment was 16.4±8.2 months. Treatment outcome of the patients was determined as cure in 34 (53.1%), default in 18 (28.1%), treatment failure in 1 (1.6%) and exitus in 3 (4.7%) patients. Also, in 8 (12.5%) patients treatment was incomplete and continued. Adverse effects of the drugs were seen in 39 (60.9%) patients with the most frequency of gastrointestinal disturbance (51.5%), psychiatric disorders (15.6%), dermatological effects (12.5%). In logistic regression analysis only presence of cavity and the extensive disease were found to be associated with poor bacteriologic response (OR=1.5, 95% CI: 1.23-1.82, P=0.01 and OR=2, 95% CI: 1.42-2.79, P=0.00, respectively). CONCLUSIONS: Although radiological findings might affect the bacteriologic response, MDR TB is a treatable disease if regular and appropriate treatment regimen is administered.

The role of CD14 gene promoter polymorphism in tuberculosis susceptibility.

BACKGROUND: CD14 is expressed principally by cells of monocyte/macrophage lineage and plays a pivotal role in the innate immunity to intracellular infections. Recent research findings have revealed an association between the CD14 gene promoter polymorphism and several major infectious diseases. OBJECTIVE: The aim of the present study was to investigate the association between the CD14-159C/T polymorphism and tuberculosis in a Turkish population. METHODS: For this purpose, 88 consecutive patients with tuberculosis (63 pulmonary, 25 extrapulmonary) and 116 control subjects were enrolled into a prospective study. We determined CD14-159 genotypes by polymerase chain reaction - restriction fragment length polymorphism analysis and also measured serum concentrations of soluble CD14 (sCD14) by using a quantitative sandwich enzyme immunoassay technique. RESULTS: There was no significant difference in terms of genotype distribution between patients with tuberculosis (CC 18.2%, CT 48.9%, TT 33.0%) and controls (CC 12.9%, CT 50.9%, TT 36.2%) or between patients with pulmonary and extrapulmonary tuberculosis. Serum levels of sCD14 were significantly increased in patients with active tuberculosis compared to those with inactive tuberculosis and healthy controls (p<0.001). However, levels of sCD14 were not associated with any genotypes of CD14-159. CONCLUSION: The genotyping findings of the present study do not support a role for the CD14-159C/T polymorphism in the development of tuberculosis, at least in the geographical region of central Anatolia. Significantly elevated serum sCD14 levels in patients with active disease reflect the importance of the mononuclear phagocytic system activation in tuberculosis.

Are all granulomatous lesions tuberculosis?

INTRODUCTION: Granulomatous reactions are seen in a wide variety of diseases. METHODS: We present 3 cases referred to our clinic with presumptive diagnosis of tuberculosis (TB) were diagnosed as nontuberculous granulomatous diseases. RESULTS: Three cases were diagnosed as Tularemia, Cat-Scratch Disease (CSD) and idiopathic granulomatous mastitis (IGM) respectively. CONCLUSION: In countries with high incidence of TB, TB is considered firstly in differential diagnosis of granulomatous diseases. Detailed anamnesis and physical examinations should be done in differential diagnosis of granulomatous diseases, and TB must be excluded.

Correlation of plasma transforming growth factor beta 1 with asthma control test.

Assessment of asthma with a control test is suggested as a relevant approach for recent years. Ideally, an asthma control test should apply not only to clinical manifestations but also to laboratory markers of inflammation as well. Until now, this could not be performed because of the lack of a confirmed marker which indicates inflammation. A fibrotic mediator TGF-beta 1 has been reported as a key mediator of remodeling in asthma. The aim of this study is to evaluate plasma TGF-beta 1 level in stable asthmatic sufferers and to investigate its correlation with the asthma control test. Stable asthmatic sufferers and healthy controls were recruited for this study. After obtaining demographic information, skin prick and asthma control tests were performed. Blood samples were collected for plasma TGF-beta 1 level. Any contributing factors that may affect plasma TGF-beta 1 level were excluded from both groups. Thirty-five atopic, 35 nonatopic asthmatic sufferers and 15 healthy control subjects were included for this study. The mean age was 38 +/- 10 (years) and 61% were female. When the asthmatic group compared with the control group, plasma TGF-beta 1 level was significantly higher in the asthmatic group (41.7 +/- 12.6 ng/mL versus 27.6 +/- 13 ng/mL) (p < 0.05) whereas it was similar among the atopic and nonatopic groups (41.8 +/- 14.2 ng/mL versus 41.6 +/- 11 ng/mL) (p > 0.05). Spearman Correlation Analysis results pointed positive correlation between uncontrolled asthma and plasma TGF-beta 1 level. This study shows that plasma TGF-beta 1 level may be a systemic marker of asthma control.

Helicobacter pylori in bronchiectasis: a polymerase chain reaction assay in bronchoalveolar lavage fluid and bronchiectatic lung tissue.

BACKGROUND: A number of studies have implicated an association between H. pylori and diverse extra-gastroduodenal pathologies. Chronic inflammation and increased immune response have been observed in bronchiectasis, likely gastroduodenal inflammatory diseases. H. pylori has been found in the trachea-bronchial aspirates of mechanically ventilated patients. Furthermore, the seroprevalence of H. pylori was found to be significantly higher in patients with bronchiectasis than in the control group. The present study was performed to investigate the possible role of H. pylori in the pathogenesis of bronchiectasis. METHODS: Prospectively, bronchoalveolar lavage fluid (BALF) was obtained from patients with bronchiectasis (n=26) and control (n=20). BALF was subjected to polymerase chain reaction (PCR) to determine the presence of H. pylori and serum IgG against H. pylori was determined with micro-ELISA kit. In addition, PCR was performed to determine H. pylori in surgically removed lung tissues from patients with bronchiectasis (n=97). RESULTS: H. pylori DNA was not detected in the BALF or in lung tissue samples. In addition, anti-H. pylori IgG level in patients with bronchiectasis did not show statistically significant difference from that of the control. CONCLUSIONS: Our study provided evidence that there might be no direct association between H. pylori and bronchiectasis; however, the indirect role of soluble products of H. pylori could not be excluded.

[The role of serum neopterin level in the evaluation of activation and response to treatment in the patients with pulmonary tuberculosis]. / Akciger tüberkülozlu hastalarda aktivasyon ve tedaviye yanitin degerlendirilmesinde serum neopterin düzeyinin yeri.

Neopterin is an important parameter showing cell mediated immunity activation. In this study we aimed to determine whether serum neopterin level could be used as a marker in the evaluation of tuberculosis activation and response to treatment. The study comprised 40 new case smear positive pulmonary tuberculosis patients and 40 healthy control. Serum neopterin levels were measured both before the treatment and 2nd month of the treatment in the patient group. The association between serum neopterin level and clinical, radiological and bacteriological parameters were also investigated. In patients with pulmonary tuberculosis the mean levels of serum neopterin were 35.1+/-13.4 nmol/L before the treatment and 21.2+/-10.4 nmol/L in the 2nd month of the treatment. In the control group, serum neopterin level was 19+/-10.4 nmol/L. The serum neopterin levels of the patients were significantly higher than the control group (p=0.001). Also, there was significant difference between serum neopterin levels before the treatment and the 2nd month of the treatment (p=0.000). Serum neopterin level was higher in the group with extensive disease than the cases with limited disease (p=0.02). In conclusion, we think that serum neopterin level might be used as a reliable immunological marker in the evaluation of tuberculosis activation and response to treatment.

Evaluation of the relationship between cockroach sensitivity and house-dust-mite sensitivity in Turkish asthmatic patients.

Exposure to cockroach has been identified as an important source of indoor allergens in patients with asthma and allergic rhinitis. We evaluated the relationship between cockroach sensitivity and other allergens in patients with asthma. A total of 114 patients, defined asthma according to GINA, were enrolled in this study. A questionnaire including age, sex, duration of asthma, history of cockroach presence at home, and total IgE, blood eosinophil count, pulmonary function tests, standard skin prick test additional cockroach and shrimp allergen were performed. There were 84 (73.7%) female and 30 (26.3%) male patients with a mean age of 38.1+10.1 years. The average duration of asthma was 7.7+7.2 years. Sixty five (57%) patients were determined atopic and 49 (43%) nonatopic. Pollen allergen was the most common allergen in 59 (51.8%) patients with asthma, and second common allergen was mite allergen in 43 (37.7%) patients. Cockroach sensitivity were detected in 23 (20.2%) of 114 all asthmatics and 23 (35%) of atopic asthmatics. High rates of house-dust-mite allergy (73.9%) was determined in patients with cockroach sensitivity (P<0.05), while we found no relationship with other allergens. There was no difference for cockroach sensitivity between rural and urban population. Cockroach sensitivity was more common in mild bronchial asthmatics and a female predominance was observed. In addition, there was no association between shrimp and cockroach sensitivity. As a result, a high rate of cockroach sensitivity alone or with mite sensitivity was seen in patients with bronchial asthma in Turkish population. Because of cross-reactivity between mites and cockroach, cockroach sensitivity should be investigated in patients with house-dust-mite allergy. In addition, a high rate of cockroach sensitivity, in terms of IgE sensitization, may be important for the development of new sensitizations.

The assessment of validity of different asthma diagnostic tools in adults.

BACKGROUND: The diagnosis of asthma is based on the presence of symptoms. Lung function measurements such as forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) variability and airway hyperresponsiveness support the clinical diagnosis. However, asthma is still an under- or overdiagnosed disease. OBJECTIVES: The aim of this study was to identify which test(s) is the most valuable for making the diagnosis of asthma by using patients with asthma-like symptoms as a reference population. METHODS: One hundred patients admitted to an asthma outpatient clinic of an education and research hospital and 23 non-smoking healthy control subjects were included in this study. An asthma questionnaire, spirometric tests, monitoring of PEF variability during two weeks, non-specific bronchial challenge test with methacoline, skin prick tests (SPT) with common aeroallergens, measurements of serum total IgE and blood eosinophil counts were applied to all cases. RESULTS: Sixty of one hundred patients were diagnosed with asthma, whereas the 40 remaining participant were accepted as pseudoasthma due to a diagnosis of another cause for their symptoms. The sensitivity and specificity of the methacholine challenge test was 96.5% and 78.4%, respectively. While the most sensitive test was a methacholine challenge test, the most specific test was the reversibility test. The test with the highest correlation of a positive result and asthma was the reversibility test. However, the highest correlation with a negative result was found with the methacholine challenge test. SPT positivity, serum total IgE and eosinophilia had low sensitivity and moderate specificity. The most specific question was "have you had an attack of shortness of breath that came on during the day when you were at rest at any time?", whereas the most sensitive question was "have you had an attack of shortness of breath that came on following strenuous activity at any time?" In addition, the questions "have you had an attack of shortness of breath that came on following strenuous activity at any time?" and "have you woken up with an attack of wheezing at any time?" had significant correlation with the results of the methacholine challenge test. CONCLUSIONS: We have shown that the methacholine challenge test is the most valuable diagnostic tool for asthma. In addition, there is a significant correlation between the methacholine challenge test and some patient symptoms.