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Background: Vascular endothelial growth factor (VEGF) may play a role in pleural fluid formation, as it represents a potent inducer of capillary permeability. We aimed to investigate the diagnostic utility of VEGF levels in pleural fluid and serum in patients with pleural effusions with initially negative diagnostic work up. Methods: Seventy-one patients with exudative lymphocytic pleural effusions undiagnosed after initial diagnostic work up were enrolled in this prospective study and their clinical course was followed up to 24 months. VEGF levels were measured in serum and pleural fluid by using immunoenzymometric assay. Results: During the follow up period, in 43 patients the pleural effusion was eventually attributed to malignancy while in the rest 28 patients it was due to non-malignant causes (benign and unknown origin). Patients with malignancy had significantly higher VEGF levels in pleural fluid compared to patients with non-malignant effusions (1,506 vs. 588 pg/dL, P=0.0001), while no statistically significant difference was found in the VEGF serum levels between the two groups. Conclusions: Pleural VEGF levels may be helpful in identifying malignant pleural effusion (MPE) in patients with negative diagnostic work up at the initial assessment and help in selecting patients for more invasive procedures.

To assess the value of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) as prognostic serum markers for intraperitoneal adhesions.Postoperative adhesions are associated with serious complications responsible for increased patient's morbidity.Forty-eight rabbits were used and randomized into groups A, B, C, and D. Abdominal laparotomy and experimental adhesion formation model was carried out. In group A, 60 mL of N/S 0.9% were instilled intraperitoneally, in group B 60 mL of icodextrin 4% were instilled intraperitoneally, in group C 0.1 mL/kg of dimetindene maleate were administered intravenously, and in group D both agents were administered. Prior to euthanasia 0.5 mL of blood was obtained. The type, the surface area of adhesions, and serum concentration of MMPs were assessed.The mean surface area and Zuhlke classification of adhesions of groups B, C, and D has been proved to be significantly lower compared to group A. Serum MMP-2 levels were significantly higher in groups B and D than in group A, while group D was higher when compared to group C. Serum MMP-9 levels were significantly higher in group D compared to groups A, B, and C. Serum MMP-9 was the most accurate test to differentiate between animals with and without adhesions with a sensitivity of 81.8% and a specificity of 100% at a cut-off point of 21.5 (AUC = 0.934).The administration of icodextrin 4% and dimetindene maleate seems to prevent postoperative adhesion formation. Serum levels of MMP-2 and MMP-9 may serve as prognostic markers to identify postoperative adhesions.

Eur J Clin Invest 2011; 41 (4): 349–356 Abstract Background The imbalance between oxidants and antioxidants is referred to as oxidative stress and has been associated with various respiratory disorders. The aim of this study was the assessment of 8-isoprostane (8-iso-PGF2α) and Cu/Zn superoxide dismutase (Cu/Zn SOD) in exudative pleural effusions in order to examine the diagnostic accuracy of these markers in the differentiation between complicated and uncomplicated parapneumonic effusions. Methods The study included 214 consecutive patients with pleural effusions [68 parapneumonic (31 uncomplicated parapneumonic, 20 complicated parapneumonic, 17 empyemas), 24 tuberculous, 88 malignant and 34 transudates]. 8-Isoprostane and Cu/Zn SOD were determined by ELISA in pleural fluid and serum. Results Parapneumonic effusions were characterized by higher pleural fluid 8-isoprostane levels compared to transudative, malignant and tuberculous effusions. Pleural fluid Cu/Zn SOD levels were lower in transudates, while serum levels were higher in transudative compared to all exudative pleural effusions. Both pleural fluid 8-isoprostane and Cu/Zn SOD were higher in complicated parapneumonic effusions and empyemas compared to uncomplicated parapneumonic effusions. Pleural fluid 8-isoprostane was the most accurate test to differentiate between complicated and uncomplicated parapneumonic pleural effusions with a sensitivity of 100% and a specificity of 58·1% at a cut-off point of 35·1 (AUC = 0·848). Conclusions Pleural fluid 8-isoprostane and Cu/Zn SOD may provide useful information for the differentiation between uncomplicated and complicated parapneumonic effusions and empyemas.

Background Matrix metalloproteinase-9 (MMP-9) plasma levels correlate with C-reactive protein (CRP) concentrations and they are both increased in adults with obstructive sleep apnea (OSA). No studies have evaluated MMP-9 levels in children with sleep apnea and CRP is not consistently elevated in pediatric OSA. The aim of this investigation was to evaluate the association of severity of OSA, adiposity, and CRP with MMP-9 plasma levels in Greek children. Methods Consecutive children with snoring who underwent polysomnography and were found to have OSA (obstructive apnea–hypopnea index—OAHI ≥ 1 episode/hr) were recruited. Subjects without OSA (OAHI 0.05) and CRP concentrations (0.22 ± 0.29 mg/dl vs. 0.21 ± 0.36 vs. 0.13 ± 0.16 mg/dl; P > 0.05). In multiple linear regression, body mass index (P = 0.027) and CRP levels (P = 0.008), but not OAHI or SpO2 nadir (P > 0.05), were significantly related to MMP-9 values. Conclusions Adiposity and systemic inflammation unrelated to OSA severity, modulate MMP-9 levels in Greek children. Pediatr Pulmonol. 2010; 45:693–699. © 2010 Wiley-Liss, Inc.

The aim of this study was to determine the impact of HRCT-confirmed emphysema on biomarkers evaluating airway and systemic inflammation in COPD patients. Forty-nine consecutive male COPD outpatients with stable COPD were divided in two groups according to the presence or absence of emphysema on HRCT. Patients underwent pulmonary function tests, plus assessment of exercise capacity, body composition and quality of life. Biomarkers were measured in serum (CRP, interleukin-6, TNF-alpha, leptin, adiponectin, osteocalcin, insulin growth factor-1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole blood (B-type natriuretic peptide). TNF-alpha, 8-isoprostane and pH were additionally measured in exhaled breath condensate. Patients with emphysema had more severe lung function impairment, lower body-mass index and fat-free mass index, and poorer quality of life. Additionally, they presented increased systemic oxidative stress and plasma fibrinogen and lower BNP compared to patients without emphysema. After proper adjustment for disease severity, all differences remained with the exceptions of body-mass index, fat-free mass index and BNP. COPD patients with HRCT-confirmed emphysema present increased systemic oxidative stress and fibrinogen, suggesting that they may be more prone to the systemic consequences of COPD compared to patients without emphysema.

Background Idiopathic pulmonary fibrosis (IPF) is a fatal illness characterized by progressive fibrosis resulting in severe dyspnea and impairment of lung function. Although the mechanisms by which lung fibrosis develops are not fully ascertained, recent findings suggest that oxidative stress may play an important role in the pathogenesis of tissue fibrosis. Aim To evaluate the oxidative stress in the serum of patients with IPF and to explore the relationship between oxidative stress levels, dyspnea and impairment of lung function. Material and methods Blood samples from 21 untreated patients with IPF, sequentially recruited over a period of 2 years, and 12 controls were analyzed. The level of oxidative stress in the blood was determined through a spectrophotometric procedure (D-ROMs test). FVC and DLCO were measured in all patients. The level of dyspnea was assessed by the Medical Research Council (MRC) chronic dyspnea scale. Results Serum levels of oxidative stress were significantly increased in patients with IPF compared to controls (mean±SEM: 356.8±14 and 201±10 Carratelli units respectively, p p 0.01 , r = - 0.79 ) and with DLCO ( p 0.01 , r = - 0.75 ). Furthermore, oxidative stress was significantly correlated with MRC dyspnea score ( p 0.01 , r = 0.87 ). Oxidative stress measurements were highly reproducible on two consecutive measurements in the same patients. Conclusion The levels of systemic oxidative stress are enhanced in patients with IPF and could provide useful information about the classification of IPF severity. Strategies to reduce the oxidant burden in IPF may be beneficial in reducing the progressive deterioration of these patients.

Background: Non-dipping pattern of circadian blood pressure in preeclampsia is associated with an increased risk of cardiovascular disease. The pathogenetic mechanisms of this relationship are still unclear. We investigated whether non-dipping in preeclampsia could relate to endothelial activation or damage. Methods: Participants, 20 women with normal pregnancy (mean age 29.9 ± 5.7 years) and 31 women with preeclampsia (mean age 29.1 ± 5.1 years), un- derwent 24-hour ambulatory blood pressure monitoring. Plasma levels of von Willebrand factor (vWf), marker of endothelial damage and of soluble adhesion molecules (sVCAM-1, sICAM-1), and markers of endothelial activation were determined using commercially available enzyme-linked immunoassays. Results: Based on whether the nocturnal mean arterial pressure (MAP) relative to the daytime MAP declined by less than 10%, 21 women with preeclampsia were categorized as non-dippers. Compared to healthy pregnant women, patients with preeclampsia showed significantly enhanced levels of vWf (206.9 ± 40.6 vs. 123 ± 24 IU/dl;pConclusion: Nocturnal hypertension in preeclampsia is associated with elevated levels of molecules related to endothelial damage. Endothelial damage is a recognized pathogenetic factor for atherosclerosis and history of preeclampsia is a risk factor for cardiovascular disease. In this context, possible clinical im-plications of our findings deserve further investigation.

Acute-phase markers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), have been studied in inflammatory and malignant disorders. We examined the diagnostic value of these markers for the differentiation among parapneumonic, tuberculous and malignant effusions. We studied 124 patients with pleural effusions, classified as exudates [total (n=97), parapneumonic (n=15), tuberculous (n=25), malignant (n=57)] and transudates due to congestive heart failure (n=27). CRP, IL-6 and TNF-alpha were measured in pleural fluid and serum. Pleural fluid CRP was higher in parapneumonic compared to tuberculous and malignant effusions, providing 100% sensitivity for a cut-off point of 5.3mg/dL. IL-6 was higher in both parapneumonic and tuberculous compared to malignant effusions. TNF-alpha was higher in tuberculous compared to malignant effusions, providing 96.0% sensitivity, and 93.0% specificity for a cut-off point of 88.1 pg/mL. Pleural fluid CRP levels were lower than serum in all groups, probably reflecting systemic inflammation, whereas IL-6 and TNF-alpha were higher in pleural fluid indicating local production. Our data suggest that these markers may provide useful information for the differentiation of infectious and malignant effusions in clinical practice. However, further studies are needed for the validation of these findings in usual clinical circumstances.

Background and Aim. Hyaluronic acid (HA) is a component of extracellular matrix and may play a role in the pleural inflammation which is implicated in parapneumonic effusions.The aim of the current study was to investigate HA levels in serum and pleura in patients with parapneumonic effusions. Methods. We prospectively studied pleural and serum levels of HA in 58 patients with pleural effusions due to infection (complicated and uncomplicated parapneumonic effusions), malignant effusions and transudative effusions due to congestive heart failure. In addition to HA, TNF-α and IL-1β levels were determined in pleural fluid and serum by ELISA. Results. The median±SD HA levels (pg/ml) in pleural fluid of patients with complicated effusions (39.058±11.208) were significantly increased (p

Study objectives: Oxidative stress has been associated with various respiratory disorders. We tested the hypothesis that exudates would present higher levels of oxidative stress compared to transudates, expressing the increased local oxidative burst in the former. Design: Prospective, cross-sectional study. Patients or participants: One hundred six consecutive patients who had undergone thoracentesis were studied. Ninety patients with a final diagnosis of pleural effusion were further analyzed. Setting: The respiratory department and a clinical laboratory of a tertiary hospital. Interventions: Subjects underwent diagnostic thoracentesis, and standard biochemical parameters ( ie , total protein, lactate dehydrogenase, and albumin levels) were measured in pleural fluid and serum. Oxidative stress levels were assessed with a commercially available method (d-ROMs test; Diacron; Grosseto, Italy) that uses conventional Carratelli units (UCarr). In 14 patients, duplicate measurements of oxidative stress and a second thoracentesis were performed on the following day for the assessment of the repeatability of measurements. Receiver operating characteristic (ROC) analysis was performed in order to determine the optimal cutoff level for the differentiation between exudates and transudates. Measurements and results: Oxidative stress levels were higher in exudates compared to transudates (mean [± SD] stress level, 274 ± 72 vs 126 ± 34 UCarr, respectively; p Conclusions: Oxidative stress levels are higher in exudative pleural effusions compared to transudative effusions, probably due to reactive oxygen species produced in the former.

Study objectives. To assess serum amyloid alpha (SAA) pleural fluid levels in parapneumonic effusion (PPE) and to investigate SAA diagnostic performance in PPE diagnosis and outcome.Methods. We studied prospectively 57 consecutive patients with PPE (empyema (EMP), complicated (CPE), and uncomplicated parapneumonic effusion (UPE)). SAA, CRP, TNF-α, IL-1β, and IL-6 levels were evaluated in serum and pleural fluid at baseline. Patients were followed for 6-months to detect pleural thickening/loculations.Results. Pleural SAA levels (mg/dL) median(IQR) were significantly higher in CPE compared to UPE (P<0.04); CRP levels were higher in EMP and CPE compared to UPE (P<0.01). There was no significant difference between IL-1β, IL-6, TNF-α level in different PPE forms. No significant association between SAA levels and 6-month outcome was found. At 6-months, patients with no evidence of loculations/thickening had significantly higher pleural fluid pH, glucose levels (P=0.03), lower LDH (P=0.005), IL-1β levels (P=0.001) compared to patients who presented pleural loculations/thickening.Conclusions. SAA is increased in complicated PPE, and it might be useful as a biomarker for UPE and CPE diagnosis. SAA levels did not demonstrate considerable diagnostic performance in identifying patients who develop pleural thickening/loculations after a PPE.

Background: Matrix metalloproteinases (MMPs) have been implicated in the escalation of fibrosis and remodeling which are central to the subsequent progression of a parapneumonic pleural effusion to empyema. Objectives: The aim of this study was the assessment of MMP-2, MMP-8 and MMP-9 in parapneumonic pleural effusions in order to examine their value in the differentiation between uncomplicated and complicated parapneumonic effusions. Methods: The study included 208 consecutive patients with pleural effusions [60 parapneumonic (27 uncomplicated parapneumonic, 17 complicated parapneumonic, 16 empyemas), 24 tuberculous, 89 malignant and 35 transudates]. Concentrations of pleural fluid and serum MMP-2, MMP-8 and MMP-9 were determined by immunoassay. Results: Pleural fluid MMP-8 and MMP-9 levels were higher in complicated parapneumonic effusions or empyema than in uncomplicated effusions, while their serum levels were higher in complicated parapneumonic effusions. MMP-2 levels were higher in uncomplicated than in complicated parapneumonic effusions or empyema. Pleural fluid MMP-2/MMP-9 ratio was the best marker to differentiate complicated from uncomplicated parapneumonic effusions, with a sensitivity of 94.1% and a specificity of 77.8% at a cut-off point of 1.32 (AUC = 0.887). Conclusions: Pleural fluid MMP-2, MMP-8 and MMP-9 may provide useful information for differentiating between uncomplicated and complicated parapneumonic effusions.

Background: Many patients with pneumonia develop pleural effusions. Pleural fluid vascular endothelial growth factor (VEGF) levels are known to be elevated in complicated parapneumonic effusion and seem to play a major role in the fibrotic process in the pleura. Objectives: To test whether VEGF levels in pleural effusions of infectious origin correlate with the residual pleural thickening. Methods: VEGF levels were measured in the pleural fluid of 45 patients with pleural effusion of infectious origin. Patients were reassessed 3 months after hospital discharge and residual pleural thickening (RPT) was recorded using a simple chest radiograph. Results: Pleural fluid VEGF was higher in empyemas compared to simple parapneumonic and complicated parapneumonic effusions. RPT was higher in patients with empyemas compared to simple parapneumonic effusions. Patients with RPT >2 mm had higher pleural fluid LDH and pleural fluid to serum LDH ratio, lower glucose and pH and higher VEGF levels. However, patients with RPT ≧10 mm differed only in pleural fluid VEGF levels. Pleural fluid VEGF levels correlated to RPT and to pleural fluid pH. VEGF presented moderate performance for the prediction of RPT 3 months after hospital discharge. Its performance was comparable to that of pleural fluid glucose and pH for the development of a radiologically significant RPT >2 mm, whereas it was the only statistically significant predictor of a clinically significant RPT ≧10 mm. Conclusion: VEGF levels are elevated in complicated parapneumonic effusions and empyemas compared to simple parapneumonic effusions and are a significant predictor for the development of clinically significant RPT.

A local redox imbalance has been reported in pulmonary sarcoidosis. However, so far no study has described a systemic redox imbalance in this context. The aim of the present study was to evaluate the systemic oxidative stress in patients with sarcoidosis and determine its relationship to treatment and indices of disease severity.35 patients with histologically proven pulmonary sarcoidosis and 13 healthy volunteers were included in the study. All patients were studied during a stable phase of their disease. Systemic oxidative stress was quantified in serum with the use of a commercially available spectrophotometric method (D-ROM test) which determines overall oxidative stress, by measuring total hydroperoxides. Oxidative stress was expressed in conventional units, i.e. Carratelli Units (UCarr), where 1 UCarr corresponds to 0.8 mg/L H(2)O(2).Serum oxidative stress levels were significantly higher in patients with sarcoidosis compared to those of normal subjects (390+/-25 vs 300+/-18 UCarr respectively, p=0.04). Patients not receiving systemic corticosteroids had higher levels of oxidative stress compared to steroid-treated patients (461.5+/-38 vs 315+/-20, p0.01) and compared to controls (461.5+/-38 vs 300+/-18 UCarr, p0.01). Oxidative stress did not correlate with diffusion lung capacity (DLCO), partial arterial oxygen tension (PaO(2)), MRC dyspnoea scale or chest X-ray stage.Systemic oxidative stress is increased in patients with stable pulmonary sarcoidosis who do not receive systemic corticosteroids. This finding suggests a sustained oxidative burden even when clinical, functional and radiological criteria indicate disease stability.

Adenotonsillar tissue of children with obstructive sleep-disordered breathing (SDB) has increased content of cysteinyl leukotrienes (CysLTs) and expression of CysLTs receptors. Furthermore, CysLTs concentrations in the nasal exhaled breath condensate of children with sleep apnea are elevated.To investigate the relationship between urine levels of CysLTs and severity of SDB in children.Morning urine concentrations of CysLTs were measured in children with symptoms of SDB and in control subjects with recurrent tonsillitis and without snoring who underwent polysomnography and were expressed in pg/mL per mg/dL of urine creatinine.Nineteen children with moderate-to-severe SDB (mean [+/- SD] age, 5.4 +/- 1.6 years; obstructive apnea-hypopnea index [OAHI]: 14.4 +/- 9.6 episodes/h), 29 subjects with mild SDB (5.1 +/- 1.5 years; OAHI: 2.9 +/- 0.8 episodes/h), 26 children with primary snoring (PS) [7 +/- 2.6 years; OAHI: 1.1 +/- 0.3 episodes/h], and 18 control subjects (6.4 +/- 2.5 years; OAHI: 0.7 +/- 0.3 episodes/h) were studied. Children with moderate-to severe SDB had higher log-transformed urine CysLTs levels than those with mild SDB, PS, or control subjects (2.39 +/- 0.51 vs 2.06 +/- 0.26 vs 2.11 +/- 0.25 vs 1.86 +/- 0.28; p0.05). Log-transformed CysLTs concentration, tonsillar size, and body mass index z score were significant predictors of log-transformed OAHI (p0.01).Urine excretion of CysLTs is related to SDB severity in children. This finding indicates that 5-lipoxygenase pathway products participate in the pathogenesis of obstructive sleep apnea in childhood or alternatively that SDB promotes CysLTs biosynthesis.

The acute effect of secondhand smoke (SHS) on lung function and the duration of system disruption remain unknown.To assess the SHS effects and their duration on lung function and inflammatory markers.In a randomized single-blind crossover experiment data were obtained from 16 (8 women) nonsmoking adults at baseline and at 0, 1, and 3 hours after a 1-hour SHS exposure set at bar/restaurant SHS levels.Serum and urine cotinine, lung function, and cytokines IL-4, IL-5, IL-6, tumor necrosis factor (TNF)-alpha, and IFN-gamma. At 0 hours most lung function parameters were significantly reduced (indicative: FEV(1), 4.3 +/- 0.4 vs. 3.8 +/- 0.3 L; FEV(1)/FVC, 0.9 +/- 0.1 vs. 0.8 +/- 0.1; P0.05) but at 3 hours they were at baseline levels. In contrast, cotinine (serum, 8.9 +/- 3.2 vs. 35.5 +/- 10.2 ng x ml(-1)), IL-4 (41.3 +/- 5.8 vs. 44.2 +/- 4.5 pg x ml(-1)), IL-5 (36.1 +/- 3.2 vs. 60.1 +/- 7.0 pg x ml(-1)), IL-6 (2.5 +/- 0.3 vs. 7.6 +/- 1.4 pg x ml(-1)) and IFN-gamma (0.3 +/- 0.2 vs. 0.6 +/- 0.2 IU x ml(-1)) at 3 hours were higher than at baseline (P0.05). IL-4 and TNF-alpha increased only in men, whereas IL-5, IL-6, and IFN-gamma were different between sexes after exposure (P0.05). Regression analyses revealed inverse associations of FEV(1) and FEV(1)/FVC ratio with IL-5 (P0.05) in men and with IL-5 (P = 0.01), IL-6 (P0.001), IFN-gamma (P = 0.034) and serum cotinine (P0.001) in women.We conclude that 1 hour of SHS exposure at bar/restaurant levels is accompanied by significant decrements on lung function and marked increases in inflammatory cytokines, particularly in men. More importantly, whereas most smoke-induced effects on lung function appear to recede within 60 minutes, inflammatory cytokines remain elevated for at least 3 hours after exposure to SHS.

Background Accumulating evidence confirms the presence of pan-airway inflammation in allergic rhinitis patients. Smoking is known to affect the asthmatic airway inflammation. However, no study has evaluated the impact of smoking on airway inflammation of allergic rhinitis patients. Objective The aim of the present study was to evaluate the impact of smoking on inflammatory and oxidative stress biomarkers in patients with seasonal allergic rhinitis, using non-invasive methods for sample collection. Methods Forty patients with seasonal allergic rhinitis (20 smokers and 20 non-smokers) and 30 healthy subjects (15 smokers and 15 non-smokers) were recruited for the study during pollen season. All subjects were submitted to measurement of the fraction of exhaled NO (FeNO), exhaled breath condensate (EBC) collection, nasal lavage collection, pre- and post-bronchodilation spirometry and metacholine bronchial challenge testing. pH, leukotriene B 4 (LTB 4 ) and 8-isoprostane were determined in EBC and nasal lavage samples. Results Patients with allergic rhinitis presented higher LTB 4 and 8-isoprostane levels in nasal lavage (P< 0.0001 for both comparisons), with no significant differences between smokers and non-smokers. Patients with allergic rhinitis also presented higher LTB 4 levels and lower pH in EBC (P

The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-alpha in EBC and serum of patients with primary lung cancer prior to the initiation of any treatment, in order to evaluate their possible diagnostic role. Furthermore, associations between VEGF, 8-isoprostane and TNF-alpha levels in EBC and serum with clinicopathologic factors were investigated. We enrolled 30 patients with lung cancer (mean age 65.2+/-10.5 years) and 15 age and gender-matched healthy smokers as controls. Serum and EBC were collected before any treatment. TNF-alpha, VEGF and 8-isoprostane levels in EBC and serum were analyzed by an immunoenzymatic method (ELISA). A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-alpha, both in EBC (52.9+/-5.0 pg/ml vs. 19.4+/-3.9 pg/ml, p0.0001) and serum (44.5+/-6.3 pg/ml vs. 22.2+/-4.3 pg/ml, p=0.035). Moreover, EBC VEGF levels were higher in patients with T3-T4 tumor stage compared to T1-T2 (9.3+/-2.8 pg/ml vs. 2.3+/-0.7pg/ml, p=0.047). A statistically significant correlation was also observed between serum and EBC values of VEGF (r=0.52, p=0.019). In addition, serum levels of VEGF were higher in lung cancer patients than in controls (369.3+/-55.1 pg/ml vs. 180.5+/-14.7 pg/ml, p=0.046). VEGF serum levels were also found higher in patients with advanced stage of disease (IIIB-IV) and distant nodal metastasis (N2-N3). No differences were observed in 8-isoprostane in EBC between lung cancer patients and controls. In contrast, serum 8-isoprostane levels were higher in lung cancer patients compared to controls (24.9+/-3.6 pg/ml vs. 12.9+/-1.6 pg/ml, p=0.027) and were higher in patients with advanced disease. All three biomarkers presented acceptable reproducibility in the EBC on two consecutive days. In conclusion, we have shown that TNF-alpha, VEGF and 8-isoprostane are elevated in the serum of lung cancer patients and increased serum VEGF and 8-isoprostane levels are related to advanced disease. In EBC, increased TNF-alpha levels were observed in lung cancer patients, whereas increased VEGF levels were observed in advanced T-stage. Further longitudinal studies are warranted for the evaluation of the prognostic role of these biomarkers in lung cancer.

The pathways underlying chronic obstructive pulmonary disease exacerbations (ECOPD) remain unclear. This study describes the clinical, functional and biochemical changes during recovery from ECOPD. Thirty hospitalized patients with Anthonisen's type-I ECOPD were evaluated on days 0 (admission), 3, 10 and 40. A five-symptom score (TSS), performance status and quality of life were evaluated. Post-bronchodilator spirometry, blood gases, oxidative stress, C-reactive protein (CRP), serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and fibrinogen were also measured. Patients were classified as early- or late-recoverers, based on whether dyspnea had returned to pre-exacerbation level by day 10. Most clinical, functional and biochemical parameters improved during follow-up. CRP and IL-6 levels reduced on Day 3 (p

Pleural effusion is a common complication of various diseases. Conventional methods are not always capable of establishing the cause of pleural effusion, so alternative tests are needed. The aim of this study was to explore means of discriminating between different pleural effusion groups, malignant, parapneumonic and tuberculous, based on the combined function of seven biological markers. Adenosine deaminase (ADA), interferon-gamma, C-reactive protein (CRP), carcinoembryonic antigen, interleukin-6, tumour necrosis factor-alpha and vascular endothelial growth factor concentration levels were measured in pleural fluid from 45 patients with malignant, 15 with parapneumonic and 12 with tuberculous pleural effusion. Receiver operating characteristic curve analysis, multinomial logit modelling and canonical variate analysis were applied to discriminate the pleural effusion groups. The three groups could be discriminated successfully using the measured markers. The most important parameters for discrimination were ADA and CRP concentration levels. An individual with an ADA concentration level of45 U.L(-1) and a CRP concentration of4 mg.dL(-1) was more likely to belong to the tuberculous pleural effusion group, whereas one with an ADA concentration level of40 U.L(-1) and a CRP concentration of6 mg.dL(-1) was more likely to belong to the parapneumonic pleural effusion group, and one with a CRP concentration of4 mg.dL(-1) to the malignant pleural effusion group. The combination of adenosine deaminase and C-reactive protein levels might be sufficient for discriminating between the three different groups of exudative pleural effusion: malignant, tuberculous and parapneumonic.

Summary Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors. We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02±1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy). The levels of oxidative stress in patients were higher than those in normal subjects (555.3±30.35 UCarr vs. 360.1±17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1±38.42pg/ml vs. 298.8±19.89pg/ml, respectively, p =0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer ( r =0.542, p =0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients ( p =0.023), performance status ( p =0.004) and age ( p =0.004). In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer.

Objective Cardiac secretion of brain natriuretic peptide (BNP) increases with the progression of congestive heart failure (CHF). The plasma measurement of BNP emerged recently as a useful, cost-effective biomarker for the diagnosis and prognosis of CHF. Methods BNP assay is useful for evaluating patients with acute dyspnea, because a low level can help rule out CHF in primary care settings and reduce the demand for echocardiography. Equally, BNP level can be particularly useful in recognizing heart failure in a patient with acute dyspnea and a history of chronic obstructive pulmonary disease. Results However, although the clinical use of BNP as a biomarker in CHF is increasing, the specificity of BNP in CHF is not strong, suggesting that other mechanisms beyond simple ventricular stretch stimulate BNP release. Multiple disorders in the intensive care unit, apart from CHF, cause elevated BNP levels, including cardiovascular disease states such as ischemia, arrhythmias, cardiac hypertrophy, and coronary endothelial dysfunction, as well as disorders of no cardiac origin, such as sepsis, septic shock, and acute respiratory distress syndrome. Moreover, the impact of increased BNP in patients with sepsis is not clear. The relationship between BNP and both left ventricular ejection fraction and left-sided filling pressures is weak, and data on the prognostic impact of high BNP levels in patients with sepsis are conflicting. Conclusion Nevertheless, this review highlights the potential benefits of BNP in the recognition and management of heart failure, and defines the gray zones of BNP levels; it also identifies conditions influencing BNP levels in relation to a certain heart failure and describes conditions of no cardiac origin with increased BNP.

Context: Active smoking influences normal metabolic status and thyroid function. Objective: The objective was to assess experimentally the effects of 1 h of moderate passive smoking in a controlled simulated bar/restaurant environment on the metabolism and thyroid hormone levels in healthy nonsmokers. Participants: Eighteen (nine females, nine males) healthy individuals (mean ± sd: age, 25.3 ± 3.1 yr; height, 174.0 ± 10.1 cm; weight, 65.2 ± 13.7 kg) participated in the study. Design: In repeated-measures randomized blocks, participants visited the laboratory on 2 consecutive days. In the experimental condition, they were exposed to 1 h of moderate passive smoking at a carbon monoxide concentration of 23 ± 1 ppm in an environmental chamber, whereas in the control condition participants remained in the same chamber for 1 h breathing normal atmospheric air. Main Outcome Measures: In both conditions, cotinine serum and urine levels, resting energy expenditure (REE), as well as concentration of T3, free T4, and TSH were assessed before participants entered the chamber and immediately after their exit. Heart rate and blood pressure were tested in 10-min intervals during all REE assessments. Results: The mean ± sd difference of serum and urine cotinine levels (−0.27 ± 3.94 vs. 14.01 ± 6.54 and 0.05 ± 2.07 vs. 7.23 ± 3.75, respectively), REE (6.73 ± 98.06 vs. 80.58 ± 120.91) as well as T3 and free T4 (0.05 ± 0.11 vs. 0.13 ± 0.12 and 0.02 ± 0.15 vs. 0.22 ± 0.20) were increased in the experimental compared with the control condition at baseline and follow-up (P < 0.05). No statistically significant variation was observed in the mean difference of the remaining parameters (P > 0.05). Serum and urine cotinine values were linearly associated with REE (P < 0.05). Conclusion: One hour of passive smoking at bar/restaurant levels is accompanied by significant increases in metabolism and thyroid hormone levels.

Oxidative stress has been associated with various respiratory disorders. We tested the hypothesis that exudates would present higher levels of oxidative stress compared to transudates, expressing the increased local oxidative burst in the former.Prospective, cross-sectional study.One hundred six consecutive patients who had undergone thoracentesis were studied. Ninety patients with a final diagnosis of pleural effusion were further analyzed.The respiratory department and a clinical laboratory of a tertiary hospital.Subjects underwent diagnostic thoracentesis, and standard biochemical parameters (ie, total protein, lactate dehydrogenase, and albumin levels) were measured in pleural fluid and serum. Oxidative stress levels were assessed with a commercially available method (d-ROMs test; Diacron; Grosseto, Italy) that uses conventional Carratelli units (UCarr). In 14 patients, duplicate measurements of oxidative stress and a second thoracentesis were performed on the following day for the assessment of the repeatability of measurements. Receiver operating characteristic (ROC) analysis was performed in order to determine the optimal cutoff level for the differentiation between exudates and transudates.Oxidative stress levels were higher in exudates compared to transudates (mean [+/- SD] stress level, 274 +/- 72 vs 126 +/- 34 UCarr, respectively; p0.0001). No significant differences were found among the levels of oxidative stress in exudative effusions of different etiologies. The area under the ROC curve was 0.992 (95% confidence interval, 0.945 to 0.997), and the method provided high sensitivity (96.8%), high specificity (96.3%), and high accuracy (96.7%) for the diagnosis of exudates at a cutoff level for oxidative stress of 186 UCarr. Consecutive measurements of oxidative stress in the same samples and on fluid from two different thoracenteses performed on 2 consecutive days presented excellent repeatability.Oxidative stress levels are higher in exudative pleural effusions compared to transudative effusions, probably due to reactive oxygen species produced in the former.

SUMMARY Haemodialysis using a bicarbonate concentrate (bicarbonate dialysis) is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper ratios of acid and bicarbonate concentrates in dialysis fluid can result in an iatrogenically induced metabolic acidosis. The following report presents a case of acute metabolic acidosis, which resulted from the accidental use of an inappropriate bicarbonate concentrate for haemodialysis treatment. Awareness of the problem and a rapid examination of the dialysis fluid in patients who unexpectedly deteriorate rather than improve with haemodialysis may help in averting potentially severe complications due to errors in the concentrate selection. Conductivity cell devises are not suitable for the control of the acid-base composition of the dialysis fluid (dialysate), therefore, monitoring of the dialysate pH in addition to conductivity should become part of the equipment in haemodialysis machines.

Background/Aims: Insulin resistance is a well-known phenomenon in uremia. Resistin, a recently discovered insulin inhibitor secreted by adipocytes, is associated with obesity and insulin resistance in mice. Adiponectin, also secreted by adipocytes, is known to reduce insulin resistance in humans. The aim of the present study was to address the hypothesis that changes in resistin or adiponectin serum levels may relate to body composition and to insulin resistance in patients with end-stage renal disease. Methods: In a cross-sectional study, 33 non-diabetic patients (24 males and 9 females, mean age 61.5 ± 15.8 years) with end-stage renal disease on chronic hemodialysis (treatment duration 41 ± 31 months) that lacked signs of infection were enrolled. The control group consisted of 33, matched for age, sex and body mass index (BMI), healthy volunteers (22 males, 11 females, mean age 62.6 ± 12.1 years). BMI (kg/m2) was calculated from body weight and height. Body fat (%) was measured by means of bioelectrical impedance. Blood samples were taken always in the morning after a 12-hour fasting period before and after the hemodialysis session. Resistin and adiponectin serum concentrations were measured by enzyme immunoassays and insulin by an electrochemiluminescence immunoassay. The post-treatment values were corrected regarding the hemoconcentration. The homeostasis model assessment index (HOMA-R) was calculated as an estimate of insulin resistance from the fasting glucose and insulin serum levels. Results: Pre-treatment resistin serum levels were significantly increased in hemodialysis patients compared to healthy controls (19.2 ± 6.2 vs. 3.9 ± 1.8 ng/ml; p < 0.001). Hemodialysis did not alter resistin levels, as pre- and post-treatment levels were not different when corrected for hemoconcentration (19.2 ± 6.2 vs. 18.7 ± 5.0 ng/ml; p = 0.54). Adiponectin levels were also increased in hemodialysis patients compared to healthy controls (25.4 ± 21.5 vs. 10.5 ± 5.9 µg/ml; p < 0.001). A significant inverse correlation was observed between the serum adiponectin levels before the hemodialysis session on the one hand and the BMI (r = –0.527, p = 0.002), the HOMA-R (r = –0.378, p < 0.05) and the fasting insulin levels (r = –0.397, p < 0.05) on the other. However, no significant correlation was observed between serum resistin levels on the one hand versus HOMA-R index (3.2 ± 3.9 mmol·µIU/ml; r = –0.098, p = 0.59), insulin levels (13.3 ± 14.4 mU/l; r = –0.073, p = 0.69), glucose levels (89 ± 13 mg/dl; r = –0.049, p = 0.78), BMI (25.6 ± 3.7 kg/m2; r = –0.041, p = 0.82) and body fat content (26.4 ± 8.4%; r = –0.018, p = 0.94) on the other hand. Conclusion: Resistin serum levels are significantly elevated in non-diabetic patients with end-stage renal disease that are treated by hemodialysis. The hemodialysis procedure does not affect the resistin levels. Along with previous observations in patients with renal insufficiency in the pre-dialysis stage, our findings implicate an important role of the kidney in resistin elimination. However, increased resistin serum levels in hemodialysis patients are not related to reduced insulin sensitivity encountered in uremia.

the levels of VEGF in patients with tuberculous pleural effusions. We studied VEGF levels in the pleural fluid and serum of 15 patients (9 men and 6 women; mean age, 61.26 17.07 years [ SD]) with tuberculous pleural effusions. Fifteen patients (12 men and 3 women; mean age, 69.23 9.98 years) with transudative pleural effusions due to congestive heart failure (CHF) served as control subjects. Tuberculous pleural effusions were diagnosed by positive culture findings for Mycobacterium tuberculosis or a pleural biopsy specimen showing typical epithelial cell caseating granulomas. All CHF patients had a history of heart failure due to systolic dysfunction (ejection fraction 45%) and presented with bilateral transudative pleural effusions that improved with appropriate treatment with diuretics. The characterization of pleural effusions as transudative or exudative was done according to Light’s criteria.2 VEGF levels were measured with a commercially available enzymeimmunosorbent assay kit (Biosource Europe S.A.; Nivelles; Belgium) according to the protocol of the manufacturer. The levels of VEGF in the pleural fluid of patients with tuberculous pleural effusions were significantly higher compared with the levels of VEGF in the pleural fluid of CHF patients (236.4 156.1 pg/mL vs 59.3 26.98 pg/mL, respectively; p 0.0002). Similar results were observed in the serum of patients with tuberculous effusions and CHF (456.1 295.8 pg/mL vs 217.2 103.8 pg/mL, respectively; p 0.0063). Interestingly, the levels of VEGF in patients with tuberculosis were significantly higher in the serum compared with the pleural fluid (236.4 156.1 pg/mL vs 456.1 295.8 pg/mL, p 0.017) [Fig 1]. The reports of measurement of VEGF levels in tuberculous pleural effusions are scarce.3 The elevated levels of VEGF in the tuberculous effusions of our patients confirm the previously available data. Additionally, the elevated levels in the serum of these patients compared with the CHF control subjects suggest that serum VEGF may be a marker of disease activity in patients with tuberculous pleural effusions, as it is in patients with active parenchymal tuberculosis.1 However, the origin of the VEGF in tuberculous effusions is not clear. In a study by Kraft et al,3 the VEGF levels in malignant pleural effusions were several-fold higher compared to matched serum samples, being suggestive of a significant local release of this cytokine from the tumor within the pleural cavity. Additionally, VEGF has been reported as a major regulator of angiogenesis with an important role in the development of granulomas.5 However, VEGF is a potent inducer of vascular permeability, and may thus represent a significant mediator in pleural fluid formation.6 The significantly higher levels of VEGF in the serum compared to the pleural fluid of our patients are suggestive of the latter role of VEGF, being responsible, at least in part, for the increased vascular permeability that leads to the formation of tuberculous pleural effusions. This is the first study to our knowledge that examines the levels of VEGF both in the pleural fluid and serum of patients with tuberculous pleural effusions, suggesting a possible role of this mediator in the formation of such effusions.

Background. The aim of our study was to identify predictive factors for the development of residual pleural thickening (RPT) in patients with tuberculous pleurisy (TP). Methods. A retrospective study of patients with pleural tuberculosis. The clinical and radiological characteristics, and measurements of microbiological and biochemical parameters or markers such as adenosine deaminase (ADA), interferon-γ (IFN-γ) and vascular endothelial growth factor (VEGF) in pleural fluid were studied. Results. Thirty one patients (24 male and 7 female) with a mean age of 55.9 years were studied. There were 25 (80.6%) patients with RPT > 2 mm and 6 (19.4%) patients without RPT. Ten patients (32.2%) had RPT ≥ 10 mm. The rate of pleural thickening was less in small effusions (p

Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.