High-Tidal-Volume Mechanical Ventilation and Lung Inflammation in Intensive Care Patients With Normal Lungs.

BACKGROUND: This study was conducted to investigate whether high-tidal-volume mechanical ventilation is associated with increased lung inflammation compared with low-tidal-volume mechanical ventilation in critically ill patients with no evidence of lung injury. METHODS: In this prospective, single-blind, randomized (1:1), parallel-group study, 18 critically ill patients with normal lungs were randomly assigned to receive mechanical ventilation with a tidal volume of either 6 mL/kg (low tidal volume) or 12 mL/kg (high tidal volume) during the first 4 days in the intensive care unit. RESULTS: At baseline and at 24, 48, and 96 hours, exhaled breath condensate was collected to measure interleukin 1ß, interleukin 10, tumor necrosis factor α, and total nitric oxide metabolites. Interleukin 1ß levels in exhaled breath condensate were significantly increased at 24 hours compared with baseline in the high-tidal-volume group but not in the low-tidal-volume group. The interleukin 1ß increase in the high-tidal-volume group was transient. Exhaled breath condensate levels of interleukin 1ß, interleukin 10, tumor necrosis factor α, and total nitric oxide metabolites did not differ significantly between the high-tidal-volume and low-tidal-volume groups at any time point. CONCLUSION: Short-term mechanical ventilation with a tidal volume of 12 mL/kg may trigger inflammatory responses in the lungs of intensive care unit patients without preexisting lung injury.

The impact of N-acetylcysteine and ascorbic acid in contrast-induced nephropathy in critical care patients: an open-label randomized controlled study.

BACKGROUND: The aim was to investigate whether the use of N-acetylcysteine and ascorbic acid reduce contrast-induced nephropathy incidence in critical care patients. METHODS: This was a one-center, two-arm, prospective, randomized, open-label, controlled trial in the Intensive Care Unit of the University Hospital of Larissa, Greece. Patients with stable renal function, who underwent non urgent contrast-enhanced computed tomography for diagnostic purposes, were included in the study. Patients in the treatment group (NacA, n = 60) received intravenously N-acetylcysteine (1200 mg) and ascorbic acid (2 g) dissolved separately in 100 ml of normal saline 2 hours before, and at 10 hours and 18 hours following the infusion of contrast agent, while control group patients (CG, n = 64) received only normal saline. All patients received additional hydration. Contrast-induced nephropathy was defined as relative increase by 25% of the baseline values of serum creatinine. RESULTS: Contrast-induced nephropathy in NacA and CG were 18.33% and 15.6%, respectively (p = 0.81). The percentage change median (interquartile range (IR)) of serum cystatin-C (mg/L) from baseline in patients who underwent contrast-induced tomography, were 37.23% (28.53) and 93.20% (46.90) in NacA and in CG, respectively (p = 0.03). The 8-isoprostane serum levels in NacA were significantly lower compared to CG at 2 hours (p = 0.012) and 24 hours (p = 0.006) following radiocontrast infusion. Multivariate analysis revealed that contrast-induced nephropathy was independently associated with a higher baseline ratio of serum urea/creatinine (odds ratio, 1.02; 95 CI%, 1.00-1.05) and with the use of nephrotoxic medications (odds ratio, 0.24; 95 CI%, 0.06-0.94). CONCLUSION: Intravenous administration of N-acetylcysteine and ascorbic acid failed to reduce contrast-induced nephropathy in critically ill patients who underwent contrast-enhanced computed tomography, despite a significant reduction of 8-isoprostane levels in treated patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01017796 . Registered on 20 November 2009.

Clinical Significance of Circulating Osteopontin Levels in Patients With Lung Cancer and Correlation With VEGF and MMP-9.

Osteopontin (OPN) is a multifunctional cytokine involved in carcinogenesis. Serum levels of OPN, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) were measured by ELISA in 90 lung cancer patients. OPN levels were elevated in patients compared to controls (p <.0001). Smokers, patients with worse performance status, and weight loss exhibited higher OPN levels (p =.0012,.00036, and.0003, respectively). Increased OPN levels were associated with worse survival (p =.0018). Finally, OPN levels were positively correlated with both VEGF (p =.0008) and MMP-9 (p <.0001). OPN might serve as a prognostic biomarker, and the positive correlation between OPN and both VEGF and MMP-9 could implicate new insights in tumor angiogenesis.

Non-Invasive Ventilation (NIV) and Homeostatic Model Assessment (HOMA) Index in Stable Chronic Obstructive Pulmonary Disease (COPD) Patients with Chronic Hypercapnic Respiratory Failure: A Pilot Study.

The effects of Non-invasive Ventilation (NIV) on Insulin Resistance (IR) in stable Chronic Obstructive Pulmonary Disease (COPD) patients have not been fully explored. The aim of this study was to assess the effects of NIV on IR and adiponectin levels during one year application of NIV in stable COPD patients with Chronic Hypercapnic Respiratory Failure. Twenty-five (25) stable COPD patients with Chronic Hypercapnic Respiratory Failure and with no self-reported comorbidities completed the study. NIV was administered in the spontaneous/timed mode via a full face mask using a bi-level positive airway pressure system. Spirometry, blood pressure, arterial blood gases, dyspnea, daytime sleepiness, serum fasting glucose and insulin levels were assessed. IR was assessed with the calculation of the Homeostatic Model Assessment (HOMA) index. Adiponectin was measured with radioimmunoassay. Study participants were re-evaluated on the first, third, sixth, ninth and twelfth month after the initial evaluation. There was a significant improvement in FEV1 values from the first month (34.1 ± 11.6% vs 37 ± 12.3%, p = 0.05). There was a significant decrease in IR by the ninth month of NIV use (3.4 ± 2.3 vs 2.2 ± 1.4, p < 0.0001), while adiponectin levels significantly improved from the first month of NIV use. Stepwise regression analysis revealed that baseline HOMA index was associated with paCO2 (ß = 0.07 ± 0.02, p = 0.001), while baseline adiponectin levels were associated with FVC (ß = 0.05 ± 0.02, p = 0.035) and the concentration of serum bicarbonate (HCO3-) (-ß = 0.18 ± 0.06, p = 0.002). Insulin sensitivity and glucose metabolism as well as adiponectin levels improved along with the improvements in respiratory failure.

Pleural transport physiology: insights from biological marker measurements in transudates.

AIMS: The aim of this study was to evaluate the physicochemical properties of the pleural mesothelial barrier and of the biological markers that facilitate or eliminate the passage of molecules through the pleura. METHODS AND MATERIAL: Pleural fluid samples from sixty-five patients with heart failure were analyzed. The biological markers studied were lactate dehydrogenase (LDH), adenosine deaminase (ADA), interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), carcinoembryonic antigen (CEA), copper/zinc superoxide dismutase (CuZnSOD), matrix metalloproteinase-2 (MMP-2), -3 (MMP-3), -7(MMP-7), -8 (MMP-8) and -9 (MMP-9). Based on the pleural fluid/serum ratio, these molecules were divided into three groups: a) the LDH-like group with a pleural fluid/serum ratio between 0,4 and 0,8 (LDH, CEA, CuZnSOD, ADA, CRP, MMP-8), b) molecules with a pleural fluid/serum ratio less than 0,4 (MMP-7 and MMP-9) and c) molecules with a pleural fluid/serum ratio equal or above 1 (TNF-α, IL-6, MMP-2 and MMP-3). RESULTS: No correlation between the molecular radius and the pleural fluid to serum ratio of the above biological markers was found. CONCLUSIONS: The molecular size is not a major determinant for the passage of molecules through the mesothelial barrier. Several other factors may influence the transport of the above molecules to pleural cavity, such as their charge and shape.

Systemic and airway inflammation and the presence of emphysema in patients with COPD.

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.