Overexpression of AQP1 has recently been shown to be an independent prognostic factor in pleural mesothelioma favoring survival. This paper presents a data mining and bioinformatics approach towards the evaluation of the gene expression profile of AQP1 in malignant pleural mesothelioma and of AQP1 associated markers in the context of mesothelioma disease phenotype, CDKN2A gene deletion, sex and asbestos exposure. The data generated were thus again subjected to differential expression profile analysis. Here we report that AQP1 is overexpressed in epithelioid mesothelioma and identify TRIP6 and EFEMP2 as candidate genes for further investigation in mesothelioma.

Abstract Fetuin-A is a liver protein that may serve as an inhibitor of systemic inflammation in humans. In the present study we assessed the levels of fetuin-A in COPD patients in stable condition and on exacerbation in an attempt to evaluate it as a clinically relevant biomarker that may serve as predictor of exacerbations of COPD (ECOPD). One hundred COPD outpatients (GOLD stage I to IV) were enrolled in a tertiary University hospital and were submitted to a detailed evaluation, including pulmonary function testing, exercise capacity, quality of life and evaluation of the presence of metabolic syndrome and serum CRP. All patients were followed-up for 1 year, and 36 were re-evaluated at the onset of an ECOPD. Forty otherwise healthy smokers served as controls. Serum fetuin-A levels were reproducible at baseline, 6 and 12 months. COPD patients presented lower levels of fetuin compared to controls [394.5 (321.8-419.6) vs. 487.3 (441.0-548.0) mg/L, p < 0.001]. COPD patients with GOLD stage IV had lower fetuin-A levels compared to stages I-II and III (p < 0.05). Fetuin-A was significantly reduced at the onset of an ECOPD compared to baseline (p < 0.001) and the time to the first ECOPD significantly different between patients with high and low levels of fetuin-A [HR 2.163 (95%CI 1.104-4.238), p = 0.024). The results of the present study suggest that fetuin-A is a reproducible and clinically relevant biomarker in patients with COPD that may be useful in the identification of exacerbation-prone patients.

Objective. The mechanisms underlying the relationship between obesity and asthma have not been fully established. Data in the literature suggest that adipose tissue-derived hormones may be implicated. However, no definite conclusions regarding the role of leptin and adiponectin with asthma are available. No studies have examined the role of ghrelin in asthma. Methods. We assessed the circulating concentrations of leptin, adiponectin, and ghrelin in 32 postmenopausal stable asthma patients, 37 female asthmatics during exacerbations and 8 weeks later, and 22 controls. We examined the relationship between the three peptides and indexes of pulmonary function, airway inflammation, and atopy. Results. Stable asthma patients exhibited higher leptin and lower ghrelin concentrations compared with controls. Patients with severe asthma had higher leptin and lower adiponectin levels versus patients with mild to moderate asthma. Both leptin concentrations and leptin/adiponectin ratio served as markers for discriminating asthma patients from controls on the one hand, and severe from mild to moderate asthmatics on the other. Leptin levels were inversely correlated with both FEV(1)/FVC and FEF(25-75) in patients with mild to moderate asthma. Atopic asthma patients had higher leptin concentrations than nonatopic asthma patients. There was a positive correlation between serum leptin and total IgE levels in atopic asthmatics. Finally, serum leptin levels and leptin/adiponectin ratio were significantly increased during asthma exacerbations, while adiponectin and ghrelin levels were significantly decreased. Conclusion. Our findings suggest that leptin, adiponectin, and ghrelin may play a significant role in the pathogenesis of asthma during both stable state and asthma exacerbation, independent of obesity.

Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index < 1 episode h(-1); n = 31); (ii) mild obstructive sleep apnea (snoring, apnea-hypopnea index = 1-5 episodes h(-1); n = 71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apnea-hypopnea index > 5 episodes∙h(-1); n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea.

OBJECTIVES: Assess whether age influences standard biochemical parameters used in the differential diagnosis of transudative and exudative pleural effusions. DESIGN AND METHODS: We retrospectively analyzed data from the database of our clinic from 225 patients with pleural effusions categorized based on their final diagnosis in 5 groups: transudates 41 (18%), uncomplicated parapneumonic 26 (12%), complicated parapneumonic 20 (9%), tuberculosis 35 (15%) and lung cancer 103 (46%). We tested whether age correlated with pleural fluid protein or lactate dehydrogenase. RESULTS: There was a statistically significant inverse correlation only between the age and the pleural fluid protein content in patients with uncomplicated parapneumonic effusions with correlation coefficient r=-0.6 [(95% CI=-0.8 to -0.28); p=0.001]. Linear regression analysis showed that this association is given by the equation: age=101.998-10.03 protein. In the same group of patients age was not correlated with serum protein content. CONCLUSIONS: Our study shows that age may be a confounding factor in the differential diagnosis of transudative and exudative pleural effusions. Clinicians should be aware of this finding especially when dealing with elders.

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240 min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H(2)O(2) and NO(2)(-)/NO(3)(-) measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240 min. Exhaled breath condensate pH decreased immediately after exposure (p < 0.001) and returned to baseline by 180 min, whereas H(2)O(2) increased at 120 min and remained increased at 240 min (p = 0.001). No changes in exhaled NO and NO(2)/NO(3) were observed, while decreases in FEV(1) (p < 0.001) and FEV(1)/FVC (p < 0.001) were observed after exposure and returned to baseline by 180 min. A 1-h exposure to secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4 h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28.

OBJECTIVE: The effect of IGF-1 in the human pleural permeability and the underlying mechanisms involved were investigated. DESIGN: Specimens from thoracic surgical patients were mounted in Ussing chambers. Solutions containing IGF-1 (1nM-100nM) and IGF-1 Receptor Inhibitor (1μΜ), amiloride 10μM (Na(+) channel blocker) and ouabain 1mM (Na(+)-K(+) pump inhibitor) were used in order to investigate receptor and ion transporter involvement respectively. Trans-mesothelial Resistance (R(TM)) across the pleural membrane was determined as a permeability indicator. Immunohistochemistry for IGF-1 receptors was performed. RESULTS: IGF-1 increased R(TM) when added on the interstitial surface for all concentrations (p=.008, 1nM-100nM) and decreased it on the mesothelial surface for higher concentrations (p=.046, 100nM). Amiloride and ouabain inhibited this effect. The IGF-1 Receptor Inhibitor also totally inhibited this effect. Immonuhistochemistry demonstrated the presence of IGF-1 receptors in the pleura. CONCLUSIONS: It is concluded that IGF-1 changes the electrophysiology of the human parietal pleura by hindering the normal ion transportation and therefore the pleural fluid recycling process. This event is achieved after IGF-1 interaction with its receptor which is present in the human pleura.

BACKGROUND:: The aim of the present study was to develop a simple prognostic rule that could classify patients with pulmonary embolism (PE) into categories of increased risk of 30-day mortality. METHODS:: One hundred patients with PE were enrolled. Clinical and laboratory findings were recorded on admission for each patient. Differences between groups' survival and death were tested, and the association with the 30-day mortality was determined. RESULTS:: Three variables had a significant effect on survival: age, Charlson index and the alveolar to arterial (A-a) gradient. A receiver operating characteristic analysis was performed, and the cut-off points used for the comparison of survival were 67 years of age, A-a gradient over 52.8 mm Hg and Charlson index over 2. By combining these variables, a score was established for distinguishing patients with PE who are at high risk. This score was also validated in a group of 30 consecutive patients admitted to the hospital for PE Additionally, a tree method was applied and showed that for patients with a history of diabetes and Charlson index >3, the expected outcome is death. CONCLUSIONS:: The results of this study suggest that patients with PE could be stratified into categories of increasing risk of 30-day mortality using a simple score based only on routinely available variables. Future studies are needed to validate our prognostic model in a large cohort of patients with PE.

Background: We recently showed that the mRNA levels of mismatch repair (MMR) proteins in non-small cell lung carcinoma (NSCLC) tissue specimens and the phenotypic translation of molecular MMR data refines the biology of the MMR system with consequent diagnostic implications in the clinical assessment of lung cancer patients.
Methods: hMLH1 and hMSH2 mRNA expression was previously evaluated by qPCR for 29 NSCLC patients (13 with squamous cell carcinoma [SQC] and 16 with adenocarcinoma [ADC]) and MMR mRNA levels were converted into clinically distinct phenotypic entities. In this study, we evaluated the correlation of the hMSH2 and hMLH1 mRNA phenotypes with patient survival and their response to adjuvant chemotherapy. 
Results: hMSH2 and hMLH1 mRNA phenotypic distribution differed between SQC and ADC. The MMR phenotypes differed also between advanced and early stage SQC. SQC patients with an increased hMSH2 expression had a better outcome than patients with a reduced hMSH2 expression. However, ADC patients with an increased hMSH2 expression had a poor outcome compared to those with low hMSH2 levels. SQC patients with a high hMSH2 expression exhibited a better response to adjuvant chemotherapy, whereas ADC patients with high hMSH2 levels had a poor response. ADC patients with low hMSH2 levels showed good response to adjuvant chemotherapy compared to SQC patients bearing the same phenotypic profile. 
Conclusions: Our findings show that MMR mRNA phenotypes may be added to the known biological differences between SQC and ADC. hMLH1 and hMSH2 phenotypes distributed differently according to the NSCLC stage. Distinct MMR mRNA phenotypes in SQC and ADC corresponded to patient response to adjuvant chemotherapy.

The objective of this study was to evaluate the female sexual function in relation to hormonal status in pre- and postmenopausal women with obstructive sleep apnea (OSA). A total of 43 premenopausal (mean age 42.1±4.9) and 58 postmenopausal (mean age 59.9±4.8) women were included in the study. All women filled out the Epworth sleepiness scale (ESS), the Beck Depression Inventory (BDI) and the Female Sexual Function Index (FSFI). Testosterone, estradiol and progesterone were measured. After polysomnography, women were allocated to a not-severe OSA group (Apnea-Hypopnea Index (AHI) 10-30) and a severe OSA group (AHI >30). Healthy subjects comprised the control group. Severe OSA women in both pre- and post-menopausal group were found to have significantly lower mean FSFI score (16.5±4.0 and 16.9±4.7, respectively) compared with not-severe OSA (23.4±5.5, P<0.01 and 21.8±7.5, P<0.05) and control subjects (27.0±5.5, P<0.01 and 24.0±6.7, P<0.01). Progesterone, which was significantly lower in severe OSA premenopausal women (0.26±0.2) compared with not-severe OSA (0.55±0.14, P<0.01) and control group (0.62±0.16, P<0.01), correlated significantly with FSFI (r=0.39, P<0.01). Our study demonstrated that OSA is associated with sexual dysfunction in both premenopausal and postmenopausal women in a dose-related fashion. Regarding premenopausal women, our results indicated that progesterone may play a role in the association between OSA and female sexual dysfunction.

PURPOSE: We aimed to investigate whether systemic oxidative stress is increased in patients with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 18 patients with severe OSAS and 13 controls were included in the study. Inclusion criteria for OSAS patients were: snoring and apnea-hypopnea index (AHI) of >30 in full polysomnography, no previous treatment for OSAS, non-smoking status, and a medical history of being free of comorbidities known to increase oxidative stress. Controls were recruited among subjects assessed for snoring in the Sleep Laboratory Department if they had AHI<5. At baseline, patients were evaluated by the Epworth Sleepiness Scale and underwent spirometry, echocardiography, and full polysomnographic study. Blood samples were collected for evaluation of oxidative stress biomarkers [protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, 8-isoprostane, thiobarbituric acid-reactive substances (TBARS), catalase activity, Cu-Zn superoxide dysmutase (SOD), total antioxidant capacity (TAC)] before and on the morning following polysomnography. RESULTS: The overnight (morning-night) change (%) of GSH/GSSG ratio and GSH was significantly different between OSAS and controls (p = 0.03 and p = 0.048, respectively). Plasma protein carbonyls, erythrocyte catalase activity, 8-isoprostane, SOD, TBARS, and TAC plasma values were not different between OSAS and controls (p > 0.05). No significant correlation was found between changes in the levels of biomarkers and AHI, arousal, or desaturation index. CONCLUSION: The present prospective investigation in a population free of comorbidities or factors which may increase systemic oxidative stress provides evidence that obstructive sleep apnea per se might be associated with increased oxidative burden possibly via GSH/GSSG pathway.