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1.  Characteristics of prevalent and new COPD cases in Greece: the GOLDEN study 
Greece has one of the highest rates of smoking and chronic obstructive pulmonary disease (COPD) in Europe.
The study aimed to record both the disease characteristics among a sample of Greek COPD patients and the nationwide rates of newly diagnosed COPD cases.
In this noninterventional, epidemiological cross-sectional study, a representative nationwide sample of 45 respiratory centers provided data on the following: 1) the demographic and clinical characteristics of COPD patients and 2) newly diagnosed COPD cases monitored over a period of 6 months by each physician.
Data from 6,125 COPD patients were collected. Advanced age (median age: 68 years), male predominance (71.3%), largely overweight status with median body mass index (BMI) =27.5 kg/m2, high percentage of current and ex-smokers (89.8%), and presence of comorbidities (81.9%) were evident in the sample. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 criteria, majority of the COPD patients had moderate or severe airflow limitation (61%). Severity of airflow limitation was significantly associated with older age, male sex, obesity, ex-smoking status, and presence of comorbidity (all P-values <0.001). A total of 61.3% of the patients received medication, mostly bronchodilators (64.4%) and fixed-dose combinations of long-acting β2-agonists and inhaled corticosteroids (39.9%), while 35.9% reported taking medication on demand. The majority (81.1%) of patients reported a preference for fewer inhalations of their bronchodilator therapy. Based on the mixed-effect Poisson model, the rate of newly diagnosed COPD cases was estimated to be 18.2% (95% confidence interval: 14.9–22.3) per pulmonologist/3 months. Of those newly diagnosed, the majority of patients had mild or moderate airflow limitation (78.2%).
The Greek Obstructive Lung Disease Epidemiology and health ecoNomics study reflected the real-life profile of COPD patients and provided evidence on the profile of new COPD cases in Greece. Various demographic factors were delineated, which can assist in designing more effective diagnostic and management strategies for COPD in Greece.
PMCID: PMC4516213
COPD; characteristics; newly diagnosed; epidemiology; prevalent cases; new cases; health care system; health care management; nationwide sampling
2.  Physiology of pericardial fluid production and drainage 
The pericardium is one of the serosal cavities of the mammals. It consists of two anatomical structures closely connected, an external sac of fibrous connective tissue, that is called fibrous pericardium and an internal that is called serous pericardium coating the internal surface of the fibrous pericardium (parietal layer) and the heart (visceral layer) forming the pericardial space. Between these two layers a small amount of fluid exists that is called pericardial fluid. The pericardial fluid is a product of ultrafiltration and is considered to be drained by lymphatic capillary bed mainly. Under normal conditions it provides lubrication during heart beating while the mesothelial cells that line the membrane may also have a role in the absorption of the pericardial fluid along with the pericardial lymphatics. Here, we provide a review of the the current literature regarding the physiology of the pericardial space and the regulation of pericardial fluid turnover and highlight the areas that need to be further investigated.
PMCID: PMC4364155  PMID: 25852564
mesothelium; pericardiac fluid turnover; pericardium; serosal membranes; transmembrane transport
3.  52. Smoking cessation in hospitalized patients with comorbidities 
Journal of Thoracic Disease  2015;7(Suppl 1):AB052.
Smoking cessation programs in hospitalized patients are effective, with increased smoking cessation indicators and better cost efficiency, when compared to those in outpatients. Hospitalization is an excellent smoking cessation intervention opportunity in different groups of patients with cardiovascular comorbidity being investigated more than any other.
The purpose of this study was to investigate the efficacy of smoking cessation intervention in hospitalized patients with respiratory comorbidities using increased supportive—counseling and administration of varenicline (full intervention), in relation to the provision of a single inpatient counseling session.
Smoking cessation was investigated in 100 smoking patients admitted to the 1st Pulmonary department of the General Hospital of Kavala; upon admission: asthma crisis (17 patients/4♂ & 13♀), chronic obstructive pulmonary disease (COPD) exacerbation (38 patients/32♂ & 6♀) or community pneumonia (45 patients 30♂ & 15♀). Patients during hospitalization were interviewed individually and the smoking history was recorded along with counseling at least one hour daily. Subsequently 44 patients (28♂ & 16♀) were enrolled in full-intervention program, while 56 (38♂ & 18♀) refused to continue after having received a counseling session. Follow up was until until completing six months of joining the program. The finding of abstinence was measuring CO in exhaled air.
The 28 out of the 44 patients receiving the integrated intervention successfully stopped smoking (63.6%) compared to 14 out of 56 (25%) patients which received a single session. More effective integrated intervention was observed in patients with asthma (71.4%), then in patients with community-acquired pneumonia (63%) and in patients with COPD (60%). The successful quitting rate after full intervention was similar in men and women (64.2% and 62.5% respectively).
Complete cessation interventions in hospitalized respiratory patients are particularly successful and therefore beneficial to the health systems and should be considered for integration into the main activities of a pulmonary clinic.
PMCID: PMC4332068
Smoking cessation; spirometry; chronic obstructive pulmonary disease (COPD)
4.  The prevalence of obstructive sleep apnea-hypopnea syndrome-related symptoms and their relation to airflow limitation in an elderly population receiving home care 
Both airflow limitation and obstructive sleep apnea-hypopnea syndrome (OSAHS)-related symptoms are most prevalent in the elderly population. Previous studies revealed significant associations between OSAHS-related symptoms and obstructive airway diseases in the general population. However, other studies showed that the frequency of OSAHS-related symptoms in patients with obstructive airway diseases decreases after the age of 60 and older.
To investigate the prevalence of OSAHS-related symptoms (snoring, breathing pauses, and excessive daytime sleepiness [EDS]) and their relations to airflow limitation, for people over 65 years old.
A full screening spirometry program was performed in a total of 490 aging participants (mean age 77.5 years – range 65–98) who were attending 16 home care settings in central Greece. Airflow limitation was assessed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric criteria (FEV1/FVC <70%). The Berlin Questionnaire and the Epworth Sleepiness Scale were used to screen individuals for OSAHS-related symptoms. Bivariate associations were described using odds ratio (OR) with 95% confidence intervals (CI).
Airflow limitation prevalence was 17.1% (male 24.2% and female 9.9%) and was strongly related to male gender and smoking status. The prevalence rates of frequent snoring, breathing pauses, and EDS were 28.1%, 12.9%, and 11.6%, respectively. However, participants with airflow limitation were less likely to report breathing pauses, frequent snoring, EDS, and obesity. Finally, frequent snoring was significantly more common in males than females.
This study revealed decreased frequency of OSAHS-related symptoms in participants with airflow limitation suggesting that OSAHS-related symptoms and airflow limitation are not related in our elderly population.
PMCID: PMC4199847  PMID: 25336942
sleep apnea syndrome; obstructive airway diseases; excessive daytime sleepiness; snoring
5.  Telemetric Detection of Chronic Obstructive Pulmonary Disease and Investigation of Quality of Life for People Working in Shipbuilding Industry 
Acta Informatica Medica  2014;22(5):315-319.
Chronic Obstructive Pulmonary Disease (COPD) has a significant impact on quality of life-related health.
It was the detection of Chronic Obstructive Pulmonary Disease by using telemetric methods and the investigation of the quality of life for people working in Shipbuilding Industry compared with a control group.
A group of one hundred men working in the shipbuilding industry aged 51.8 ± 8.2 years old and a control group of one hundred men of the general population aged 51.1 ± 6.4 years were studied. All participants completed the General Health Questionnaire – 28, the Fagerstrom test and a form with demographic characteristics. Pulmonary function test results were electronically sent to a specialist for evaluation.
People working in the shipbuilding zone had significantly lower values (p<0.001) in FVC, FEV1 and FEV1/FVC compared with the general population participants. Worse social functionality was exhibited by workers in the shipbuilding zone, people with elementary education, unemployed and by those suffering from comorbidities (p <0.001).
Health level and its individual dimensions are both associated with health self-assessment and occupational and economic status. The coexistence of chronic diseases and smoking dependence affects emotion and social functioning of individuals.
PMCID: PMC4272847  PMID: 25568580
Chronic Obstructive Pulmonary Disease; Quality of life; Telemetry
6.  Long-term exposure to muscarinic agonists decreases expression of contractile proteins and responsiveness of rabbit tracheal smooth muscle cells 
Chronic airway diseases, like asthma or COPD, are characterized by excessive acetylcholine release and airway remodeling. The aim of this study was to investigate the long-term effect of muscarinic agonists on the phenotype and proliferation of rabbit tracheal airway smooth muscle cells (ASMCs).
ASMCs were serum starved before treatment with muscarinic agonists. Cell phenotype was studied by optical microscopy and indirect immunofluorescence, using smooth muscle α-actin, desmin and SM-Myosin Heavy Chain (SM-MHC) antibodies. [N-methyl-3H]scopolamine binding studies were performed in order to assess M3 muscarinic receptor expression on isolated cell membranes. Contractility studies were performed on isolated ASMCs treated with muscarinic agonists. Proliferation was estimated using methyl-[3H]thymidine incorporation, MTT or cell counting methods. Involvement of PI3K and MAPK signalling pathways was studied by cell incubation with the pathway inhibitors LY294002 and PD98059 respectively.
Prolonged culture of ASMCs with acetylcholine, carbachol or FBS, reduced the expression of α-actin, desmin and SM-MHC compared to cells cultured in serum free medium. Treatment of ASMCs with muscarinic agonists for 3-15 days decreased muscarinic receptor expression and their responsiveness to muscarinic stimulation. Acetylcholine and carbachol induced DNA synthesis and increased cell number, of ASMCs that had acquired a contractile phenotype by 7 day serum starvation. This effect was mediated via a PI3K and MAPK dependent mechanism.
Prolonged exposure of rabbit ASMCs to muscarinic agonists decreases the expression of smooth muscle specific marker proteins, down-regulates muscarinic receptors and decreases ASMC contractile responsiveness. Muscarinic agonists are mitogenic, via the PI3K and MAPK signalling pathways.
PMCID: PMC3995846  PMID: 24607024
Airway smooth muscle; Acetylcholine; Carbachol; Phenotype; Proliferation
7.  Sex discrepancies in COPD patients and burden of the disease in females: a nationwide study in Greece (Greek Obstructive Lung Disease Epidemiology and health ecoNomics: GOLDEN study) 
The prevalence of chronic obstructive pulmonary disease (COPD) in females appears to be increasing. Recent studies have revealed that the percentage of women with COPD in Greece is approximately 12.5%.
To evaluate the burden of COPD among males and females in Greece through a nationwide cross-sectional survey and to explore sex differences regarding functional characteristics and exacerbation frequency.
Data collection was completed in a 6-month period. The present study followed a nationwide sampling approach of respiratory medicine physicians. The sampling approach included three steps: 1) estimation of expected incidence and prevalence of COPD cases in each prefecture of Greece and in total; 2) estimation of expected incidence of COPD cases per physician in each prefecture; and 3) creation of a frame of three different sampling zones. Following this sampling, data were provided by 199 respiratory physicians.
The participating physicians provided data from 6,125 COPD patients. Female patients represented 28.7% of the study participants. Female COPD patients were, on average, 5 years younger than male COPD patients. Never smokers accounted for 9.4% within female patients, compared to 2.7% of males (P<0.001). Female patients were characterized by milder forms of the disease. Comorbidities were more prevalent in men, with the exception of gastroesophageal reflux (14.6% versus 17.1% for men and women, respectively, P=0.013). Female COPD patients had a higher expected number of outpatient visits per year (by 8.9%) than males (P<0.001), although hospital admissions did not differ significantly between sexes (P=0.116). Females had fewer absences from work due to COPD per year, by 19.0% (P<0.001), compared to males.
The differences observed between male and female COPD patients provide valuable information which could aid the prevention and management of COPD in Greece.
PMCID: PMC3933352  PMID: 24600217
chronic obstructive pulmonary disease; exacerbations; comorbidities
9.  Ashtrays and Signage as Determinants of a Smoke-Free Legislation’s Success 
PLoS ONE  2013;8(9):e72945.
Successful smoke-free legislation is dependent on political will, enforcement and societal support. We report the success and pitfalls of a non-enforced nationwide smoke-free legislation in Greece, as well as ways in which compliance and enforcement-related factors, including ashtrays and signage, may impact indoor secondhand smoke (SHS) concentrations.
A follow-up study of venues (n = 150, at baseline, n = 75 at 2-year follow-up) in Greece assessed indoor particulate matter with a diameter less than 2.5 micrometers (PM2.5) concentrations attributable to SHS smoke every six months for two years (n = 455 venue/measurements).
Following the implementation of the 2010 smoke-free legislation, mean PM2.5 concentrations attributable to SHS fell from 175.3 µg/m3 pre-ban to 84.52 µg/m3 immediately post-ban, increasing over subsequent waves (103.8 µg/m3 and 158.2 µg/m3 respectively). Controlling for potential influential factors such as ventilation, time of day, day of week, city and venue type, all post-ban measurements were still lower than during the pre-ban period (Wave 2 beta: −118.7, Wave 3 beta: −87.6, and Wave 4 beta: −69.9). Outdoor or indoor signage banning smoking was not found to affect SHS concentrations (beta: −10.9, p = 0.667 and beta: −18.1, p = 0.464 respectively). However, ashtray or ashtray equivalents were strong determinants of the existence of indoor SHS (beta: +67 µg/m3, p = 0.017).
While the public may be supportive of smoke-free legislation, adherence may decline rapidly if enforcement is limited or nonexistent. Moreover, enforcement agencies should also focus on the comprehensive removal of ashtray equivalents that could act as cues for smoking within a venue.
PMCID: PMC3762932  PMID: 24023795
10.  Heterozygous Alterations of TNFRSF13B/TACI in Tonsillar Hypertrophy and Sarcoidosis 
TNFRSF13B/TACI defects have been associated with CVID pathogenesis and/or phenotype, especially the development of benign lymphoproliferation and autoimmunity. Our purpose was to investigate the role of TNFRSF13B/TACI defects in the pathogenesis of two common lymphoproliferative disorders, namely, sarcoidosis and tonsillar hypertrophy (TH). 105 patients (71 with sarcoidosis and 34 with TH, including 19 without infectious causative and 15 due to Haemophilus influenzae) were analyzed for TNFRSF13B/TACI defects. Two out of 19 TH patients without infectious cause (10.5%) and 2 patients with sarcoidosis (2.8%) displayed rare TNFRSF13B/TACI defects (I87N, L69TfsX12, E36L, and R202H, resp.). Both mutations identified in TH patients have been assessed as deleterious for protein function, while the patient with the R202H mutation and sarcoidosis exhibited also sIgG4D. Our study further supports the notion that TNFRSF13B/TACI defects alone do not result in CVID but may be also found frequently in distinct clinical phenotypes, including benign lymphoproliferation and IgG subclass deficiencies.
PMCID: PMC3727192  PMID: 23956760
12.  Endothelial Progenitor Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis: An Evolving Concept 
PLoS ONE  2013;8(1):e53658.
Idiopathic pulmonary fibrosis (IPF) has been associated with abnormal vascular remodeling. Bone marrow derived endothelial progenitor cells (EPCs) are considered to possess lung tissue repair and vascular remodeling properties.
The study aimed to assess early EPCs levels and EPCs endogenous vascular endothelial growth factor (VEGF) expression in IPF. In order to examine alterations in the mobilization of EPCs from the bone marrow we measured plasma VEGF.
Main Results
Twenty-three patients with IPF and fifteen healthy subjects were included. The number of early EPCs colonies was markedly reduced in IPF patients vs controls (6.00±6.49 vs 49.68±16.73, respectively, p<0.001). EPCs were further decreased in patients presenting systolic pulmonary arterial pressure (sPAP)≥35 mmHg. The number of colonies per well correlated negatively with P(A-a)O2 (r =  −0.750, p<0.001). Additionally, VEGF mRNA levels were significantly increased in IPF patients. There were no differences observed in VEGF plasma levels in IPF patients when compared to controls.
The current data suggest that inadequate levels of early EPCs may potentially contribute to suppressed repair and recovery of the damaged pulmonary endothelium and thereby may drive the sequence of events in profibrogenic direction. Increased VEGFmRNA levels in the clinical context of IPF may represent a compensatory mechanism to overcome reduced EPCs levels.
PMCID: PMC3544914  PMID: 23341966
13.  Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer 
Clinics  2012;67(12):1373-1378.
The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival.
We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxia-inducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice.
A significant difference (p = 0.022) in hypoxia-inducible factor 1α expression was observed between non-small cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxia-inducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p = 0.001) when all types of lung cancer were examined, either collectively or separately.
The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.
PMCID: PMC3521798  PMID: 23295589
Hypoxia-Inducible Factor 1α; Lung Cancer; Vascular Endothelial Growth Factor; Small Cell Lung Cancer; Non-small Cell Lung Cancer
14.  Two-year mortality of patients with COPD in primary health care: an observational study 
Chronic obstructive pulmonary disease (COPD) remains a significant cause of morbidity and mortality, with high rates of underdiagnosis. There are no studies about following up COPD patients in primary health care. The aim of the current study was to estimate two-year mortality for COPD patients in primary care and assess the parameters associated with mortality.
A total of 263 patients with a new COPD diagnosis were followed up for two years. Follow-up included phone contacts every six months for assessment of vital status, and re-examination visits every year after the initial diagnosis. Visits included performance on spirometry, assessment of smoking status, evaluation of adherence with treatment, and assessment of the number of exacerbations during the previous year.
One hundred and eighteen patients with COPD completed the study. The overall mortality was 27.9%. Most patients had quit smoking two years after the initial diagnosis, whereas the percentage of patients showing high adherence with treatment was 68%. Parameters associated with two-year mortality were age and coronary heart disease comorbidity.
The mortality of patients with COPD in primary care remains significantly high, whereas adherence with treatment remains significant low. Age, smoking status, and a history of depression are major determinants of mortality in primary health care.
PMCID: PMC3468116  PMID: 23055771
chronic obstructive pulmonary disease; mortality; primary health care; depression
15.  Smoking among adolescents in Northern Greece: a large cross-sectional study about risk and preventive factors 
The aim of the present study was to investigate epidemiological data about cigarette smoking in relation with risk and preventive factors among Greek adolescents.
We randomly selected 10% of the whole number of schools in Northern Greece (133 schools, 18,904 participants were included). Two anonymous questionnaires (smoker's and non-smoker's) were both distributed to all students so they selected and filled in only one. A parental signed informed consent was obtained using an informative leaflet about adolescent smoking.
The main findings of the study were: a) 14.2% of the adolescents (mean age+/−SD: 15.3+/−1.7 years) reported regular smoking (24.1% in the age group 16–18 years), b) 84.2% of the current smokers reported daily use, c) students who live in urban and semirural areas smoke more frequently than those in rural areas, d) students in technically oriented schools smoke twice as frequent compared to those in general education, e) risk factors for smoking: male gender, low educational level of parents, friends who smoke (OR: 10.01, 95%CI: 8.53-11.74, p<0.001), frequent visits to internet cafes (OR:1.53, 95%CI: 1.35-1.74, p<0.001), parents, siblings (OR:2.24, 95%CI: 1.99-2.51, p<0.001) and favorite artist (OR:1.18, 95%CI: 1.04-1.33, p=0.009) who smoke, f) protective factors against smoking: participation in sports (OR:0.59, 95%CI: 0.53-0.67, p<0.001), watching television (OR:0.74, 95%CI 0.66-0.84, p<0.001) and influence by health warning messages on cigarette packets (OR:0.42, 95%CI: 0.37, 0.48, p<0.001).
Even though prevalence of cigarette smoking is not too high among Greek adolescents, frequency of everyday cigarette use is alarming. We identified many social and lifestyle risk and preventive factors that should be incorporated in a national smoking prevention program among Greek adolescents.
PMCID: PMC3511804  PMID: 22963755
16.  Prisoners and cigarettes or ‘imprisoned in cigarettes’? What helps prisoners quit smoking? 
BMC Public Health  2012;12:508.
The aim of the study was, despite the special characteristics of prisons, to identify the features which led prisoners who attended the Smoking Cessation Centre at the Kassavetia Detention Centre in Volos (region of Thessaly, in the central part of mainland Greece) to quit smoking.
Personal interviews with 204 male prisoners irrespective of smoking habitus over the period June 2008 to December 2010 were obtained. Information about medical history, history of tobacco use and addiction to narcotic use was obtained and imprisonment status was recorded. Pharmaceutical treatment (Varenicline) and counselling or only counselling were suggested as alternative strategies to them in order to help quit smoking. SPSS v15.0 software was employed, descriptive statistics were used, and a X2 independence test and Student’s t-test were performed.
Of the sample examined, 75.5% (154) were smokers. They were mainly Greeks (51.5%), single (53.4%) and had not gratuated from a high school (secondary education level) (70.6%). 59.75% begun smoking early ( ≤14 years of age ) and 64.9% were highly addicted according to Fagerstrom Tolerance Questionnaire. 74% (114) of all smokers at the prison attended the Smoking Cessation Centre. Of them, 30.7% were able to quit smoking at 3 months but 1 year later there were 20.2% ex-smokers. The key characteristics of those who were able to be ex-smokers were a change in smoking habits (decreased) compared to when free (p = .001), previous attempts to quit (while incarcerated and in general) (p = .001), average dependence levels (p < .001), started smoking after 21 years of age (p = .032), no history of addictive substance use (p = .029), being already prisoners for a longer period of time (p = .019), a limited number (3.9 ± 3.4) of prisoners per cell (p < .001) and in particular a limited number (2.8 ± 3.2) of smokers in the cell (p < .001).
Average dependence, a past free of addictive substance abuse and a better environment of daily living for certain prisoners (as far as the number of cellmates was concerned) had a catalytic impact on prisoners finally managed to quit smoking.
PMCID: PMC3433336  PMID: 22768845
Quit smoking intervention; Prison; Smoking cessation centre; Imprisonment status; Smoking cellmates; Attempts to quit smoking
17.  The Floppy Eyelid Syndrome: Evaluating Lid Laxity and Its Correlation to Sleep Apnea Syndrome and Body Mass Index 
ISRN Ophthalmology  2012;2012:650892.
Background. The aim of this study is to present a method of lid laxity evaluation and investigate whether there is an association between floppy eyelid syndrome (FES) and body mass index (BMI) in sleep apnea syndrome (SAS) patients compared to normal subjects. Method. A total of 135 participants (81 patients with SAS and 54 normal subjects) had a full ophthalmologic examination. The presence of FES was estimated in relation to SAS and BMI. Results. The floppy eyelid was characterized “hyperelastic,” “FES stage 1 (asymptomatic),” or “FES stage 2 (symptomatic)” depending on its laxity capacity. Hyperelastic floppy eyelid in SAS patients was statistically significant (P < 0.05) when compared to normals. Similarly, the presence of hyperelasticity in high-BMI SAS patients was also statistically significant (P < 0.05) when compared to low-BMI SAS patients. Floppy eyelid syndrome was more frequent in SAS patients than in normal subjects (P < 0.05), but no association was found between FES and obesity (P > 0.05). Conclusion. A classification of FES is proposed based on lid laxity. In addition to this, our data suggests a clear association of hyperelasticity and FES to SAS patients but no association between obesity and FES.
PMCID: PMC3914272  PMID: 24558590
18.  Matrix metalloproteinases 2 and 9 increase permeability of sheep pleura in vitro 
BMC Physiology  2012;12:2.
Matrix metalloproteinases (MMPs) 2 and 9 are two gelatinase members which have been found elevated in exudative pleural effusions. In endothelial cells these MMPs increase paracellular permeability via the disruption of tight junction (TJ) proteins occludin and claudin. In the present study it was investigated if MMP2 and MMP9 alter permeability properties of the pleura tissue by degradation of TJ proteins in pleural mesothelium.
In the present study the transmesothelial resistance (RTM) of sheep pleura tissue was recorded in Ussing chambers after the addition of MMP2 or MMP9. Both enzymes reduced RTM of the pleura, implying an increase in pleural permeability. The localization and expression of TJ proteins, occludin and claudin-1, were assessed after incubation with MMPs by indirect immunofluorescence and western blot analysis. Our results revealed that incubation with MMPs did not alter neither proteins localization at cell periphery nor their expression.
MMP2 and MMP9 increase the permeability of sheep pleura and this finding suggests a role for MMPs in pleural fluid formation. Tight junction proteins remain intact after incubation with MMPs, contrary to previous studies which have shown TJ degradation by MMPs. Probably MMP2 and MMP9 augment pleural permeability via other mechanisms.
PMCID: PMC3337816  PMID: 22424238
19.  Varenicline as a smoking cessation aid in a Greek population: a subanalysis of an observational study 
Tobacco Induced Diseases  2012;10(1):1.
Greece has the highest proportion of smokers in the European Union with 42% of Greeks admitting that they smoke, based on a 2009 survey. This post-hoc analysis of a prospective, observational study evaluated the effectiveness and safety profile of the smoking cessation aid varenicline, as well as potential predictors of quit success in a Greek population.
Participants were prescribed varenicline according to the recommendations of the European Summary of Product Characteristics (1 mg twice daily). The 7-day point prevalence of abstinence at Week 12 was determined based on verbal reporting using a nicotine use inventory. Abstinence was confirmed by carbon monoxide measurements of exhaled air at the last visit of the study. The safety profile of varenicline was also assessed.
At baseline, the Greek subsample (n = 196) had a mean age of 42.6 years, with 54.6% of them being men. Participants had a smoking history of 23.5 years and a Fagerström Test for Nicotine Dependence total score of 6.6. After 12 weeks of varenicline therapy, 70.4% (95% CI, 64.0-76.7) of all participants had quit smoking. This increased to 86.2% among participants who had taken the study medication for 80% of the planned number of treatment days. Age was a significant predictor of quit success. The most frequently observed treatment-emergent adverse event was nausea, occurring in 13.3% of participants.
In this 'real-world' observational study, 70.4% of Greek smokers successfully quit smoking after 12 weeks of varenicline therapy, providing support that varenicline is an effective smoking cessation medication. Further studies with longer follow-up are warranted.
Trial Registration NCT00669240
PMCID: PMC3395840  PMID: 22300423
smoking cessation; Greece; varenicline; real world; observational
20.  Serum Amyloid Alpha in Parapneumonic Effusions 
Mediators of Inflammation  2011;2011:237638.
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.
PMCID: PMC3163023  PMID: 21876610
21.  Ocular disease awareness and pattern of ocular manifestation in patients with biopsy-proven lung sarcoidosis 
The aim of this research is to study the patterns of ocular involvement in patients with biopsy-proven lung sarcoidosis and estimate the level of patients’ awareness of possible ocular complications of sarcoidosis.
Fifty patients with biopsy-proven lung sarcoidosis were referred from the Department of Respiratory Medicine, University Hospital of Larissa, Greece.
The most prominent ocular symptom was foreign body sensation in 15/50 patients (30%); only 6/50 of our patients (12%) were completely asymptomatic with respect to ocular symptoms. Anterior segment findings were: episcleritis in 8/50 patients (16%), iris nodules in 9/50 patients (18%), and cataract in 19/50 patients (38%). Periphlebitis was observed in 8/50 patients (16%), periarteritis in 8/50 patients (16%), epiretinal membrane in 6/50 patients (12%), and branch retinal vein occlusion in 7/50 of our patients (14%). Ten out of 50 patients (20%) had never visited an ophthalmologist before, whereas eight out of 50 patients (16%) had undergone an ophthalmic exam more than 2 years ago.
Eye involvement is common in patient with biopsy-proven lung sarcoidosis and may occur even without prominent ocular symptoms.
PMCID: PMC3223338  PMID: 21748542
Awareness; Ocular; Perivasculitis; Sarcoidosis; Uveitis
22.  Ocular disease awareness and pattern of ocular manifestation in patients with biopsy-proven lung sarcoidosis 
The aim of this research is to study the patterns of ocular involvement in patients with biopsy-proven lung sarcoidosis and estimate the level of patients’ awareness of possible ocular complications of sarcoidosis.
Fifty patients with biopsy-proven lung sarcoidosis were referred from the Department of Respiratory Medicine, University Hospital of Larissa, Greece.
The most prominent ocular symptom was foreign body sensation in 15/50 patients (30%); only 6/50 of our patients (12%) were completely asymptomatic with respect to ocular symptoms. Anterior segment findings were: episcleritis in 8/50 patients (16%), iris nodules in 9/50 patients (18%), and cataract in 19/50 patients (38%). Periphlebitis was observed in 8/50 patients (16%), periarteritis in 8/50 patients (16%), epiretinal membrane in 6/50 patients (12%), and branch retinal vein occlusion in 7/50 of our patients (14%). Ten out of 50 patients (20%) had never visited an ophthalmologist before, whereas eight out of 50 patients (16%) had undergone an ophthalmic exam more than 2 years ago.
Eye involvement is common in patient with biopsy-proven lung sarcoidosis and may occur even without prominent ocular symptoms.
PMCID: PMC3223338  PMID: 21748542
Awareness; Ocular; Perivasculitis; Sarcoidosis; Uveitis
23.  Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers 
Respiratory Research  2011;12(1):67.
Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status.
EBC was collected from 161 patients with stable COPD and 112 controls (current and ex-smokers). EBC pH was measured after Argon deaeration and all subjects underwent pulmonary function testing.
EBC pH was lower in COPD patients compared to controls [7.21 (7.02, 7.44) vs. 7.50 (7.40, 7.66); p < 0.001] and ex-smokers with COPD had lower EBC pH compared to current smokers [7.16 (6.89, 7.36) vs 7.24 (7.09, 7.54), p = 0.03]. In ex-smokers with COPD, EBC pH was lower in patients with GOLD stage III and IV compared to patients with stage I disease (p = 0.026 and 0.004 respectively). No differences were observed among current smokers with different disease severity. EBC pH levels in ex-smokers were associated with static hyperinflation (as expressed by IC/TLC ratio), air trapping (as expressed by RV/TLC ratio) and diffusing capacity for carbon monoxide, whereas no associations were observed in current smokers.
Endogenous airway acidification is related to disease severity and to parameters expressing hyperinflation and air trapping in ex-smokers with COPD. The possible role of EBC pH in COPD needs to be further evaluated in longitudinal studies.
PMCID: PMC3120669  PMID: 21600044
24.  The role of leptin in the respiratory system: an overview 
Respiratory Research  2010;11(1):152.
Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have proposed an important role for leptin in lung maturation and development. Studies further suggest a significant impact of leptin on specific respiratory diseases, including obstructive sleep apnoea-hypopnoea syndrome, asthma, COPD and lung cancer. However, as new investigations are under way, the picture is becoming more complex. The scope of this review is to decode the existing data concerning the actions of leptin in the lung and provide a detailed description of leptin's involvement in the most common disorders of the respiratory system.
PMCID: PMC2988727  PMID: 21040518
25.  Body Composition in Severe Refractory Asthma: Comparison with COPD Patients and Healthy Smokers 
PLoS ONE  2010;5(10):e13233.
Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD) whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA) on fat free mass (FFM) has not been investigated.
Methodology and Principal Findings
213 subjects (70 healthy smokers, 71 COPD patients and 72 asthma patients) without significant comorbidities were included in the study. In all patients, body composition assessment (using bioelectrical impendance analysis, skinfold and anthropometric measurements) and spirometry were performed. Differences in fat free mass index (FFMI) between groups were assessed and determinants of FFMI in asthma were evaluated. Patients with SRA had lower values of FFMI compared to patients with mild-to-moderate asthma [18.0(17.3–18.3)–19.5(18.4–21.5), p<0.001], despite the fact that they were more obese. The levels of FFMI in SRA were lower than those of GOLD stage I–III COPD and comparable to those of stage IV COPD patients [18.0(17.3–18.3)–18.8(17.8–20.1), p = ns]. These differences were present even after proper adjustments for sex, age, smoking status, daily dose of inhaled corticosteroids (ICS) and daily use of oral corticosteroids (OCS). In multivariate analysis, independent predictors of FFMI in asthmatic patients were age, use of OCS and the presence of SRA, but not smoking, sex or cumulative dose of ICS used.
Conclusions and Significance
SRA is related to the presence of low FFMI that is comparable to that of GOLD stage IV COPD. The impact of this observation on asthma mechanisms and outcomes should be further investigated in large prospective studies.
PMCID: PMC2950851  PMID: 20949085

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