The need to follow a multidisciplinary strategy in chronic obstructive pulmonary disease (COPD) management and rehabilitation in community settings in Greece raises significant questions, given the severe austerity measures being imposed at present. The aim of this study was to investigate the clinical profile of patients with COPD along with the care provided in rural community settings in Greece.
Two primary health care centers and 200 newly diagnosed patients over a 12-month period were involved in the study. A self-assessment questionnaire, including questions about smoking habits, the presence of comorbidities and chronic respiratory symptoms, as well as the COPD Assessment Test were used. Spirometry was performed with a dry spirometer. Obstructive spirometry was defined as forced expiratory volume in 1 second/forced vital capacity ratio <0.7, according to Global Initiative for Chronic Obstructive Lung Disease guidelines.
Males comprised 70% of the sample, with cough and sputum being the prominent signs. Regarding COPD staging, 68.5% were classified in stages I/II. Arterial hypertension and coronary heart disease were the most common comorbidities. Current smokers accounted for 88.5%, while 88% were heavy drinkers. A general practitioner made the diagnosis in 68.5% of the cases, among which offspring and spouses provided home care in 38% and 8% of the cases, respectively, while an informal caregiver other than a relative was reported in 34% of the cases. No caregiver (self-care) was reported in 20% of the cases. All patients of stage III and IV had a COPD Assessment Test score >10.
Patients with COPD dwelling in the community exhibit an overall mild-to-moderate type of COPD. General practitioner is in charge of COPD management. Informal caregiving is the major type of home care, with nonfamily members playing a significant role. The patients’ profile permits limited optimism about their future perspective and urges for immediate action at primary care level.
COPD; primary care; Greece; caregiver; general practitioner
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.
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.
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.
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.
Vascular endothelial growth factor (VEGF); malignant pleural effusions (MPEs); lymphocytic pleural effusion; diagnostic biomarker
Chronic Obstructive Pulmonary Disease (COPD) is one of the top leading causes of death and disability, and its management is focused on reducing risk factors, relieving symptoms, and preventing exacerbations. The study aim was to describe COPD prescribing patterns in Greece by using existing health administrative data for outpatients.
This is a retrospective cross-sectional study based on prescriptions collected by the largest social insurance fund, during the first and last trimester of 2012. Selection criteria were the prescription of specific active substances and a COPD diagnosis. Extracted information included active substance, strength, pharmaceutical form and number of packages prescribed, diagnosis, time of dispensing, as well as insurees’ age, gender, percentage of co-payment and social security unique number. Statistical analysis included descriptive statistics and logistic regression.
174,357 patients received medicines for COPD during the study period. Patients were almost equally distributed between male and female, and age above 55 years was strongly correlated with COPD. Most patients received a long-acting beta agonist plus inhaled corticosteroid combination (LABA +ICS), followed by long-acting muscarinic agonist (LAMA). 63% patients belonging in the 35–54 age received LABA+ICS. LAMA was prescribed more frequently among males and was strongly correlated with COPD.
The study provides big data analysis of Greek COPD prescribing patterns. It highlights the need for appropriate COPD classification in primary care illustrating the role of electronic prescribing in ensuring appropriate prescribing. Moreover, it indicates possible gender differences in treatment response or disease severity, and the impact of statutory co-payments on prescribing.
The purpose of this study is to identify the prevalence of osteoporosis in male patients with chronic obstructive pulmonary disease (COPD) by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and to compare the diagnostic abilities of the above methods. Thirty-seven male patients with established COPD were examined with DXA and standard QCT in lumbar spine, including L1, L2, and L3 vertebrae. T-scores and bone mineral density values were calculated by DXA and QCT method, respectively. Comparative assessment of the findings was performed and statistical analysis was applied. QCT measurements found more COPD patients with impaired bone mineral density compared to DXA, namely, 13 (35.1%) versus 12 (32.4%) patients with osteopenia and 16 (43.2%) versus 9 (16.2%) patients with osteoporosis (p = 0.04). More vertebrae were found with osteoporosis by QCT compared to DXA (p = 0.03). The prevalence of osteoporosis among male patients with COPD is increased and DXA may underestimate this risk. QCT measurements have an improved discriminating ability to identify low BMD compared to DXA measurements because QCT is able to overcome diagnostic pitfalls including aortic calcifications and degenerative spinal osteophytes.
The high prevalence of smoking (80%) in Greek correctional institutions is anticipated to result in high prevalence of COPD in such settings.
The aim of the Greek obstructive luNg disease epidemiOlogy and health economics Study In corrective institutionS (GNOSIS) is to determine the prevalence of smoking and COPD among inmates and to assess the health-related quality of life.
GNOSIS, a cross-sectional epidemiological study, was conducted between March 2011 and December 2011 in seven correctional institutions in Greece.
A total of 552 participants, 91.3% male, median age of 43.0 years (interquartile range: 35–53), were enrolled. COPD prevalence was 6.0% and was found to increase with age (18.6% among those ≥60 years), length of prison stay, and length of sentence. Of the participants diagnosed with COPD, 36.4% were diagnosed with Global initiative for chronic Obstructive Lung Disease (GOLD) stage I and 51.5% were diagnosed with stage II. Dyspnea severity was assessed as grades 0–1 on the medical research council dyspnea scale for 88.3%, while 31% reported ≥2 COPD exacerbations in the past year. Seventy-nine percent of the total number of the participants were smokers, with a median smoking of 20.0 cigarettes per day, while 42.9% were assessed as having a strong addiction to nicotine. The median EuroQol visual analog scale score was 70.0 (interquartile range: 60.0–90.0). Problems in the dimension of anxiety/depression were reported by 82.8%.
The results of the study support the notion that the prevalence of COPD among inmates of Greek correctional institutions may increase in the following years. The findings underscore the importance of taking actions to limit COPD prevalence and its risk factors in the Greek correctional system.
smoking; stress; correctional institutions; Greece; prevention; public health
Obstructive sleep apnoea–hypopnea syndrome (OSAHS) and multimorbidity are common in elderly patients, but a potential link between the two conditions remains unclear. This study aimed to assess the prevalence of OSAHS, chronic multimorbidity and their relation in older adults in primary care settings. A screening study was performed in a cross-section of 490 elderly adults (mean age 77.5 years, 51 % male) receiving home care services in Thessaly, central Greece. The Berlin Questionnaire was employed to assess the likelihood for OSAHS and the Epworth Sleepiness Scale to assess daytime sleepiness. Multimorbidity was defined as a documented history of at least two chronic diseases. The prevalence of high risk for OSAHS, excessive daytime sleepiness and multimorbidity was 33.5, 11.6 and 63.9 %, respectively. None of the study subjects had a confirmed diagnosis for OSAHS prior to this study. A marked dose–response association between a high pre-test likelihood for OSAHS and multimorbidity was noted in patients with two [adjusted odds ratio (OR) 3.13; 95 % confidence interval (CI) 1.85–5.30) and three or more (adjusted OR 4.22; 95 % CI 2.55–6.96) chronic morbidities, independently of age, sex and smoking status. This association persisted across different levels for OSAHS risk in the Berlin questionnaire, was insensitive to varying definitions of multimorbidity and more pronounced in patients with excessive daytime sleepiness. These findings point out that primary care physicians who care for elderly patients who present with several, common and burdensome, chronic diseases should expect to find this multimorbidity often coinciding with undetected, and therefore untreated, OSAHS. Thus it is crucial to consider OSAHS as an important co-morbidity in older adults and systematically screen for OSAHS in primary care practice.
Obstructive sleep apnoea syndrome; Chronic diseases; Comorbidity; Multimorbidity; Screening; Epidemiology; General practice
COPD exacerbations and hospitalizations have been associated with poor prognosis for the COPD patient.
To evaluate the frequency and risk factors of COPD exacerbations, hospitalizations, and admissions to intensive care units (ICUs) in Greece by a nationwide cross-sectional study.
Materials and methods
A nationwide observational, multicenter, cross-sectional study was conducted in the clinical practice setting of respiratory medicine physicians over a 6 month-period (October 2010 to March 2011). A total of 6,125 COPD patients were recruited by 199 respiratory physicians.
Participants had a median age of 68.0 years, 71.3% were males, and 71.8% suffered from comorbidities. The median disease duration was 10.0 years. Of the patients, 45.3% were classified as having GOLD (Global initiative for chronic Obstructive Lung Disease) stage III or IV COPD. Patients with four or more comorbidities had 78.5% and threefold-higher than expected number of exacerbations and hospitalizations, respectively, as well as fivefold-higher risk of admission to the ICU compared to those with no comorbidities. Obese patients had 6.2% fewer expected exacerbations compared to those with a normal body mass index. Patients with GOLD stage IV had 74.5% and fivefold-higher expected number of exacerbations and hospitalizations, respectively, and nearly threefold-higher risk of admission to the ICU compared to stage I patients. An additional risk factor for exacerbations and hospitalizations was low compliance with treatment: 45% of patients reported forgetting to take their medication, and 81% reported a preference for a treatment with a lower dosing frequency.
Comorbidities, disease severity, and compliance with treatment were identified as the most notable risk factors for exacerbations, hospitalizations, and ICU admissions. The results point to the need for a multifactorial approach for the COPD patient and for the development of strategies that can increase patient compliance with treatment.
COPD; exacerbations; hospitalizations; ICU admissions; risk factors
Lung cancer is the leading cause of cancer mortality worldwide, mainly due to late diagnosis, poor prognosis and tumor heterogeneity. Thus, the need for biomarkers that will aid classification, treatment and monitoring remains intense and challenging and depends on the better understanding of the tumor pathobiology and underlying mechanisms. The deregulation of gene expression is a hallmark of cancer and a critical parameter is the stability of mRNAs that may lead to increased oncogene and/or decreased tumor suppressor transcript and protein levels. The shortening of mRNA poly(A) tails determines mRNA stability, as it is usually the first step in mRNA degradation, and is catalyzed by deadenylases. Herein, we assess the clinical significance of deadenylases and we study their role on gene expression in squamous cell lung carcinoma (SCC).
Computational transcriptomic analysis from a publicly available microarray was performed in order to examine the expression of deadenylases in SCC patient samples. Subsequently we employed real-time PCR in clinical samples in order to validate the bioinformatics results regarding the gene expression of deadenylases. Selected deadenylases were silenced in NCI-H520 and Hep2 human cancer cell lines and the effect on gene expression was analyzed with cDNA microarrays.
The in silico analysis revealed that the expression of several deadenylases is altered in SCC. Quantitative real-time PCR showed that four deadenylases, PARN, CNOT6, CNOT7 and NOC, are differentially expressed in our SCC clinical samples. PARN overexpression correlated with younger patient age and CNOT6 overexpression with non-metastatic tumors. Kaplan-Meier analysis suggests that increased levels of PARN and NOC correlate with significantly increased survival. Gene expression analysis upon PARN and NOC silencing in lung cancer cells revealed gene expression deregulation that was functionally enriched for gene ontologies related to cell adhesion, cell junction, muscle contraction and metabolism.
Our results highlight the clinical significance of PARN and NOC on the survival in SCC diagnosed patients. We demonstrate that the enzymes are implicated in important phenotypes pertinent to cancer biology and provide information on their role in the regulation of gene expression in SCC. Overall, our results support an emerging role for deadenylases in SCC and contribute to the understanding of their role in cancer biology.
Electronic supplementary material
The online version of this article (doi:10.1186/s12943-015-0457-3) contains supplementary material, which is available to authorized users.
Deadenylases; Prognostic value; Lung cancer; mRNA degradation; Squamous lung carcinoma
For the realization of “2015 UN Millennium Development Goals”, a question arises pertaining to the course of tuberculosis in Greece and its relationship to patient adherence to treatment, given the fact that the country is undergoing a financial crisis and is a gateway for economic migrants.
The study concerned 1179 patients of the anti-TBdepartment, “Sotiria” General Chest Diseases Hospital, Athens, Greece collaborating with the National Reference Centre of Mycobacteria, covering a year before the financial crisis, 2007 and 2010-11, the first years of the crisis. A special recording form was used, on the basis of a specific protocol.
Out of 954 patients were diagnosed with tuberculosis disease, 657 of which were foreigners. Out of 791 patients residing in the same area, 632 were foreigners. Of the patients who proceeded to a first self-discontinuation of the medication, only 38.3% (n=18) completed the treatment, while 40.4% of them self-discontinued within the first month. Duration of treatment was 6.68±3.54 months for those (n=805) with no discontinuation and 7.48±3.68 months for those (n=149) with at least one discontinuation, regardless of the etiology p= 0,032. Cases increased during financial crisis, with gradual decrease in mean treatment duration for patients with first line treatment to 7.77±3.81 months in 2007, and 6.53±3.47 and 6.40±3.31 months in 2010 and 2011, respectively.
Since the beginning of treatment measurable signs of either adherent/non-adherent behavior appeared, affecting mean treatment duration and completion. Duration of treatment decreased in the years of financial crisis. Migrants ghettoization calls for implementation of DOTS.
Tuberculosis; DOT; migrants; adherence; treatment completion; ghettoization; financial crisis
Evidence on the association of leptin and adiponectin and smoking is limited and discordant. Leptin and adiponectin represent the most abundant adipokines in human plasma that play crucial roles in the pathophysiology of metabolic syndrome, atherosclerosis and insulin resistance. Leptin up-regulates the expression of several pro-inflammatory cytokines and is increased upon weight gain. Adiponectin has been shown to possess insulin sensitizing, anti -inflammatory and anti-atherogenic properties and is increased upon weight reduction. Our aim was to assess the effects of smoking cessation on serum leptin and adiponectin levels.
We assessed the changes in serum leptin and adiponectin levels, serum CRP levels and BMI in apparently healthy smokers after 3 and 6 months of abstinence from smoking. Successful cessation was confirmed by an exhaled carbon monoxide measurement. 26 healthy non-smokers were recruited as controls.
Among the sample group, 32 subjects had quitted smoking at 3 months and 29 subjects at 6 months. Samples’ leptin increased significantly from baseline to three months (mean change 3.76 ng/ml [95 % CI 0.89, 6.64], p =0.012) and then decreased significantly from three to six months of smoking cessation (mean change -4,29 ng/ml [95 % CI −7.34, −6.64], p = 0.008). Samples’ adiponectin increased significantly from baseline to three months of abstinence from smoking (mean change 2.34 [95 % CI −0.05, 4.73], p −0.05). BMI was significantly increased (mean change 2.03 kg/m2 [95 % CI 1.60, 2.46], p <0.05), while CRP decreased significantly from baseline to 6 months of smoking cessation (mean change −0.68 mg/dl [95 % CI −1.06, −0.30], p = 0.001).
Smoking quitters’ leptin levels appear to increase 3 months after smoking cessation and then decrease from 3 to 6 months of abstinence from smoking. Adiponectin levels increase during the first trimester of smoking cessation. The decrease in CRP levels indicates that the low grade inflammation observed in smokers is gradually restored. The alterations of serum leptin and adiponectin after 6 months of smoking cessation suggest the same but do not reach statistically significant levels. Weight gain and changes in fat distribution may attenuate the beneficial effects of smoking cessation.
Leptin; Adiponectin; Smoking; Cessation; Tobacco
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.
COPD; characteristics; newly diagnosed; epidemiology; prevalent cases; new cases; health care system; health care management; nationwide sampling
The health level of the population and the way people perceive it has been associated with their physical and mental health, as well as with their social and occupational characteristics.
The comparative assessment of mental and health level in shipbuilding industry workers and general population and its relationship to social and economic parameters.
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 were studied. All participants completed the General Health Questionnaire – 28 and Fagerstrom test and a form with demographic, occupational and economic status characteristics. The statistical software SPSS 17.0 was used for data analysis.
Twenty–six percent of the general population and 47% of men working in the shipbuilding industry assessed their health as moderate/poor. Higher median values of anxiety and depressive symptomatology were observed in individuals characterizing their health as moderate/poor (p<0.001), their work as physically too demanding and in individuals with high dependency on smoking (p<0.05). With regard to the parameter of physical complaints, people working in the shipbuilding industry, non-active employees and those with comorbidities were found more burdened in relation to the general population (p<0.05). Depressive disorders were more common in those stating that their economic situation had been significantly deteriorated and in individuals with chronic diseases, which also showed reduced social functioning (p<0.05).
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.
health level; self-reported health; unemployment; social- economic status
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.
mesothelium; pericardiac fluid turnover; pericardium; serosal membranes; transmembrane transport
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.
Smoking cessation; spirometry; chronic obstructive pulmonary disease (COPD)
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.
sleep apnea syndrome; obstructive airway diseases; excessive daytime sleepiness; snoring
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.
Chronic Obstructive Pulmonary Disease; Quality of life; Telemetry
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.
Airway smooth muscle; Acetylcholine; Carbachol; Phenotype; Proliferation
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.
chronic obstructive pulmonary disease; exacerbations; comorbidities
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.
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.
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.
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.
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.
Hypoxia-Inducible Factor 1α; Lung Cancer; Vascular Endothelial Growth Factor; Small Cell Lung Cancer; Non-small Cell Lung Cancer
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.
chronic obstructive pulmonary disease; mortality; primary health care; depression