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1.  The Epidemiology of Pulmonary Nontuberculous Mycobacteria: Data from a General Hospital in Athens, Greece, 2007–2013 
Pulmonary Medicine  2014;2014:894976.
Background. The epidemiology of pulmonary nontuberculous mycobacteria (NTM) in Greece is largely unknown. Objectives. To determine the incidence and the demographic, microbiological, and clinical characteristics of patients with pulmonary NTM infection and pulmonary NTM disease. Methods. A retrospective review of the demographic, microbiological, and clinical characteristics of patients with NTM culture-positive respiratory specimens from January 2007 to May 2013. Results. A total of 120 patients were identified with at least one respiratory NTM isolate and 56 patients (46%) fulfilled the microbiological ATS/IDSA criteria for NTM disease. Of patients with adequate data, 16% fulfilled the complete ATS/IDSA criteria for NTM disease. The incidence of pulmonary NTM infection and disease was 18.9 and 8.8 per 100.000 inpatients and outpatients, respectively. The spectrum of NTM species was high (13 species) and predominated by M. avium-intracellulare complex (M. avium (13%), M. intracellulare (10%)), M. gordonae (14%), and M. fortuitum (12%). The ratio of isolation of NTM to M. tuberculosis in all hospitalized patients was 0.59. Conclusions. The first data on the epidemiology of pulmonary NTM in Athens, Greece, are presented. NTM infection is common in patients with chronic respiratory disease. However, only a significantly smaller proportion of patients fulfill the criteria for NTM disease.
PMCID: PMC4123541  PMID: 25132991
2.  Pulmonary biomarkers in COPD exacerbations: a systematic review 
Respiratory Research  2013;14(1):111.
Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems. Innovative sampling techniques have led to the identification of several pulmonary biomarkers. Although some molecules are promising, their usefulness in clinical practice is not yet established. Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD. We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method. Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further. Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment. According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels. Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis. Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited. In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes. However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use. Clinical trials that incorporate biomarkers in decisional algorithms are required.
PMCID: PMC4014989  PMID: 24143945
COPD (chronic obstructive pulmonary disease); Exacerbations of COPD; Biomarkers; Airway inflammation; Cytokines; Spontaneous sputum; Induced sputum; Exhaled breath condensate; Fractional exhaled nitric oxide; Bronchoalveolar lavage
3.  Alveolar adenoma: an extremely rare innocent coin lesion 
Alveolar adenoma is an extremely rare benign tumour of the lung. Less than 30 cases have been reported in the English literature. A 42-year-old asymptomatic female who presented with a solitary peripheral pulmonary nodule on chest roentgenogram underwent thoracoscopic wedge resection and was diagnosed with this rare tumour. The indolent clinical progression and the absence of recurrence and metastasis after complete resection are the most important characteristics of this tumour. The classical solitary pulmonary nodule is a common and vexing problem. Nodules are extremely common in clinical practice and challenging to manage. Solitary pulmonary nodules can represent different specific lung diseases, focal non-specific inflammations, and primary and secondary malignant tumours. Identification of malignant nodules is important because they represent a potentially curable form of lung cancer.
PMCID: PMC3290358  PMID: 22159242
Alveolar adenoma; Thyroid transcription factor; Type II pneumocyte; Immunohistochemistry; Lung tumour
4.  Respiratory tract mortality in cement workers: a proportionate mortality study 
The evidence regarding the association between lung cancer and occupational exposure to cement is controversial. This study investigated causes of deaths from cancer of respiratory tract among cement workers.
The deaths of the Greek Cement Workers Compensation Scheme were analyzed covering the period 1969-1998. All respiratory, lung, laryngeal and urinary bladder cancer proportionate mortality were calculated for cement production, maintenance, and office workers in the cement industry. Mortality from urinary bladder cancer was used as an indirect indicator of the confounding effect of smoking.
Mortality from all respiratory cancer was significantly increased in cement production workers (PMR = 1.91; 95% CI 1.54 to 2.33). The proportionate mortality from lung cancer was significantly elevated (PMR = 2.05; 95% CI 1.65 to 2.52). A statistically significant increase in proportionate mortality due to respiratory (PMR = 1.7; 95% CI 1.2 to 2.34). and lung cancer (PMR = 1.67;95% CI = 1.15-2.34) among maintenance workers has been observed. The PMR among the three groups of workers (production, maintenance, office) did differ significantly for lung cancer (p = 0.001), while the PMR for urinary bladder cancer found to be similar among the three groups of cement workers.
Cement production, and maintenance workers presented increased lung and respiratory cancer proportionate mortality, and this finding probably cannot be explained by the confounding effect of smoking alone. Further research including use of prospective cohort studies is needed in order to establish a causal association between occupational exposure to cement and risk of lung cancer.
PMCID: PMC3425084  PMID: 22738120
5.  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
6.  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
7.  "Show me the money": a fair criticism of economic studies on inhaled bronchodilators for COPD 
Chronic obstructive pulmonary disease (COPD) represents a significant burden for healthcare systems that is expected to grow further in the future. Inhaled long-acting bronchodilators, including tiotropium, represent the cornerstone of management of COPD patients. Economic studies evaluating the cost-effectiveness ratio of inhaled bronchodilators have to take into account several parameters, including the reduction of COPD exacerbations and related hospitalizations, as well as disease modification and improvement in quality of life and mortality. At an era when the healthcare resources are unlikely to grow as quickly as demand, economic analyses remain the cornerstone for the justification of the broad use of medication with an acceptable cost-effectiveness ratio. The greatest importance of such studies in COPD is the identification of subgroups of patients that will have the most benefit with an acceptable cost-effectiveness ratio for the healthcare providers. The development of models that will incorporate a global evaluation of the different aspects of this multi-component disease, in order to provide the best available care to each individual patient is urgently needed.
PMCID: PMC2946282  PMID: 20843312
8.  Prevalence of chronic diseases and morbidity in primary health care in central Greece: An epidemiological study 
In Greece there is lack of large epidemiological studies regarding morbidity and mortality in primary health care. The aim of the present study was to estimate the prevalence and morbidity of the most common diseases in a large population sample from primary health care.
Four primary health centres were randomly selected. During one year period, 12 visits were performed in each centre, one per month, in random order and all visitors willing to participate in the study were included. Data on morbidity of each subject were recorded after performing an interview with the participant and checking his medical records, medical history and current medication. Diseases were coded using the international classification of primary care (ICPC) system.
In total 20,299 subjects were recorded. The results revealed significant variations in morbidity between genders and age groups. However, in all age groups, diseases of the circulatory system were most prevalent, followed by endocrine, metabolic, musculoskeletal and respiratory diseases. Osteoporosis was significantly more prevalent in females compared to males, whereas skin and eye disorders were more prevalent in subjects below 65 years old. COPD prevalence was very low compared to worldwide data.
The present study revealed great variations in the prevalence of the diseases between genders and age groups. Our data justify the urgent need for the development of electronic health records that may help in the design of new prevention strategies in primary health care.
PMCID: PMC2939599  PMID: 20799979
9.  Association of TLR4-T399I Polymorphism with Chronic Obstructive Pulmonary Disease in Smokers 
Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.
PMCID: PMC2822240  PMID: 20169003
10.  Tuberculous disseminated lymphadenopathy in an immunocompetent non-HIV patient: a case report 
In cases of patients with disseminated lymphadenopathy, the differential diagnosis has to include both benign and malignant causes, including sarcoidosis, metastatic disease, lymphoma and, although rarely present, tuberculosis. Tuberculosis is still one of the most frequently occurring infectious diseases worldwide. However, disseminated mycobacterial lymphadenitis is rare in immunocompetent patients.
Case presentation
We present the case of a 56-year-old Caucasian Greek male, who was immunocompetent and HIV negative, with a two-month history of recurring fever, loss of appetite and disseminated lymphadenopathy. The patient was diagnosed with mycobacterial lymphadenopathy.
This case highlights the need for suspicion in order to identify mycobacterial infection in patients with generalized lymphadenopathy, since misdiagnosis is possible and may lead to fatal complications for the patient.
PMCID: PMC2803839  PMID: 20062745
11.  Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis 
The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.
Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography.
Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure.
Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.
PMCID: PMC2685370  PMID: 19426547
12.  The Effects of Adaptive Servo Ventilation on Cerebral Vascular Reactivity in Patients With Congestive Heart Failure and Sleep-Disordered Breathing 
Sleep  2007;30(5):648-653.
Study Objective:
Hypercapnic cerebral vascular reactivity (HCVR) is reduced in patients with congestive heart failure (CHF) and sleep-disordered breathing (SDB); this may be associated with an increased risk of stroke. We tested the hypothesis that reversal of SDB in CHF patients using adaptive servo ventilation (ASV) would increase morning HCVR.
Interventional, cross-over clinical study.
Research sleep laboratory.
Ten CHF patients with SDB, predominantly obstructive sleep apnea.
The HCVR was measured from the change in middle cerebral artery velocity, using pulsed Doppler ultrasound. HCVR was determined during the evening (before) and morning (after) 1 night of sleep on ASV and 1 night of spontaneous sleep (control).
Measurements and Results:
Compared with the control situation, ASV decreased the apnea-hypopnea index (group mean ± SEM, control: 48 ± 12, ASV: 4 ± 1 events per hour). HCVR was 23% lower in the morning, compared with the evening, on the control night (evening: 1.3 ± 0.2, morning: 1.0 ± 0.2 cm/sec per mm Hg, P < 0.05) and 27% lower following the ASV night (evening: 1.5 ± 0.2, morning: 1.1 ± 0.2 cm/sec per mm Hg, P < 0.05). The effect of ASV on the evening-to-morning reduction in HCVR was not significant, compared with the control night (0.02 cm/sec per mm Hg, 95% confidence interval: −0.28, 0.32 P = 0.89).
In CHF patients with SDB, HCVR was reduced in the morning compared with the evening. However, removal of SDB for 1 night did not reverse the reduced HCVR. The relatively low morning HCVR could be linked with an increased risk of stroke.
PMCID: PMC2652635  PMID: 17552381
Cerebral blood flow; heart failure; middle cerebral artery velocity; sleep; transcranial Doppler ultrasound
13.  Clinical implications for Vascular Endothelial Growth Factor in the lung: friend or foe? 
Respiratory Research  2006;7(1):128.
Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis which has multiple effects in lung development and physiology. VEGF is expressed in several parts of the lung and the pleura while it has been shown that changes in its expression play a significant role in the pathophysiology of some of the most common respiratory disorders, such as acute lung injury, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, idiopathic pulmonary fibrosis, pulmonary hypertension, pleural disease, and lung cancer. However, the exact role of VEGF in the lung is not clear yet, as there is contradictory evidence that suggests either a protective or a harmful role. VEGF seems to interfere in a different manner, depending on its amount, the location, and the underlying pathologic process in lung tissue. The lack of VEGF in some disease entities may provide implications for its substitution, whereas its overexpression in other lung disorders has led to interventions for the attenuation of its action. Many efforts have been made in order to regulate the expression of VEGF and anti-VEGF antibodies are already in use for the management of lung cancer. Further research is still needed for the complete understanding of the exact role of VEGF in health and disease, in order to take advantage of its benefits and avoid its adverse effects. The scope of the present review is to summarize from a clinical point of view the changes in VEGF expression in several disorders of the respiratory system and focus on its diagnostic and therapeutic implications.
PMCID: PMC1629021  PMID: 17044926
14.  Bilious pericardial effusion at initial presentation in a patient with lung cancer 
Cardiac tamponade as the initial manifestation of metastatic cancer is a rare clinical entity. Furthermore, a thoraco-biliary fistula is another rare complication of echinococcosis due to rupture of hydatid cysts located at the upper surface of the liver to the pleural or pericardial cavity. We report a case of non-small cell lung cancer with a coexisting hepatic hydatid cyst presenting as a bilious pericardial effusion.
Case report
A 66-year-old patient presented with cardiac tamponade of unknown origin. Chest CT-scan demonstrated a left central lung tumor, a smaller peripheral one, bilateral pleural effusions and a hydatid cyst on the dome of the liver in close contact to the diaphragm and pericardium. Pericardiotomy with drainage was performed, followed by bleomycin pleurodesis. The possible mechanism for the bilious pericardial effusion might be the presence of a pericardio-biliary fistula created by the hepatic hydatid cyst.
This is the first case of a bilious pericardial effusion at initial presentation in a patient with lung cancer with coexisting hepatic hydatid cyst.
PMCID: PMC280706  PMID: 14613553
Bile; pericardial effusion; cardiac tamponade; hydatid disease; lung cancer; pericardio-biliary fistula

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