Papers by Demosthenes Bouros
Background Statins and angiotensin-converting enzyme (ACE) inhibitors are widely used in the trea... more Background Statins and angiotensin-converting enzyme (ACE) inhibitors are widely used in the treatment of cardiovascular diseases and arterial hypertension respectively, and several studies in experimental and animal models suggest their anti-inflammatory and immunomodulatory effect. However, we are lacking big trials that prove the potential benefit on clinical outcome and reduced hospital stay in community acquired pneumonia (CAP) patients. Aim of the study was to determine whether the use of statins and ACE inhibitors reduces the length of hospitalization in patients with CAP.
Journal of thoracic disease, 2018
Reports point out lung toxicity of chemotherapeutic agents and radiation therapy in cancer patien... more Reports point out lung toxicity of chemotherapeutic agents and radiation therapy in cancer patients. The aim of our study was to assess lung function after sequential chemoradiation therapy in patients with lung cancer. Fifteen lung cancer patients participated the study and underwent lung function assessment before and after sequential treatment of chemotherapy with the 3 most applied platinum-based combinations: of vinorelbine (VN) 6 patients, gemcitabine (GEM) 4 patients and etoposide (EP) 5 patients and radiation therapy. Lung function tests were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DL) and carbon monoxide transfer coefficient (Kco). Mean patients' age was 58±9.4 years (42-75 years). Male patients were 14 (93.3%), all smokers. Overall, after chemoradiation treatment significant changes were noted in FEV1 (P=0.012), FVC (P=0.046), TLC (P=0.04) from baseline. The drop from b...
European Respiratory Journal, Sep 1, 2014
Background : The role of rigid thoracoscopy under local anesthesia in pleural infection is unknow... more Background : The role of rigid thoracoscopy under local anesthesia in pleural infection is unknown as few studies reported results, none of them prospective and randomized. The aim of our study was to evaluate the efficacy of medical thoracoscopy in comparison to the treatment with pleural drainage in pleural infection. Methods : Between 01/2008 and 08/2013, 63 patients (median age 54, 52 males) with primary non-tuberculous pleural infection were treated in our department. We compared characteristics and outcome of patients with pleural infection, who underwent rigid thoracoscopy under local anesthesia only, versus classic chest tube drainage. Results All 63 patients initially received antibiotic treatment for their infection. 21 patients (18 early and 3 late) underwent thoracoscopy under local anesthesia and 42 chest tube drainage for the treatment of their pleural infection. No significant difference was observed in age, gender, presence of comorbidities, pleural pH, LDH, proteins, serum CRP, or amount of drained fluid between the two groups. Significant difference in favor of thoracoscopy was observed in total days of hospitalization (p=0.01), days of pleural drainage (p=0.02), referral to surgery (p=0.02). A trend towards a worst outcome of patients referred from another hospital was noted overall (p=0.09), but especially in relation to the classic treatment (p=0.06). Conclusion : In this retrospective cohort study medical thoracoscopy provides better results than chest tube drainage in an experienced center of the management of patients with pleural infections. These results should be further confirmed by a prospective randomized study.
European Respiratory Journal, Sep 1, 2014
Background: Idiopathic Pulmonary Fibrosis (IPF) is associated with a prothrombotic state. Aim: To... more Background: Idiopathic Pulmonary Fibrosis (IPF) is associated with a prothrombotic state. Aim: To evaluate platelet activation, expressed as Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in recently diagnosed IPF patients in comparison with an age- and BMI-matched control group, and to explore possible correlations between these levels and respiratory function in IPF patients. Materials and methods: This study included 56 IPF patients (age 64.9±7.4 years, BMI 28.55±4.41 Kg/m2) and 79 controls (age 64.2±5.9 years, BMI 28.92±2.98 Kg/m2; p=0.546 and p=0.559 respectively). Results: As expected, respiratory function was significantly impaired in IPF patients vs. controls in terms of FEV1 (67.15±23.13 vs. 102.62±15.89 %predicted, p<0.001), FVC (65.32±20.99 vs. 95.24±16.09 %predicted, p<0.001), FEV1/FVC (83.07±14.97 vs. 87.5±6.39; p=0.041) and PaO2 (67.13±10.32 vs. 81.51±15.15 mmHg; p<0.001). In IPF patients DLCO was 36.42±16.34 %predicted and TLC was 61.79±16.64 %predicted. Platelet count was significant lower in IPF patients compared to controls (230,286±59,859 vs 255,608±75,010 cells/ml; p=0.038). On the contrary, MPV was higher in these patients vs. controls (10.35±1.23 vs 9.85±1.23 fl; p=0.024). Difference in PDW was not statistically significant (13.46±1.99 vs. 13.34±2.36 fl, p=0.766). Correlation analysis revealed no association between MPV and FVC (r=-0.1497, p=0.275) nor between MPV and DLCO (r=0.035, p=0.798) and MPV and TLC (r=0.032, p=0.820). Conclusions: Platelet activation, expressed as MPV, is higher in IPF patients and is accompanied by a lower platelet count. This finding could be used as an initial biomarker in IPF patients, but further analysis is required.
Respiratory research, Jan 21, 2005
The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic ... more The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.
Respiratory research, Jan 25, 2006
The past ten years parallels have been drawn between the biology of cancer and pulmonary fibrosis... more The past ten years parallels have been drawn between the biology of cancer and pulmonary fibrosis. The unremitting recruitment and maintenance of the altered fibroblast phenotype with generation and proliferation of immortal myofibroblasts is reminiscent with the transformation of cancer cells. A hallmark of tumorigenesis is the production of new blood vessels to facilitate tumor growth and mediate organ-specific metastases. On the other hand several chronic fibroproliferative disorders including fibrotic lung diseases are associated with aberrant angiogenesis. Angiogenesis, the process of new blood vessel formation is under strict regulation determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively. While numerous studies have examined so far the interplay between aberrant vascular and matrix remodeling the relative role of angiogenesis in the initiation and/or progression of the fibrotic cascade still ...
Respiratory Medicine, 2002
Proinflammatorycytokines Interleukin-1b (IL-1b) and Interleukin-6 (IL-6) playa significantroleint... more Proinflammatorycytokines Interleukin-1b (IL-1b) and Interleukin-6 (IL-6) playa significantroleinthe pathogenetic processesrelated to various malignant andinflammatoryconditions.Leukocytosis, thrombocytosis andincreased acute phase protein levels are part of a systemic inflammatory response.In this study, we measured the concentrations of IL-1b, IL-6 and ferritin as well as hemoglobin, lactate dehydrogenase (LDH),C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 23 patients (male15, female 8, median age 68 years) with lung cancer and reactive thrombocytosis (LCRT), in 27 (male18, female 9, median age 64 years) with benign inflammatory lung disorder (BILD) and18 (male 10, female 8, median age 62 years) lung cancer patients with a normal plateletcount (LCNP).IL-1blevels were significantly higherinthe three patientgroupsin comparisonwith control subjects (Po0.001) but without significantdifference among the three patient groups.IL-6 was higher in all three patients groups but only in the BILD group it was significantly higher than the control group (Po0.05).However, no significantdifference in IL-6 serumlevels was found between the two lung cancer groups. CRP and LDH were significantly higher in the LCRT group in comparison with the other two patient groups (Po0.01and 0.001, respectively), while ferritin was higher in both lung cancer groups in comparison with theBILD group (Po0.001).Our data suggestthat in lung cancer patients, reactive thrombocytosisis part ofthe systemicinflammatory reaction for which IL-1b and IL-6 may be intermediate but not independent mediators.
BMC pulmonary medicine, Jan 12, 2004
A number of subjects, especially the very young and the elderly, are unable to cooperate and to p... more A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD20 FEV1. We studied 170 normal subjects, 100 male and 70 female (mean +/- SD age, 38 +/- 8.5 and 35 +/- 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD100Rint, EI) as well as by percent dose response ratio (DRR). BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthma...
Respiratory Medicine, 2011
Background: Hospitalization attributed to severe exacerbations is the major cost driver of Chroni... more Background: Hospitalization attributed to severe exacerbations is the major cost driver of Chronic Obstructive Pulmonary Disease (COPD). Given that in Greece no previous studies have addressed the economic burden of COPD, the aim of the study was to examine the hospitalization cost of COPD patients with severe exacerbations in the region of Thrace. Methods: Sample consisted of 142 COPD patients with severe exacerbations who were admitted to the pneumonology department of the University Teaching Hospital of Alexandroupolis (UTHA) in 2006 and 2007. Data collection was performed retrospectively and resource utilization was derived from patients' files. General Linear Model univariate analysis was applied in order to test the influence of disease severity on costs. Results: Mean actual cost per severe exacerbation was V1711; the amount of V621 is reimbursed by social security funds. Price discrepancies are observed between the actual and the nominal cost per patient in all disease stage categories. Mean hospitalization cost per COPD patient increases slightly with the severity of the disease. However, in the very severe stage it greatly increases mainly due to Intensive Care Unit (ICU) admission. In multivariate analysis the length of stay and the stage of the disease were both related to significantly
Background. Interstitial lung disease (ILD) is the most common complication of systemic sclerosis... more Background. Interstitial lung disease (ILD) is the most common complication of systemic sclerosis (SSc) with treatment ineffective. Objective: The aim of this meta-analysis was to provide an estimate of the safety and efficacy profile of Mycophenolate Mofetil (MMF) or sodium (MMS) in SSc-ILD patients. Materials and Methods. All studies were reviewed systematically. The main end-points were safety and efficacy profile as estimated by forced vital capacity (FVC)% and diffusion capacity of the lung for carbon monoxide (DL CO)% of the predicted normal value (%pred.) before and after treatment in patients with SSc-ILD. Quality assessment and data extraction were performed independently by two reviewers. Results. Seventeen studies were reviewed systematically. Six studies, one prospective, were eligible for analysis encompassing 69 patients, including 10 subjects from our, yet unpublished, retrospective study. There was no statistically significant difference in both efficacy outcomes of interest, including FVC% pred. (weighted mean difference 1.48, 95% confidence interval (CI): −2.77 to 5.72, P = 0.49) and DL CO % pred. (weighted mean difference −0.83, 95% CI: −4.75 to 3.09, P = 0.93). No cases of clinically significant side effects were documented. Conclusions. Meta-analysis data suggest that MMF is a safe therapeutic modality which was associated with functional stabilization in patients with SSc-ILD.
Tobacco Induced Diseases, 2010
Background: Smoking and smoking cessation are considered to be associated with weight changes. We... more Background: Smoking and smoking cessation are considered to be associated with weight changes. We have recently shown that smoking acutely increases plasma levels of ghrelin, a known orexigenic hormone. Obestatin is a peptide encoded by the ghrelin gene, which opposes ghrelin effects on food intake. We conducted a study in adult volunteers measuring plasma levels of obestatin immediately after initiation of smoking. Methods: 31 volunteers (mean age 32.2 ± 9.2 years and mean BMI 25.7 ± 4.1), 17 smokers and 14 non-smokers, were enrolled in our study. The 2 groups were matched in age and BMI. Plasma obestatin concentrations were determined at baseline (T0), 2 (T2), 5 (T5), 15 (T15), and 60 (T60) minutes after the initiation of smoking. Results: In all 31 subjects, no significant difference in the mean values of plasma obestatin levels was observed from baseline at T2, T5, T15 and T60 after initiation of smoking (overall p = 0.15). However, a trend for higher obestatin levels was noted in smokers vs non-smokers (overall p = 0.069), which was not related to the pack-years. Conclusion: On the contrary with ghrelin's response after smoking initiation, there is no such an acute response of plasma obestatin levels.
Respiratory Research, 2009
Background: Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogene... more Background: Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4) has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM)-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP). Methods: Experimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6-to 8wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects. Results: A gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients. Conclusion: Our data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease.
Respiratory Medicine, 2008
Tracheal stenosis may be attributed to several conditions including trauma, infection, tumour or ... more Tracheal stenosis may be attributed to several conditions including trauma, infection, tumour or congenital and collagen vascular diseases. Despite improvement in the design of tracheal tubes, however, tracheal stenosis following intubation still remains an important cause for tracheal obstruction, which may be life threatening and often misdiagnosed. On the other hand, studies have exerted the impact of mechanical ventilation as a risk factor for pulmonary embolism. Here, we describe for the first time, an otherwise healthy patient who was mechanically ventilated due to a labor accident and developed acute pulmonary embolism that was further complicated with post-intubation tracheal stenosis. The patient was treated with anticoagulant therapy and oral corticosteroids and was further referred to a specialist centre for consideration for non-surgical endoscopic treatment.
Respiration, 2010
Background: Obstructive sleep apnea syndrome (OSAS) is associated with impaired glucose metabolis... more Background: Obstructive sleep apnea syndrome (OSAS) is associated with impaired glucose metabolism and insulin resistance. Retinol-binding protein-4 (RBP-4) is an adipokine, hypothesized to induce insulin resistance. Objectives: The aim of the study was to explore the association between serum RBP-4 levels and OSAS severity in nondiabetic, adherent to therapy OSAS patients and to investigate the role of continuous positive airway pressure (CPAP) in the alteration of RBP-4 levels. Methods: OSAS patients (n = 62) without comorbidities or medication use were included. Fasting RBP-4, glucose and insulin levels, HbA1c, homeostatic model assessment of insulin resistance index and lipid profile were measured at baseline and after 6 months of CPAP use. Patients were divided into group A (with fasting glucose levels <110 mg/dl, n = 47), and group B (with impaired fasting glucose (IFG), i.e. fasting glucose levels ≧110 mg/dl, n = 15). Results: RBP-4 levels were not associated with apnea-re...
Respiration, 2012
Over the past 10 years, the widespread clinical applicability of semi-invasive and noninvasive di... more Over the past 10 years, the widespread clinical applicability of semi-invasive and noninvasive diagnostic tools including medical thoracoscopy and ultrasonography has expanded the occurrence of pleural effusions to include several rare diseases such as granulomatous, connective tissue and autoimmune disorders including sarcoidosis, granulomatosis with polyangiitis (Wegener’s), systemic sclerosis, lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, amyloidosis, Langerhans cell histiocytosis, and others. The purpose of this review is to summarize the current state of the knowledge regarding pathogenetic mechanisms of pleural involvement in rare disease entities and to highlight the need for more efforts to understand the underlying mechanisms for a more effective therapy.
Respiration, 2010
The use of intrapleural instillation of recombinant tissue plasminogen activator (r-tPA) in the t... more The use of intrapleural instillation of recombinant tissue plasminogen activator (r-tPA) in the treatment of pleural infection may increase pleural fluid drainage associated with a clinical and imaging improvement, leading to a faster resolution. The use of r-tPA is generally well tolerated. Here we report 2 cases of massive pleural hemorrhage resulting in life-threatening hypovolemia, in 2 patients treated with intrapleural r-tPA for a pleural infection, who were simultaneously receiving systemic anticoagulation (1 therapeutic, the second prophylactic) with low-molecular weight heparin. It appears that the decision of treating pleural infection with r-tPA in patients receiving therapeutic or prophylactic systemic anticoagulation must be well balanced and in case of association of these compounds, close monitoring is necessary.
Journal of Translational Medicine, 2011
Background Idiopathic pulmonary fibrosis represents a lethal form of progressive fibrotic lung di... more Background Idiopathic pulmonary fibrosis represents a lethal form of progressive fibrotic lung disorder with gradually increasing incidence worldwide. Despite intense research efforts its pathogenesis is still elusive and controversial reflecting in the current disappointing status regarding its treatment. Patients and Methods: We report the first protocol proposal of a prospective, unicentric, non-randomized, phase Ib clinical trial to study the safety and tolerability of the adipose-derived stem cells (ADSCs) stromal vascular fraction (SVF) as a therapeutic agent in IPF. After careful patient selection based on functional criteria (forced vital capacity-FVC > 50%, diffuse lung capacity for carbon monoxide-DLCO > 35% of the predicted values) all eligible subjects will be subjected to lipoaspiration resulting in the isolation of approximately 100- 500 gr of adipose tissue. After preparation, isolation and labelling ADSCs-SVF will be endobronchially infused to both lower lobes ...
Journal of Translational Medicine, 2013
Introduction Regenerative medicine and particular adult stem cells represent an alternative optio... more Introduction Regenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their use for the treatment of this dismal disease. Patients and methods To this end, we conducted a phase Ib, non-randomized, clinical trial to study the safety of three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)-stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per infusion) in patients with IPF (n=14) of mild to moderate disease severity (forced vital capacity –FVC>50% predicted value and diffusion lung capacity for carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence of treatment emergent adverse events ...
Journal of Occupational Medicine and Toxicology, 2011
Background: Biological monitoring of healthy workers exposed to hazardous dusts lack validated sc... more Background: Biological monitoring of healthy workers exposed to hazardous dusts lack validated screening tools. Induced sputum (IS) cellular profile was compared with bronchoalveolar lavage fluid (BALF) profile in asbestos exposed workers in order to assess its usefulness in monitoring workers exposed to asbestos for a long period of time. Methods: IS and BALF analysis was performed in 39 workers of a car brakes and clutches factory that uses chrysotile asbestos. Selection criteria were an employment history of > 15 years and the absence of a diagnosis of pneumonoconiosis. The type of cells, the existence of dust cells, of iron laden macrophages and of asbestos bodies were assessed and compared between IS and BALF samples. Results: 35 IS samples (90%) had dust cells, 34 (87%) iron laden macrophages and in 8 samples (21%) asbestos bodies were found. In most samples neutrophils were dominated. Samples with asbestos bodies (ABs) had significantly higher lymphocytes and lower neutrophils count compared with the samples without ABs. Macrophages and neutrophils in IS and BALF exhibited significant interrelations (Spearman's rho: 0.26-0.29, p < 0.05) while IS lymphocytes count showed an inverse relation with BALF neutrophils (Spearman's rho:-0.36). Neutrophils and dust cells were highly correlated between the samples (Spearman's rho: 0.35, p < 0.05) while IS dust cells and lymphocytes were inversely related (Spearman's rho:-0.36, p < 0.05). More years of employment in the company was related with more neutrophils (Spearman's rho: 0.26) and less lymphocytes (Spearman's rho:-0.33) count. In multivariate analysis the presence of AB in IS samples was strongly related to the presence of asbestos bodies and lymphocytes count in BALF samples. Conclusions: IS and BALF analysis showed a similar cellular profile indicating that IS sampling in exposed workers to asbestos as a less invasive and expensive method may be useful in providing an insight both for inhalation of dusts and inflammatory processes in the lung.
Journal of medical case reports, Jan 12, 2009
Organising pneumonia is a distinct histopathological entity characterized by intra-alveolar buds ... more Organising pneumonia is a distinct histopathological entity characterized by intra-alveolar buds of granulation tissue, called Masson bodies, which mainly comprise of activated fibroblasts and loose connective tissue. This histopathologic pattern has been described in idiopathic cases, characterizing cryptogenic organising pneumonia as well as in the context of pulmonary infection, drug-induced pneumonitis and following lung transplantation. Although distinct as a clinical and pathological entity, community organising pneumonia may present with atypical clinical and pathological features, such as intra-alveolar fillings of fibrin balls and organising tissue that resembles acute respiratory distress syndrome or diffuse alveolar damage. The latter characteristics constitute a recently described anatomoclinical entity called acute fibrinous and organising pneumonia.
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Papers by Demosthenes Bouros