Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great morbidity and mortality... more Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great morbidity and mortality, disease. Since the beginning of the disease cannot be detected with precision and by using only FEV1 to monitor the evolution of the disease, the Natural History of COPD is rather obscure and sometimes controversial. Therefore, the terms EARLY COPD and MILD COPD have been used indistinguishably in the medical literature. In this review we discuss the two terms trying to clarify some of the definition issues, starting with a synopsis of the Naturel History of the disease. We recommend to use the term EARLY COPD for the pre-clinical stage of the disease (stage 0) and the term MILD COPD when the diagnosis is confirmed by spirometry and FEV1 is above 80% predicted. However, COPD is a complex disease and spirometric evaluation alone (MILD COPD, stage I), cannot fully describe the clinical status of the patient. We conclude that biomarkers to detect the starting point and been able to follow...
Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citr... more Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in ...
International journal of chronic obstructive pulmonary disease, 2007
Recently, angiogenesis and pulmonary vascular remodeling in COPD has been investigated. It has be... more Recently, angiogenesis and pulmonary vascular remodeling in COPD has been investigated. It has been hypothesized that endothelial dysfunction might be an initiating event that promotes vessel remodeling in COPD. Inflammatory tissue--a pivotal pathological feature of COPD--often hypoxic, can induce angiogenesis through upregulation of factors such as VEGF or FGF and regulators of angiogenesis such as chemokines (CXC family), acting either as angiogenic or angiostatic. Angiopoietins are distinct molecules that act in association with VEGF at different stages of angiogenic process. The regulation of angiogenesis is determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively, not yet elucidated in detail in COPD. Recent studies suggested an increased expression of VEGF in pulmonary muscular arteries of patients with moderate COPD and also in smokers with normal lung function. This was also associated with enla...
Sarcoidosis is thought to be a T-helper type 1 cytokine (Th2 cytokine) mediated disorder. Induced... more Sarcoidosis is thought to be a T-helper type 1 cytokine (Th2 cytokine) mediated disorder. Induced sputum (IS) has been proposed as a useful non-invasive method, mainly for the assessment of the airway diseases. The aim of this study was to explore induced sputum (IS) CD4+ Th1 T-lymphocyte subpopulation and to compare them with those of bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. We studied prospectively 21 patients (12 female, 9 male) of median age 46 yr (range, 25-65) with sarcoidosis and 10 normal subjects (5 female, 5 male) of median age 39 yr (range, 26-60). IS was performed with hypertonic saline solution using an ultrasonic nebulizer. BALF was performed within 10 days of IS. After stimulation of sputum lymphocytes with phorbol-myristate-acetate, we used double immunocytochemical methods to identify CD4+ IFN-gamma positive and IL-4 positive cells (Th1 and Th2, respectively). Sarcoidosis patients had an increased number of CD4+ -IFN-gamma producing cells in...
Canadian respiratory journal : journal of the Canadian Thoracic Society
To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol ... more To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h). A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study. Five centres in four countries - one centre each in France, Greece and Italy, and two centres in the Netherlands. Forty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV1 1.17 L (range 0.56 to 1.77 L). Patients inhaled single doses of formoterol dry powder (12 and 24 mg), single doses of salmeterol (50 and 100 mg) and matching placebo on five separate days. The estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for th...
Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great morbidity and mortality... more Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great morbidity and mortality, disease. Since the beginning of the disease cannot be detected with precision and by using only FEV1 to monitor the evolution of the disease, the Natural History of COPD is rather obscure and sometimes controversial. Therefore, the terms EARLY COPD and MILD COPD have been used indistinguishably in the medical literature. In this review we discuss the two terms trying to clarify some of the definition issues, starting with a synopsis of the Naturel History of the disease. We recommend to use the term EARLY COPD for the pre-clinical stage of the disease (stage 0) and the term MILD COPD when the diagnosis is confirmed by spirometry and FEV1 is above 80% predicted. However, COPD is a complex disease and spirometric evaluation alone (MILD COPD, stage I), cannot fully describe the clinical status of the patient. We conclude that biomarkers to detect the starting point and been able to follow...
Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citr... more Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in ...
International journal of chronic obstructive pulmonary disease, 2007
Recently, angiogenesis and pulmonary vascular remodeling in COPD has been investigated. It has be... more Recently, angiogenesis and pulmonary vascular remodeling in COPD has been investigated. It has been hypothesized that endothelial dysfunction might be an initiating event that promotes vessel remodeling in COPD. Inflammatory tissue--a pivotal pathological feature of COPD--often hypoxic, can induce angiogenesis through upregulation of factors such as VEGF or FGF and regulators of angiogenesis such as chemokines (CXC family), acting either as angiogenic or angiostatic. Angiopoietins are distinct molecules that act in association with VEGF at different stages of angiogenic process. The regulation of angiogenesis is determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively, not yet elucidated in detail in COPD. Recent studies suggested an increased expression of VEGF in pulmonary muscular arteries of patients with moderate COPD and also in smokers with normal lung function. This was also associated with enla...
Sarcoidosis is thought to be a T-helper type 1 cytokine (Th2 cytokine) mediated disorder. Induced... more Sarcoidosis is thought to be a T-helper type 1 cytokine (Th2 cytokine) mediated disorder. Induced sputum (IS) has been proposed as a useful non-invasive method, mainly for the assessment of the airway diseases. The aim of this study was to explore induced sputum (IS) CD4+ Th1 T-lymphocyte subpopulation and to compare them with those of bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. We studied prospectively 21 patients (12 female, 9 male) of median age 46 yr (range, 25-65) with sarcoidosis and 10 normal subjects (5 female, 5 male) of median age 39 yr (range, 26-60). IS was performed with hypertonic saline solution using an ultrasonic nebulizer. BALF was performed within 10 days of IS. After stimulation of sputum lymphocytes with phorbol-myristate-acetate, we used double immunocytochemical methods to identify CD4+ IFN-gamma positive and IL-4 positive cells (Th1 and Th2, respectively). Sarcoidosis patients had an increased number of CD4+ -IFN-gamma producing cells in...
Canadian respiratory journal : journal of the Canadian Thoracic Society
To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol ... more To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h). A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study. Five centres in four countries - one centre each in France, Greece and Italy, and two centres in the Netherlands. Forty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV1 1.17 L (range 0.56 to 1.77 L). Patients inhaled single doses of formoterol dry powder (12 and 24 mg), single doses of salmeterol (50 and 100 mg) and matching placebo on five separate days. The estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for th...
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Papers by Nikolaos Siafakas