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    Epaminondas Kosmas

    PURPOSE: BODE index, a more representative index to classify severity of chronic obstructive pulmonary disease (COPD), has been shown to improve after pulmonary rehabilitation (PR) (Cote CG. Eur Respir J 2005). That improvement was... more
    PURPOSE: BODE index, a more representative index to classify severity of chronic obstructive pulmonary disease (COPD), has been shown to improve after pulmonary rehabilitation (PR) (Cote CG. Eur Respir J 2005). That improvement was attributed mainly to improvements ...
    PURPOSE: Pulmonary rehabilitation (PR) is a beneficial treatment for patients with chronic obstructive pulmonary disease (COPD). Our aims were to define the patients' adherence impact on PR outcomes and to prognosticate... more
    PURPOSE: Pulmonary rehabilitation (PR) is a beneficial treatment for patients with chronic obstructive pulmonary disease (COPD). Our aims were to define the patients' adherence impact on PR outcomes and to prognosticate patients' compliance. Since smoking ...
    Background: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. Objectives: The aims of this study were to investigate... more
    Background: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. Objectives: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on
    There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients... more
    There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53+/-7 versus 61+/-6%) along with a reduced LVPER (2.82+/-0.58 versus 3.82+/-0.77 end-diastolic volumes x s(-1)). Furthermore, OSA patients had significantly lower LVPFR (2.67+/-0.71 versus 3.93+/-0.58 end-diastolic volumes x s(-1)) and delayed TPFR (0.19+/-0.04 versus 0.15+/-0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.
    Our study involves a preliminary phase II trial, which evaluates the activity, feasibility and tolerability of a sequential combination of docetaxel and gemcitabine followed by docetaxel and carboplatin, as first-line treatment for... more
    Our study involves a preliminary phase II trial, which evaluates the activity, feasibility and tolerability of a sequential combination of docetaxel and gemcitabine followed by docetaxel and carboplatin, as first-line treatment for inoperable NSCLC. Twenty-six chemo-naïve patients aged less than 75 years with histologically or cytologically confirmed unresectable stage IIIB, IV or relapsed post-operative metastatic NSCLC were included in the study. Gemcitabine 1,250 mg/m(2) was administered and was followed by docetaxel 65 mg/m(2). Treatment was administered on days 1 and 14 in a 28-day cycle for three consecutive cycles. If patients had no progressive disease after three cycles of chemotherapy, they received another three cycles of docetaxel 65 mg/m(2) followed by carboplatin AUC5 on day 1 in a 21-day cycle. Recombinant human granocyte colony-stimulating factor (rhG-CSF) was given prophylactically. In addition, all patients received standard pre- and post- treatment with oral dexam...
    Theophylline, a known phosphodiesterase inhibitor, has been widely used as an additional bronchodilator in asthmatic patients who are not adequately controlled on high-doses of inhaled steroids. However, there is growing evidence that... more
    Theophylline, a known phosphodiesterase inhibitor, has been widely used as an additional bronchodilator in asthmatic patients who are not adequately controlled on high-doses of inhaled steroids. However, there is growing evidence that theophylline may also have anti-inflammatory or immunomodulatory effects in asthma. This study investigated whether theophylline administration has an impact on serum levels of interleukin (IL)-4 and IL-5 in asthmatic patients. Eight asymptomatic patients aged 30+/-1.5 yrs (mean +/- SEM) with mild atopic asthma were given a single daily dose of theophylline 150 mg or placebo in an on (theophylline)-off (placebo)-on (theophylline)-off (placebo) protocol with a 3-week duration of each on- or off- interval. Determination of serum IL-4 and IL-5 was done at baseline for all subjects and on the last day of each 3-week interval for the patients under study. Serum IL-4 levels were: 35+/-6 (baseline), 19+/-3 (on-1 interval), 29.5+/-4 (off-2), 15+/-2 (on-3) and ...
    The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing;... more
    The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; AC(T)) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFL(T)) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. In this cross-sectional study we have assessed for the first time the phase III slope, AC(T) and EFL(T) in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800%pred in GOLD IV). A close correlation was found of slope with GOLD (r = 0.77). AC(T) was absent in smokers with normal spirometry and in most patients with mild COPD. EFL(T) first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV(1)/FVC ratio from GOLD I to IV. A reduction of FEV(1) occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of AC(T). Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV.
    ... Pulmonary Rehabilitation and Improvement of BODE Index: Correlations with Alterations in Anxiety, Depression and Quality of Life. EN Kosmas, MD 1 , P. Kavoura, MD 1 , M. Harikiopoulou, MD 1 , SV Dumitru, MD 1 , EP Theodorakopoulou, MD... more
    ... Pulmonary Rehabilitation and Improvement of BODE Index: Correlations with Alterations in Anxiety, Depression and Quality of Life. EN Kosmas, MD 1 , P. Kavoura, MD 1 , M. Harikiopoulou, MD 1 , SV Dumitru, MD 1 , EP Theodorakopoulou, MD 1 , G. Birba, ...
    Significant positive effects, particularly on psychological state in patients who completed the follow-up pulmonary rehabilitation programs, are indicated by a large number of studies. Yet, a remarkable proportion of selected patients... more
    Significant positive effects, particularly on psychological state in patients who completed the follow-up pulmonary rehabilitation programs, are indicated by a large number of studies. Yet, a remarkable proportion of selected patients drop out from these programs. In this study, we investigated existing differences on psychological variables among COPD patients who complete and those who drop out from pulmonary rehabilitation programs. The study included 144 patients, 43 (29.9%) of whom did not complete the program. SCL-90 was used for the assessment of psychological symptoms. On the SCL-90-R scale 55.6% of patients had abnormal findings. Patients who discontinued the program had higher rates of depression and somatization compared to those who completed it. Regarding the psychopathology scales of SCL-90R, we found that patients who discontinued the program showed higher levels of psychopathology on the scales of somatization, depression, paranoid ideation, and psychotism compared to those who completed the program. The final regression model showed that patients with low educational status and psychotism were more likely to leave the program. In conclusion, psychopathology contributes to patients dropping out from a COPD rehabilitation program; thus, psychological assessment prior to inclusion in rehabilitation programs may reduce dropouts.
    ABSTRACT Since leg muscles receive the majority of cardiac output and consume a large proportion of total oxygen consumption (VO2) during cycle exercise, maximum leg blood flow may be an important determinant of peak VO2 (VO2peak). We... more
    ABSTRACT Since leg muscles receive the majority of cardiac output and consume a large proportion of total oxygen consumption (VO2) during cycle exercise, maximum leg blood flow may be an important determinant of peak VO2 (VO2peak). We investigated the relationships between parameters of active hyperemia after thigh tourniquet occlusion (alone or with calf exercise) with whole body peak exercise capacity during maximum cycle exercise. Twenty-one healthy male subjects, aged 19-39 yr. performed maximum incremental cycle exercise. Calf blood flow, conductance (blood flow/mean blood pressure), vasodilatory capacity (peak/baseline conductance), and duration of vasodilation were then determined with venous occlusive plethysmography under two conditions: 1) after thigh tourniquet occlusion for 10 min; 2) after ischemic calf exercise (thigh tourniquet occlusion with calf exercise to exhaustion). Group mean VO2peak was 120 +/- 35% (standard deviation) predicted. There was a significant relationship between VO2peak/ lean body mass and peak calf conductance after maximum ischemic calf exercise (r = 0.556; P < 0.01). However, VO2peak/lean body mass was more closely correlated with the duration of vasodilation after thigh tourniquet occlusion with ischemic calf exercise (r = 0.861; P < 0.001). These results suggest that the duration of calf vasodilation after maximal ischemic calf exercise appears to be a better index of cycle exercise capacity in healthy subjects.
    It is known that, in stable asthmatics at rest, tidal expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are seldom present. This study investigated whether stable asthmatics develop tidal EFL and DH during exercise with... more
    It is known that, in stable asthmatics at rest, tidal expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are seldom present. This study investigated whether stable asthmatics develop tidal EFL and DH during exercise with concurrent limitation of maximal exercise work rate (WRmax). A total of 20 asthmatics in a stable condition and aged 32+/-13 yrs (mean+/-SD) with a forced expiratory volume in one second (FEV1) of 101+/-21% of the predicted value were studied. Only three patients exhibited an FEV1 below the normal limits. On a first visit, patients performed a symptom-limited incremental (20 W.min(-1)) bicycle exercise test. On the second visit, the occurrence of EFL (using the negative expiratory pressure technique) and DH (via reduction in inspiratory capacity) were assessed at rest and when cycling at 33, 66 and 90% of their predetermined WRmax. FEV1 was measured to detect exercise-induced asthma, 5 and 15 min after stopping exercise at 90% WRmax. Only one patient showed EFL at rest, whereas 13 showed EFL and DH during exercise. In these 13 asthmatics, exercise capacity was significantly reduced (WRmax 75+/-9% pred) compared to the seven non-EFL patients (WRmax 95+/-13% pred). Moreover, a significant correlation of WRmax (% pred) to the change in inspiratory capacity (percentage of resting value) from rest to 90% WRmax was found. Tidal EFL during exercise was not associated with exercise-induced asthma, which was detected in only three patients. In conclusion, tidal expiratory flow limitation and dynamic hyperinflation during exercise are common in stable asthmatics with normal spirometric results and without exercise-induced asthma, and may contribute to reduction in exercise capacity.
    The aim of this study was to determine whether diaphragmatic fatigue develops over the course of the night in patients with obstructive sleep apnoea (OSA). Patients with severe OSA underwent overnight polysomnography with the addition of... more
    The aim of this study was to determine whether diaphragmatic fatigue develops over the course of the night in patients with obstructive sleep apnoea (OSA). Patients with severe OSA underwent overnight polysomnography with the addition of gastric and oesophageal catheters for measurement of transdiaphragmatic pressure (Pdi) (n = 7) and a gastro-oesophageal electrode for determination of diaphragmatic electromyogram (EMGdi) (n = 5). Analyses of Pdi and EMGdi were performed to detect fatigue during the large inspiratory efforts at the end of apnoeas in Stage 2 sleep at the beginning and end of the night. Measurements included Pdi values, shape analysis of the Pdi waveform, the relaxation rate (tau R) of Pdi, EMGdi and its relationship to Pdi, and the centroid frequency (fc) of EMGdi. End of apnoeic Pdi and EMGdi increased from the beginning to end of the night (e.g. 19 +/- 14% increase in Pdi; p < 0.05). The rate of increase in Pdi and EMGdi during apnoeas did not change. The Pdi versus EMGdi relationship was linear, and remained unchanged over the course of the night. There was no significant change in the shape of the Pdi waveform, and there were no changes in tau R from the beginning to the end of the night (0.13 +/- 0.01 s for both periods). There was also no shift in the fc of the EMGdi power spectrum (94 +/- 5 vs 93 +/- 6 Hz; NS), and no change in the relationship of fc to Pdi or EMGdi from the beginning to the end of the night. These findings do not support the development of diaphragmatic fatigue over the course of the night in obstructive sleep apnoea.
    Recent animal studies have demonstrated that selective blockade of ATP-sensitive K+ (KATP) channels of vascular smooth muscle results in a significant increase in peripheral vascular tone. The main aim of this study was to assess whether... more
    Recent animal studies have demonstrated that selective blockade of ATP-sensitive K+ (KATP) channels of vascular smooth muscle results in a significant increase in peripheral vascular tone. The main aim of this study was to assess whether glyburide, a selective blocker of KATP channels and commonly used antidiabetic agent, influences resting blood flow and reactive hyperemic response of peripheral tissues of normal subjects. Baseline calf blood flow was measured non-invasively in six normal subjects with femoral venous occlusive plethysmography. Calf blood flow was also serially measured every 30-60 s after the release of calf arterial occlusion (10 min duration). Reactive hyperemia was expressed in terms of peak post-occlusive flow, duration of hyperemia and reactive hyperemic volume. In each subject, baseline flow and reactive hyperemia were measured before (control) and every hour for 5 h after the oral ingestion of either 7.5 mg glyburide or a placebo on two separate days. Baseline calf flow declined by 30 and 42% of control values after 1 and 2 h of glyburide intake (P < 0.05) with a return to control values by hours 3, 4 and 5. Peak post-occlusive flow after 1, 2 and 3 h of glyburide ingestion was lower than control values by 22, 30 and 28%, respectively (P < 0.05). The duration of reactive hyperemia after 2 and 3 h of glyburide ingestion was significantly longer than control values (P < 0.05), whereas reactive hyperemic volume remained unaffected by glyburide intake. Placebo elicited no significant changes in baseline flow or reactive hyperemia throughout the 5-h experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)
    Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins,... more
    Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 +/- 3 years (mean +/- SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1 beta and IL-6 were found to be 15-fold higher on admission (122 +/- 9 pg mL-1 and 60 +/- 4 pg mL-1 respectively), whereas TNF-alpha was three-fold higher (102 +/- 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 +/- 1 mg L-1), whereas fibronectin levels were reduced (242 +/- 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-alpha serum level (127 +/- 7 vs. 86 +/- 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-alpha (-7.2 +/- 0.7 vs. -3.8 +/- 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 +/- 3.0 vs. -54.6 +/- 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 +/- 1.0 vs. 11.7 +/- 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.
    Gender differences in resting pulmonary function are attributable to the smaller lung volumes in women relative to men. We sought to investigate whether the pattern of response in operational lung volumes during exercise is different... more
    Gender differences in resting pulmonary function are attributable to the smaller lung volumes in women relative to men. We sought to investigate whether the pattern of response in operational lung volumes during exercise is different between men and women of similar fitness levels. Breath-by-breath volume changes of the entire chest wall ( V(.)( CW)) and its rib cage ( V(.)( Rc)) and abdominal ( V(.)( Ab)) compartments were studied by optoelectronic plethysmography in 15 healthy subjects (10 men) who underwent a symptom-limited ( W (peak)) incremental bicycle test. The pattern of change in end-inspiratory and end-expiratory V(.)( CW) ( V(.)( CW,EI) and V(.)( CW,EE), respectively) did not differ between the sexes. With increasing workload the decrease in V(.)( CW,EE) was almost entirely attributable to a reduction in end-expiratory V(.)( Ab), whereas the increase in V(.)( CW,EI) was due to the increase in end-inspiratory V(.)( Rc) in both sexes. In men, at W (peak) tidal volume [ V(.)( T), 2.7 (0.2) l] and inspiratory capacity [IC, 3.4 (0.2) l] were significantly greater than in women [1.8 (0.2) and 2.6 (0.2) l, respectively]. However, after controlling for lung size using forced vital capacity (FVC) as a surrogate, the differences between men and women were eliminated [ V(.)( T) /FVC 49 (3) and 45 (3) respectively, and IC/FVC 63 (2) and 65 (3) respectively]. All data are presented as mean (SE). In both men and women the contribution of the rib cage compartment to V(.)( T) expansion was significantly greater than that of the abdominal compartment. We conclude that gender differences in operational lung volumes in response to progressive exercise are principally attributable to differences related to lung size, whereas compartmental chest wall kinematics do not differ among sexes.
    Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as... more
    Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as a result of recurrent respiratory tract infections. Since activation of complement leads to influx of inflammatory cells into the lung parenchyma with subsequent release of elastases and oxidants that cause damage to elastic lung tissue, we postulated that there might be a quantitative relationship between complement consumption and degree of elastic tissue destruction. In this study, we tried to investigate possible correlations between serum levels of C3 and C4 and degree of emphysema among patients with COPD of the bronchitic type. We studied 20 patients with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant fluctuations of serum C3 and C4 levels over a 3-month period by performing detailed lung function tests, recording of emphysema score in chest radiogram, and the incidence of infective exacerbations during the past 3 years. Measured C3 and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively). Significant correlations were observed between levels of C4 and (1) incidence of respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2) radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01), forced expiratory flow rate at 50% of vital capacity, percent of predicted (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01), and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01). These results suggest that patients with chronic bronchitis with the lowest levels of C4 are those experiencing more frequent respiratory infections, tend to have more signs indicative of emphysema in their chest radiograph, have a more prominent small airways dysfunction and gas trapping, and present a greater defect in lung elastic recoil.
    Although obesity promotes tidal expiratory flow limitation (EFL), with concurrent dynamic hyperinflation (DH), intrinsic PEEP (PEEPi) and risk of low lung volume injury, the prevalence and magnitude of EFL, DH and PEEPi have not yet been... more
    Although obesity promotes tidal expiratory flow limitation (EFL), with concurrent dynamic hyperinflation (DH), intrinsic PEEP (PEEPi) and risk of low lung volume injury, the prevalence and magnitude of EFL, DH and PEEPi have not yet been studied in mechanically ventilated morbidly obese subjects. In 15 postoperative mechanically ventilated morbidly obese subjects, we assessed the prevalence of EFL [using the negative expiratory pressure (NEP) technique], PEEPi, DH, respiratory mechanics, arterial oxygenation and PEEPi inequality index as well as the levels of PEEP required to abolish EFL. In supine position at zero PEEP, 10 patients exhibited EFL with a significantly higher PEEPi and DH and a significantly lower PEEPi inequality index than found in the five non-EFL (NEFL) subjects. Impaired gas exchange was found in all cases without significant differences between the EFL and NEFL subjects. Application of 7.5 +/- 2.5 cm H2O of PEEP (range: 4-16) abolished EFL with a reduction of PEEPi and DH and an increase in FRC and the PEEPi inequality index but no significant effect on gas exchange. The present study indicates that: (a) on zero PEEP, EFL is present in most postoperative mechanically ventilated morbidly obese subjects; (b) EFL (and concurrent risk of low lung volume injury) is abolished with appropriate levels of PEEP; and (c) impaired gas exchange is common in these patients, probably mainly due to atelectasis.
    An association between activation of the renin-angiotensin system and enhanced erythropoiesis has been observed in patients with several diseases, including congestive heart failure and hypertension. Our goal was to examine whether the... more
    An association between activation of the renin-angiotensin system and enhanced erythropoiesis has been observed in patients with several diseases, including congestive heart failure and hypertension. Our goal was to examine whether the renin-angiotensin system is associated with secondary erythrocytosis in patients with chronic obstructive pulmonary disease (COPD). Plasma renin activity, plasma aldosterone concentration, serum erythropoietin level, and serum angiotensin converting enzyme (ACE) activity were measured in 12 patients with COPD and secondary erythrocytosis [mean (+/-SD) hematocrit of 53% +/- 3%] and in 12 matched controls with COPD who did not have erythrocytosis (hematocrit 45% +/- 5%). All patients had chronic hypoxemia (PaO2 <60 mm Hg). Both plasma renin and aldosterone levels were threefold greater in patients with secondary erythrocytosis compared to controls. No difference in erythropoietin levels was observed between patients with or without secondary erythrocytosis. Renin levels (r = 0.45; P = 0.02) but not erythropoietin levels (r = 0.15; P = 0.47) were correlated with hematocrit in the entire sample. Renin levels and PaO2 were the only variables independently and significantly associated with hematocrit values in a multiple linear regression model. Activation of the renin-angiotensin system is associated with the development of secondary erythrocytosis in chronically hypoxemic patients with COPD. The exact mechanism is not yet fully understood, but angiotensin II may be responsible for inappropriately sustained erythropoietin secretion or direct stimulation of erythroid progenitors.