Petros Bakakos

Attikon University Hospital, Athínai, Attica, Greece

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Publications (30)102.22 Total impact

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    ABSTRACT: Abstract Background and Objective: Angiopoietin-2 (Ang-2) is an important mediator of angiogenesis and has been implicated in many inflammatory diseases. COPD is characterized by systemic inflammation, which is enhanced during exacerbations and may be assessed by measuring serum C-reactive protein (CRP). The aim of the study was to evaluate serum CRP and Ang-2 levels on the first (D1) and seventh day (D7) of hospitalization due to a COPD exacerbation and to examine possible associations of CRP and Ang-2 levels and kinetics with the length of hospital stay and outcome. Methods: We conducted a prospective study and evaluated 90 patients admitted to the hospital with a diagnosis of an acute exacerbation of COPD. A venous blood sample was obtained from all patients on D1 and D7 of hospitalization, for the measurement of Ang-2 and CRP. Results: Serum Ang-2 levels were significantly higher on D1 compared to D7 during the course of COPD exacerbation (p < 0.001). Serum CRP levels were also significantly higher on D1 compared to D7 (p < 0.001). Serum Ang-2 presented a significant positive correlation with CRP levels both on D1 and D7 (r = 0.315 and r = 0.228, respectively). Patients with unfavorable outcome had significantly higher Ang-2 levels both on D1 (p = 0.04) and D7 (p = 0.01). Conclusions: Serum Ang-2 levels are elevated at the onset of COPD exacerbations and are positively associated with CRP levels. Ang-2 levels decrease during the course of COPD exacerbations in patients with favorable outcome. Serum Ang-2 may serve as a biomarker that could predict the outcome of a COPD exacerbation.
    COPD Journal of Chronic Obstructive Pulmonary Disease 10/2013; · 2.31 Impact Factor
  • COPD Journal of Chronic Obstructive Pulmonary Disease 10/2013; 10(5):557-9. · 2.31 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor in asthma. Cysteinyl leukotrienes (Cyst-LTs) have been implicated in vascular permeability in asthma. Cyst-LTs receptor antagonists modulate vascular permeability by reducing VEGF expression. We aimed to determine the levels of VEGF and Cyst-LTs in sputum supernatants of patients with asthma and to investigate possible associations within them and with airway vascular permeability (AVP) index. Possible confounding factors were also assessed. One hundred twenty one patients with asthma (38 with severe refractory asthma, 41 smokers) and 30 healthy subjects (15 smokers) were studied. All subjects underwent lung function tests, and sputum induction for cell count identification and VEGF, Cyst-LTs, measurement in supernatants. AVP index was also assessed. Both VEGF & Cyst-LTs (pg/ml) levels were significantly elevated in patients with asthma compared to normal subjects (median, interquartile ranges 845 [487-1034] vs. 432 (327-654) and 209 [171-296] vs. 92 [75-114] respectively, p < 0.001 for both). Multivariate regression analysis in the whole group showed a significant association of Cyst-LTs levels in sputum supernatants with VEGF levels in sputum supernatants and AVP index. A similar positive association was observed between VEGF levels in sputum supernatants and AVP index. The presence of Severe asthma was a significant covariate for both associations. Our results indicate that Cyst-LTs may modulate vascular permeability by up-regulating VEGF expression. The above effect seems to be affected by asthma severity.
    Respiratory medicine 07/2013; · 2.33 Impact Factor
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    ABSTRACT: BACKGROUND: Smoking is associated with worse asthma outcomes and may modify airway inflammation. Such modification may be mediated through an effect on prostaglandin E2 (PGE2 ) and cysteinyl leukotrienes (Cyst-LTs). OBJECTIVE: We aimed to determine the levels of both PGE2 and Cyst-LTs in sputum supernatants of patients with asthma and to investigate the effect of smoking habit as well as their associations with inflammatory cells, bronchial hyperresponsiveness (BHR) and lung function. METHODS: Ninety-eight patients to asthma (47 smokers) and 40 healthy subjects (20 smokers) were studied. All subjects underwent sputum induction for cell count identification, PGE2 and Cyst-LTs levels measurement in supernatants, pulmonary function tests and BHR to methacholine. RESULTS: Patients with asthma had significantly higher levels of both Cyst-LTs and PGE2 in sputum supernatants compared to healthy subjects [median (interquartile ranges) 432 (287, 575) vs. 91.5 (73.5, 111) pg/mL and 654 (456,789) vs. 117.5 (92,157) pg/mL, respectively, P < 0.001 for both comparisons]. Smoking asthmatics had significantly higher Cyst-LTs and PGE2 levels compared to non-smoking asthmatics. Cyst-LTs levels in sputum supernatant of smoking asthmatics presented a significant positive association with sputum eosinophils, while PGE2 levels were positively associated with sputum neutrophils. CONCLUSIONS: The increased concentrations of PGE2 and Cyst-LTs in sputum supernatants of smoking asthma are consistent with an up-regulation of these two mediators in this specific phenotype of asthma. Furthermore, Cyst-LTs are associated with eosinophilic inflammation, while PGE2 is associated with the presence of neutrophilic inflammation in smoking asthma.
    Clinical & Experimental Allergy 06/2013; 43(6):616-624. · 4.79 Impact Factor
  • Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 05/2013; 110(5):316-21. · 3.45 Impact Factor
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    ABSTRACT: BACKGROUND: A variety of studies have demonstrated improvement in quality of life and depressive symptoms in obstructive sleep apnea (OSA) patients after continuous positive airway pressure (CPAP) treatment. However, very little is known about the effect of OSA treatment on physical activity and energy consumption. OBJECTIVES: The aim of this study was to evaluate the changes in depression, physical activity, energy expenditure, and quality of life (QoL) in OSA patients before and after CPAP therapy. METHODS: Forty-one patients with OSA as revealed by polysomnography, were included to the study. They responded to the generic World Health Organization Quality of Life (WHOQoL) questionnaire, to the specific-disease Quebec Sleep Questionnaire, and to Center for Epidemiologic Studies Depression Scale (CES-D) in order to evaluate QoL and the incidence of depression. In addition, all patients wore an accelerometer which measured physical activity and energy expenditure during a week. At least 6 months after initiation of CPAP treatment (mean time, 9 months) we re-examined 24 patients who met the compliance with the treatment criteria. RESULTS: Patients after CPAP therapy had significantly higher scores in all domains of the Quebec Sleep Questionnaire and in the domains of physical health/level of independence and psychological health/spirituality of the WHOQoL. Depression scores were also better in CES-D after treatment. However, despite the improvement in QoL and psychological status, CPAP therapy had no impact on physical activity and energy expenditure. CONCLUSIONS: CPAP therapy improves QoL and lessens depressive symptoms in our group of well-treated OSA patients. However, physical activity and energy expenditure did not present statistically significant improvement in the same group of OSA patients.
    Sleep And Breathing 02/2013; · 2.26 Impact Factor
  • Current drug targets 12/2012; · 3.93 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a complex, multicomponent disease at the clinical, cellular, and molecular levels. Over the past few years there has been a growing interest in the field of biomarkers in COPD and a large number of studies have evaluated potential candidate molecules in different patient settings. Data on systemic biomarkers from large cohorts, including the well-characterized population of the ECLIPSE study, are now available and provide exciting information on the association of biomarkers with clinically important outcomes, including exacerbations, hospitalizations and mortality. Moreover, recent research has provided proof for the existence of distinct "systemic inflammatory" phenotypes. This review summarizes the currently available evidence on systemic biomarkers in COPD, providing clinically relevant information on the possible role of systemic biomarkers in the evaluation of disease activity and severity, phenotypes, outcomes, COPD exacerbations and treatment response and guidance. Despite the fact that no single biomarker is currently ready to characterize sufficiently the status of COPD patients, guide treatment options, and predict future events, our current knowledge is definitely more advanced than a few years ago and the future of biomarkers looks even more promising.
    Current drug targets 12/2012; · 3.93 Impact Factor
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    ABSTRACT: Smoking may modify the inflammatory pattern of the asthmatic airways. Osteopontin (OPN) has been associated with inflammation and fibrosis. In asthma, sputum levels of OPN are elevated and have been related to the underlying severity and to mediators expressing remodeling and inflammation. To evaluate the levels of OPN in sputum supernatants of asthmatic patients and to investigate the possible role of smoking as well as associations with mediators and cells involved in the inflammatory and remodeling process. We studied 103 asthma patients (49 smokers) and 40 healthy subjects (20 smokers) who underwent lung function tests, bronchial hyperresponsiveness to methacholine, and sputum induction for cell count identification and measurement of OPN, TGF-β1, IL-8, IL-13 and ECP in sputum supernatants. The concentrations of all mediators were measured using enzyme immunoassays. OPN levels (pg/ml) were significantly higher in smoking asthmatics compared to non-smoking asthmatics, and both non-smoking and smoking controls [median (interquartile ranges) 1120 (651,1817) vs. 197 (118,341) vs. 50 (42,70) vs. 102 (77,110)pg/ml, respectively; p<0.001]. Regression analysis provided significant associations between OPN and sputum neutrophils, IL-8 and TGF-β1, the most significant being the one with TGF-β1. These associations were present only in smoking asthmatics. Smoking habit significantly affects sputum OPN levels in asthma. The associations of OPN with sputum neutrophils, TGF-β1 and IL-8 in smoking asthmatics suggest a possible role for OPN in the neutrophilic inflammation and remodeling process in this phenotype of asthma.
    Cytokine 10/2012; · 2.52 Impact Factor
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    ABSTRACT: Pathological features of chronic obstructive pulmonary disease (COPD) include lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of angiopoietins in sputum supernatants of patients with COPD and investigated their possible association with mediators and cells involved in the inflammatory and remodeling process. Fifty-nine patients with COPD, 25 healthy smokers and 20 healthy non-smokers were studied. All subjects underwent lung function tests, sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-2 levels were significantly higher in patients with COPD compared to healthy smokers and healthy non-smokers [median, interquartile ranges pg/ml, 267 (147-367) vs. 112 (67-171) and 98 (95-107), respectively; p<0.001]. Regression analysis showed a significant association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in COPD, the strongest being with VEGF. Our results indicate that induced sputum Ang-2 levels are higher in COPD compared to healthy smokers and healthy non-smokers. Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a possible role for Ang-2 in the pathogenesis of the disease.
    Cytokine 04/2012; 58(3):455-60. · 2.52 Impact Factor
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    ABSTRACT: Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes. Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA. Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes.
    Allergy 03/2012; 67(3):396-402. · 5.88 Impact Factor
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    ABSTRACT: COPD is a multicomponent disease and systemic inflammation represents one of the possible mechanisms responsible for its systemic manifestations, including skeletal muscle weakness and cachexia. Fat-free mass index (FFMI) that reflects the skeletal muscle mass, has been shown to be associated with both dyspnoea and exercise capacity. We hypothesized that the multidimensional BODE index, that reflects the multicomponent nature of COPD, might be related to biomarkers of systemic inflammation. We further evaluated associations between FFMI and systemic inflammation. BODE index and FFMI were calculated in 222 stable COPD patients and 132 smokers or ex-smokers with normal lung function. Systemic inflammation was evaluated with the measurement of leptin, adiponectin, CRP, IL-6, and TNF-α in serum samples of COPD patients. In patients with COPD, both BODE index and FFMI presented significant positive and negative associations respectively with leptin levels (R(2) 0.61 and 0.65, respectively), whereas FFMI presented an additional negative association with the levels of TNF-α (R(2) 0.38). No significant associations were observed in smokers or ex-smokers with normal lung function. Both BODE index and FFMI, are related to the circulating levels of leptin in patients with COPD, suggesting a possible role for leptin in the systemic component of COPD. The additional association of FFMI with TNF-α may further support a role of systemic inflammation in muscle wasting in COPD.
    COPD Journal of Chronic Obstructive Pulmonary Disease 12/2011; 8(6):408-13. · 2.31 Impact Factor
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    ABSTRACT: Smoking is thought to modify the pattern of airway inflammation. Induced sputum provides useful information on cellular phenotype in inflammatory airways disorders; however, it is time-consuming and difficult to implement in everyday clinical practice. The aim of this study was to determine whether exhaled NO (FeNO) and exhaled breath condensate (EBC) pH differed in asthmatic smokers compared with asthmatic non-smokers and healthy subjects, and to evaluate the performance of FeNO and EBC pH for predicting the cellular phenotype of induced sputum. Asthmatic smokers (n = 40) and non-smoking asthmatic patients (n = 43) were recruited for the study. Healthy smoking (n = 30) or non-smoking (n = 30) subjects served as controls. FeNO and EBC pH were measured and all subjects underwent sputum induction for assessment of cell counts. EBC pH was significantly lower in asthmatic smokers compared with non-smokers (P < 0.01). FeNO levels were also significantly lower in asthmatic smokers compared with non-smokers (P < 0.001). EBC pH was inversely associated with sputum eosinophils in both asthmatic smokers and non-smokers (P < 0.001), whereas it was inversely associated with sputum neutrophils only in asthmatic smokers (P < 0.001). FeNO was positively associated with sputum eosinophils both in asthmatic smokers and non-smokers (P < 0.001) but was not associated with sputum neutrophils. In asthmatic smokers, FeNO was a better predictor of sputum eosinophilia, whereas EBC pH was a better predictor of sputum neutrophilia. A combination of FeNO ≤ 14 ppb together with EBC pH > 7.20 predicted the paucigranulocytic induced sputum phenotype. EBC pH and FeNO levels were significantly lower in asthmatic smokers compared with non-smokers. Combined specific cut-off levels for FeNO and EBC pH may predict the paucigranulocytic phenotype in asthmatic smokers.
    Respirology 05/2011; 16(5):811-8. · 2.78 Impact Factor
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    ABSTRACT: During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders and mainly asthma and chronic obstructive pulmonary disease (COPD). Sputum induction is generally a well-tolerated and safe procedure and a European Respiratory Society Task Force has published a comprehensive review on sputum methodology. Induced sputum cell count and, to a lesser extent, mediator measurements have been particularly well validated. In asthma, the sputum and the cell culture supernatant can be used for the measurement of a variety of soluble mediators, including eosinophil-derived proteins, nitric oxide (NO) derivatives, cytokines and remodelling-associated proteins. Sputum eosinophilia (> 3%) is a classic feature of asthma although half of the patients seems to be non eosinophilic. Measuring the percentage of sputum eosinophils has proved to be useful in the clinical arena in helping to predict short term response to inhaled corticosteroids (ICS) and tailor the dose of ICS in the severe patients but there is scope for the application of other induced sputum markers potentially useful in clinical practice. The widespread application of induced sputum in asthma across the spectrum of disease severity has given insight into the relationship between airway function and airway inflammation, proposed new disease phenotypes and defined which of these phenotypes respond to current therapy, and perhaps most importantly provided an additional tool to guide the clinical management of asthmatic patients. To date sputum induction is the only non-invasive measure of airway inflammation that has a clearly proven role in asthma management.
    Current Medicinal Chemistry 03/2011; 18(10):1415-22. · 4.07 Impact Factor
  • Current Medicinal Chemistry 03/2011; 18(10):1413-4. · 4.07 Impact Factor
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    ABSTRACT: Cytokines are key players in the biological processes of malignant tumors and special interest has been focused on cytokines exerting tumor and anti-tumor properties, such as vascular endothelial growth factor (VEGF) and Interleukin-18 (IL-18). Aim of this study was to assess IL-18 and VEGF levels in induced sputum of lung cancer patients at diagnosis, and assess their possible association with the histological type of cancer, the stage and the overall patient survival. Seventy six patients with a diagnosis of lung cancer were recruited and were followed up for 48months. Thirteen healthy smokers and 16 healthy non-smokers were used as control groups. VEGF and IL-18 were measured by ELISA in sputum supernatants at the time of diagnosis. Lung cancer patients had significantly higher baseline IL-18 and VEGF levels compared to healthy controls (p<0.001). No difference was found in IL-18 and VEGF levels between the various stages in non-small cell lung cancer (NSCLC) and between limited and extended small cell lung cancer (SCLC). However, the ratio of VEGF/IL-18 was significantly higher in NSCLC compared to SCLC patients (p=0.018). In extended SCLC overall survival was inversely associated with baseline sputum VEGF levels (p=0.034) and estimated mortality risk was 1.14 (95% CI 1.006-1.283) for an increase of 100pg/ml in VEGF levels. Such association was not found regarding baseline IL-18 levels. VEGF levels in induced sputum may have a prognostic role in the survival of SCLC. The ratio VEGF/IL-18 in induced sputum differs between NSCLC and SCLC, indicating differences in angiogenesis mechanisms and/or immunological response in these two major histological types of lung cancer.
    Cytokine 03/2011; 54(3):277-81. · 2.52 Impact Factor
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    ABSTRACT: Systemic inflammation may represent a possible cause of anemia. Previous data support that anemic patients with COPD present high erythropoietin (EPO) levels, suggestive of EPO resistance, possibly mediated through inflammatory mechanisms. We aimed to determine whether systemic inflammation, which is usually up-regulated during exacerbations of COPD (ECOPD) is associated with low hemoglobin levels expressing erythropoietin resistance. Hemoglobin (Hb), EPO and serum biomarkers of systemic inflammation [CRP, TNF-α, fibrinogen and IL-6] were assessed at three time points (admission, resolution and stable phases) in a selected cohort of 93 COPD patients. Hemoglobin levels were significantly lower on admission compared to resolution and stable phases (median 12.1 g/dl [interquartile ranges 11.2-12.7], vs 13.5 [12.4-14.3] vs 13.4 [12.7-14.08], respectively p=0.002), whereas EPO was significantly higher on admission compared to resolution and stable phases. A negative association between Hb and IL-6 and a positive association between EPO and IL-6 were observed only during the acute phase of exacerbation. EPO and Hb were negatively associated during the acute phase, whereas they were positively associated during discharge and stable phase. In this observational study we have shown that during admission for ECOPD Hb levels are decreased and EPO levels are increased. We have also identified a negative association between Hb and EPO. The above association is mainly related to increased IL-6 levels, indicating a possible EPO resistance through the mechanism of increased systemic inflammatory process.
    European Journal of Internal Medicine 02/2011; 22(1):103-7. · 2.05 Impact Factor
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    ABSTRACT: 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.
    Respiratory research 01/2011; 12:67. · 3.64 Impact Factor
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    ABSTRACT: The lung is the organ with the highest exposure to ambient air in the entire human architecture. Due to its large surface area and blood supply, the lung is susceptible to oxidative injury in the form of myriads of reactive oxygen species (ROS) and free radicals. In order to provide defense against the oxidative burden, the lungs produce various endogenous agents called antioxidants. The antioxidant species help the lungs ward off the deleterious consequences of a wide variety of oxidants/ROS, either of endogenous or environmental origin. Several mechanisms are related to the potential connection between COPD and oxidative stress. One of the most important actions of the oxidative stress is the influence of the molecular mechanisms involved in the expression proinflammatory genes. There is plenty of evidence supporting an imbalance between oxidants and antioxidants in the lung and systemic circulation of smokers and COPD patients. Detection of the oxidative burden and evaluation of their progression and phenotypes by oxidative stress biomarkers have proven challenging and difficult. Both invasive and non-invasive techniques have provided different biomarkers which contribute to the oxidative burden of the airways. An effective wide-spectrum antioxidant therapy with bioavailability is urgently needed to control the local and systemic oxidative burst in COPD. In that direction, several antioxidant agents have been evaluated as potential candidates for the management of COPD. However, despite some encouraging results, clinical trials so far have failed to elaborately define the type of antioxidant, the regimen and the time period of treatment that may improve clinically meaningful outcomes in patients with COPD.
    Current drug targets 01/2011; 12(4):469-77. · 3.93 Impact Factor
  • 09/2010;

Publication Stats

104 Citations
208 Downloads
2k Views
102.22 Total Impact Points

Institutions

  • 2010–2013
    • Attikon University Hospital
      Athínai, Attica, Greece
  • 2008–2012
    • Νοσοκομείο Σωτηρία
      Athínai, Attica, Greece
  • 2011
    • National and Kapodistrian University of Athens
      Athínai, Attica, Greece
  • 2008–2011
    • Athens State University
      Athens, Alabama, United States