41. Early Changes in eDiary COPD Symptoms Predict Clinically Relevant Treatment Response at 12 Weeks: Analysis from the CRYSTAL Study.
Kostikas K, Aalamian-Mattheis M, Pagano VA, Nunez X, Fogel R, Patalano F, Clemens A.
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Early detection of treatment response is important in the long-term treatment and management of patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated whether early improvement in symptoms, recorded in the first 7 or 14 days via an electronic diary (eDiary) compared with baseline, can predict clinically meaningful treatment responders at 12 weeks. CRYSTAL was a 12-week, randomized, open-label study that demonstrated the increased effectiveness of indacaterol/glycopyrronium (IND/GLY) or glycopyrronium (GLY), after a direct switch from on-going baseline therapies, in patients with symptomatic COPD and moderate airflow obstruction. The co-primary endpoints were trough forced expiratory volume in 1 second (FEV
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42. Serum osteopontin in patients with lung cancer and chronic obstructive pulmonary disease: does the co-existence make the difference?
Petta V, Loukides S, Kostikas K, Papaioannou AI, Papatheodorou G, Cholidou K, Tomos I, Papiris S, Koulouris NG, Bakakos P.
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43. IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes.
Egli A, Mandal J, Schumann DM, Roth M, Thomas B, Lorne Tyrrell D, Blasi F, Kostikas K, Boersma W, Milenkovic B, Lacoma A, Rentsch K, Rohde GGU, Louis R, Aerts JG, Welte T, Torres A, Tamm M, Stolz D.
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44. Serum Surfactant Protein Levels in Patients Admitted to the Hospital with Acute COPD Exacerbation.
Papaioannou AI, Konstantelou E, Papaporfyriou A, Bartziokas K, Spathis A, Bakakos P, Loukides S, Koulouris N, Papiris S, Kostikas K.
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Surfactant proteins (SPs) have been studied in COPD patients as biomarkers of disease severity and as predictive factors of unfavorable outcomes. The aim of this exploratory study was to evaluate serum levels of SP-A, SP-B, SP-C, and SP-D in patients with COPD both during AECOPD and in stability and to test their possible associations with disease severity and with the development of new exacerbation events. 20 consecutive COPD patients hospitalized for AECOPD were included. Serum SP levels were measured on admission, at discharge, and on stability. SP-A levels were significantly lower both on admission and at discharge in patients with early relapse compared to those with late or no relapse (29.2 ± 9.1 vs. 43.9 ± 16.9 ng/ml, p = 0.037, and 24.3 ± 2.8 vs. 39.3 ± 14.2 ng/ml, p = 0.011, respectively). SP-B levels were found to have a trend to be higher at discharge and significantly higher on stability in patients experiencing an early relapse compared to those with late or no relapse (52.5 ± 31.6 vs. 31.4 ± 32.3 ng/ml, p = 0.052 and 64.8 ± 32.6 vs. 32.8 ± 25.6 ng/ml, p = 0.024, respectively). Finally, the ROC analysis showed that serum SP-A, SP-B, and SP-C levels at discharge, seemed to be significant predictors of early relapse. Our conclusion is that serum levels of SPs might be related to disease outcomes in COPD patients.
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45. Blood Eosinophils as Biomarkers to Drive Treatment Choices in Asthma and COPD.
Kostikas K, Brindicci C, Patalano F.
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46. At the Root: Defining and Halting Progression of Early Chronic Obstructive Pulmonary Disease.
Martinez FJ, Han MK, Allinson JP, Barr RG, Boucher RC, Calverley PMA, Celli BR, Christenson SA, Crystal RG, Fagerås M, Freeman CM, Groenke L, Hoffman EA, Kesimer M, Kostikas K, Paine R, Rafii S, Rennard SI, Segal LN, Shaykhiev R, Stevenson C, Tal-Singer R, Vestbo J, Woodruff PG, Curtis JL, Wedzicha JA.
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47. Using simple blood count for the diagnosis of pulmonary embolism in chronic obstructive pulmonary disease exacerbations: are we there yet?
Papaioannou AI, Papiris S, Kostikas K.
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48. Exhaled breath temperature in optimally treated asthmatics: severity and underlying mechanisms.
Ntontsi P, Bakakos P, Papathanasiou E, Tsilogianni Z, Kostikas K, Hillas G, Papatheodorou G, Koulouris N, Papiris S, Loukides S.
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49. Emphysematous Phenotype is Characterized by Low Blood Eosinophils: A Cross-Sectional Study.
Papaioannou AI, Kostikas K, Papaporfyriou A, Angelakis L, Papathanasiou E, Hillas G, Mazioti A, Bakakos P, Koulouris N, Papiris S, Loukides S.
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Sputum and blood eosinophils are proposed as candidate biomarkers for the identification of chronic obstructive pulmonary disease (COPD) patients at risk for exacerbation and treatment response. In this study, we evaluated the associations of eosinophils with the presence of emphysema in COPD patients. Induced sputum and blood eosinophil measurements were performed in consecutive COPD patients. Patients underwent lung function testing and high resolution computed tomography (HRCT) of the chest and the presence of emphysema was quantified. Patients with emphysematous lesions in ≥15% of the pulmonary parenchyma were considered having significant emphysema. Ninety-eight patients were included in the study. Patients with significant emphysema had lower blood eosinophil counts compared to patients without emphysema [median (IQR) 34.6 (0.0, 63.0) vs. 169.0 (110.0, 260.0) cells/µL, p < 0.001]; similar results were observed for the percentage (%) of blood eosinophils, but no difference was observed for sputum eosinophils. The differences were evident in frequent and non-frequent exacerbators and irrespective of the use of inhaled corticosteroids (ICS). Patients with significant emphysema in HRCT present lower levels of blood eosinophils and these differences were present irrespective of the frequent exacerbator history or the use of ICS. Blood eosinophils may not represent a clinically relevant biomarker in the presence of emphysema.
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50. Dual Bronchodilation Response by Exacerbation History and Eosinophilia in the FLAME Study.
Papi A, Kostikas K, Wedzicha JA, Vogelmeier CF, Roche N, Shen S, Banerji D, Fogel R, Patalano F, Chapman KR.
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51. Treatment with long acting muscarinic antagonists stimulates serum levels of irisin in patients with COPD.
Mandal J, Roth M, Papakonstantinou E, Sun Q, Costa L, Boeck L, Scherr A, Rakic J, Louis R, Milenkovic B, Boersma W, Kostikas K, Blasi F, Aerts J, Rohde G, Lacoma A, Torres A, Welte T, Tamm M, Stolz D.
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Long acting muscarinic antagonists (LAMA) are currently considered the therapeutic mainstay for patients with COPD and have been shown to improve clinical outcomes including symptoms, exercise capacity and airflow limitation. Irisin, is a newly discovered hormone-like myokine generated by skeletal muscle cells in response to exercise and it is suggested to regulate energy expenditure and exercise capacity. The aim of the present study was to investigate if treatment with LAMA alters serum irisin levels in patients with COPD. Irisin was assessed by ELISA in the serum of 506 patients with COPD, GOLD II-IV, with a smoking history >10 PY, who were included in the PROMISE-COPD cohort. The effect of inhaled LAMA on serum irisin levels was evaluated in a proof-of-concept cohort of 40 COPD patients. Univariate linear regression analysis revealed that there was a significant negative association of irisin with age-adjusted Charlson score (p = 0.003) and a positive association of irisin with 6-min walking distance (6MWD) (p = 0.018) and treatment with LAMA (p = 0.004) but not with LABA or ICS. Multivariate analysis revealed that the association of irisin with LAMA treatment remains significant after adjustment for age-adjusted score and 6MWD. In the proof-of-concept cohort a single inhalation of LAMA stimulated serum irisin levels after 4 h. These findings imply that treatment of COPD patients with LAMA increase circulating irisin, thus explaining some of the beneficial extra-pulmonary effects of these drugs when used in the treatment of COPD.
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52. The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis.
Tsikrika S, Dimakou K, Papaioannou AI, Hillas G, Thanos L, Kostikas K, Loukides S, Papiris S, Koulouris N, Bakakos P.
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53. Prevalence of lung function impairment among Greek cement production workers: a cross-sectional study.
Rachiotis G, Kostikas K, Pinotsi D, Hadjichristodoulou C, Drivas S.
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Greece is a significant cement producing country. The aim of this study was to investigate the prevalence and risk factors of lung function impairment among Greek cement workers. One hundred thirty- seven cement production workers participated in this study. In addition, 110 employees not exposed to cement dust comprised the control group. The concentration of cement total dust at workplace varied from 1.1 to 11.6 mg/m
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54. Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial.
Vogelmeier CF, Gaga M, Aalamian-Mattheis M, Greulich T, Marin JM, Castellani W, Ninane V, Lane S, Nunez X, Patalano F, Clemens A, Kostikas K.
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55. Response to Indacaterol/Glycopyrronium (IND/GLY) by Sex in Patients with COPD: A Pooled Analysis from the IGNITE Program.
Tsiligianni I, Mezzi K, Fucile S, Kostikas K, Shen S, Banerji D, Fogel R.
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In this pooled analysis, we compared the effect of indacaterol/glycopyrronium (IND/GLY) by sex versus other commonly used chronic obstructive pulmonary disease (COPD) treatments and placebo. Male and female patients with moderate-to-very-severe COPD who had participated in six randomized controlled trials were included in the analysis. Baseline demographics and disease characteristics were analyzed by sex, and any differences noted. The effects of IND/GLY versus salmeterol/fluticasone (SFC), glycopyrronium, tiotropium and placebo, on lung function and the patient-reported outcomes (health status, dyspnea, rescue medication use and symptoms) were assessed by sex after 26 weeks treatment. The analysis population comprised 4719 men and 1389 women. Most baseline parameters differed significantly between men and women. Nonetheless, despite these differences in baseline characteristics, IND/GLY significantly improved lung function versus placebo (p < 0.0001) and all active comparators (p < 0.01) in men and women. Overall, IND/GLY showed better improvement in dyspnea and health status compared with all other treatments in both sex. Greater reduction of rescue medication use was observed with IND/GLY versus placebo and other treatments (all p < 0.01 expect IND/GLY versus SFC). Although some variability was observed, improvements in health status, dyspnea, rescue medication use and symptoms were generally larger in women than in men. Irrespective of sex, IND/GLY provided superior efficacy to monotherapy or SFC in both men and women. Small differences in efficacy response by sex were observed, which should be evaluated further in prospective clinical studies. Nevertheless, the benefits observed with IND/GLY confirm dual bronchodilator as the preferred therapy in patients with moderate-to-very-severe COPD regardless of sex.
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56. Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits.
Vasilopoulou M, Papaioannou AI, Kaltsakas G, Louvaris Z, Chynkiamis N, Spetsioti S, Kortianou E, Genimata SA, Palamidas A, Kostikas K, Koulouris NG, Vogiatzis I.
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Pulmonary rehabilitation (PR) remains grossly underutilised by suitable patients worldwide. We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease (COPD) exacerbations, hospitalisations and emergency department (ED) visits.Following completion of an initial 2-month PR programme this prospective, randomised controlled trial (between December 2013 and July 2015) compared 12 months of home-based maintenance tele-rehabilitation (n=47) with 12 months of hospital-based, outpatient, maintenance rehabilitation (n=50) and also to 12 months of usual care treatment (n=50) without initial PR.In a multivariate analysis during the 12-month follow-up, both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1) acute COPD exacerbation (incidence rate ratio (IRR) 0.517, 95% CI 0.389-0.687, and IRR 0.635, 95% CI 0.473-0.853), respectively, and 2) hospitalisations for acute COPD exacerbation (IRR 0.189, 95% CI 0.100-0.358, and IRR 0.375, 95% CI 0.207-0.681), respectively. However, only home-based maintenance tele-rehabilitation and not hospital-based, outpatient, maintenance PR was an independent predictor of ED visits (IRR 0.116, 95% CI 0.072-0.185).Home-based maintenance tele-rehabilitation is equally effective as hospital-based, outpatient, maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations. In addition, it encounters a lower risk for ED visits, thereby constituting a potentially effective alternative strategy to hospital-based, outpatient, maintenance PR.
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57. Serum periostin in patients hospitalized for COPD exacerbations.
Konstantelou E, Papaioannou AI, Loukides S, Bartziokas K, Papaporfyriou A, Papatheodorou G, Bakakos P, Papiris S, Koulouris N, Kostikas K.
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Serum periostin has been proposed as a surrogate biomarker of Th2 inflammatory response in patients with asthma, but its predictive role in hospitalized patients with COPD has not been evaluated. The aim of the present observational prospective cohort study was to evaluate the possible role of serum periostin as predictor of outcome in COPD patients hospitalized for AECOPD. Serum periostin was measured on admission and at discharge in patients admitted to the hospital for a COPD exacerbation. Patients were followed-up for 1year for future exacerbations, hospitalizations and mortality. 155 consecutive patients admitted to the hospital for AECOPD were included to the study. Periostin levels on admission were elevated compared to discharge [34.7 (25.2-52.2) vs. 25.9 (17.4-41.0) ng/mL, p=0.003], but serum periostin levels did not differ between patients with or without prolonged hospitalization, or those who required non-invasive ventilation, intubation, or died during hospitalization. Frequent exacerbators had higher serum periostin levels at the time of discharge compared to non-frequent exacerbators [37.9 (26.6, 64.5) vs. 23.9 (16.2, 37.9), p<0.001]. Periostin levels above the median value (25ng/mL) were not related to the time of next exacerbation, time of next COPD hospitalization, (p=0.858) or time to death. The role of serum periostin levels as a predictive biomarker of future risk in hospitalized patients with COPD is of limited value.
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58. The effect of indacaterol/glycopyrronium versus tiotropium or salmeterol/fluticasone on the prevention of clinically important deterioration in COPD.
Anzueto AR, Vogelmeier CF, Kostikas K, Mezzi K, Fucile S, Bader G, Shen S, Banerji D, Fogel R.
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59. A European Respiratory Society technical standard: exhaled biomarkers in lung disease.
Horváth I, Barnes PJ, Loukides S, Sterk PJ, Högman M, Olin AC, Amann A, Antus B, Baraldi E, Bikov A, Boots AW, Bos LD, Brinkman P, Bucca C, Carpagnano GE, Corradi M, Cristescu S, de Jongste JC, Dinh-Xuan AT, Dompeling E, Fens N, Fowler S, Hohlfeld JM, Holz O, Jöbsis Q, Van De Kant K, Knobel HH, Kostikas K, Lehtimäki L, Lundberg J, Montuschi P, Van Muylem A, Pennazza G, Reinhold P, Ricciardolo FLM, Rosias P, Santonico M, van der Schee MP, van Schooten FJ, Spanevello A, Tonia T, Vink TJ.
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Breath tests cover the fraction of nitric oxide in expired gas (
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60. Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes.
Ntontsi P, Loukides S, Bakakos P, Kostikas K, Papatheodorou G, Papathanassiou E, Hillas G, Koulouris N, Papiris S, Papaioannou AI.
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