Nikolaos Koulouris

Plasma leptin and adiponectin in COPD exacerbations: Associations with inflammatory biomarkers

BACKGROUND Various systemic inflammatory markers have been evaluated for their value in acute exacerbations of chronic obstructive pulmonary disease (COPD). Leptin and adiponectin have been linked to acute exacerbations and stable COPD. OBJECTIVES To assess plasma leptin, adiponectin and their ratio in acute exacerbations of COPD and to study possible associations with inflammatory biomarkers. METHODS Plasma leptin, adiponectin and their ratio (L/A) and serum biomarkers of systemic inflammation C-reactive protein (CRP), Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were assessed at three time points (admission, resolution and stable phase - 8 weeks after resolution) in a selected cohort of 63 COPD patients hospitalized for acute exacerbations. Subjects with comorbidities related to adipose tissue hormones were meticulously excluded. MEASUREMENTS AND MAIN RESULTS All systemic inflammatory biomarkers, leptin and L/A ratio were elevated during admission compared to resolution and stable phase (mean L/A ratio 2.6 vs. 1.57 vs. 1.22, respectively; p<0.0001), whereas adiponectin was elevated at resolution compared to admission. Log leptin, adiponectin and L/A ratio were significantly associated with variables of systemic inflammation, after proper adjustments, both on admission and in stable condition. In stepwise multiple linear regression models, IL-6 and TNF-alpha present the most significant associations with leptin, adiponectin and their ratio. CONCLUSIONS Our data suggest that both leptin and adiponectin are associated with the systemic inflammatory process during exacerbations of COPD. The most significant associations seem to be those with IL-6 and TNF-alpha.

Inflammation and Immune Response in COPD: Where Do We Stand?

Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs). Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients

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.

Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen

Abstract Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. Phylogenetic analysis of the virus showed close similarity with other human MERS-CoVs from the recent Jeddah outbreak in Saudi Arabia. Immunoglobulin G (IgG) titres peaked 3 weeks after the onset of illness, whilst IgM levels remained constantly elevated during the follow-up period (second to fifth week of illness). Serological testing confirmed by virus neutralisation assay detected an additional case that was a close contact of the patient.

Hemoglobin, erythropoietin and systemic inflammation in exacerbations of chronic obstructive pulmonary disease

BACKGROUND 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. OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Cardiovascular effects of high-intensity interval aerobic training combined with strength exercise in patients with chronic heart failure. A randomized phase III clinical trial

BACKGROUND The aim of this work was to evaluate the effect of high-intensity interval exercise (i.e., 30s at 100% of max workload, followed by 30s at rest, 45 min 3 days/week working-out schedule for 12 weeks) on left ventricular function and aortic elastic properties among chronic heart failure (CHF) patients. METHODS This study is a phase III clinical trial. Of the 100 consecutive CHF patients (NYHA classes II-IV, ejection fraction<50%) that were randomly allocated, 72 completed the study (exercise training group, n=33, 63 ± 9 years, 88% men, and control group, n=39, 56 ± 11 years, 82% men). All patients underwent cardiopulmonary stress test, non-invasive high-fidelity tonometry of the radial artery, pulse wave velocity measurement using a SphygmoCor device and echocardiography before and after the completion of the training program. RESULTS Both groups reported similar medical characteristics and physical activity status. General mixed effects models revealed that the intervention group reduced pulse wave velocity by 9% (p=0.05); Emv/Vp by 14% (p=0.06); E to A ratio by 24% (p=0.004), E to Emv ratio by 8% (p=0.05), MLHFQ score by 66% (p=0.003) and the depression score by 19% (p=0.5); increased augmentation index by 29%; VTI by 4% (p=0.05), 6-minute-walk distance up to 13% (p=0.05), peak oxygen uptake by 28% (p=0.001) and peak power by 25% (p=0.005). There were no significant changes in the control group. CONCLUSION Interval high-intensity aerobic training, combined with strength exercise, seems to benefit aortic dilatation capacity and augmented systolic pressure in parallel with improvement in left ventricular diastolic function and quality of life.

High intensity, interval exercise improves quality of life of patients with chronic heart failure: a randomized controlled trial

BACKGROUND The aim of this study was to evaluate the effect of high intensity, interval exercise on quality of life (QoL) and depression status, in chronic heart failure (CHF) patients. METHODS A randomized controlled trial (phase III). Of the 100 consecutive CHF patients (NYHA classes II-IV, ejection fraction ≤ 50%) that were randomly allocated to exercise intervention (n = 50, high-intensity intermittent endurance training 30 s at 100% of max workload, 30 s at rest, for 45 min/day-by-12 weeks) or no exercise advice (n = 50), 72 (exercise group, n = 33, 63 ± 9 years, 88% men, 70% ischemic CHF and control group, n = 39, 56 ± 11 years, 82% men, 70% ischemic CHF) completed the study. QoL was assessed using the validated and translated Minnesota Living with Heart Failure questionnaire. Depressive symptomatology was evaluated using the validated and translated Zung Depression Rating Scale (ZDRS). Maximal oxygen uptake (VO(2max)) and carbon dioxide production (VCO(2max)) were also measured breath-by-breath. RESULTS Data analysis demonstrated that in the intervention group MLHFQ score was reduced by 66% (P = 0.003); 6-min-walk distance increased by 13% (P < 0.05), VO(2max) level increased by 31% (P = 0.001), VCO(2max) level increased by 28% (P = 0.001) and peak power output increased by 25% (P = 0.001), as compared with the control group. CONCLUSION High intensity, systematic aerobic training, could be strongly encouraged in CHF patients, since it improves QoL, by favorably modifying their fitness level.

Increased levels of osteopontin in sputum supernatant of smoking asthmatics.

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.

Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits

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. Home tele-rehabilitation reduces risk of COPD exacerbation; is effective alternative to in-hospital rehabilitation http://ow.ly/T17g30ap9cY

Vascular endothelial growth factor and cysteinyl leukotrienes in sputum supernatant of patients with asthma

BACKGROUND 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. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.