Sleep and Breathing Conference highlights 2023: a summary by ERS Assembly 4.

This paper presents some of the highlights of the Sleep and Breathing Conference 2023 https://bit.ly/46MxJml.

Role of endothelial dysfunction in the severity of COVID­19 infection (Review).

COVID­19 patients with severe infection have been observed to have elevated auto­antibodies (AAs) against angiotensin II receptor type 1 (AT1R) and endothelin (ET) 1 receptor type A (ETAR), compared with healthy controls and patients with favorable (mild) infection. AT1R and ETAR are G protein­coupled receptors, located on vascular smooth muscle cells, fibroblasts, immune and endothelial cells, and are activated by angiotensin II (Ang II) and ET1 respectively. AAs that are specific for these receptors have a functional role similar to the natural ligands, but with a more prolonged vasoconstrictive effect. They also induce the production of fibroblast collagen, the release of reactive oxygen species and the secretion of proinflammatory cytokines (including IL­6, IL­8 and TNF­α) by immune cells. Despite the presence of AAs in severe COVID­19 infected patients, their contribution and implication in the severity of the disease is still not well understood and further studies are warranted. The present review described the major vascular homeostasis systems [ET and renin­angiotensin­aldosterone system (RAAS)], the vital regulative role of nitric oxide, the AAs, and finally the administration of angiotensin II receptor blockers (ARBs), so as to provide more insight into the interplay that exists among these components and their contribution to the severity, prognosis and possible treatment of COVID­19.

ERS International Congress 2020 Virtual: highlights from the Respiratory Intensive Care Assembly.

During the virtual European Respiratory Society Congress 2020, early career members summarised the sessions organised by the Respiratory Intensive Care Assembly. The topics covered included diagnostic strategies in patients admitted to the intensive care unit with acute respiratory failure, with a focus on patients with interstitial lung disease and for obvious reasons, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These sessions are summarised in this article, with take-home messages highlighted.

Left ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease - a step forward in cardiovascular comorbidome.

Chronic obstructive pulmonary disease (COPD) augments the likelihood of having left ventricular diastolic dysfunction (LVDD)-precursor of heart failure with preserved ejection fraction (HFpEF). LVDD shares overlapping symptomatology (cough and dyspnea) with COPD. Stress induced LVDD is indicative of masked HFpEF. Our aim was to evaluate the predictive value of inflammatory, oxidative stress, cardio-pulmonary and echocardiographic parameters at rest for the diagnosis of stress LVDD in non-severe COPD patients, who complain of exertional dyspnea and are free of overt cardiovascular diseases. A total of 104 COPD patients (26 patients with mild and 78 with moderate COPD) underwent echocardiography before cardio-pulmonary exercise testing (CPET) and 1-2 minutes after peak exercise. Patients were divided into two groups based on peak average E/e': patients with stress induced left ventricular diastolic dysfunction (LVDD)-E/e' > 15 masked HFpEF and patients without LVDD-without masked HFpEF. CPET and echocardiographic parameters at rest were measured and their predictive value for stress E/e' was analysed. Markers for inflammation (resistin, prostaglandine E2) and oxidative stress (8-isoprostanes) were also determined. Stress induced LVDD occurred in 67/104 patients (64%). Those patients showed higher VE/VCO2 slope. None of the CPET parameters was an independent predictor for stress LVDD.Except for prostglandine E2, none of the inflammatory or oxidative stress markers correlated to stress E/e'. The best independent predictors for stress LVDD (masked HFpEF) were RAVI, right ventricular parasternal diameter and RV E/A >0.75. Their combination predicted stress LVDD with the accuracy of 91.2%. There is a high prevalence of masked HFpEF in non-severe COPD with exertional dyspnea, free of overt cardiovascular disease. RAVI, right ventricular parasternal diameter and RV E/A >0.75 were the only independent clinical predictors of masked HFpEF. 288.

The Role of Stress Echocardiography in the Early Detection of Diastolic Dysfunction in Non-Severe Chronic Obstructive Pulmonary Disease Patients. / O Papel da Ecocardiografia sob Estresse na Detecção Precoce de Disfunção Diastólica em Pacientes com Doença Pulmonar Obstrutiva Crônica Não Grave.

BACKGROUND: Exertional dyspnea is a common complaint of patients with heart failure with preserved ejection fraction (HFpEF) and chronic obstructive pulmonary disease (COPD). HFpEF is common in COPD and is an independent risk factor for disease progression and exacerbation. Early detection, therefore, has great clinical relevance. OBJECTIVES: The aim of the study is to detect the frequency of masked HFpEF in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease, and to analyze the correlation between masked HFpEF and the cardiopulmonary exercise testing (CPET) parameters. METHODS: We applied the CPET in 104 non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. Echocardiography was performed before and at peak CPET. Cut-off values for stress-induced left and right ventricular diastolic dysfunction (LVDD/ RVDD) were E/e'>15; E/e'>6, respectively. Correlation analysis was done between CPET parameters and stress E/e'. A p-value <0.05 was considered significant. RESULTS: 64% of the patients had stress-induced LVDD; 78% had stress-induced RVDD. Both groups with stress LVDD and RVDD achieved lower load, lower V'O2 and O2-pulse, besides showing reduced ventilatory efficiency (higher VE/VCO2 slopes). None of the CPET parameters were correlated to stress-induced left or right E/e'. CONCLUSION: There is a high prevalence of stress-induced diastolic dysfunction in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. None of the CPET parameters correlates to stress-induced E/e'. This demands the performance of Exercise stress echocardiography (ESE) and CPET for the early detection and proper management of masked HFpEF in this population. (Arq Bras Cardiol. 2021; 116(2):259-265).

FUNDAMENTO: A dispneia por esforço é uma queixa comum de pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEP) e doença pulmonar obstrutiva crônica (DPOC). A ICFEP é comum na DPOC e é um fator de risco independente para a progressão e exacerbação da doença. A detecção precoce, portanto, tem grande relevância clínica. OBJETIVOS: O objetivo deste estudo foi detectar a frequência de ICFEP mascarada em pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular manifesta, e analisar a correlação entre ICFEP mascarada e os parâmetros do teste cardiopulmonar de exercício (TCPE). MÉTODOS: Aplicamos o TCPE em 104 pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular evidente. A ecocardiografia foi realizada antes e no pico do TCPE. Os valores de corte para disfunção diastólica ventricular esquerda e direita induzida por estresse (DDVE/DDVD) foram E/e' >15; E/e' >6, respectivamente. A análise de correlação foi feita entre os parâmetros do TCPE e o estresse E/d'. Valor de p<0,05 foi considerado significativo. RESULTADOS: 64% dos pacientes tinham DDVE induzida por estresse; 78% tinham DDVD induzida por estresse. Ambos os grupos com estresse DDVE e DDVD obtiveram carga menor, V'O2 e pulso de O2 mais baixos, além de apresentarem redução na eficiência ventilatória (maiores inclinações de VE/VCO2). Nenhum dos parâmetros do TCPE foram correlacionados com E/e' DDVE/DDVD induzida por estresse. CONCLUSÃO: Há uma alta prevalência de disfunção diastólica induzida por estresse em pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular evidente. Nenhum dos parâmetros do TCPE se correlaciona com E/e' induzida por estresse. Isso demanda a realização de Ecocardiografia sob estresse por exercício (EES) e TCPE para detecção precoce e manejo adequado da ICFEP mascarada nesta população. (Arq Bras Cardiol. 2021; 116(2):259-265).

O Papel da Ecocardiografia sob Estresse na Detecção Precoce de Disfunção Diastólica em Pacientes com Doença Pulmonar Obstrutiva Crônica Não Grave / The Role of Stress Echocardiography in the Early Detection of Diastolic Dysfunction in Non-Severe Chronic Obstructive Pulmonary Disease Patients

Resumo Fundamento A dispneia por esforço é uma queixa comum de pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEP) e doença pulmonar obstrutiva crônica (DPOC). A ICFEP é comum na DPOC e é um fator de risco independente para a progressão e exacerbação da doença. A detecção precoce, portanto, tem grande relevância clínica. Objetivos O objetivo deste estudo foi detectar a frequência de ICFEP mascarada em pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular manifesta, e analisar a correlação entre ICFEP mascarada e os parâmetros do teste cardiopulmonar de exercício (TCPE). Métodos Aplicamos o TCPE em 104 pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular evidente. A ecocardiografia foi realizada antes e no pico do TCPE. Os valores de corte para disfunção diastólica ventricular esquerda e direita induzida por estresse (DDVE/DDVD) foram E/e' >15; E/e' >6, respectivamente. A análise de correlação foi feita entre os parâmetros do TCPE e o estresse E/d'. Valor de p<0,05 foi considerado significativo. Resultados 64% dos pacientes tinham DDVE induzida por estresse; 78% tinham DDVD induzida por estresse. Ambos os grupos com estresse DDVE e DDVD obtiveram carga menor, V'O2 e pulso de O2 mais baixos, além de apresentarem redução na eficiência ventilatória (maiores inclinações de VE/VCO2). Nenhum dos parâmetros do TCPE foram correlacionados com E/e' DDVE/DDVD induzida por estresse. Conclusão Há uma alta prevalência de disfunção diastólica induzida por estresse em pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular evidente. Nenhum dos parâmetros do TCPE se correlaciona com E/e' induzida por estresse. Isso demanda a realização de Ecocardiografia sob estresse por exercício (EES) e TCPE para detecção precoce e manejo adequado da ICFEP mascarada nesta população. (Arq Bras Cardiol. 2021; 116(2):259-265)

Abstract Background Exertional dyspnea is a common complaint of patients with heart failure with preserved ejection fraction (HFpEF) and chronic obstructive pulmonary disease (COPD). HFpEF is common in COPD and is an independent risk factor for disease progression and exacerbation. Early detection, therefore, has great clinical relevance. Objectives The aim of the study is to detect the frequency of masked HFpEF in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease, and to analyze the correlation between masked HFpEF and the cardiopulmonary exercise testing (CPET) parameters. Methods We applied the CPET in 104 non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. Echocardiography was performed before and at peak CPET. Cut-off values for stress-induced left and right ventricular diastolic dysfunction (LVDD/ RVDD) were E/e'>15; E/e'>6, respectively. Correlation analysis was done between CPET parameters and stress E/e'. A p-value <0.05 was considered significant. Results 64% of the patients had stress-induced LVDD; 78% had stress-induced RVDD. Both groups with stress LVDD and RVDD achieved lower load, lower V'O2 and O2-pulse, besides showing reduced ventilatory efficiency (higher VE/VCO2 slopes). None of the CPET parameters were correlated to stress-induced left or right E/e'. Conclusion There is a high prevalence of stress-induced diastolic dysfunction in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. None of the CPET parameters correlates to stress-induced E/e'. This demands the performance of Exercise stress echocardiography (ESE) and CPET for the early detection and proper management of masked HFpEF in this population. (Arq Bras Cardiol. 2021; 116(2):259-265)

The link between dynamic hyperinflation, autonomic dysfunction and exercise testing parameters with masked heart failure in patients with non-severe obstructive pulmonary disease.

OBJECTIVES: Autonomic dysfunction (AD) and dynamic hyperinflation (DH) have been implicated as pathophysiological mechanisms of heart failure with preserved ejection fraction (HFpEF) in chronic obstructive pulmonary disease (COPD) patients. Their association, however, remains elusive: The aims of the study were: (1) to determine the prevalence of AD and DH in non-severe COPD patients, with exertional dyspnea, without clinically overt cardio-vascular (CV) comorbidities; (2) to analyze the correlation and clinical significance between DH, AD, and maksed HFpEF. METHODS: We applied CPET in 68 subjects. Echocardiography was performed before CPET and 1-2 min after peak exercise. IC manoeuvres were applied. Patients were divided into two groups: patients with and without masked HFpEF. Wilkoff method calculated the meatabolic - chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined. RESULTS: The prevalence of CI was 77 vs. 52% in patients with/without masked HFpEF; of abnormal HRR - 98 vs. 62% respectively; of DH - 53 vs. 29%. ICdyn was associated with AD. Univariate regression showed association between masked HFpEF, ICdyn, HRR, oxygenuptake ('VO2), 'VO2 at anaerobic threshold, oxygen (O2) pulse and 'VE/'VCO2 slope. None of these parameters is an independent predictor for masked HFpEF. CONCLUSIONS: DH, AD, and masked HFpEF are prevalent in non-severe COPD patients, who complain of exertional dyspnea and are free of clinically overt CV comorbidities. DH is independently associated with AD. Neither AD, nor DH and CPET are independent predictors for masked HFpEF.

The 'right way' to the left chamber in non-severe COPD: Echocardiographic predictors for stress-induced left ventricular diastolic dysfunction.

OBJECTIVE: Dyspnea is a major complaint of both chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction (HFpEF). It often remains underdiagnosed in COPD patients when only echocardiography at rest is performed. The aim of this study was to evaluate the predictive value of cardiopulmonary and echocardiographic parameters at rest for the diagnosis of HFpEF in non-severe COPD patients who complain of exertional dyspnea and have no overt cardiovascular disease. METHODS: A total of 104 COPD patients underwent echocardiography before cardiopulmonary exercise testing (CPET) and 1-2 minutes after peak exercise. The patients were divided into 2 groups based on peak E/e' measurements: patients with masked HFpEF-stress and left ventricular diastolic dysfunction (LVDD; E/e'>15), and patients without masked HFpEF (without stress LVDD). CPET and echocardiographic parameters at rest were measured and the predictive value for stress E/e' was analyzed. RESULTS: Stress LVDD occurred in 67 of 104 patients (64%). These patients achieved a lower work load, lower 'VO2 consumption, lower minute ventilation, and higher 'VE/'VCO2 slope in comparison with patients without stress LVDD. None of the CPET values correlated with stress E/e'. The best independent predictors for stress LVDD were right atrium volume index (RAVI), right ventricle (RV) parasternal diameter, and RV E/A >0.75. The combination of these echocardiographic parameters predicted HFpEF with an accuracy of 91.2%. CONCLUSION: There is a high prevalence of stress LVDD in non-severe COPD patients with exertional dyspnea who remain free of overt cardiovascular disease. RAVI, RV parasternal diameter, and RV E/A >0.75 were the only independent predictors of stress LVDD.

Echocardiographic predictors of stress induced right ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary vasculopathy, right heart structural and functional abnormalities occur even in normoxemic chronic obstructive pulmonary disease (COPD) patients. Despite being associated with functional limitation, exacerbations, and disease progression, their detection and proper management is still delayed. AIM: Our aim was to establish the frequency of stress-induced right ventricular diastolic dysfunction (RVDD) in non-severe COPD patients, free of overt cardiovascular disease, who complain of exertional dyspnea and to look for echocardiographic predictors of it. MATERIALS AND METHODS: We applied cardio-pulmonary exercise testing (CPET) in 104 non-severe, COPD patients. A ramp protocol was performed. Echocardiography was done before and 1-2 min after peak exercise. Cut-off values for stress induced RVDD were E/e' >6. Receiver operating curves were constructed for echo parameters at rest to determine if any of them may discriminate stress induced RV E/e'>6 or <6. Uni- and multivariable linear regression analysis was also performed to assess the predictive power of each of them. A p-value < 0.05 was considered significant. RESULTS: A total of 78% of the patients had stress-induced RVDD. Right atrium volume index (RAVI) (cut-off >20.55 ml/m2; sensitivity - 86%; specificity - 86%), RV wall thickness (RVWT) (cut-off >5.25 mm; sensitivity - 100%; specificity - 63%), and RV E/A ratio at rest (cut-off >1.05; sensitivity - 79.7%; specificity - 90.5%) were the best predictors of stress RV E/e. In univariate regression analysis E/A showed the highest OR 19.73 (95% CI - 18.52-21.01); followed by RAVI - OR 3.82; (95% CI - 2.04-7.14). CONCLUSION: There is a high prevalence of stress-induced RVDD in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. RAVI, RVWT, E/A, and E/e' ratio at rest may be used as predictors for stress RVDD and may facilitate patients' risk stratification and proper management.

Autonomic dysfunction, cardio-pulmonary exercise testing and masked heart failure with preserved ejection fraction in non-severe chronic obstructive pulmonary disease.

BACKGROUND: Autonomic dysfunction (AD) and cardiopulmonary exercise testing (CPET) parameters have been associated with masked heart failure with preserved ejection fraction (HFpEF) in the general population. Their clinical significance for masked HFpEF in chronic obstructive pulmonary disease (COPD) is however elusive. AIM: The aim of the study was to determine the prevalence, correlation and clinical significance of AD and CPET with masked HFpEF, in non-severe COPD patients, complaining of exertional dyspnoea, without clinically overt cardio-vascular (CV) comorbidities. METHODS AND RESULTS: We applied CPET and echocardiography in 68 COPD subjects. Echocardiography was performed before CPET and 1-2 min after peak exercise. Patients were divided into two groups: patients with and without masked HFpEF. Peak E/e' - 15 was applied as a cut-off. Chronotropic incompetence (CI) was assumed if both failure to reach the target heart rate (HR) on exercise and diminished heart rate reserve <80% occurred. Abnormal HR recovery (HRR) was taken if the decline is <12 beats within the first minute after exercise cessation. Univariate regression showed association between masked HFpEF, HRR, VO2, VO2 at AT, oxygen pulse and VE/VCO2 slope. The multivariate regression demonstrated HRR as the only independent predictor of masked HFpEF - (OR 10.28; 95% CI (3.55-29.80)). CONCLUSION: Abnormal HRR is the only independent predictor of masked HFpEF in non-severe COPD patients. Despite of being associated with masked HFpEF, the lower VO2, lower oxygen pulse, higher VE/VCO2 slope and lower exercise load seem to be the consequences, rather than the triggers for it.

Stress echocardiography for left ventricular diastolic dysfunction detection in patients with non-severe chronic obstructive pulmonary disease: a cross-sectional study.

AIM: To assess whether the simultaneous performance of exercise stress echocardiography and cardio-pulmonary testing (ESE-CPET) may facilitate the timely diagnosis of subclinical left ventricular diastolic dysfunction (LVDD) in patients with non-severe chronic obstructive pulmonary disease (COPD), preserved left ventricular systolic function, and exertional dyspnea or exercise intolerance. METHODS: This cross-sectional study, conducted between May 2017 and April 2018, involved 104 non-severe COPD patients with exertional dyspnea and preserved ejection fraction who underwent echocardiography before CPET and 1-2 minutes after peak exercise. Based on the peak E/e' ratio, patients were divided into the group with stress-induced LVDD - E/e'>15 and the group without stress-induced LVDD. We assessed the association between LVDD and the following CPET variables: minute ventilation, peak oxygen uptake (VO2), ventilatory efficiency, heart rate reserve, and blood pressure. RESULTS: During ESE-CPET, stress-induced LVDD occurred in 67/104 patients (64%). These patients had lower work load, peak VO2, O2 pulse, and minute ventilation (VE), and higher VE/VCO2 slope than patients without stress-induced LVDD (35.18±10.4 vs 37.01±11.11, P<0.05). None of the CPET variables correlated with E/e'. CONCLUSION: Combined ESE-CPET may distinguish masked LVDD in patients with non-severe COPD with exertional dyspnea and preserved left ventricular systolic function. None of the CPET variables was a predictor for subclinical LVDD.

Epigenetic Targets for Therapeutic Approaches in COPD and Asthma. Nutrigenomics ­ Possible or Illusive.

Oxidative stress generated by cigarette smoking, environmental pollution, or other noxious particles leads to epigenetic changes in the cells of the respiratory tract. They reflect cell adaptation in response to chronic exposure to external factors. Although there is no change in the genetic code, epigenetic changes may be heritable and translated from one generation to another, accumulating abnormalities and rendering cells into entirely different phenotype, causing disease. DNA methylation, post-translation histone modification, ubiquitination, sumoylation and miRNA transcriptional regulation are the major processes that are responsible for the epigenetic control of gene expression. All of them are reversible. They can be regulated by targeting specific enzymes/proteins involved in the process in order to mitigate inflammation. Chronic respiratory diseases have epigenetic signatures that affect gene expression in the lung. Targeting them provides the development of novel diagnostic and therapeutic approaches in respiratory medicine. Nutrigenomics reveals the beneficial effect of natural phytochemicals, affecting key steps in the signaling pathways of chronic respiratory diseases.

Biomarkers in COPD - Challenging, Real or Illusive.

Biomarker research in COPD is becoming the most rapidly progressing sphere in respiratory medicine. Although "omics" generate a huge amount of biomarkers, fibrinogen is the only one validated by the European Medicines Agency. Thousands of studies analyzing different biological samples from the respiratory tract, collected in different ways, using various kits and techniques are generating more and more data, rendering biomarkers very confusing rather than having practical value. It seems that in order to be applicable and validated, biomarkers should be analysed in an accurately described cohort of patients, homogeneous in disease severity and activity. As COPD has multiple mechanisms of pathobiology it raises the issue of which is the most appropriate biological sample reflecting each of them. Unified criteria for tissue sampling, validated kits for respiratory tract probes and standardized technologies should be announced. The review presents the biomarkers that are currently validated and raises the problem of standardization.

8-isoprostanes and resistin as markers of vascular damage in non-hypersomnolent obstructive sleep apnoea patients.

BACKGROUND: Oxidative stress and inflammation are assumed as the main pathological triggers for vascular damage in hypersomnolent obstructive sleep apnoea (OSA) patients, whereas their exact role in less symptomatic population is currently unknown. AIM: To determine whether oxidative stress (urinary 8-isoprostane concentration) and inflammation (plasma resistin levels) are associated with vascular damage in non-hypersomnolent (Epworth Sleep Score <11) OSA patients. METHODS: A total of 325 consecutive patients have undergone standard polysomnography, and 256 of them were diagnosed with OSA. Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Only 86 patients with ESS <11 participated in the study. The control group was presented by 45 subjects without OSA. Endothelial function was assessed by ultrasonographic measurement of flow-mediated dilatation (FMD). Intima-media thickness (IMT) and ankle-brachial index (ABI) were determined by ultrasonography. Urinary 8-isoprostanes (Cayman Chemical, USA) were measured, applying mass spectrometry. Resistin (RayBio_ Human ResistinCat#:ELH-Resistin-001) plasma levels were detected by ELISA. RESULTS: In patients with OSA, flow-mediated dilatation was significantly lower than in control subjects (4·62% ±1·9) and (7·1% ±2·8), respectively (P: 0·013). The prevalence of plaques in a.carotis communis was higher in OSA (16% versus 4%). The same is observed regarding a.tibialis posterior (81% vs. 29%). The average IMT and ABI in OSA and in the control group were, respectively, (IMT - 800 µm versus. 666 µm); (ABI -1·06 versus 1·20). Urinary isoprostanes were higher in OSA patients (0·091 versus 0·078) and correlated negatively to FMD (r: -0·825, P: 0·00), IMT (r: -0·324, P: 0·003) and ABI (r: -0·226, P: 0·043). No association between resistin and the degree of vascular injury was found. CONCLUSIONS: In comparison with the control group, increased prevalence of endothelial dysfunction and vascular damage was established in OSA patients without excessive daytime sleepiness. Urinary 8-isoprostanes (oxidative stress markers) are closely associated with FMD (endothelial dysfunction), IMT and ABI (vascular damage). Resistin plasma levels correlated neither to FMD, nor to IMT or ABI.

Resistin - the link between adipose tissue dysfunction and insulin resistance in patients with obstructive sleep apnea.

BACKGROUND: Resistin is an adipocytokine, associated with obesity and inflammation. Its exact role in insulin resistance and diabetes in the general population is still controversial. The relation between resistin plasma levels, insulin resistance and risk of impaired glucose metabolism in OSA patients has not been investigated. MATERIALS AND METHODS: Plasma levels of resistin were measured in 67 patients with OSA and impaired glucose metabolism. 34,7% (23/67) had diabetes; 40% (27/67) patients had impаired glucose tolerance(IGT); 25,3%(17/67) had normal glucose metabolism (NGM). The association between resistin, BMI, obesity, markers of insulin resistance, oxidative stress and sleep study characteristics was analysed. The different groups of patients were compared in regards to glucometabolic parameters and biomarkers of oxidative stress - isoprostanes and insulin resistance - free fatty acids (FFA). RESULTS: Plasma levels of resistin were higher in patients with diabetes (6,12 ±5,93ng/ml), compared to those with IGT (3,85±2,81ng/ml, p-0,021) and NGM (3,77±3,23, p-0,043). Resistin did not differ between patients with IGT and NGM (p-0,954). In OSA patients with BMI>40 resistin plasma levels correlated neither to the clinical parameters (BMI, IRI, HOMA-I, HbA1C, AHI, desaturation index), nor to the biomarkers of oxidative stress and insulin resistance. Free fatty acids (0,232>0,177mmol/l, p-0,037) were higher in diabetics in comparison to NGM. CONCLUSIONS: Plasma resistin levels in OSA patients with BMI>40 are independent of insulin resistance and are not associated with the parameters, characterising the oxidative stress or severity of OSA. Resistin could be used in a multiple panel of clinical and biomarkers to discern patients with diabetes from those with IGT; in OSA patients with BMI >40 resistin together with HbA1C could discern patients with diabetes from those with NGM. In OSA patients with BMI >40 FFA and HbA1C are useful clinical markers in assessing the risk of dysglycaemia among patients with normal and IGT.

The role of small heat-shock protein αB-crystalline (HspB5) in COPD pathogenesis.

BACKGROUND: αB-crystallin (HspB5) is a chaperone whose role as a marker of innate immunity activation as well as its therapeutic potential have recently been investigated in several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain-Barré syndrome. AIM: The aim of this study is to determine the role of αB-crystallin in chronic obstructive pulmonary disease (COPD) pathogenesis and inflammation. MATERIALS: Plasma levels of αB-crystallin were studied in 163 patients: 52 healthy non-COPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-II; 43 COPD smokers in GOLD stages III-IV. Forty-eight patients were diagnosed with acute inflammatory respiratory disease. The plasma levels of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay (Calbiochem), and were confirmed with Western blotting. Tissue expression of the protein was compared in three different groups of patients: COPD smokers, COPD nonsmokers, and in patients with age-related emphysema. RESULTS: The mean level of anti-αB-crystallin antibodies in non-COPD smokers was 0.291 nm. In COPD smokers it was 0.352 nm and, in patients with inflammatory lung diseases, 0.433 nm. There was a statistically significant difference between COPD smokers and healthy non-COPD smokers (P = 0.010). The same could be observed comparing the group of patients with acute inflammation and non-COPD healthy smokers (P = 0.007). There was no statistically significant difference between patients with mild/moderate inflammation and those with severe COPD. Tissue detection of the protein showed that it was significantly overexpressed in COPD smokers in comparison to COPD nonsmokers and was only slightly expressed in patients with age-related emphysema. CONCLUSION: αB-crystallin is increased in patients with inflammatory lung diseases. Though unspecific, it could be used in a panel of markers discerning COPD smokers from healthy nonsmokers. As αB-crystallin is a regulator of innate immunity and a therapeutic anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be explored further.

Inflammatory cytokines at admission--independent prognostic markers in patients with acute coronary syndrome and hyperglycaemia.

BACKGROUND: The clinical significance of inflammatory cytokines as independent prognostic markers in patients with acute coronary syndrome (ACS) and hyperglycaemia remains uncertain. AIM: To determine the value of inflammatory biomarkers as independent prognostic indicators and their relation with hyperglycaemia in ACS patients. METHODS: TNF-α and hsCRP were defined 48 h after admission and indicators for hyperglycaemia were calculated in 256 consecutive patients with ACS. A correlation analysis with standard clinical variables--EF, maximum CK, CK-MB, troponin and different indices for hyperglycaemia was performed. Patients were followed up for 12 months. RESULTS: Baseline TNF-α correlated neither to EF, nor to the enzymes for myocardial necrosis (P>0.05). In contrast, hsCRP correlated negatively with EF (P=0.001) and positively with maximum CK, CK-MB, troponin (P=0.0001) irrespectively of the glucose status. TNF-α was associated with fasting glycaemia, HGI and TAG (P=0.033/0.041/0.018) and hsCRP-with indicators for acute, persistent and chronic glycaemia in all patients. Moreover, hsCRP was an independent marker for six-month survival (P=0.024). TAG was a stronger six-month survival predictor than hsCRP (P=0.010/0.024). CONCLUSION: hsCRP and TNF-α have clinical significance regardless of the glucose metabolic status. hsCRP is an independent marker for six-month survival. TAG is the better predictor for poor outcome than hsCRP.

Clinical significance of hyperglycaemia in acute coronary syndrome patients.

BACKGROUND: The clinical significance of moment measurements (admission and fasting glycaemia), persistent (hyperglycaemic index, HGI; time average glucose, TAG; mean glucose; maximum glucose) or chronic hyperglycaemia (HbA1c), estimated average glucose, eAG) is still elusive in clinical practice. AIM: To identify the clinical significance of hyperglycaemia in ACS. METHODS: The study included 226 consecutive patients with ACS. Indicators for hyperglycaemia were defined, calculated and a correlation analysis with standard parameters-EF, maximum CPK, maximum CPK-MB and troponin was performed. Patients were followed up for 12 months. RESULTS: Indicators for persistent and chronic hyperglycaemia correlated neither to ejection fraction, nor to the enzymes for myocardial necrosis (P > 0.05). In contrast, acute hyperglycaemia correlated negatively with ventricular systolic dysfunction (P = 0.001/0.007) and positively with maximum CPK, MB and troponin (P = 0.0001/0.008). TAG was an independent predictor for 6-month re-hospitalization (P = 0.027) because of cardiac complications. CONCLUSION: Glycaemia at admission and fasting glucose could be used as metabolic surrogate markers for ventricular systolic dysfunction and TAG as an independent surrogate marker for six-month re-hospitalization. None of the indicators for hyperglycaemia could be used as independent prognostic factors for survival. Hyperglycaemia rather reflects an underlying impairment in glucose metabolism.

Expression analysis of angiogenesis-related genes in Bulgarian patients with early-stage non-small cell lung cancer.

AIMS AND BACKGROUND: Angiogenesis is a key process in the early stages of tumor development. In this study we aimed to evaluate the expression of a panel of angiogenesis-related genes in a group of Bulgarian patients with early-stage non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: We analyzed the expression of 84 genes associated with the angiogenic process in 12 NSCLCs of two histological subtypes: 7 adenocarcinomas and 5 squamous cell carcinomas. Eight peripheral nontumorous tissues were used as controls. We performed real-time PCR on pathway-specific gene arrays (SABiosciences). RESULTS: Our pilot study identified upregulated genes in early-stage NSCLC including growth factors (TGFA and EFNA3), the adhesion molecule THBS2, cytokines and chemokines (MDK, CXCL9, CXCL10), and the serine protease PLAU. Several genes showed downregulation including one growth factor (FIGF), the receptors for growth factors TEK and S1PR1 as well as adhesion molecules (COL4A3 and CDH5), the cytokine IL6, the matrix protein LEP and the transcription factor NOTCH4. The study demonstrated deregulated genes specific for the two histological subtypes including the transcription factor HAND2, which was overexpressed in squamous cell carcinomas but not adenocarcinomas. CONCLUSIONS: Despite the limited number of patients, our results demonstrated the potential of angiogenesis-related genes as biomarkers in the early stages of NSCLC development.