endothelin-1 and Pulmonary-Disease--Chronic-Obstructive

Topics: Electrocardiography; Endothelin-1; Humans; Hypertension, Pulmonary; Hypoxia; Lung; Magnetic Resonance Imaging; Nitric Oxide; Pulmonary Disease, Chronic Obstructive; Radiography; Spirometry

Some patients with COPD are prone to frequent exacerbations, which are an important determinant of health status. Such patients have elevated airway cytokine levels, suggesting the presence of increased inflammation that may increase their susceptibility to exacerbation. The inflammatory response during a COPD exacerbation is variable, but increases in interleukin-6 levels during the exacerbation are related to the presence of a common cold. Rhinovirus infection is the most important etiologic factor in COPD exacerbations and is an important target for preventive therapy. The reduction of COPD exacerbations will have an important impact on the considerable morbidity and mortality associated with COPD.

Topics: Endothelin-1; Environmental Pollution; Humans; Inflammation; Interleukin-6; Interleukin-8; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections

To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension (PAH) in patients of chronic obstructive pulmonary disease (COPD) associated with chronic cor pulmonale (CCP) during exacerbation.. Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group. The control group received standard treatment with antibiotics, antiasthmatic and expectorant medications, and oxygenation; and the ligustrazine treatment group received ligustrazine treatment (80 mg/d; i.v.; for 2 weeks) in addition to the standard treatment. Before and at the end of 2 week treatment, the clinic responses of the two regimens were evaluated, plasma levels of endothelin-1 (ET-1) and nitric oxide (NO) were determined; arterial oxygen partial pressure (PaO2, mean pulmonary arterial pressure (mPAP), outflow tract of right ventricle (RVOT), and internal diameter of right ventricle (RV) were measured.. Good clinic benefits were achieved in both the standard and ligustrazine regimens, plasma level of ET-1, values of mPAP, RV and RVOT decreased significantly, plasma level of NO and PaO2 values decreased (all P < 0.01 vs pre-treatment to all parameters). Compared with the control group, ligustrazine greatly enhanced the clinic efficacy from 77.1% to 97.1% (P < 0.05), and also resulted in more significant changes of all these parameters (P < 0.01 vs control group for all parameters). For both groups, the levels of plasma ET-1 were positively correlated with values of mPAP, RVOT, and RV (r = 0.710, 0.853, and 0.766, respectively, all P = 0.000), and negatively correlated with plasma NO and PaO2 (r = - 0.823, and - 0.752, respectively, all P = 0.000).. Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area. The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells, thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.

Topics: Altitude; Blood Gas Analysis; Chronic Disease; Endothelin-1; Humans; Hypertension, Pulmonary; Nitric Oxide; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pyrazines; Respiration

PH (pulmonary hypertension) often complicates the disease course of patients with COPD (chronic obstructive pulmonary disease) and is an indication of a worse prognosis. In the present study, we assessed whether pravastatin administration was effective in improving PH and exercise capacity in COPD patients with PH, and whether the pulmonary protection was mediated by inhibiting ET-1 (endothelin-1) production. In a double-blind parallel design, 53 COPD patients with PH were randomly assigned to receive either placebo or pravastatin (40 mg/day) over a period of 6 months at a medical centre. Baseline characteristics were similar in both groups. The exercise time remained stable throughout the study in the placebo group. After 6 months, the exercise time significantly increased 52% from 660+/-352 to 1006+/-316 s (P<0.0001) in pravastatin-treated patients. With pravastatin, echocardiographically derived systolic PAP (pulmonary artery pressure) decreased significantly from 47+/-8 to 40+/-6 mmHg. There was significant improvement in the Borg dyspnoea score after administering pravastatin. Despite unchanged plasma ET-1 levels throughout the study, urinary excretion of the peptide was decreased and significantly correlated with an improvement in exercise time in pravastatin-treated patients (r=-0.47, P=0.01). In conclusion, pravastatin significantly improved exercise tolerance, and decreased PH and dyspnoea during exercise in COPD patients with PH, probably by inhibiting ET-1 synthesis.

Topics: Adult; Aged; Aged, 80 and over; Endothelin-1; Exercise Tolerance; Female; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Pulmonary; Lipids; Male; Middle Aged; Pravastatin; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

To study the effects of 25% Angelica sinensis injection on hemodynamics, endothelin-1 (ET-1), angiotensin-II (AT-II), endogenous digitalis-like factor (EDF), pulmonary function and arterial blood gas in the patients with chronic obstructive pulmonary disease (COPD) complicated pulmonary hypertension.. Sixty COPD patients complicated with pulmonary hypertension in remission stage were randomly divided into two groups, 30 cases in each. The Angelica group and the control group were treated with Angelica sinensis injection and 5% glucose injection (250 ml, intravenous dripping per day for 10 days) respectively. It was designed to investigate the changes of hemodynamics, ET-1, AT-II, EDF, pulmonary function and arterial blood gas.. The levels of mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), blood ET-1, AT-II and EDF were reduced by (18 +/- 5)%, (27 +/- 8)%, (20 +/- 6)%, (36 +/- 9)%, (38 +/- 11)% respectively, and PaO2 was increased in Angelica group (P < 0.05 or P < 0.01). There were insignificant differences of the above parameters in the control group, and no changes of pulmonary function in both groups.. Twenty-five Percent of Angelica injection can improve pulmonary hemodynamics through influencing the metabolism of ET-1, AT-II and EDF as well as increase PaO2 of the body.

Topics: Aged; Angiotensin II; Drugs, Chinese Herbal; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Vasodilator Agents

Topics: C-Reactive Protein; Endothelin-1; Humans; Hypertension, Pulmonary; Interleukin-10; Interleukin-6; Oxygen; Pulmonary Disease, Chronic Obstructive

Aging is a risk factor for many chronic noncommunicable diseases, including chronic obstructive pulmonary disease (COPD), which is often associated with cardiovascular disease (CVD). Moreover, aging is associated with a mild form of systemic inflammation. The aim of our study was to analyze the relationship between age, systemic and vascular inflammation, and the presence of CVD comorbidities in a stable COPD population. Forty COPD patients were divided into 2 age groups (<65 and ≥65 years of age), from which we collected the following inflammatory biomarkers: C-reactive protein, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1). Elderly COPD patients had more frequent exacerbation events per year (2 vs 1, P = .06), a higher prevalence of CVD (3 vs 2, P = .04), more limited exercise tolerance (6-minute walking test distance, 343 [283-403] vs 434 [384-484]; P = .02), and mild systemic inflammation (TNF-α, 9.02 [7.08-10.96] vs 6.48 [5.21-7.76]; P = .03; ET-1, 2.24 [1.76-2.71] vs 1.67 [1.36-1.98] pg/mL; P = .04). A weak correlation between age and ET-1 (r = 0.32, P = .04) was observed. Mild systemic inflammation, characterized by a slightly increased level of TNF-α, and endothelial dysfunction, marked by elevated ET-1, could be liaisons between aging, COPD, and CVD comorbidities.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Endothelin-1; Humans; Inflammation; Lung; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha; Vascular Diseases

Chronic Obstructive Pulmonary Disease (COPD), which is caused by various proinflammatory cytokines, will present some kinds of complication with progression such as Pulmonary Artery Hypertension (PAH). CRP (C-Reactive Protein) and ET-1(Endotheline-1) play pivotal function in inflammatory responses. The aim of this study is to investigate the prognosis value of CRP and ET-1 in COPD patients with pulmonary artery hypertension. CRP and ET-1 were measured in the plasma, sputum and exhaled breath condensate (EBC) of 55 COPD patients, 75 COPD patients with PAH and 57 healthy controls. Then, we analyzed the influence of these two proteins on the lung function, pulmonary artery pressure, exercise capacity and other clinical indices. The amount of CRP and ET-1 were the highest in COPD patients with PAH, followed by the COPD patients and the healthy controls. And there were statistically significant differences (p<0.05). The amount of CRP and ET-1 were negatively correlated with the lung function and exercise capacity, positively correlated with the pulmonary artery pressure. CRP and ET-1 are two valuable indicators in the diagnosis of COPD patients with PAH in clinic.

Topics: Aged; Biomarkers; Body Mass Index; Breath Tests; C-Reactive Protein; Case-Control Studies; Endothelin-1; Exercise; Female; Humans; Hypertension, Pulmonary; Male; Prognosis; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Smoking; Sputum

Introduction: Chronic obstructive pulmonary disease (COPD) is the main cause of progression chronic pulmonary heart (CPH), it is a serious worldwide problem. The combination of COPD with essential arterial hypertension (EAH) ranges from 4 to 27.7% with increasing age. The aim: To evaluate endothelium function changes by the level of metabolites of nitric oxide, endothelin-1(ET-1), values of ultrasonic diagnosis of the humeral artery (HA), intracardial hemodynamics of the left ventricle in patients with CPH in combination with EAH.. Materials and methods: The research is involved 175 patients. Indicators of endothelial function by the level of nitric oxide metabolites, ET - 1, ultrasound intracardiac hemodynamics of the left ventricle of the heart were studied.. Results: The patients with CPH in combination with EAH in compensation stage have reduced level of nitric oxide in comparison with patients with CPH without EAH and healthy. To a large extent, reducing of nitric oxide level in decompensation stage indicates about contribution of combined pathology and requires ED correction. On the contrary increased concentration of ET-1 in decompensation stage indicate about combined pathology and demands correction of endothelial cell function.. Conclusions: Thus, patients with CPH in combination with EAH are characterized by more pronounced changes in endothelial dysfunction toward an increase in the level of vasoconstrictor factors, a decreasing of vasodilators, which is confirmed by ultrasound diagnosis of HA and reflected in the peculiarities of the intracardiac hemodynamic state.

Topics: Comorbidity; Endothelin-1; Heart Ventricles; Hemodynamics; Humans; Nitric Oxide; Pulmonary Disease, Chronic Obstructive

Soluble urokinase-type plasminogen activator receptor (suPAR) is upregulated by inflammation and plays a role in the pathogenesis of atherosclerosis. Chronic obstructive pulmonary disease (COPD) is associated with enhanced systemic inflammation and increased risk for atherosclerosis, however, studies analysing the circulating suPAR levels in COPD are contradictory. The aim of the study was to investigate plasma suPAR concentrations together with markers of arterial stiffness in COPD.. Twenty-four patients with COPD and 18 non-COPD, control subjects participated in the study. Plasma suPAR was measured, together with lung volumes, symptom burden, exacerbation history, markers of arterial stiffness and soluble inflammatory biomarkers, such as endothelin-1, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6).. Plasma suPAR levels are elevated in COPD and relate to arterial stiffness. Our results suggest that suPAR may be a potential link between COPD and atherosclerosis.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Endothelin-1; Female; Forced Expiratory Volume; Humans; Interleukin-6; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Receptors, Urokinase Plasminogen Activator; Severity of Illness Index; Up-Regulation; Vascular Stiffness; Vital Capacity

Pulmonary artery smooth muscle cells (PASMCs) from neprilysin (NEP) null mice exhibit a synthetic phenotype and increased activation of Rho GTPases compared with their wild-type counterparts. Although Rho GTPases are known to promote a contractile SMC phenotype, we hypothesize that their sustained activity decreases SM-protein expression in these cells.. PASMCs isolated from wild-type and NEP. Sustained Rho activation in NEP

Topics: Actins; Animals; Becaplermin; Calcium-Binding Proteins; Calponins; Cell Movement; Cell Proliferation; Cells, Cultured; Endothelin-1; Enzyme Activation; ets-Domain Protein Elk-1; Genotype; Humans; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins; Muscle Proteins; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neprilysin; Phenotype; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; rho GTP-Binding Proteins; Signal Transduction; Smooth Muscle Myosins

Chronic obstructive pulmonary disease is a common comorbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other comorbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV.. Longitudinal observational study.. Total 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, and TNFα), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates.. In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse forced expiratory volume in one second (FEV1) percentage-predicted, and higher sCD163 associated with worse FEV1/forced vital capacity. IL-6, TNFα, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up.. Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of chronic obstructive pulmonary disease in HIV-infected persons.

Topics: Antigens, CD; Cytokines; Endothelial Cells; Endothelin-1; HIV Infections; Humans; Longitudinal Studies; Male; Middle Aged; Monocytes; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

COPD exacerbation is a life-threatening condition with acute dyspnoea caused by respiratory or circulatory distress. The significance and co-presence of lung hyperinflation, bronchial obstruction, and changes in haemodynamics in the course of COPD exacerbation treatment have not been well described yet in course of a single study. Our aim was to evaluate the influence of COPD exacerbation treatment on bronchial obstruction, pulmonary hyperinflation, and possible changes of right and left ventricle haemodynamics in relation to the patient's clinical status.. A total of 40 patients (90% males), 67 ± 8 years old, with COPD were assessed pre- and post-exacerbation treatment by the following: respiratory function tests, transthoracic echocardiography, 6MWT, endothelin-1 (ET-1) and NT-proBNP serum concentrations, and MRC scale.. A significant decrease in RV%TLC (%) and mean pulmonary artery pressure (PAPmean) [mm Hg] was observed: pre -RV%TLC: 64.3 ± 9.0; post-RV%TLC 60.6 ± 11.1; p = 0.03; pre-PAPmean: 41.2 ± 11.2; post-PAPmean: 39.1 ± 12.1; p = 0.029, coupled with a significant increase of FEV1 [L]-preFEV1: 1.0 ± 0.4, post-FEV1: 1.2 ± 0.5; p < 0.001. A trend for reduced right ventricle systolic pressure (RVSP) [mm Hg]: pre-treatment: 44.5 ± 12.9; post-treatment: 36.3 ± 14.3; p = 0.068 and ET-1 [fmol/ml]: pre-treatment: 1.7 ± 2.8; post-treatment: 1.3 ± 1.9; p = 0.076, but not for NT-proBNP was noticed. Improvement of both, 6MWT [m]: pre-treatment: 294 ± 132; post-treatment: 415 ± 102; p < 0.001 and MRC [pts.]: pre-treatment: 3.3 ± 0.8; post-treatment: 1.8 ± 0.9; p < 0.001, were noticed. 6MWT correlated with RV%TLC (p < 0.05; r = -0.46; r = -0.53; respectively) and FEV1 (p < 0.05; r = 0.55; r = 0.60, respectively) on admission as well as on discharge. There was no such correlation with RVSP or PAPmean.. Pulmonary hyperinflation and bronchial obstruction may be reduced by effective COPD exacerbation treatment and are accompanied by clinical improvement. The mPAP reduction observed in the course of treatment was not correlated with the results of 6MWT and MRC score.

Topics: Aged; Blood Gas Analysis; Echocardiography; Endothelin-1; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

To evaluate the vascular endothelium in patients with cardiopulmonary disease, by studying the levels of endothelin-1 (ET-1) and C-type natriuretic peptide (CNP).. Examinations were conducted in 212 dwellers of the Astrakhan Region, including 40 patients with chronic obstructive pulmonary disease (COPD) concurrent with hypertensive disease (HD), 40 patients with COPD concurrent with coronary heart disease (CHD), 27 somatically healthy individuals, 35 patients with Stage II HD, 35 patients with Functional Classes II and III CHD, and 35 patients with moderate and severe COPD.. The patients with COPD concurrent with HD and CHD were found to have endothelial dysfunction manifesting itself in the overproduction of ET-1 and CNP. The level of CNP was statistically significantly higher in the COPD + HD group than in the HD and COPD groups whereas in the COPD + HD group the level of ET-1 remained comparable to that in the COPD and HD groups. This indicates that CNP is a more sensitive indirect marker of endothelial dysfunction and that nitric oxide deficiency is aggravated in the concurrence of COPD and HD as compared to a mononosological entity (HD, COPD).. The concurrence of COPD and CHD is more unfavorable for the development and severity of endothelial dysfunction, which may lead to mutual aggravation syndrome, the rapider progression of the diseases, and the increased frequency of complications.

Topics: Comorbidity; Coronary Disease; Disease Progression; Endothelin-1; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, C-Type; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive

To investigate the reactivity of intrapulmonary arterial rings to vasoactive substances as thromboxane A2 and endothelin-1 in patients with chronic obstructive pulmonary disease (COPD).. Intrapulmonary arterial rings isolated from patients with normal lung function and COPD were mounted in a Multi Myograph system to determine the reactivity of the intrapulmonary arterial rings to 60 mmol/L KCl, thromboxane A2 analogue U46619 and endothelin-1 before and after preconditioning with the COX synthase inhibitor indomethacin.. The reactivity of intrapulmonary arterial rings to U46619 and endothelin-1 was significantly decreased in patients with COPD. The reactivity to U46619 was dramatically decreased in patients with normal lung function after application of indomethacin.. The reactivity of intrapulmonary arterial rings is significantly decreased in patients with COPD.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aged; Endothelin-1; Female; Humans; In Vitro Techniques; Indomethacin; Male; Middle Aged; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Thromboxane A2

Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown.. Test associations of endothelial biomarkers with FEV1 using instrumental variables.. Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets.. ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative.. Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.

Topics: Biomarkers; Black People; Cohort Studies; E-Selectin; Endothelin-1; Endothelium, Vascular; Female; Gene Expression; Humans; Intercellular Adhesion Molecule-1; Lung; Male; Middle Aged; P-Selectin; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Spirometry; White People

Combined pulmonary fibrosis and emphysema (CPFE) is a computed tomography (CT)-defined syndrome of combined pulmonary fibrosis and emphysema, characterized by subnormal spirometry, impairment of gas exchange, and high prevalence of pulmonary hypertension. Although endothelin-1 (ET-1) plays an important role in the development of lung fibrosis as well as in pulmonary hypertension, no ET-1-targeted therapy is currently recommended. Here we report a case of CPFE successfully treated with ambrisentan, an endothelin-A receptor antagonist, and also discuss the biologic mechanisms underlying the observed therapeutic effects. A 79-year-old man with chronic obstructive pulmonary disease (COPD) was referred to our respiratory unit as an outpatient for dyspnea. Clinical, radiologic, and laboratory findings suggested a diagnosis of chronic hypoxemic, type 1 respiratory failure, due to combined pulmonary fibrosis and emphysema, complicated by severe, precapillary pulmonary hypertension. Pharmacologic treatment with ambrisentan induced an initial improvement in clinical symptoms that proved to be very relevant 9 months later. In order to investigate the biologic mechanisms underlying the clinical effects of ambrisentan, we performed an "in vitro" study on primary cultures of fibrotic human lung fibroblasts, as well as on human umbilical vein endothelial cells, incubated for 24 and 48 h with ET-1, in the absence or presence of an overnight treatment with ambrisentan. ET-1 significantly increased cell proliferation and mitogen-activated protein kinase activation (P < 0.01). These effects were significantly (P < 0.01) inhibited by ambrisentan in both cell cultures. In conclusion, we hypothesize that the clinical benefits induced by ambrisentan in this patient with CPFE can be attributed to its vasodilator and anti-proliferative actions, exerted on pulmonary the vascular bed and lung fibroblasts.

Topics: Aged; Emphysema; Endothelin A Receptor Antagonists; Endothelin-1; Human Umbilical Vein Endothelial Cells; Humans; Hypertension, Pulmonary; Male; Phenylpropionates; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Pyridazines; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome

To analyze the systemic manifestations of vascular endothelial damage, the activation of hemostatic and inflammatory responses in patients with an infectious inflammation-dependent exacerbation of chronic obstructive pulmonary disease (COPD).. The paper provides the data of examinations of 111 patients with the clinical signs of an infectious inflammation-dependent exacerbation of COPD who had 2 or 3 positive criteria elaborated by N. Anthonisen et al. (1987). The patients were divided into 2 phenotypically different subgroups: 1) 92 (82.9%) COPD patients without clinical manifestations of bronchoectasis; 2) 19 (17.1%) patients with COPD concurrent with documented bronchiectasis. The patient subgroups were matched for smoking status and the characteristics of COPD and respiratory failure. The investigators assessed the time course of changes in the serum level of endothelin-1 (ET-1), the aggregation function of platelets, and the plasma concentrations of D-dimers and homocysteine in patients with COPD compared to healthy, never smokers (n = 35) and smokers (n = 27).. An increase in the levels of the endothelial dysfunction markers ET-1 and homocysteine was found in patients with COPD, which was comparable with the changes in these indicators in the group of smokers. In both subgroups, the rise in plasma D-dimer levels was more pronounced in the patients with a COPD exacerbation than in the smokers. Its therapy with systemic and inhaled glucocorticosteroids reduced C-reactive protein and ET-1 levels in both patient subgroups and in D-dimers in subgroup 1. Elevated D-dimer levels remained when achieving remission, which points to the risk of thrombogenic and thromboembolic events in the patients with an infectious inflammation-dependent exacerbation of COPD and concomitant circulatory system diseases.. The patients with an infectious inflammation-dependent exacerbation of COPD are observed to have elevated peripheral blood markers of endothelial dysfunction and thrombinemia. These changes are pathogenetically caused by smoking or neutrophilic inflammation and associated with a higher risk of thrombogenic events.

Topics: Adult; Biomarkers; Bronchiectasis; Endothelin-1; Endothelium, Vascular; Female; Hemostasis; Homocysteine; Humans; Inflammation; Male; Pulmonary Disease, Chronic Obstructive; Smoking

To examine the correlation of the changes in the serum markers (C-reactive protein, endothelin-1, interleukin-6, and brain natriuretic peptide) with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension secondary to COPD.. A total of 174 COPD patients with acute exacerbation, admitted between February 2011 and February, 2013, were enrolled in this study, with 43 volunteers with normal pulmonary functions as controls. Pulmonary arterial pressure was determined by Doppler echocardiograph, and the severities (mild, moderate and severe) of PH secondary to COPD was evaluated. The levels of serum markers were determined using ELISA kits.. The levels of serum markers in patients with COPD was significantly elevated compared with those of the control subjects (P<0.05), and further increased in patients with pulmonary hypertension secondary to COPD (P<0.05). A positive correlation was found between these serum markers and pulmonary artery pressure in COPD patients with mild and moderate pulmonary hypertension. In patients with severe pulmonary hypertension, only the serum level of brain natriuretic peptide continued to increase with pulmonary artery pressure (P<0.05), and the other markers did not further increase.. Early and combined examination of these serum markers in patients with COPD can help to identify pulmonary hypertension in early stage and estimate the severity of pulmonary hypertension. Hemodynamic monitoring of the changes of these serum markers can be of important clinical value in the treatment of pulmonary hypertension secondary to COPD and in evaluation of the prognosis of COPD.

Topics: Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Interleukin-6; Male; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive

Posterior reversible encephalopathy syndrome (PRES) has been associated with many conditions - particularly inflammatory, neoplastic and following organ failure. We submit that Chronic Obstructive Pulmonary Disease (COPD) is a significant predisposing factor for a number of these cases. Increased levels of circulating TNF-alpha, IL-1 and endothelin-1 (ET-1) are herein proposed as key mediators of this association. This theory builds on the central role of endothelial dysfunction in the pathogenesis of PRES. To our knowledge, no association of PRES and COPD has been made to date. We believe that it has practical implications: it suggests a lower threshold for MRI scans in certain patients. We suggest that the diagnosis of PRES should particularly be considered in ICU patients with typical signs (seizures, blindness, encephalopathy). Prompt recognition may lead to changes in management.

Topics: Blood-Brain Barrier; Endothelin-1; Humans; Interleukin-1; Magnetic Resonance Imaging; Models, Biological; Posterior Leukoencephalopathy Syndrome; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide that may lead to impaired exercise tolerance. In this study we exhibit the relationship between two endothelin-1 (+134 3A/4A and G198T) SNPs involved in COPD and their association to impaired exercise tolerance.. The study population consisted of 22 COPD smokers and 32 smoking controls which underwent pulmonary function tests to assess forced expiratory volume for 1 second (FEV1), forced vital capacity (FVC), as well as cardiopulmonary exercise testing. Single nucleotide polymorphism were isolated using Real-Time PCR.. The distribution of both genotypes (3A3A, 3A4A, 4A4A for the +134 3A/4A and GG, GT, TT for the G198T) did not different among patients and non-COPD smoking controls. Multivariate analysis showed that the 3A4A and GG genotypes in the COPD group were independently associated with better V'O2max values (Odd's Ratio (OR) = 12.5, 95% CI = -0.85-25.1, p = 0.049, and OR = 6.1, 95% CI = 0.83-11.4, p = 0.026, respectively). On the contrary analogous analysis in the non-COPD control group, showed that the 3A3A genotype was independently associated with increased V'O2/pulse (OR = 51.5, 95% CI = 17.2-85.7, p = 0.005) and the 3A4A genotype with increased DVE/DVCO2 value (OR = 3.8, 95% CI = -0.27-7.9, p = 0.054).. Our results show that endothelin-1 gene is implicated in exercise performance in COPD patients and might play a role in adaptation of the cardiopulmonary system to exercise.

Topics: Adult; Aged; Endothelin-1; Exercise Test; Female; Genotype; Humans; Lung; Male; Middle Aged; Pilot Projects; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive

The phenotypic expression of COPD consists of pulmonary emphysema and chronic bronchitis. An imprecise phenotypic definition may result in inconsistencies among genetic studies regarding COPD pathogenesis. Endothelin-1 gene polymorphisms have been linked to increased susceptibility of COPD development. The present study examined the involvement of +138 insA/delA and G198T ET-1 polymorphisms with emphysematous and bronchitic COPD phenotypes.. In order to narrow down the phenotypic choices to either COPD-associated pulmonary emphysema or chronic bronchitis, a DLCO < 60% predicted threshold was chosen as an indicator of severe emphysema. 116 COPD smokers and 74 non-related, non-COPD smokers were evaluated.. Statistical analysis showed that the 4A allele of the +138insA/delA SNP and the 4A:T haplotype were associated predominantly with a chronic bronchitis phenotype, whereas the TT genotype of the G198T SNP was found to be protective from emphysema development.. The presence of both the 4A and T allele seems to modify the final expression of COPD towards a chronic bronchitis phenotype, since the G:3A haplotype was associated with a predominantly emphysematous phenotype in our study.

Topics: Endothelin-1; Forced Expiratory Volume; Genetics, Population; Genotype; Haplotypes; Humans; Phenotype; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; White People

Chronic obstructive pulmonary disease (COPD) is characterized by the presence of a low-grade systemic inflammation that is implicated in the pathogenesis of numerous extrapulmonary manifestations, such as hypogonadism. Endothelin-1 (ET-1) is a molecule that demonstrates pro-inflammatory properties and can augment the airway and systemic inflammation. Single nucleotide polymorphisms (SNPs) of the ET-1 gene that increase ET-1 serum levels are an important area of investigation. We examined the alterations in inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] and in the levels of testosterone, free testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in a group of male COPD smokers when compared to their age-matched controls and how these alterations relate to the presence of a functional ET-1 SNP, the adenine insertion SNP +138 insA/delA.. In this case control study, 80 male control smokers and 82 male COPD smokers were recruited for comparison. Among the male COPD smokers, 37 were carriers of the +138 insA/delA SNP. Two COPD subgroups according to genotype were formed: (1) A group of 45 males homozygous for the wild type allele (3A/3A) and (2) a group of 37 males heterozygous for the mutant allele (3A/4A).. Levels of testosterone and free testosterone were lower in the COPD group and even lower in the 3A/4A COPD group. CRP and ESR levels were higher in both COPD groups, but their elevation was statistically significant only for the 3A/4A COPD group. Testosterone and free testosterone levels correlated positively with PaO2 for both COPD groups. An inverse correlation between testosterone and CRP was demonstrated for the 3A/4A COPD subgroup.. Levels of testosterone correlated to FEV1, hypoxemia and weakly to CRP. The synchronous presence of the +138 insA/delA SNP resulted in even greater sex hormone level decline probably due to the presence of a more intense systemic inflammation.

Topics: C-Reactive Protein; Case-Control Studies; Endothelin-1; Follicle Stimulating Hormone; Forced Expiratory Volume; Genotype; Gonadal Steroid Hormones; Humans; Inflammation; Luteinizing Hormone; Male; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Smoking

The levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were investigated to analyze the systemic inflammation in chronic obstructive pulmonary disease (COPD) patients with and without pulmonary hypertension.. From January 2006 to December 2010, 89 patients with COPD were enrolled in our hospital. There were 67 males and 22 females, with a mean age of (70 ± 7) and a mean FEV(1) of (47 ± 13)%. Pulmonary pressure was assessed by Doppler echocardiography. The levels of plasma BNP, TNF-α and ET-1 were measured by enzyme-linked immunosorbent assay kits. High-sensitivity plasma CRP level was assessed by chemiluminescent immunoassay.. Forty-two patients were classified as COPD with pulmonary hypertension group and 47 patients as COPD without pulmonary hypertension group. The level of CRP [51.4 mg/L (20.1 - 92.0) mg/L], ET-1 [5.9 ng/L (3.7 - 10.4) ng/L] and BNP [303.2 ng/L (112.5 - 824.7) ng/L] in patients with pulmonary hypertension were significantly higher than in that in patients without hypertension, CRP [26.7 mg/L (11.5 - 62.9) mg/L], ET-1 [2.1 ng/L (1.3 - 4.7) ng/L] and BNP [143.7 ng/L (85.5 - 306.7) ng/L]. The level of TNF-α showed no difference between the 2 groups [8.5 ng/L (4.8 - 13.7) ng/L and 6.7 ng/L (3.2 - 10.3) ng/L], respectively. Multivariate analysis showed that PaO₂ (P < 0.05), CRP (P < 0.05) and BNP (P < 0.05) could predict pulmonary hypertension independently.. The level of CRP, ET-1 and BNP were related to pulmonary hypertension in COPD patients, suggesting that systemic inflammation play a role in the pathogenesis of pulmonary hypertension in COPD.

Topics: Aged; C-Reactive Protein; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

Endothelin-1 (ET-1) has been implicated in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) for establishing an inflammatory loop in the respiratory mucosa that could become independent from the initial irritant factor. Common causes of COPD exacerbations are associated with elevated ET-1 sputum concentrations. Genetic variants of the ET-1 gene, that lead to elevated ET-1 peptide levels, have not been investigated in COPD. We performed a case control, genetic study to assess possible associations of two polymorphisms of the ET-1 gene, an adenine insertion (+134 insA/delA) and a guanine to thymine transversion (G198T) with the COPD phenotype and disease severity. The genotypes of 209 subjects, 107 COPD smokers (patients) and 102 non-COPD smokers (controls) were examined. Statistical analysis revealed that the 3A/4A and 4A/4A genotypes were more common (P<0.01) in patients. Moreover, a protective effect against COPD of the TT genotype (G198T) was exhibited. COPD smokers were carrying more frequently the GG genotype and less frequently the TT genotype (P=0.047). Diplotypic analysis revealed that subjects carrying the 3A3A;TT genotype had a lower risk of COPD development (P=0.027). Within the COPD patient group carriers of the GT genotype had more often mild or moderate COPD compared to patients carrying the GG genotype (P=0.004). Haplotypic distribution revealed that carriers of the 4A:T and 4A:G haplotypes were in increased risk of COPD development. Additionally, patients with the 3A:G haplotype were in increased risk of developing severe COPD, whereas patients with the 3A:T and 4A:T had most probably mild-moderate COPD.

Topics: Case-Control Studies; Disease Progression; Endothelin-1; Female; Genotype; Humans; Male; Middle Aged; Phenotype; Polymorphism, Genetic; Pulmonary Disease, Chronic Obstructive; Risk Factors; Smoking

Regular use of beta(2)-adrenoceptor agonists may enhance non-specific airway responsiveness and inflammation. In earlier experimental studies, we showed that prolonged in vitro fenoterol exposure induced airway sensitization via perturbed epithelial regulation of bronchoconstriction. The aim of the present work was to examine the involvement of inflammatory mediator genes and proinflammatory cells and to investigate the role of the bronchial epithelium in these untoward effects. Bronchial tissues were surgically removed from 17 ex-smokers. Bronchial rings and primary cultures of bronchial epithelial cells were incubated with 0.1microM fenoterol for 15h. Levels of mRNA-expression were analyzed using a real-time quantitative reverse transcription-polymerase chain reaction array. Bronchial rings were contracted with endothelin-1 and immune cell infiltration was assessed by immunohistochemistry. Compared to paired controls, fenoterol up-regulated the mRNAs of cytokines/proteins implicated in the recruitment of T and B cells or the activation and proliferation of bronchial epithelial cells (CCL20/MIP-3alpha, FOXA2, PPAR-gamma) in isolated bronchi and in cultured epithelial cells. Fenoterol exposure significantly enhanced CD8(+)-T and differentiated CD138(+)-B-cells infiltration into the bronchi, especially the subepithelial area. Increase in CD8 or CD138 labeling-intensity strongly correlated with rise in maximal contraction to endothelin-1 induced by fenoterol exposure. In summary, our results show that fenoterol modulates the T and B cells chemotaxis possibly via the epithelial chemokine secretion in isolated bronchi from ex-smokers. They also suggest that the infiltration of resident T and B cells into the subepithelial area is associated with an increase in airway responsiveness due to fenoterol exposure.

Topics: Adrenergic beta-Agonists; Aged; B-Lymphocytes; Bronchi; Bronchial Hyperreactivity; Bronchoconstriction; Bronchoconstrictor Agents; CD8-Positive T-Lymphocytes; Cells, Cultured; Chemotaxis, Leukocyte; Cytokines; Dose-Response Relationship, Drug; Endothelin-1; Epithelial Cells; Female; Fenoterol; Gene Expression Regulation; Humans; Immunohistochemistry; Inflammation Mediators; Lung Neoplasms; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Receptors, Adrenergic, beta; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Smoking Cessation; Time Factors

Endothelin-1 (ET-1) is a potent vasoconstrictor and bronchoconstrictor but it has been shown to have also proinflammatory properties. Its ability to attract inflammatory cells in its site of production, upregulates the synthesis of adhesion molecules and stimulates the release of cytokines. The fact that cytokines have the ability to induce its synthesis and release, creates a dynamic loop for self-preservation and augmentation of the airway inflammation in Chronic Obstructive Pulmonary Disease (COPD), even after the ceasing of the noxious stimulus, i.e., cigarette smoke. Therefore, functional polymorphisms that may lead to increased levels of ET-1 may also cause an increased susceptibility to COPD development.. We analyzed the longitudinal effect on lung function of two ET-1 gene polymorphisms in a population of 190 smokers (95 non-COPD and 95 COPD smokers). The two polymorphisms involved an insertion polymorphism (+138 adenine insertion 3A/4A, 138bp downstream from the transcription start site, exon 1) and a single nucleotide transversion polymorphism on exon 5 (G/T, Lys198Asn). A total of 190 subjects were enrolled in the study for each polymorphism and were followed for 3 years by annual spirometry sessions.. The adjusted annual decline of forced expiratory volume in 1 second (dFEV1) was greater for those having at least one copy of the mutated gene ins/delA compared to those with the wild type allele both in the non-COPD smokers group (mean difference in dFEV, of 19.4 ml/year, p = 0.004) and COPD smokers (mean difference in dFEV1 of 11.15 ml/year, p = 0.003). On the contrary, those heterozygous for the Lys198Asn polymorphism were found to have a slower decline in FEV1 compared to those homozygous for the wild type allele. The non-COPD smokers group had a gain-in-loss of 11,24 ml/year (p < 0.001) while the COPD-smokers group had a slower decline of 11.42 ml/year (p = 0.002). Those homozygous for the polymorphisms examined show an even greater deviation from those with the wild type allele but due to the small number comprising their group, the results don't have enough statistical power. Though, they still show the trend of the effect the polymorphisms have on annual FEV1 decline.. The present data shows that ET-1 and its functional polymorphisms may be implicated in COPD phenotype and severity.

Topics: Adult; Aged; Alleles; Endothelin-1; Exons; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Phenotype; Pilot Projects; Polymorphism, Genetic; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Smoking; Spirometry

Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD. However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD. The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension. The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension. Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) ≥35 mmHg assessed by Doppler echocardiography. Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension. There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups. For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels. These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients.

Topics: Aged; Blood Pressure; C-Reactive Protein; Echocardiography, Doppler; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

Endothelin-1 (ET-1) and Nitric Oxide (NO) are crucial mediators for establishing pulmonary artery hypertension (PAH). We tested the hypothesis that their imbalance might also occur in COPD patients with PAH.. The aims of the study were to measure exhaled breath condensate (EBC) and circulating levels of ET-1, as well as exhaled NO (FENO) levels by, respectively, a specific enzyme immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD with PAH (12), COPD only (36), and healthy individuals (15). In order to evaluate pulmonary-artery systolic pressure (PaPs), all COPD patients underwent Echo-Doppler assessment.. Significantly increased exhaled and circulating levels of ET-1 were found in COPD with PAH compared to both COPD (p < 0.0001) only, and healthy controls (p < 0.0001). In COPD with PAH, linear regression analysis showed good correlation between ET-1 in EBC and PaPs (r = 0.621; p = 0.031), and between arterial levels of ET-1 and PaPs (r = 0.648; p = 0.022), while arterial levels of ET-1 inversely correlated with FEV1%, (r = -0.59, p = 0.043), and PaPs negatively correlated to PaO2 (r = -0.618; p = 0.032). Significantly reduced levels of FENO were found in COPD associated with PAH, compared to COPD only (22.92 +/- 11.38 vs.35.07 +/- 17.53 ppb; p = 0.03). Thus, we observed an imbalanced output in the breath between ET-1 and NO, as expression of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to COPD only. Whether this imbalance is an early cause or result of PAH due to COPD is still unknown and deserves further investigations.

Topics: Aged; Biomarkers; Blood Gas Analysis; Blood Pressure; Breath Tests; Case-Control Studies; Endothelin-1; Exhalation; Female; Forced Expiratory Volume; Humans; Hypertension, Pulmonary; Linear Models; Male; Middle Aged; Nitric Oxide; Pulmonary Disease, Chronic Obstructive

Inducible cyclooxygenase (COX-2) and inflammatory cytokines play important roles in inflammatory processes of chronic obstructive pulmonary disease (COPD). Endothelin-1 (ET-1) might be also involved in the pathophysilogical processes in COPD. In the present study, we determined whether ET-1 could regulate the expression of COX-2 and alter the production of interleukin-8 (IL-8) in human pulmonary epithelial cells (A549). Induced sputum samples were collected from 13 stable COPD patients and 14 healthy subjects. The COX-2 protein, ET-1, PGE(2) and IL-8 in these sputum samples were analyzed. A549 cells were incubated with ET-1 in the presence or absence of celecoxib, a selective COX-2 inhibitor. The expression of COX-2 protein in the cell and the amounts of PGE(2) and IL-8 in the medium were measured. The levels of COX-2 protein, ET-1, PGE(2) and IL-8 were significantly increased in induced sputum from COPD patients when compared to healthy subjects. ET-1 increased the expression of COX-2 protein, as well as the production of PGE(2) in A549 cells. Increased production of PGE(2) was inhibited by celecoxib. ET-1 also increased the production of IL-8. Interestingly, ET-1-induced production of IL-8 was also inhibited by celecoxib. These findings indicate that ET-1 plays important roles in regulating COX-2 expression and production of IL-8 in A549 cells. ET-1 mediated production of IL-8 is likely through a COX-2-dependent mechanism.

Topics: Aged; Cell Line, Tumor; Cyclooxygenase 2; Dinoprostone; Endothelin-1; Epithelial Cells; Female; Humans; Interleukin-8; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sputum

Plasma endothelin and adrenomedullin are increased in patients with pulmonary arterial hypertension, hypoxia, and pulmonary infections, conditions that predict survival in patients with COPD. We investigated whether plasma pro-endothelin-1 (proET-1) and/or pro-adrenomedullin (proADM) on admission to the hospital for acute exacerbation predict survival in patients with COPD.. We examined 167 patients who had been admitted to the hospital for acute exacerbation, and we followed them up for 2 years. We measured plasma C-terminal (CT) proET-1 and mid-regional (MR) proADM on hospital admission, after 14 to 18 days, and after 6 months. In addition to plasma CT proET-1 and MR proADM, we assessed with Cox regression univariate and multivariate analyses the predictive value of clinical, functional, and laboratory parameters on 2-year survival. We analyzed the time to death by Kaplan-Meier curves.. Compared to recovery and stable state, CT-proET-1 and MR-proADM were significantly increased on hospital admission (p < 0.001 and p = 0.002, respectively). MR-proADM, but not CT-proET-1, was associated with increased in-hospital mortality (p = 0.049) and independently predicted 2-year survival (p = 0.017). ProADM plasma levels > 0.84 nmol/L on hospital admission increased the mortality risk within 2 years from 13 to 32% (p = 0.004). By contrast, age (p = 0.779), Charlson comorbidity score (p = 0.971), body mass index (p = 0.802), FEV(1) percent predicted (p = 0.741), PAo(2) (p = 0.744), PAco(2) (p = 0.284), leukocyte counts (p = 0.333), C-reactive protein (p = 0.772), procalcitonin (p = 0.069), pulmonary arterial hypertension (p = 0.971), and CT-proET-1 (p = 0.223) were not independently associated with 2-year survival.. This study shows that plasma proADM but not plasma proET-1 on admission to the hospital for acute exacerbation independently predicts survival, thus suggesting that this biomarker could be used to predict prognosis in patients with COPD.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Endothelin-1; Female; Follow-Up Studies; Hospital Mortality; Humans; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Patient Admission; Predictive Value of Tests; Protein Precursors; Pulmonary Disease, Chronic Obstructive

Topics: Benzamides; Cell Division; Drug Therapy, Combination; Endothelin-1; Endothelium, Vascular; Fibromuscular Dysplasia; Humans; Hypertension, Pulmonary; Imatinib Mesylate; Muscle, Smooth, Vascular; Phosphodiesterase Inhibitors; Piperazines; Prostaglandins; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Pyrimidines; Vasodilator Agents

Endothelin-1 (ET-1) has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). The ET-1 levels are elevated during exacerbations of asthma and COPD in bronchoalveolar lavage, serum, and sputum and fails with treatment of the exacerbations. Hypoxemia stimulates ET-1 secretion.. The aim of this study was to examine the serum ET-1 levels in stable asthmatic and COPD patients.. We examined 48 COPD and 26 asthmatic patients and 34 normal subjects. We collected arterial samples to measure baseline ET-1 levels in all patients and in the control group, during the day. All the patients underwent formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, and oxyhemoglobin desaturation. Twelve of the COPD patients and six of the asthmatic patients were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of the COPD patients desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, 5 min after the first period of desaturation in each of the 19 desaturators COPD patients. None of the 20 asthmatic patients exhibited oxyhemoglobin desaturation during sleep.. Baseline arterial ET-1 levels during the day were significantly higher in "desaturators" COPD patients (2.08+/-0.28 pg/ml) compared to "non-desaturators" COPD patients (1.38+/-0.16 pg/ml) (P<0.001) and to asthmatics (0.7+/-0.85 pg/ml) (P<0.001). ET-1 Levels in normal subjects were 1.221+/-0.02 pg/ml. In "desaturators" COPD patients ET-1 levels during the night, 5 min after the first oxyhemoglobin desaturation, were significantly higher (4.28+/-1.10 pg/ml) compared to those during the day (2.08+/-0.28 pg/ml) (P<0.001). A significant negative correlation was observed between ET-1 levels and degree of desaturation during the day (P=0.005, r=0.632) and during the night (P<0.001, r=0.930) in "desaturators" COPD patients.. According to our results: (1) ET-1 levels were significantly higher in "desaturators" COPD patients than in "non-desaturators" COPD and in asthmatics; (2) ET-1 levels were significantly higher during the night than during the day in "desaturators" COPD patients; (3) the degree of desaturation correlated negatively with the ET-1 levels in "desaturators" COPD patients, both during daytime and nighttime. These findings are consistent with the hypothesis that ET-1 is implicated in the pathophysiology of asthma and COPD, especially if nocturnal, nonapneic, oxyhemoglobin desaturation exists.

Topics: Asthma; Biomarkers; Endothelin-1; Forced Expiratory Volume; Humans; Middle Aged; Oxygen; Pulmonary Disease, Chronic Obstructive; Vital Capacity

The effects of endothelin-1 (ET-1) on pulmonary vascular tone depend on the complex interplay of ET-1-induced vasoconstriction and vasodilation due to the secondary generation of endothelium-derived vasorelaxants. Therefore, it is likely that the response to ET-1 varies, depending on whether it is applied to the luminal or adventitial side of pulmonary vessels. Therefore, this study was designed to determine the change in luminal ET-1 levels during exercise in patients with chronic obstructive pulmonary disease (COPD).. All subjects performed a constant-load exercise test for 5 minutes on the ergometer with right heart catheterization while breathing room air or oxygen. ET-1 levels at rest, just after exercise, and 1 hour after exercise were measured in the pulmonary capillary wedge region.. Thirty-six patients with COPD.. While breathing room air, ET-1 levels did not significantly differ between at rest, just after exercise and 1 hour after exercise [at rest; 4.15 (0.43) pg/ml, just after exercise; 4.15 (0.44) pg/ml, 1 hour after exercise; 4.13 (0.42) pg/ml]. In contrast, while breathing oxygen, ET-1 levels were significantly higher just after exercise [4.41 (0.43) pg/ml] than at rest [3.90 (0.37) pg/ml, p=0.0116] and 1 hour after exercise [3.93 (0.38) pg/ml, p=0.0246]. The change in ET-1 levels between before and just after exercise (delta ET-1) was negatively correlated with change in mPAP (delta mPAP) (r=-0.638, p=0.0001). However, delta ET-1 was not significantly correlated with any FEV1 (% predicted), DLCO, PaO2, or baseline pulmonary hemodynamics.. The impairment of ET-1 release into the luminal side was observed in patients with COPD during exercise while breathing room air. However, oxygen supplementation reversed the capacity of ET-1 release, and delta ET-1 with exercise was negatively correlated with delta mPAP.

Topics: Aged; Air; Endothelin-1; Exercise Test; Humans; Male; Middle Aged; Oxygen; Pulmonary Circulation; Pulmonary Disease, Chronic Obstructive; Respiration; Respiratory Function Tests

The peptide endothelin-1 (ET-1) plays an unknown role in the pathogenesis and progression of two important neonatal pulmonary disorders, chronic lung disease (CLD) of prematurity and persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (INO) is a proven vasodilator therapy in PPHN and is an experimental therapy in CLD. We sought to determine the effects, if any, of the interaction of inhaled INO with ET-1 in these two separate disorders. Infants (n=21) with PPHN (mean gestation age, 39.4 weeks; mean birth weight, 3470 g) were treated with INO. All infants were <72 h of age at baseline. Plasma obtained at baseline and after 24 h of INO therapy was assessed for ET-1. The change in ET-1 levels with INO was inversely correlated with change in arterial partial pressure of O(2) (r=-0.71, P=0.0003). A separate group of 33 patients with CLD (mean gestational age, 27 weeks; mean birth weight, 740 g; mean age, 19 days) had tracheal aspirate levels of ET-1 obtained before, during, and after 7 days' administration of INO. Values were normalized by soluble secretory component of IgA. Tracheal aspirate ET-1 levels were detectable before INO therapy. There was no significant change during or after treatment with INO. There was not a significant correlation between baseline fractional inspired O(2) and ET-1 levels. There was a non-significant trend in the correlation between the change in ET-1 and the change in interleukin-8 levels in tracheal aspirate. This report confirms the presence of ET-1 in tracheal aspirate of premature infants who are developing CLD and reaffirms the presence of ET-1 in plasma of infants with PPHN. Short-term INO therapy was associated with a decrease in plasma ET-1 levels in PPHN, but did not affect tracheal aspirate ET-1 in CLD. Given the vasconstrictive, profibrotic, and proinflammatory properties of ET-1, specific ET-1 receptor antagonists could be considered as candidates for trials as adjunct therapy in either or both of these disorders.

Topics: Administration, Inhalation; Biomarkers; Endothelin-1; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Nitric Oxide; Persistent Fetal Circulation Syndrome; Pulmonary Disease, Chronic Obstructive

To study the therapeutic mechanism of combination therapy of ligustrazine and nitrendipine in treating patients with chronic obstructive pulmonary disease (COPD).. Thirty COPD patients divided in to 3 groups (10 in each) were treated with ligustrazine, nitrendipine and ligustrazine plus nitrendipine respectively, and the changes of hemorrheologic parameters, plasma endothelin (ET-1), thromboxane A2(TXA2) and platelet-P-selectin (CD62P) before and after treatment were observed.. The combination therapy of ligustrazine and nitrendipine could lower the levels of plasma ET-1, TXA2, CD62P and the hemorrheologic parameters.. Combination of ligustrazine and nitrendipine showed a therapeutic effect better than that of the two drugs used separately. Its effect in lowering pulmonary circulation resistance is related with the lowering of plasma vaso-contrictive factor and the changing of hemorrheologic properties. The integrated traditional Chinese and western medical therapy is valuable in treating COPD.

Topics: Aged; Drug Therapy, Combination; Endothelin-1; Female; Humans; Male; Middle Aged; Nitrendipine; P-Selectin; Pulmonary Disease, Chronic Obstructive; Pyrazines; Thromboxane B2; Vasodilator Agents

Pulmonary hypertension (PH) is an important factor in the prognosis of cases of chronic obstructive pulmonary disease (COPD), and endothelin-1 (ET-1) is a major factor in the development of PH in COPD. Oxygen (O2) therapy improves the prognosis of COPD by suppressing the development of PH. We therefore assessed the correlation of PH and ET-1, and the effect of O2 therapy on the plasma ET-1 concentration. In COPD patients, the plasma ET-1 level in mixed venous blood, but not in arterial blood, was negatively correlated with mixed venous O2 tension and positively correlated with pulmonary vascular resistance. No such correlation, however, was observed in the case of plasma HANP or plasma BNP. O2 administration significantly suppressed the plasma ET-1 level. This level in mixed venous blood was thought to serve as a marker of PH in COPD. and O2 administration decreased the plasma ET-1 level in mixed venous blood. It consequently attenuated PH.

Topics: Aged; Endothelin-1; Humans; Hypertension, Pulmonary; Oxygen; Oxygen Inhalation Therapy; Prognosis; Pulmonary Disease, Chronic Obstructive