endothelin-1 and Dyspnea

The development of pulmonary hypertension (PH) and its effect on long-term survival in bronchiectasis subjects has not been explored. The present study aims to analyze the factors associated with PH and its effect on long-term survival in bronchiectasis subjects.. We prospectively evaluated 23 bronchiectasis subjects without PH and 16 with PH, as well as 20 healthy volunteers.. Bronchiectasis subjects with PH were more hypoxemic and had a greater number of involved lobes in high resolution computed tomography (HRCT) than did the bronchiectasis subjects without PH (P < 0.001 and P < 0.001, respectively). At three years, the survival rate was 95.7% for bronchiectasis subjects without PH and 56.3% for bronchiectasis with PH, and at 5 years, these rates were 95.7% and 62.5%, respectively (P = 0.002). Multivariate Cox regression analysis revealed that only the Medical Research Council (MRC) dyspnea score was independently related to poor survival in all bronchiectasis subjects (hazard ratio: 6.98; 95% CI: 2.41-20.23; P < 0.00001).. Subjects with PH are more hypoxemic and have a greater number of involvements in the lobes of the lungs. Bronchiectasis subjects with PH have worse survival than do bronchiectasis subjects without PH. MRC dyspnea score is an independent predictor of long-term survival.

Topics: Adult; Bronchiectasis; Clinical Trials as Topic; Dyspnea; Echocardiography, Doppler; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Hypoxia; Male; Middle Aged; Oxygen; Patient Outcome Assessment; Prospective Studies; Risk Factors; Survival Rate; Tomography, X-Ray Computed; Turkey; Ventricular Dysfunction, Right

Breathlessness is the most common symptom in people with pulmonary arterial hypertension and congenital heart disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls.. Raised biomarkers for inflammation were found in CHD-APAH. Significant abnormalities in airway physiology may contribute to the dyspnea but are not driven by inflammation as assessed by circulating and sputum cytokines. A relationship between increased serum endothelin-1 and airway dysfunction may relate to its bronchoconstrictive properties.

Topics: Adult; Biomarkers; Bronchoconstriction; Case-Control Studies; Databases, Factual; Dyspnea; Endothelin-1; Exercise Tolerance; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Inflammation Mediators; Lung; Male; Middle Aged; Plethysmography, Whole Body; Pneumonia; Risk Factors; Spirometry; Sputum; Up-Regulation; Walk Test

Acute dyspnea is a frequent complaint in patients attending the emergency department (ED).. To evaluate the accuracy of PCT, MR-proANP, MR-proADM, copeptin and CT-proET1 for the risk-stratification of severe acute dyspnea patients presenting to the ED.. Multicenter prospective study in adult patients with a chief complaint of acute dyspnea. Pro-hormone type biomarkers concentrations were measured on arrival. Combined primary endpoint was a poor outcome.. Three hundred and ninety-four patients were included, 137 (35%) met the primary endpoint. MR-proADM was the only biomarker associated with the primary endpoint (odds ratio 1.43 [95%CI: 1.13-1.82], p = 0.003) as were the presence of paradoxical abdominal breathing (odds ratio 2.48 [95%CI: 1.31-4.68]) or cyanosis (odds ratio 3.18 [1.46-6.89]) Conclusions: In patients with severe acute dyspnea in the ED, pro-hormone type biomarkers measurements have a low added value to clinical signs for the prediction of poor outcome.

Topics: Acute Disease; Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Dyspnea; Emergency Service, Hospital; Endothelin-1; Glycopeptides; Hormones; Humans; Peptide Fragments; Prognosis; Prospective Studies; Severity of Illness Index

Exposure to high altitude is a well-known environmental stress with physiological and metabolic consequences, with the major stressor being hypobaric hypoxia. The disruption in cellular homeostasis elicits several acute and chronic adaptations designed to diminish the stress imposed by the hypoxic insult. Highly conserved cellular machinery protects the myocardium from damage under reduced oxygen tension. In the present study, adult Sprague-Dawley rats were exposed to an altitude of 9754 m in a decompression chamber and screened on the basis of the time taken for onset of gasping. The animals were grouped as susceptible (<10 min), normal (10-25 min), and tolerant (>25 min). Histologically, susceptible animals showed increased myocardial inflammation and infiltration and greater CK-MB activity. These animals showed a three-fold increase in reactive oxygen species levels and subsequent oxidative damage to proteins and lipids as compared to control unexposed group. In tolerant animals, the damage was minimal. The resistance to damage in these animals was possibly due to enhanced myocardial antioxidant enzymes, catalase and superoxide dismutase. A significantly higher expression of HIF-1α and its responsive genes, including EPO, HO-1, and GLUT1, was seen in tolerant animals, although VEGF expression was enhanced in the susceptible group. Cytoprotective chaperones, HSP70 and HSP90, were elevated in the tolerant animals. The differential expression of these hypoxia-responsive molecules may thus act as potential biochemical markers for screening and identifying individuals susceptible to environmental stress.

Topics: Altitude; Animals; Atmospheric Pressure; Catalase; Creatine Kinase, MB Form; Dyspnea; Endothelin-1; Erythropoietin; Heme Oxygenase-1; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Malondialdehyde; Myocarditis; Myocardium; Nitric Oxide; Oxidative Stress; Protein Carbonylation; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Time Factors; Up-Regulation; Vascular Endothelial Growth Factor A

Airway remodeling in patients with severe steroid-refractory asthma might result from a reduced ability of steroid therapy to limit the transcription of remodeling factors by the bronchial epithelium.. We sought to compare the levels of transcripts encoding remodeling factors in bronchial epithelium of healthy volunteers and of asthmatic patients with either steroid-sensitive or steroid-refractory disease and to correlate these levels with hallmarks of airway remodeling.. By means of real-time quantitative PCR, we assessed the levels of 14 transcripts encoding remodeling factors, matrix metalloproteinases, and extracellular matrix proteins in laser-capture microdissected bronchial epithelium of healthy volunteers, patients with mild steroid-untreated asthma, and patients with steroid-sensitive and steroid-refractory asthma (n = 8-10 in each group). Histologic features of airway remodeling and endothelin-1 (EDN1) immunolocalization were determined by using frozen specimens.. Patients with steroid-refractory asthma had greater levels of EDN1 transcripts (4.1-fold increase, P = .026) and protein (P = .0009) in their bronchial epithelium compared with patients with steroid-sensitive asthma. EDN1 mRNA levels and protein expression in asthmatic patients were negatively correlated with prebronchodilator and postbronchodilator FEV(1) value (r(2) >or= 0.193, P

Topics: Adjuvants, Immunologic; Anti-Inflammatory Agents; Asthma; Bronchi; Dyspnea; Endothelin-1; Gene Expression Regulation; Humans; Respiratory Mucosa; Steroids