Sex hormone alterations and systemic inflammation in a group of male COPD smokers and their correlation with the +138 insA/delA endothelin-1 gene polymorphism. A case-control study.

BACKGROUND: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Association of ET-1 gene polymorphisms with COPD phenotypes in a Caucasian population.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Decline in FEV1 related to genetic polymorphisms (+138insA/delA and Lys198Asn) of the endothelin-1 gene in COPD. A pilot study.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: The present data shows that ET-1 and its functional polymorphisms may be implicated in COPD phenotype and severity.

Indications, results and complications of flexible fiberoptic bronchoscopy: a 5-year experience in a referral population in Greece.

The aim of this study was to retrospectively review the indications, results and complications of flexible fiberoptic bronchoscopy (FFB) in an University teaching Hospital. Also, we present the radiological findings for the major causes according to computed tomography of the chest performed within 48 h of fiberoptic bronchoscopy. A total of 4,098 FFBs were performed from January 1, 2003 to December 30, 2007. For diagnostic purposes, 3769 FFBs performed (92%) and for therapeutic purposes 329 FFBs (8%) performed. Haemoptysis was the most common indication for FFB (21%), followed by fever/suspected infection (19%) and chronic cough (18%). The most common results of the diagnostic workup was nonspecific inflammation of the tracheobronchial tree (31% for haemoptysis, 38.7% for fever and 48.5% for chronic cough), with malignancy ranking second (17%, 26.1% and 26% respectively). The cytological results showed adenocarcinoma to be the most common lung cancer in both sexes (37.3% for men and 39.7% for women). The mortality rate was 0.04% and the frequency for major and minor complications was 0.56% and 0.33%, respectively. In conclusion, flexible fiberoptic bronchoscopy is a safe procedure and can play a major role in both diagnosis and treatment, as long as the requisites of preparation and supervision are followed.

Does CPAP therapy improve erectile dysfunction in patients with obstructive sleep apnea syndrome?

OBJECTIVE: The aim of the study was to examine the quality of the characteristics of Erectile Dysfunction (ED) in men with Obstructive Sleep Apnea Syndrome (OSAS) and to investigate whether there is an improvement with the use of continuous positive airway pressure (CPAP) therapy. MATERIALS AND METHODS: Fifteen men with OSAS and sexual dysfunction have been investigated in this follow-up study. The treatment period was for 12 weeks and the therapeutic CPAP levels were determined during the full night of the therapeutic titration. RESULTS: In our 15 treated patients, the International Index Erectile Function (IIEF) total and all domain scores had increased after the CPAP treatment compared to the baseline, except for that of sexual desire domain. CONCLUSIONS: CPAP therapy can improve the sexual function in ED patients with OSAS.

Accuracy of pulmonary function tests in predicted exercise capacity in COPD patients.

PURPOSE: The purpose of this study was to examine exercise tolerance in patients with COPD from measurements of resting pulmonary function parameters. METHODS: A total of 57 COPD patients were administered the pulmonary function test (PFT) and cardiopulmonary exercise test. The results were analyzed and essentially linear relationships emerged when each subject's VO2 peak was plotted against his individual PFT parameters. Those significant contributors were then introduced in a stepwise multiple regression analysis to determine the best predictor of the VO2 peak. RESULTS: Stepwise multiple regressions in variables revealed that peak oxygen consumption (VO2 peak) was predicted best by the following equation: VO2 peak=(maximum voluntary ventilation x 0.024)+(forced mid-expiratory flow x 0.47)+(body surface area x 0.988)-0.913 (r=0.90; r2=0.81 SE=0.29 L/min). CONCLUSION: We conclude that exercise capacity was predicted from measurements of resting pulmonary function parameters with excellent accuracy in the COPD patient.

Can high resolution computed tomography predict lung function in patients with chronic obstructive pulmonary disease?

High-resolution computed tomography (HRCT) is a useful method for quantifying the extent of emphysema. Few reports have mentioned the relationships between HRCT scans and pulmonary function tests in chronic obstructive pulmonary disease (COPD). For diagnosis, COPD requires chronic airflow limitation and emphysema and/or chronic bronchitis. We examined 20 who were previous smokers with middle to moderate COPD. All were normocapnic with mean arterial oxygen pressure (PaO2) 77,52 +/- 16,789 mmHg. Forced spirometry, somatic plethysmography and cardiopulmonary exercise test were performed in each patient. HRCT was performed in both full inspiration and full expiration at three levels through the upper (at the aortic arch), lower (2 cm above the diaphragm), and middle lung (midpoint between upper and lower) levels. During expiration all pulmonary function parameters correlated with the HRCT grade in the middle right and left part of the lungs. The middle right part of the lung during expiration correlated statistically significant with MVV (r = -0.681, p = 0.001), forced vital capacity (FVC) (r = -0.477, p = 0.027), forced expiratory volumein 1 sec (FEV1) (r = -0.632, p = 0.002), resistance (r = 0.674, p = 0.001), residual volume (RV) (r = 0.733, p = 0.001), total lung capacity (TLC) (r = 0.696, p = 0.001), functional residual capacity (FRC) (r = 0.752, p = 0.001) and peak oxygen consumption during exercise (VO2) (r = -0.493, p = 0.023). The middle left part of the lung during expiration correlated statistically significant with MVV (r = -0.673, p = 0.001), FVC (r = -0.493, p = 0.027), FEV1 (r = -0.629, p = 0.003), resistance (r = 0.593,p = 0.005), RV (r = 0.601, p = 0.005), TLC (r = 0.546, p = 0.012), FRC (r = 0.594, p = 0.006) and peak VO2 (r = -0.525, p = 0.015). Forced expiratory volume in 1 sec (FEV1), which is a well-established measure of airflow obstruction, correlated with the HRCT grade (1) in the middle left part of the lung during inspiration (r = -0.468, p = 0.035) and during expiration (r = - 0.629, p = 0.003) (2) in the lower right lung during inspiration (r = -0.567, p = 0.007) and during expiration (r = -0.558, p = 0.008) (3) in the lower left lung during inspiration (r = -0.542, p = 0.011) and during expiration (r = -0.558, p = 0.008) (4) in the upper right lung during expiration (r = -0.469, p = 0.037) (5) in the upper left lung during expiration (r = -0.463, p = 0.035) and (6) in the middle right lung during expiration (r = -0.632, p = 0.002). According to our results HRCT was a valuable tool for evaluating the severity of COPD--especially the middle right and left part of the lungs, during expiration--and correlated well with pulmonary function tests.

Endothelin-1 levels in the pathophysiology of chronic obstructive pulmonary disease and bronchial asthma.

BACKGROUND: 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. OBJECTIVE: The aim of this study was to examine the serum ET-1 levels in stable asthmatic and COPD patients. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Abnormal origin of the left common carotid artery by innominate artery: a case of enlargement mediastinum.

An abnormal origin of the left common carotid artery is rare. A 71-year-old male was presented with a cough, fever and dyspnea. A chest radiography revealed a widening of the superior mediastinum. An abnormal origin of the left common carotid artery by innominate artery was diagnosed by angiography.

Evaluation of arterial endothelin-1 levels, before and during a sleep study, in patients with bronchial asthma and chronic obstructive pulmonary disease.

BACKGROUND: Endothelin (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, falling with treatment of the exacerbations. OBJECTIVE: The aim of this study was to examine the ET-1 blood levels in stable asthmatic patients and stable COPD patients during alertness and sleep. MATERIALS AND METHODS: We examined 48 COPD and 20 asthmatic patients. All underwent forced spirometry, measurement of SaO2 and of arterial ET-1 levels and nocturnal polysomnography. ET-1 levels were also determined during nocturnal oxyhaemoglobin desaturation. RESULTS: The daytime SaO2 level of our asthmatic patients was higher than that of our COPD patients (p < 0.001). Daytime SaO2 level of our non-desaturator COPD patients was higher than that measured in desaturator COPD patients. Nightime SaO2 level in our asthmatic patients was higher than that in our desaturator COPD patients (p < 0.001). Daytime ET-1 levels in desaturator COPD patients were higher than those observed in normal individuals, in non-desaturator COPD patients and in asthmatic patients. The COPD desaturator patients had higher levels of ET-1 during nighttime than during daytime (p < 0.001). CONCLUSION: Asthmatic patients did not exhibit desaturation of haemoglobin during the night. ET-1 levels are significantly higher in desaturator COPD patients compared with non-desaturator COPD patients, both during the day and during the night. ET-1 levels in stable COPD patients are significantly higher than in patients with stable asthma. These findings are consistent with the hypothesis that ET-1 is implicated in the pathogenesis of COPD and asthma.