Association between the severity of newly diagnosed obstructive sleep apnea and subclinical carotid atherosclerosis in patients without overt cardiovascular disease.

OBJECTIVE: Obstructive Sleep Apnea (OSA) has been associated with both subclinical and accelerated atherosclerosis; however, it still remains unknown whether this association is unique or is mediated by the higher burden of co-existing cardio-metabolic disorders frequently seen in patients with OSA. PATIENTS AND METHODS: A total of 40 subjects without clinically diagnosed cardiovascular disease (CVD) referred for polysomnography test were included in the study. Subjects with apnea/hypopnea index (AHI > 15/h) were classified as moderate/severe OSA. Subclinical changes in carotid atherosclerosis were assessed using mean carotid intima-media thickness (cIMT) and presence of atheromatic plaques on both carotid arteries. The measurement was performed using B-mode ultrasonogram. Framingham risk score was used in the approximation of cardiovascular risk. RESULTS: The mean age of our cohort was 56.8 years, 70% (n = 28) of whom were males. Moderate/severe OSA was diagnosed in 21 subjects. Both groups were well matched in terms of clinical and demographic characteristics, and cardiovascular risk profile, as shown in their respective Framingham risk scores (10.4 ± 6.6 vs. 11.8 ± 8.8, p = NS). Patients with moderate/severe OSA had a higher mean AHI, 3% oxygen desaturation index, and lower minimum nocturnal oxygen saturation than controls. No significant differences were detected in terms of C-reactive protein levels. The two groups had similar cIMT (0.66 ± 0.17 vs. 0.75 ± 0.20 p = 0.33) and presence of atheromatic plaque (50% vs. 45%, p = 1.00). CONCLUSIONS: Our study suggests that among patients with similar cardiovascular risk profile and free of overt CVD, the severity of newly diagnosed OSA was not correlated with increased inflammation or subclinical carotid atherosclerosis.

The impact of obstructive sleep apnea syndrome on renin and aldosterone.

OBJECTIVE: Obstructive Sleep Apnoea Syndrome (OSAS) is a respiratory disorder characterized by recurrent airflow obstruction caused by total or partial collapse of the upper airway. OSAS is an established independent factor of cardiovascular risk together with other risk factors such as smoking and increased lipids. The aim of our study was to measure serum levels of aldosterone and renin in OSAS patients that did not suffer from arterial hypertension and compare them to matched healthy subjects in order to reveal the impact of chronic intermittent hypoxia on the renin-angiotensin-aldosterone system. PATIENTS AND METHODS: The patients that enrolled in this study were 19 OSAS patients who had undergone overnight polysomnography and had an Apnoea Hypopnoea Index (AHI) greater than 10 events/hour. They were compared to 20 healthy non-OSAS closely matched controls. Serum aldosterone and direct renin concentration were measured by radioimmunoassay. RESULTS: Aldosterone concentration follows a diurnal variation; therefore, all blood samples were obtained at the same time (6 AM). There were no significant differences in serum aldosterone levels between the two studied groups of OSAS patients and the healthy subjects group (140.6 pg/ml ± 25.2 vs. 133.2 pg/ml ± 18.5 with p = 0.223). Similar were the results for the renin levels (25.0 ± 6.9 vs. 24.9 ± 4.4 with p = 0.360). CONCLUSIONS: Our study suggests that patients with OSAS, but without existing hypertension have aldosterone and renin levels similar to healthy subjects. According to our findings a direct connection between OSAS and the development of arterial hypertension may not be established via sympathetic system activation.

Pleural mesothelioma in a young male patient.

We present the case of a 33-year-old male patient suffering from lymphocytic pleural effusion, as a result of pleural mesothelioma. Mesothelioma is a malignant tumor of the pleura that is mainly caused by chronic exposure to asbestos fibers and more than 40 years of exposure are needed to develop the disease. Early studies on the relationship of asbestos and mesothelioma were issued in the 1960s. Fibers migrate from the parenchyma of the lung to the visceral pleura. It is widely known that asbestos is an oncogenic factor which can cause damage to DNA. A chest x-ray may reveal pleural effusion with or without pleural thickening, whereas a chest CT may also reveal pleural thickening, uniform and/or lobular. Specific tests, such as immunohistochemical staining, are used in order to help differential diagnosis. Extrapleural pneumonectomy is used as a therapeutic option which involves removal of the lung as well as both the visceral and parietal pleura, the affected part of the pericardium and diaphragm. Surgery should be followed up by radiotherapy and chemotherapy. The surgery may lead to a mean survival rate of approximately 9-21 months. The case presented underlines that in the event of pleural effusion with a lymphocyte type physicians should consider the possibility of a pleural mesothelioma during differential diagnosis, even in relatively young patients.

The impact of obstructive sleep apnea syndrome severity on physical performance and mental health. The use of SF-36 questionnaire in sleep apnea.

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is a common disorder defined by repeated episodes of airflow cessation (apneas)leading to arterial hypoxemia and sleep disruption. OSAS has been associated with increased morbidity, mortality and diminished quality of life so far. This cross-sectional study aimed to assess the impact of OSAS on patients' Quality of Life, as measured by the Medical Outcomes Study Short Form-36 (SF-36). PATIENTS AND METHODS: Two hundred and forty five subjects referred to the sleep laboratory and underwent full polysomnography overnight. Prior to sleep study onset, we registered height and weight, medical history, smoking habit, drug consumption. Afterwards, each patient completed the SF-36. Eighty subjects not diagnosed with sleep apnea [apnea hypopnea index (AHI < 5)] were excluded. Therefore, 165 subjects (121 male and 44 female) remained. RESULTS AND CONCLUSIONS: Statistical analysis revealed that in patients with respiratory disturbance index (RDI) ≥ 15, (n = 115), RDI was independently associated with lower performance in role limitations due to physical problems (p = 0.005). Additionally, RDI was the only factor associated with decreased vitality (p = 0.014) and mental health scores (p = 0.047). In the same patient subgroup, body mass index (BMI) and age were associated with poorer scores in physical functioning (p < 0.001 and p = 0.003, respectively). BMI was an independent clinical predictor of worse scores in bodily pain (p = 0.006) general health (p = 0.006), social functioning (p = 0.025) and role limitations due to emotional problems (p = 0.004).

An unexpected pulmonary arterial aneurysm in a COPD patient.

We present a case of an idiopathic pulmonary artery aneurysm in an asymptomatic patient who was treated for an irrelevant medical condition. Pulmonary artery aneurysms (PAA) are quite rare and can either be congenital or acquired. Congenital aneurysms are usually associated with cardiac malformations leading to pulmonary hypertension. Acquired aneurysms can be idiopathic or associated with infections (tuberculosis, syphilis), trauma, pulmonary valvular stenosis, or collagen diseases. Pulmonary artery aneurysms are not common and an idiopathic pulmonary artery aneurysm is a rare finding that could be diagnosed incidentally.

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.

An unexpected pulmonary infection in a patient with gastric tube interposition, reconstruction of the hypopharynx and gastric-hypopharyngeal anastomosis.

Pulmonary infection by Nocardia spp. has been recognized the last decades. Nocardia is an opportunistic pathogen in immunocompromised individuals; nevertheless, it has been recognized as an uncommon pathogen in immunocompetent patients. We report a case of pulmonary infection by Nocardia asteroides in an immunocompetent host who had a history of sulfate acid aspiration, followed by gastric tube interposition, reconstruction of the hypopharynx and gastric-hypopharyngial anastomosis.

Endothelin-1 polymorphisms involved in impaired exercise tolerance in COPD patients. A pilot study.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). DISCUSSION: 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.

The role of Endothelin-1 in obstructive sleep apnea syndrome and pulmonary arterial hypertension: pathogenesis and Endothelin-1 antagonists.

Obstructive Sleep Apnea Syndrome (OSAS) is a recognized risk factor for cardiovascular disorders and in some cases is complicated with Pulmonary Arterial Hypertension (PAH), as the endothelium is affected. Recent studies provide strong evidence for endothelial dysfunction in obstructive sleep apnea. The resultant vasoconstriction, abnormal cell proliferation and hyper-coagulability may lead to the initiation or progression of atherosclerotic cardiovascular and cerebrovascular disorders, which are frequently encountered in OSA patients. While the currently available therapies for OSAS, such as Continuous Positive Airway Pressure therapy (CPAP therapy), improve endothelial dysfunction, they are not well-tolerated by patients. CPAP therapy can reduce nocturnal hypoxemias and decrease noradrenaline circulating levels, but does not affect ET-1 plasma levels. Potent and selective Endothelin-1 receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contrasting and complicated because of the tissue-specific vasoconstrictor actions of Endothelin-B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo.

Human genes in TB infection: their role in immune response.

Tuberculosis (TB) caused by the human pathogen Mycobacterium tuberculosis, is the leading cause of morbidity and mortality caused by infectious agents worldwide. Recently, there has been an ongoing concern about the clarification of the role of specific human genes and their polymorphisms involved in TB infection. In the vast majority of individuals, innate immune pathways and T-helper 1 (Th1) cell mediated immunity are activated resulting in the lysis of the bacterium. Firstly, PTPN22 R620W polymorphism is involved in the response to cases of infection. The Arg753Gln polymorphism in TLR-2 leads to a weaker response against the M. tuberculosis. The gene of the vitamin D receptor (VDR) has a few polymorphisms (BsmI, ApaI, Taq1, FokI) whose mixed genotypes alter the immune response. Solute carrier family 11 member (SLC11A1) is a proton/divalent cation antiporter that is more familiar by its former name NRAMP1 (natural resistance associated macrophage protein 1) and can affect M. tuberculosis growth. Polymorphisms of cytokines such as IL-10, IL-6, IFN-g, TNF-a, TGF-b1 can affect the immune response in various ways. Finally, a major role is played by M. tuberculosis antigens and the Ras-associated small GTP-ase 33A. As far as we know this is the first review that collates all these polymorphisms in order to give a comprehensive image of the field, which is currently evolving.