The relationship between obstructive sleep apnea syndrome and obesity: A new perspective on the pathogenesis in terms of organ crosstalk.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a common disorder that has a major impact on public health. The connection between OSAS and obesity is very complex and likely represents an interaction between biological and lifestyle factors. Oxidative stress, inflammation and metabolic dysregulation are both actors involved in the pathogenesis of OSAS and obesity. Also, the current evidence suggests that gut microbiota plays a significant role in the emergence and progression of some metabolic disorders. When the relationship between OSAS and obesity is evaluated extensively, it is understood that they show mutual causality with each other, and that metabolic challenges such as impaired microbiota affect this bidirectional organ interaction, and by ensuing organ injury. OBJECTIVES: The aim of this study is to investigate the association between OSAS and obesity, and the effect of "organ crosstalk" on the pathogenesis of the relationship and to contribute to the diagnosis and treatment options in the light of current data. DATA SOURCE: We performed an electronic database search including PubMed, EMBASE and Web of Science. We used the following search terms: OSAS, obesity, inflammation, metabolic dysregulation and gut microbiota. CONCLUSION: Obesity and OSAS adversely affect many organs and systems. Besides the factors affecting the diagnosis of the OSAS-obesity relationship, mutual organ interactions among the respiratory system, adipose tissue and intestines should not be ignored for prevention and treatment of OSAS and obesity. Comprehensive clinical trials addressing the efficacy and efficiency of current or potential treatments on therapeutic applications in the OSAS-obesity relationship are needed.

Carotid intima-media thickness in chronic obstructive pulmonary disease and survival: A multicenter prospective study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Carotid intima-media thickness (CIMT) is a noninvasive method assessing atherosclerosis. OBJECTIVE: It was aimed to determine relationship and survival between COPD and CIMT. METHODS: CIMT was measured using Doppler ultrasound (USG) in 668 stable COPD patients at 24 centers. Patients were followed-up for 2 years. RESULTS: There were 610 patients who completed the study. There were 200 patients CIMT with <0.78 mm (group 1), and 410 with CIMT ≥ 0.78 mm (group 2). There was a significant difference at the parameters of age, gender, smoking load, biomass exposure, GOLD groups and degree of airway obstruction (FEV1) between groups 1 and 2. Our results revealed positive correlations between mean CIMT and age, smoking load (pack-years), biomass exposure (years), exacerbation rate (last year), duration of hypertension (years) and cholesterol level; negative correlations between CIMT and FEV1 (P < 0.05). According to logistic regression model, compared with group A, risk of CIMT increase was 2.2-fold in group B, 9.7-fold in group C and 4.4-fold in group D (P < 0.05). Risk of CIMT increase was also related with cholesterol level (P < 0.05). Compared with infrequent exacerbation, it was 2.8-fold in the patients with frequent exacerbation (P < 0.05). The mean survival time was slightly higher in group 1, but not significant (23.9 vs 21.8 months) (P > 0.05). CONCLUSION: This study is the first regarding CIMT with combined GOLD assessment groups. It has revealed important findings supporting the increase in atherosclerosis risk in COPD patients. We recommend Doppler USG of the carotid artery in COPD patients at severe stages.

Prognostic Value of Renal Dysfunction Indicators in Normotensive Patients With Acute Pulmonary Embolism.

INTRODUCTION: Glomerular filtration rate (GFR) and blood urea nitrogen (BUN) are important prognostic indicators for cardiovascular disease. However, data on the relationship between renal dysfunction (RD) and prognosis in patients with acute pulmonary embolism (APE) are limited. The estimated-GFR (eGFR), based on the Modification of Diet in Renal Disease (MDRD) equation, has been suggested as a possible prognostic marker in patients with APE; however, at present, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is thought to be more accurate than the MDRD equation for the estimation of RD. OBJECTIVE: We investigated whether eGFRCKD-EPI or BUN could predict adverse outcomes (AOs) better than eGFRMDRD in normotensive patients with APE. METHODS: Ninety-nine normotensive patients with APE (aged 22-96, 56% male) were enrolled in the study retrospectively. Adverse outcomes were defined as the occurrence of any of the following: death, cardiopulmonary resuscitation, use of vasopressors, thrombolysis, or mechanical ventilation. RESULTS: In univariate analyses, age, gender (male), heart rate (>110 bpm), serum creatinine, BUN, cardiac troponin (cTn) positivity, right ventricle-left ventricle ratio, eGFRMDRD, and eGFRCKD-EPI were found to be significantly different between those with and without AOs. Comparing area under the curves for AO, we found statistically significant differences between eGFRCKD-EPI and eGFRMDRD ( P = .01) but not between BUN and eGFRCKD-EPI or BUN and eGFRMDRD. Furthermore, 30-day mortality was 36% versus 11% in cTn-positive patients with an eGFRCKD-EPI < and ≥ 60 mL/min, respectively. CONCLUSION: There is a close relationship between RD and APE prognosis. We conclude eGFRCKD-EPI is a potential prognostic marker for risk stratification in normotensive patients with APE.

Effect of continuous positive airway pressure (CPAP) therapy on IL-23 in patients with obstructive sleep apnea.

Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder characterized by repeated episodes of apnea and hypopnea during sleep. Continuous positive airway pressure (CPAP) is the most effective method for treating OSAS and alleviating the patients' symptoms. The aim of this study was to assess the effect of 3-month CPAP therapy on serum levels of IL-23 in patients with OSAS. Twenty-three patients with newly diagnosed moderate-to-severe OSAS who had not yet started nasal CPAP treatment were prospectively enrolled. All of the subjects underwent simple spirometry and an overnight sleep study. Twenty-seven healthy individuals without OSAS were also recruited as the control group. Serum IL-23 and C-reactive protein (CRP) levels were measured before and after 3 months of CPAP therapy. There was no significant difference between moderate and severe OSAS patients in IL-23 and CRP, but both parameters were significantly higher than control group. The CPAP treatment produced a significant decrease in the levels of the inflammatory mediators CRP and IL-23 in patients. Changes in IL-23 were positively correlated with changes in AHI and in CRP. In conclusion, based on these results, serum IL-23 levels reflect OSAS-related systemic inflammation and are a useful marker for improvement in OSAS following CPAP therapy.

Syncope as a presentation of acute pulmonary embolism.

PURPOSE: Syncope is an atypical presentation for acute pulmonary embolism (APE). There are conflicting data concerning syncope and prognosis of APE. PATIENTS AND METHODS: One hundred and seventy-nine consecutive patients aged 22-96 years (median, 68 years) with APE were retrospectively enrolled in the study. RESULTS: Prevalence of syncope was 13% (n=23) at the time of presentation. Compared to patients without syncope, those with syncope had a higher rate of central embolism (83% vs 43%, respectively, P=0.002), right ventricular dysfunction (91% vs 68%, P=0.021), and troponin positivity (80% vs 39%, P=0.001) but not 30-day mortality (13% vs 10%, P=0.716). Multivariate analysis showed that central localization (odds ratio: 9.08) and cardiac troponin positivity (odds ratio: 4.67) were the independent correlates of the presence of syncope in the patients with APE. Frequency of cardiopulmonary disease was lower, and duration from symptom onset to hospital admission was shorter in patients with syncope (P=0.138 and 0.118, respectively), although not significant. CONCLUSION: Syncope most likely represents an intermediate condition between massive APE and hypotension. In APE patients with syncope, the prognosis seems to depend on the underlying pathology, the patient's age, comorbidities and duration from symptom onset to hospital admission, and the use of thrombolytic therapy.

Platelet Indices in Patients with Coal Workers' Pneumoconiosis.

PURPOSE: Coal workers' pneumoconiosis (CWP) is caused by an accumulation of coal particles in the lung parenchyma. Reactive oxygen species (ROS) play an important role in the pathogenesis of CWP. It is well documented that ROS stimulate platelet activation, adhesion, and aggregation. The aim of the present study was to investigate the relationship between platelet indices and CWP. METHODS: The demographic features, occupational and medical history, exposure time, and complete blood count of retired coal miners were retrospectively analysed. The control group comprised healthy subjects who had not worked underground. Chest radiographs were evaluated according to the CWP classification of the International Labour Office. RESULTS: The study population was divided into following groups: 50 controls, 97 without CWP, 142 simple pneumoconiosis (SP), 157 progressive massive fibrosis (PMF). The platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) were significantly higher in patients with CWP compared to those in patients without CWP and controls. The platelet count, MPV, and PCT were higher in patients with PMF compared to those in the SP group (p < 0.05). The results of multiple logistic regression analyses indicated that the platelet count, MPV, and PCT were independently associated with the development of CWP. CONCLUSIONS: Platelet indices may be considered as disease markers for pneumoconiosis in coal miners and as a useful indicator of the progression of pneumoconiosis.

The Impact of Obstructive Sleep Apnoea and Nasal Continuous Positive Airway Pressure on Circulating Ischaemia-Modified Albumin Concentrations.

The aim of the present study was to evaluate the impact of obstructive sleep apnoea syndrome (OSAS) and the effects of nasal continuous positive airway pressure (CPAP) on circulating ischaemia-modified albumin (IMA) concentrations. The study included 97 newly diagnosed OSAS patients and 30 nonapnoeic controls. Blood samples were obtained in the morning after polysomnography. After 3 months of CPAP treatment, 31 patients with moderate-severe OSAS were reassessed for serum IMA concentrations. Significantly higher serum IMA concentrations were measured in the OSAS group than in the control group [0.518 ± 0.091 absorbance units (ABSU), 0.415 ± 0.068 ABSU, P < 0.001]. Serum IMA concentrations correlated significantly with the apnoea-hypopnoea index, mean SaO2, desaturation index, and C-reactive protein concentrations. Multiple logistic regression analyses showed that OSAS increased the serum IMA concentration independent of age, sex, body mass index, smoking habit, and cardiovascular disease. After 3 months of treatment with CPAP, OSAS patients had significantly lower serum IMA concentrations (0.555 ± 0.062 ABSU to 0.431 ± 0.063 ABSU, P < 0.001). The results showed that OSAS is associated with elevated concentrations of IMA, which can be reversed by effective CPAP treatment.

The neutrophil-to-lymphocyte ratio in patients with obstructive sleep apnoea syndrome and its relationship with cardiovascular disease.

OBJECTIVE: To investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and obstructive sleep apnoea syndrome (OSAS) severity and whether the NLR predicts cardiovascular disease (CVD) in patients with OSAS. BACKGROUND: OSAS is known as a risk factor for CVD. An increased NLR was strongly correlated with cardiovascular outcomes in several studies. METHODS: We retrospectively examined the laboratory data for 289 patients with suspected OSAS evaluated using polysomnography. RESULTS: The study included 171 OSAS patients and 118 controls. The NLR was higher in OSAS group than control group. The NLR was significantly higher in patients with CVD than in those without (3.31 ± 1.1 vs. 1.93 ± 0.8, p = 0.002). There were also significant correlations between the NLR and apnoea-hypopnoea index, mean SaO2, and oxygen desaturation index. CONCLUSIONS: There was a significant correlation between the NLR and OSAS severity and the NLR was independently associated with CVD in patients with OSAS.

Comparison of the diagnostic value of different lymphocyte subpopulations in bronchoalveolar lavage fluid in patients with biopsy proven sarcoidosis.

BACKGROUND: Bronchoalveolar lavage is considered a helpful tool in the diagnosis of diffuse parenchimal lung diseases such as sarcoidosis. CD4/CD8 ratio is higly specific but not sensitive to distinguish sarcoidosis and other intestitial lung diseases. We aimed to compare the diagnostic value of CD4/CD8 ratio and other lmphocyte subpopulations such as CD3+16+56, CD103+, CD4+CD103+, CD8+CD103+ in bronchoalveolar lavage to distinguish sarcoidosis and other nonsarcoidosis interstitial lung diseases. METHODS: Using the bronchoscopy records from 2006 to 2013, we evaluated 68 patients with biopsy proven sarcoidosis and 72 patients with clinicoradiological and/or biopsy proven diffuse parenchimal lung diseases. Cut off values, sensitivity and specificity were given for aforementioned parameters. RESULTS: Bronchoalveolar lavage CD4/CD8 ratio, CD4+ T lymphocyte percentage, CD4+103+, CD3+CD103-, CD8+CD103+/CD103+ ratio were significantly higher in sarcoidosis than other diffuse parenchimal lung diseases whereas CD3+103+, CD3+16+56+, CD8+, CD8+CD103+, CD8+CD103+/CD8+ were significantly lower. Best cut off value of CD4/CD8 was 1.34 with sensitivity and specificity 76.4%, 79.4% respectively. The cut off values of CD4/CD8 of >3.5 and >2.5 had specificity 95.9% and 95.3%, respectively and sensitivity 52%, 41%, respectively. CONCLUSION: CD4/CD8 ratio is highly specific but not sensitive for sarcoidosis diagnosis. Thus, BAL flow cytometry is not diagnostic alone without appropriate clinicoradiological and/or histopathological findings.

Association between continuous positive airway pressure and circulating omentin levels in patients with obstructive sleep apnoea.

PURPOSE: Inflammation and oxidative stress play important roles in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). Omentin is expressed in visceral adipose tissue and is associated with the inflammatory response. The aim of this study was to assess the relationship between OSAS and omentin based on a comparison of its serum levels at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. METHODS: Ninety-six newly diagnosed OSAS patients and 31 non-apnoeic controls were enrolled in this study. Blood samples were obtained in the morning after polysomnography. Within the OSAS group, 30 patients were started on CPAP therapy and then reassessed clinically, including a blood test for serum omentin and other biochemical analysis, at 3 months. RESULTS: Serum omentin levels were significantly lower in the OSAS group than in the control group (27.7 ± 7.6 and 42.5 ± 5.2 ng/mL, P < 0.001). In the subgroup analysis, omentin concentrations were significantly lower in patients with severe OSAS than in those with mild/moderate OSAS (P < 0.001). Circulating omentin levels were significantly correlated with the apnoea-hypopnoea index (AHI), mean SaO2, oxygen desaturation index, and serum C-reactive protein levels. Treatment with CPAP resulted in a significant increase in circulating omentin levels after 3 months, from 22.7 ± 1.4 to 41.2 ± 3.3 ng/mL (P < 0.001). CONCLUSIONS: OSAS is associated with low serum omentin levels, and these levels can be reversed by effective CPAP treatment.

Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey.

BACKGROUND: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs. OBJECTIVES: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort. PATIENTS AND METHODS: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups. RESULTS: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16(+)56(+), CD103(+), CD8(+)103(+), and CD3(+)16(+)56(+) cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0.03) than in other non-sarcoidosis ILDs. CONCLUSIONS: Among BAL fluid flow cytometric parameters, CD4/CD8 and lymphocyte fraction may be helpful for distinguishing sarcoidosis from other ILDs, but they are neither specific nor diagnostic for any lung disease. Thus, a multidisciplinary diagnostic discussion is required to differentiate various ILDs.

Disseminated tuberculosis in a non immun compromised patient with a complicated diagnosis.

Tuberculosis (TB) has become a global emergency worldwide. The long time period between the exposure to TB bacillus and the onset of symptoms cause a delay in diagnosis. Herein, we report a case of 64-year-old female patient suffering from dyspepsia, anorexia, weight loss and abdominal pain for the last 8 months. Physical examination, ascites fluid evaluation, chest radiography, ultrasonographic and tomographic scans, histopathological analysis of the lymphadenopathy (LAP) and endometrial tissue revealed TB. A fourfold antituberculous treatment with isoniazid, pyrazinamide, rifampicin and ethambutol was prescribed for two months and for four months maintenance therapy with isoniazid and rifampicin was given. On the fourth month of the medical treatment the patient clinically recovered. Since the diagnosis of TB is difficult, high grade suspicion, combination of the radiologic, microbiologic and histopathological examinations are needed to achieve a diagnosis.

Prognostic value of serum procalcitonin and C-reactive protein levels in critically ill patients who developed ventilator-associated pneumonia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is an important cause of mortality and morbidity in critically ill patients. We sought to determine the prognostic value of procalcitonin (PCT) and C-reactive protein (CRP) kinetics in critically ill patients who developed VAP. METHODS: Patients who were admitted to the intensive care unit (ICU) and developed VAP were eligible. Patients were followed for 28 days after the pneumonia diagnosis and blood samples for PCT and CRP were collected on the day of the pneumonia diagnosis (D0), and days 3 (D3) and 7 (D7) after the diagnosis. Patients were grouped as survivors and non-survivors, and the mean PCT and CRP values and their kinetics were assessed. RESULTS: In total, 45 patients were enrolled. Of them, 22 (48.8%) died before day 28 after the pneumonia diagnosis. There was no significant difference between the survivor and non-survivor groups in terms of PCT on the day of pneumonia diagnosis or CRP levels at any point. However, the PCT levels days 3 and 7 were significantly higher in the non-survivor group than the survivor group. Whereas PCT levels decreased significantly from D0 to D7 in the survivor group, CRP did not. A PCT level above 1 ng/mL on day 3 was the strongest predictor of mortality, with an odds ratio of 22.6. CONCLUSION: Serum PCT was found to be a superior prognostic marker compared to CRP in terms of predicting mortality in critically ill patients who developed VAP. The PCT level on D3 was the strongest predictor of mortality in VAP.

Comparison of diagnostic values of procalcitonin, C-reactive protein and blood neutrophil/lymphocyte ratio levels in predicting bacterial infection in hospitalized patients with acute exacerbations of COPD.

BACKGROUND: Viral or bacterial upper respiratory infections are the most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Based on available data, no reliable parameter has been presented to distinguish between bacterial and nonbacterial exacerbations. Therefore, we compared the diagnostic value of procalcitonin (PCT) level, which is a newer marker for predicting bacterial infections in patients with AECOPD, to routine parameters such as C-reactive protein (CRP) levels and the neutrophil/lymphocyte (N/L) ratio. METHODS: This study included all consecutive patients who were admitted for a diagnosis of AECOPD between January 1 and March 31, 2014. PCT, CRP, and the N/L ratio were assessed in addition to cultures from tracheal aspirates or sputum on the first day of admission. Patients with a pneumonic infiltration on chest radiographs, or an extrapulmonary infection focus, or whose blood samples were not obtained for PCT and/or CRP at the same time as sputum culture were excluded from the study. RESULTS: A total of 77 patients were included with a mean age of 71.7 ± 9.5 years. Bacteria were isolated in 37.4 % of the patients. Mean PCT levels were significantly higher in patients with positive sputum cultures than in patients with negative sputum cultures. The cut-off values for PCT, CRP, and the N/L ratio for predicting a bacterial infection were 0.40 ng/mL, 91.50 mg/L, and 11.5, respectively; sensitivity was 61, 54, and 61 % respectively; specificity was 67, 52, and 58 %, respectively; and the area under the curve (AUC) values were 0.64, 0.52, and 0.58, respectively. The AUC value of PCT was significantly better for predicting bacterial infection compared with the CRP level or the N/L ratio (p = 0.042). CONCLUSION: PCT was better than CRP and the N/L ratio for predicting a bacterial infection in hospitalized patients with AECOPD. However, we find PCT not so reliable in predicting bacterial infection in AECOPD due to sensitivity and specificity of less than 80 % and a low AUC value.

Chylothorax due to leukemic infiltration in a patient with chronic lymphocytic leukemia.

Chylothorax is characterized by accumalation of milky fluid called chyle into the plural space. Most common causes of cyhlothorax are trauma or surgery of thoracic duct and malignancies. Among the malignancies lymphoma is responsible approximately 70% of cyhlothorax but other lymphocytic tumors including chronic lymphocytic leukemia (CLL) is rarely reported. A 71 years old man with known CLL, presented with dispnea and pleural effusion and diagnosed cyhlothorax due to leukemic infiltration that confirmed by immuno flow cytometric analyse.