Sclerostin in Obstructive Sleep Apnea.

Sclerostin, a glycoprotein involved in vascular calcification, could play a role in cardiovascular disorders. Obstructive sleep apnea (OSA) is frequently associated with cardiovascular comorbidities. Thus, in this study we set out to assess the level of sclerostin in patients with OSA. Sclerostin was evaluated in the serum by ELISA method in 106 patients (43 women) with OSA of the mean age of 55 ± 10 years, BMI of 33.1 ± 7.9 kg/m(2), and apnea/hypopnea index (AHI) of 29.7 ± 18.9. There were 76 (72 %) patients with cardiovascular comorbidities in the OSA group. The results were compared with those in 49 healthy control subjects. We found that the level of sclerostin was higher in the female OSA patients than that in female controls (80.1 ± 36.5 pg/ml vs. 61.4 ± 24.1 pg/ml; p < 0.05) and it correlated with AHI (rs = 0.32, p < 0.01) and desaturation index (rs = 0.34, p < 0.01). Further, in OSA women with cardiovascular comorbidities, sclerostin was higher than in women without such comorbidities (87.0 ± 37.4 pg/ml vs. 57.3 ± 22.1 pg/ml; p < 0.05). In men, there were no differences in the serum sclerostin level between the OSA and control subjects, nor was there any relationship with cardiovascular diseases. In conclusion, increased serum sclerostin coincides with the severity of OSA and its cardiovascular sequelae in female patients.

Correlations between osteoprotegerin serum levels and body composition parameters in patients with sleep apnea syndrome and the possible influence on cardiovascular risk.

INTRODUCTION: Osteoprotegerin (OPG) is a member of the tumor necrosis factor family and a key regulator in bone turnover; it plays a role in the development of many cardiovascular diseases and may be treated as a marker of vascular damage. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition. The aim of the study was to evaluate correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk. MATERIAL AND METHODS: A total of 125 patients with newly diagnosed OSA were enrolled in the study (including 34 females). The mean age was 54.48±8.81 years, mean AHI 33.16±20.44/h and mean BMI 33.76±7.18. A control group comprised 59 healthy subjects with mean age of 51.27±12.97 years and mean BMI 29.47±5.42. All subjects underwent a nocturnal respiratory polygraphy and body composition measurements were taken with bioelectrical impedance analysis. OPG serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: In OSA patients OPG correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while there was a positive correlation between osteoprotegerin and fat mass percentage (FM%). We demonstrated higher OPG serum levels in OSA patients with cardiovascular diseases than in those without comorbidities (4.01 vs 3.46pmol/l, p<0.05). CONCLUSION: Our findings, combined with previous observations in other diseases, suggest that elevated OPG serum levels together with selected body composition parameters may be helpful in identifying OSA patients with increased cardiovascular risk.

Comparative Expression of Apoptotic Markers in Lung Adenocarcinoma and Squamous Cell Carcinoma.

Lung cancer is still an oncology challenge. A 5-year survival reaches less than 20 % of patients. Apoptosis disturbances are a key step in cancer development. The evaluation of apoptosis markers has a great potential in lung cancer. The goal of our study was a comparative evaluation of apoptosis regulators: p53, Bcl-2, Bax, COX-2, and survivin in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). We also evaluated the relationship between apoptosis markers and clinicopathological parameters. Fifty six patients with non-small cell lung cancer (NSCLC) were included into the study (20 women and 36 men). AC was diagnosed in 30 and SCC in 26 cases. The evaluation of markers was performed using an immunohistochemical method on paraffin embedded tissue specimens. We used monoclonal antibodies for p53, bcl-2, and COX2-proteins (clone DO7, bcl-2/100/D5, and 4H12, respectively), Bax (B-9 clone) and survivin (clone 12C4). The results of immunostaining were viewed by light microscopy. We revealed significantly more frequent expression of Bax and survivin in lung AC than SCC (p < 0.01 and p < 0.019). Bcl-2 immunoreactivity was seen more often in AC without lymph node metastases than with metastases (p = 0.046). There was no correlation between the apoptosis markers and gender or the presence of vessel emboli. A greater variability in markers expression was seen in lung AC than SCC. There were significant differences in the Bax and survivin expression in the two major pathological types of NSCLC. We did not revealed any correlation between the markers and TNM characteristics, accept for Bcl-2 presence along with the lymph node involvement in the AC group.

Soluble ligand CD40 and uric acid as markers of atheromatosis in patients with obstructive sleep apnea.

The aim of the study was to evaluate the risk of atheromatosis in patients with obstructive sleep apnea (OSA), as based on the concentration of the pro-atherogenic soluble CD40L ligand (sCD40L) in relation to the level of uric acid. The serum levels of sCD40L and uric acid were measured in 79 OSA patients (mean apnea/hypopnea index - AHI 34.4 ± 20.9) and in 40 healthy controls. We found that sCD40L was higher in the OSA patients with hyperuricemia than that in the patients with uric acid in the normal range (sCD40L: 9.0 ng/ml vs. 8.0 ng/ml, respectively, p < 0.05). There was a positive association of sCD40L with AHI (p = 0.01) and a negative one with the mean minimal nocturnal SaO2(p < 0.05). Uric acid correlated negatively with the mean and minimal SaO2and positively with the oxygen desaturation index (p < 0.05). OSA patients with hyperuricemia also had a higher prevalence of hypertension and ischemic heart disease. We conclude that OSA patients with increased uric acid concentration have increased risk of atheromatosis, as indicated by a higher level of soluble pro-atherogenic ligand CD40, and a higher prevalence of cardiovascular adverse events.

Efficacy of noninvasive volume targeted ventilation in patients with chronic respiratory failure due to kyphoscoliosis.

Severe kyphoscoliosis can cause chronic respiratory failure. Noninvasive mechanical ventilation (NIMV) is a new optional treatment for such patients. The aim of this study was to evaluate the effectiveness of average volume-assured pressure support (AVAPS) NIMV in patients with kyphoscoliotic chronic respiratory failure. The study was performed in 12 patients (mean age 49±11 years and body mass index 27.5±7.9 kg/m2) with advanced kyphoscoliosis complicated by severe respiratory failure (PaO2 6.68±0.34 kPa, SaO2 81.7±3.1%, PaCO2 9.51±1.08 kPa) treated by the NIMV. The short-term, after 5 days, and long-term, after 1 year of home treatment, efficacy of NIMV was evaluated. We found a significant improvement of diurnal PaO2 and PaCO2 on the 5th day of NIMV (an increase of 1.4±0.3 kPa and a decrease of 1.8±0.8 kPa, respectively; p<0.05) and after one year NIMV (an increase of 2.07±0.46 kPa and a decrease of 2.68±0.85 kPa, respectively; p<0.05). There was a significant increase of mean blood oxygen saturation during sleep on the 5th day (86.2±3.2%) and after 1 year of treatment (89.4±2.1%) compared with the baseline level (83.2±3.2%). The forced vital capacity also increased after 1 year (1,024±258 ml vs. the baseline 908±267 ml; p<0.05). The NIMV was well tolerated and no patient discontinued the treatment during the observation period. We conclude that AVAPS NIMV is an effective treatment option in kyphoscoliotic patients with chronic respiratory failure, resulting in a prompt and long-term improvement of daytime and nocturnal blood gas exchange.

Efficacy of noninvasive mechanical ventilation in obese patients with chronic respiratory failure.

Chronic respiratory failure (CRF) develops in a minority of obese patients. Noninvasive mechanical ventilation (NIMV) is a new optional treatment for such patients. The aim of this study was to evaluate the effectiveness of NIMV in obese patients with CRF. The material of the study consisted of 34 obese patients (body mass index 47.3 ± 7.9 kg/m(2)) with CRF (PaO2 = 6.40 ± 0.93 kPa and PaCO2 = 8.67 ± 2.13 kPa) who were hypoxemic despite an optimal therapy. Thirteen patients had an overlap syndrome (OS) - chronic obstructive pulmonary disease (COPD) coexisting with obstructive sleep apnea syndrome (OSAS) and 21 patients had obesity-hypoventilation syndrome (OHS). Ventilation parameters were determined during polysomnography. The efficacy of NIMV was evaluated on the fifth day and after 1 year's home treatment. We observed a significant increase in the mean blood oxygen saturation during sleep in all patients; the increase was greater in patients with OHS (92.6 ± 1.4 %) than in patients with OS (90.4 ± 1.8 %). There was a significant improvement of diurnal PaO2 and PaCO2 on the fifth day of NIMV (mean PaO2 increase 2.1 kPa and PaCO2 decrease 0.9 kPa) and also after 1 year of home NIMV (mean PaO2 increase 1.9 kPa and PaCO2 decrease 2.4 kPa). Only one patient stopped treatment because of lack of tolerance during the observation period (1-3 years). In conclusion, NIMV is an effective and well tolerated treatment option in obese patients with CRF resulting in a rapid relief of respiratory disorders during sleep and a gradual, long-term improvement of gas exchange during the day, particularly in patients with OHS.