Prediction of obstructive sleep apnea syndrome in a large Greek population.

PURPOSE: We aimed to evaluate the predictive value of anthropometric measurements and self-reported symptoms of obstructive sleep apnea syndrome (OSAS) in a large number of not yet diagnosed or treated patients. Commonly used clinical indices were used to derive a prediction formula that could identify patients at low and high risk for OSAS. METHODS: Two thousand six hundred ninety patients with suspected OSAS were enrolled. We obtained weight; height; neck, waist, and hip circumference; and a measure of subjective sleepiness (Epworth sleepiness scale--ESS) prior to diagnostic polysomnography. Excessive daytime sleepiness severity (EDS) was coded as follows: 0 for ESS ≤ 3 (normal), 1 for ESS score 4-9 (normal to mild sleepiness), 2 for score 10-16 (moderate to severe sleepiness), and 3 for score >16 (severe sleepiness). Multivariate linear and logistic regression analysis was used to identify independent predictors of apnea-hypopnea index (AHI) and derive a prediction formula. RESULTS: Neck circumference (NC) in centimeters, body mass index (BMI) in kilograms per square meter, sleepiness as a code indicating EDS severity, and gender as a constant were significant predictors for AHI. The derived formula was: AHIpred = NC × 0.84 + EDS × 7.78 + BMI × 0.91 - [8.2 × gender constant (1 or 2) + 37]. The probability that this equation predicts AHI greater than 15 correctly was 78%. CONCLUSIONS: Gender, BMI, NC, and sleepiness were significant clinical predictors of OSAS in Greek subjects. Such a prediction formula can play a role in prioritizing patients for PSG evaluation, diagnosis, and initiation of treatment.

C-reactive protein evolution in obstructive sleep apnoea patients under CPAP therapy.

BACKGROUND: C-reactive protein (CRP) is recognized as a potential factor implicated in atherogenesis and associated cardiovascular morbidity. The aim of our study was to assess the CRP evolution during 1-year follow-up period in obstructive sleep apnoea (OSA) patients under CPAP treatment. METHODS: Five hundred and twenty-eight patients with newly diagnosed moderate to severe OSA were included. CRP was assessed before CPAP initiation and at the 3rd, 6th and 12th month of the follow-up period. Patients were divided into good and poor CPAP compliance groups. RESULTS: A significant reduction in CRP levels was observed after CPAP therapy (0·74±0·62mgdL(-1) vs. 0·31±0·29mgdL(-1) , P<0·001) in the whole patient group. The evolution of CRP values showed a gradual decrease at 3months with a steep decline at 6months, reaching a plateau after this time point. When the patients were divided into those with good and poor compliance with CPAP therapy, the above CRP evolution pattern was observed only in the former group. CONCLUSION: Good CPAP compliance results in a significant CRP reduction. To achieve the best positive impact on cardiovascular morbidity and mortality, a time period of at least 6months of CPAP use is required.

Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients.

Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited. p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control. Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals. Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups. Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups. On the other hand, bcl2 expression did not differ between the two groups in all three cell types. The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients. Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD.

Biomarkers in COPD.

Chronic Obstructive Pulmonary Disease is characterized by an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking. Although COPD affects the lung, it also produces significant systemic consequences. Inflammation, proteases-antiproteases imbalance, oxidative stress, tissue damage and tissue repair, apoptosis and several genes seem to be involved in the pathogenesis of the disease. The cellular and molecular events underlying COPD pathogenesis are driven by multifunctional molecules including enzymes, cytokines, chemokines, growth factors, lipid mediators and their respective receptors. A large number of biomarkers evaluated in COPD, showed a high degree of redundancy. Nevertheless, current understanding of the pathobiology of COPD suggests a number of biomarkers as potential candidates. The development of relevant markers of lung damage, pulmonary inflammation, and systemic disease will be essential to our further understanding of the natural history of COPD and the discovery of new, effective treatments for its progression. This review summarizes recent findings, on potential pulmonary biomarkers in the induced sputum, the exhaled air condensate, the peripheral blood, the urine, the bronchoalveolar lavage fluid, and in selective cases, in bronchial biopsies.

Lymphangiogenesis in COPD: another link in the pathogenesis of the disease.

BACKGROUND: New lymphatic vessels are associated with tissue injury and repair. Recent studies have shown increased lymphatic follicles formation in the lungs of COPD patients. We hypothesized that lymphatic vascular remodeling could be part of COPD pathogenesis. AIM: To investigate the lymphangiogenetic process in COPD we measured the lymphatic microvessel density (LMVD), the lymphatic invasion (L.I), and their correlation with clinical and laboratory parameters. METHODS: Lung tissue from 20 COPD patients and 20 non-COPD smokers was immunohistochemically stained for D2-40 (lymphatic endothelial cell marker), and LYVE-1 (lymphatic endothelial hyaluronan receptor 1). Both groups had similar age and smoking history. RESULTS: D2-40 and LYVE-1 were expressed in all specimens. Lymphatic invasion was presented only in COPD specimens. Lymphatic microvessel density (LMVD) as revealed by D2-40 and LYVE-1 markers was statistically significantly higher in COPD patients when compared with non-COPD smokers. Both markers (D2-40, LYVE-1) were correlated with FEV1 (% pred) (R(2) = 0.415, R(2) = 0.605, respectively). CONCLUSIONS: We report for the first time high lymphatic microvessel density and lymphatic invasion in COPD patients, related to the degree of airway obstruction. Our findings could provide novel insights in the pathogenesis of the disease.

Altered surfactant protein-A expression in type II pneumocytes in COPD.

BACKGROUND: Pulmonary surfactant protein A (SP-A) is a lectin, with multiple functions that contribute to innate host defense and the regulation of the inflammatory process in the lung. In normal conditions, SP-A seems to protect against the effects of smoking. However, studies in smokers with or without COPD are limited. METHODS: Western blots on lung tissue specimens from 60 male subjects (32 patients with COPD, 18 smokers without COPD, and 10 control nonsmokers) for SP-A and the housekeeping protein actin were carried out. Additionally, the SP-A expression pattern was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same subjects. RESULTS: Western blots revealed significantly higher SP-A levels in control nonsmokers (4.8 +/- 0.05) when compared with patients with COPD (0.6 +/- 0.7) and smokers without COPD (2.4 +/- 0.9), (P < .05). However, differences that were not statistically significant were observed in SP-A levels among the patients with COPD and the smokers without COPD (P = .12). The immunohistochemical examinations showed an increase in the overall number of type II pneumocytes per high-power field in patients with COPD, but a decreased ratio of SP-A positive type II pneumocytes to total type II pneumocytes, compared with smokers without COPD (P = .001). This ratio was also correlated with FEV(1) (percent predicted [% pred]), (r = 0.490, P = .001). The overall number of alveolar macrophages per high-power field was significantly higher in patients with COPD compared with smokers without COPD (P = .001). The ratio of SP-A positive alveolar macrophages was increased in patients with COPD when compared with smokers without COPD (P = .002), while this was correlated with airway obstruction (FEV(1), % pred) (r = 0.281, P = .04). CONCLUSIONS: Our results indicate that altered SP-A expression could be another link to COPD pathogenesis and highlights the need for further studies on surfactant markers in COPD.