Roflumilast, a phosphodiesterase-4 inhibitor, induces phagocytic activity in Greek COPD patients.

BACKGROUND: A new approach to the treatment of COPD includes controlling inflammation because of its important role in exacerbation of the disease. Recently, roflumilast has been added as a therapeutic option for COPD. Roflumilast is an oral phosphodiesterase-4 inhibitor that targets inflammatory cells involved in triggering exacerbations of COPD. The objective of the current study was to evaluate roflumilast for its contribution to phagocytic activity in COPD patients. METHODS: Twenty-one patients diagnosed with COPD received roflumilast once daily for 6 months in combination with fluticasone (an inhaled corticosteroid), salmeterol (a long-acting ß2-agonist), and tiotropium (a long-acting muscarinic antagonist) or combinations of these agents. The main inclusion criterion was stable disease for at least the previous 30 days. Neutrophils and spirometric changes, ie, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were measured in the COPD patients at indicated time points. The first sample was taken before receiving roflumilast, the second 3 months later, and the third after 6 months. Examination of defective phagocytosis was done by flow cytometry using a FagoFlowEx(®) kit. The statistical analysis was performed using Statistica software. RESULTS: Our results indicate that phagocytic activity was increased after 3 and 6 months of treatment when compared with baseline (P<0.001). Similarly, FVC and FEV1 were also increased during the 6-month period, but only FVC differed significantly from baseline (P<0.001). CONCLUSION: Although the number of patients in this study was limited, our results indicate that roflumilast induces phagocytic activity, which improves lung function.

Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment.

BACKGROUND AND AIM: Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels. MATERIALS AND METHODS: Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use. RESULTS: At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 µg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001). CONCLUSION: In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy.

Inflammatory markers in middle-aged obese subjects: does obstructive sleep apnea syndrome play a role?

BACKGROUND: Obstructive Sleep Apnea Syndrome (OSAS) is associated with inflammation, but obesity may be a confounding factor. Thus, the aim of this study was to explore differences in serum levels of inflammation markers between obese individuals with or without OSAS. METHODS: Healthy individuals (n = 61) from an outpatient obesity clinic were examined by polysomnography and blood analysis, for measurement of TNF-alpha, IL-6, CRP, and fibrinogen levels. According to Apnea-Hypopnea Index (AHI), participants were divided into two BMI-matched groups: controls (AHI < 15/h, n = 23) and OSAS patients (AHI > or = 15/h, n = 38). RESULTS: OSAS patients had significantly higher TNF-alpha levels (P < .001) while no other difference in the examined inflammation markers was recorded between groups. Overall, TNF-alpha levels were correlated with neck circumference (P < .001), AHI (P = .002), and Oxygen Desaturation Index (P = .002). CONCLUSIONS: Obese OSAS patients have elevated TNF-alpha levels compared to BMI-matched controls, suggesting a role of OSAS in promoting inflammation, possibly mediated by TNF-a.

Reduction of serum retinol-binding protein-4 levels in nondiabetic obstructive sleep apnea patients under continuous positive airway pressure treatment.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with impaired glucose metabolism and insulin resistance. Retinol-binding protein-4 (RBP-4) is an adipokine, hypothesized to induce insulin resistance. OBJECTIVES: The aim of the study was to explore the association between serum RBP-4 levels and OSAS severity in nondiabetic, adherent to therapy OSAS patients and to investigate the role of continuous positive airway pressure (CPAP) in the alteration of RBP-4 levels. METHODS: OSAS patients (n = 62) without comorbidities or medication use were included. Fasting RBP-4, glucose and insulin levels, HbA(1c), homeostatic model assessment of insulin resistance index and lipid profile were measured at baseline and after 6 months of CPAP use. Patients were divided into group A (with fasting glucose levels <110 mg/dl, n = 47), and group B (with impaired fasting glucose (IFG), i.e. fasting glucose levels ≥110 mg/dl, n = 15). RESULTS: RBP-4 levels were not associated with apnea-related indices, anthropometric characteristics or markers of glycemic control, insulin resistance or lipid profile. In group A (but not in group B), a significant reduction was observed in RBP-4 (p = 0.046), HbA(1c) (p = 0.005), LDL cholesterol (p = 0.034), and high-sensitivity C-reactive protein (hs-CRP, p = 0.033) levels after 6 months of CPAP use. CONCLUSIONS: RBP-4 levels were not correlated with sleep, anthropometric characteristics, markers of glycemic control and insulin sensitivity. OSAS patients without IFG respond well to CPAP use as evidenced by the significant reduction in RBP-4, HbA(1c) and, additionally, hs-CRP and LDL- cholesterol levels. This treatment effect is not observed in patients with IFG.

Long-term effect of continuous positive airway pressure therapy on inflammation markers of patients with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Several lines of evidence suggest immune system derangement in obstructive sleep apnea syndrome (OSAS) patients. However, no data exist on the long-term effect of continuous positive airway pressure (CPAP) treatment on systemic immunity. Hence, we sought to evaluate this effect on various immunological parameters in OSAS patients. DESIGN: Prospective case series. SETTING: Sleep unit of a general hospital. PATIENTS: Newly-diagnosed, nonsmoking, otherwise healthy OSAS male patients (n = 52) were evaluated on diagnosis and 6 months after CPAP treatment. According to compliance to CPAP use at 6-month follow-up, they were divided into 2 groups: group A (n = 32): good compliance (mean CPAP use > or = 4 h/night); and group B (n = 20): poor compliance (mean CPAP use < 4 h/night). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Blood samples were obtained at baseline and at the 6-month follow-up. Percentage and absolute count of lymphocyte subsets (by flow cytometry), serum TNF-alpha, IL-6, and uric acid levels were measured. No differences were recorded regarding the baseline anthropometric or sleep characteristics of the 2 groups. In group A, a significant decrease in the absolute count of total lymphocytes (P = 0.003), and of CD4+ cells (P = 0.001), and a decrease in TNF-alpha levels (P = 0.001) and uric acid levels (P < 0.001) was observed after CPAP application. On the contrary, no alterations occurred in any of the tested parameters in group B patients. CONCLUSIONS: The selective reduction of soluble and cellular immune response factors only in those OSAS patients who exhibited good compliance to CPAP therapy provides further evidence for an ongoing systemic immune process in OSAS.

Endothelial function markers in parkinsonian patients with hyperhomocysteinemia.

Hyperhomocysteinemia is considered a risk factor for vascular disease causing endothelial damage and consequently atherogenesis. The purpose of this study was to investigate the effect of elevated homocysteine on certain biochemical markers of endothelial function in patients with idiopathic Parkinson's disease (PD). Blood homocysteine levels were assessed in 57 PD patients and 40 matched normal controls. Investigation of the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) genotype was also performed in 43 PD patients. The following markers of endothelial function were assessed: superoxide dismutase (SOD), nitric oxide (NO), sICAM-1 and sE-selectin. Homocysteine levels were found mildly elevated in PD patients particularly in those treated with L-Dopa. MTHFR genotype did not influence significantly this finding. SOD activity was found reduced but it was not correlated to homocysteine levels. All other parameters measured were normal and were not related to hyperhomocysteinemia. Our findings indicate that mild hyperhomocysteinemia in PD patients was not associated with endothelial dysfunction.