Biomarkers of the L-Arginine/Dimethylarginine/Nitric Oxide Pathway in People with Chronic Airflow Obstruction and Obstructive Sleep Apnoea.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are common chronic diseases that are associated with chronic and intermittent hypoxemia, respectively. Patients affected by the overlap of COPD and OSA have a particularly unfavourable prognosis. The L-arginine/nitric oxide (NO) pathway plays an important role in regulating pulmonary vascular function. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) interfere with NO production. METHODS: We analysed the serum concentrations of ADMA, SDMA, L-arginine, L-citrulline, and L-ornithine in a large sample of the Icelandic general population together with chronic airflow obstruction (CAO), a key physiological marker of COPD that was assessed by post-bronchodilator spirometry (FEV1/FVC < LLN). OSA risk was determined by the multivariable apnoea prediction (MAP) index. RESULTS: 713 individuals were analysed, of whom 78 (10.9%) showed CAO and 215 (30%) had MAP > 0.5. SDMA was significantly higher in individuals with CAO (0.518 [0.461-0.616] vs. 0.494 [0.441-0.565] µmol/L; p = 0.005), but ADMA was not. However, ADMA was significantly associated with decreasing FEV1 percent predicted among those with CAO (p = 0.002). ADMA was 0.50 (0.44-0.56) µmol/L in MAP ≤ 0.5 versus 0.52 (0.46-0.58) µmol/L in MAP > 0.5 (p = 0.008). SDMA was 0.49 (0.44-0.56) µmol/L versus 0.51 (0.46-0.60) µmol/L, respectively (p = 0.004). The highest values for ADMA and SDMA were observed in individuals with overlap of CAO and MAP > 0.5, which was accompanied by lower L-citrulline levels. CONCLUSIONS: The plasma concentrations of ADMA and SDMA are elevated in COPD patients with concomitant intermittent hypoxaemia. This may account for impaired pulmonary NO production, enhanced pulmonary vasoconstriction, and disease progression.

A critical analysis of the purported role of hypoxaemia in the comorbidity of obstructive sleep apnoea and epilepsy.

Obstructive sleep apnoea (OSA) is a globally prevalent sleep disorder of significant health concern and confounded with several comorbidities resulting in adverse effect(s) on quality of life in patients afflicted with it. Of particular interest is the enigmatic high comorbidity of OSA with epilepsy, the exact underlying pathophysiology of which remains elusive despite a multitude of research performed in the last four decades. Hypoxaemia, which is an important characteristic feature found in OSA during apnoeic spells, has been implicated in the high comorbidity of OSA with epilepsy, the basis of which rests upon hypoxaemia-mediated brain damage, subcortical release phenomenon, oxidative stress and neuroinflammatory reactions. However, several studies present contradictory evidences that potentially refute the hypoxaemia-based mechanism. Additionally, the role of hypercapnia thatgenerally accompanies hypoxaemia during apnoeic spells, cannot be overlooked and is known to be potentially protective against neuronal hyperexcitability. Thus, hypoxaemia theory implicated in the high comorbidity of OSA and epilepsy appears weak and refutable. This brief paper studies and critically analyses the role of hypoxaemia in conjunction with hypercapnia in the underlying pathophysiology of the comorbidity.

Obstructive sleep apnoea: from respiratory events to coronary microvascular dysfunction.

Obstructive sleep apnoea (OSA) is an emerging and independent risk factor for cardiovascular diseases; coronary artery disease (CAD) is higher in OSA patients, even in the absence of other traditional cardiovascular risk factors. There is little evidence to show abnormalities in coronary blood flow (CBF) and disorders in coronary vascular resistance (CVR), occurring during the obstructive respiratory event, suggesting coronary microvascular dysfunction (CMD) as a potential mechanism of ischaemic heart disease (IHD) OSA-as a related consequence.

Is obstructive sleep apnoea syndrome really one of the causes of secondary polycythaemia?

BACKGROUND: It is widely believed that sleep apnoea syndrome leads to polycythaemia, but the evidence is largely anecdotal. We believe that polycythaemia is not commonly seen in patients with sleep apnoea syndrome. Therefore, we aimed to determine the relationship between polycythaemia and sleep apnoea syndrome. METHODS: The study included 335 patients diagnosed with obstructive sleep apnoea (OSA) syndrome, all of whom underwent standard nocturnal polysomnography. RESULTS: There were no significant differences in haemoglobin levels or haematocrit (P > 0.05) between the OSA groups in all patients. Of the 335 patients, only 1 male patient with severe OSA (0.3%) had clinically significant polycythaemia. According to regression analysis, there was a weak linear correlation between haemoglobin levels and lowest oxygen saturation levels in female patients (r = -0.242, P = 0.021). CONCLUSION: We think that OSA is very rarely the reason for secondary polycythaemia.

Nocturnal stem cell mobilization in patients with obstructive sleep apnoea: a pilot study.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) experience repetitive cessation of breathing during sleep, leading to intermittent hypoxaemia, excessive oxidative stress and systemic inflammation. These insults may damage the vasculature and provoke the corresponding repair response, such as stem cell mobilization to peripheral blood. This study aimed to investigate nocturnal mobilization of stem cells in OSA. METHODS: Thirty-five patients with OSA and thirteen healthy controls were enrolled. Polysomnography was performed, and severity of OSA was defined by apnoea-hypopnoea index (AHI). Peripheral venous blood was drawn after and before sleep for measurement of CD34+ cell and SDF-1α level. Stem cell mobilization was gauged by ratios of the CD34+ level in the morning to that at night or by their difference. Correlation analysis was performed to identify factors related to stem cell mobilization. RESULTS: Compared to controls, the nocturnal ratios and difference of CD34+ cell levels were larger in patients with OSA (ratios: 1·141 vs. 0·896, P = 0·036; difference: 340 vs. -166/cc blood, P = 0·036), suggestive of stem cell mobilization. The mobilization ratios were related to AHI, body mass index (BMI), SpO2 nadir, oxygen desaturation index and time sustaining hypoxaemia. After adjusting age, gender and BMI, AHI (r = 0·357, P = 0·016) and hypoxaemia-related parameter remained significant. Paired nocturnal differences in CD34+ cell count (P = 0·009) and SDF-1α (P = 0·001) were also significant in patients with OSA, but not in controls. After CPAP therapy for 6 months, the elevated mobilization ratios in patients with OSA tended to decline (P = 0·059). CONCLUSION: CD34+ stem cell mobilization during sleep was observed in OSA.