Endothelial Dysfunction and Oxidative Stress in Children With Sleep Disordered Breathing.

Sleep disordered breathing (SDB) is a spectrum of diseases ranging from primary snoring to obstructive sleep apnoea (OSA). Recent studies suggested that the prevalence of SDB childhood was 7.4%. In patients with OSA, there are intermittent episodes of complete or partial obstruction leading to intermittent desaturations and/or arousals. This would result in either stimulation of sympathetic system or suppression of the vagal tone that may persist beyond sleep. The disturbance of the autonomic nervous system would result in significant changes in the cardiovascular system. The process of intermittent hypoxaemia and subsequent re-oxygenation also damages the endothelium because of the generation of free radicals. Furthermore, the excessive negative intra-thoracic pressure swing generated during the obstruction would also affect cardiac functions. In adults, OSA has been well documented to be associated with cardiovascular abnormalities such as hypertension, ischaemic heart disease, arrhythmia and heart failure.

Oxidative stress plays a crucial role in the initiation and progression of atherosclerosis. In particular, an imbalance between superoxide and nitric oxide production could be responsible for endothelial dysfunction, a key point for atherosclerotic process. Several oxidative stress-generating enzymes, including myeloperoxidase, xanthine oxidase and nicotinamide adenine dinucleotide phosphate (NADPH) may be implicated in arterial dysfunction; NADPH oxidase represents, in human, the most important source of cellular superoxide anion production. Experimental studies performed in animal models suggest a pivotal role of NADPH oxidase in modulating arterial tone. In particular, overexpression of gp91phox (NOX2), potentiates the hemodynamic response to angiotensin II. Furthermore, individuals with impaired dilation show an overexpression of the NADPH oxidase subunit p47phox in endothelial cells.

Previously, we demonstrated that endothelial dysfunction is directly related to NADPH oxidase activation; in particular we demonstrated that in patients with NADPH oxidase subunits deletion, as chronic granulomatous disease, the oxidative stress is lower and flow-mediate dilation is higher, compared to controls. Conversely, in other diseases characterized by high rate of cardiovascular events (OSAS, Peripheral arterial disease, metabolic syndrome, obesity and hypercholesterolemia), we found an endothelial dysfunction and a NOX2 overexpression.

Recently, we assessed the association between OSAS, endothelial dysfunction and oxidative stress in adults. Interestingly, the results of our study indicated that patients with OSAS have increased NOX2-generated oxidative stress and arterial dysfunction that are partially reversed by nasal continuous positive airway pressure (nCPAP) treatment.

There is evidence in literature that cardiovascular morbidities associated with SDB are potentially reversible in children; AT may have a significant role in reversing the cardiovascular sequelae of SDB (e.g. children affected by OSA).