Upper airway dysfunction following chronic intermittent hypoxia - implications for the pathophysiology of sleep-disordered breathing

Interrupted breathing is common during sleep in normal individuals but is severe in those suffering from the obstructive sleep apnoea syndrome (OSAS). OSAS is a severe form of sleep-disordered breathing characterized by intermittent hypoxia/reoxygenation due to recurrent apnoea during sleep. There is evidence to suggest that intermittent hypoxia (IH) alters the respiratory control system at multiple levels. Potentially 'adaptive' and 'maladaptive' effects of IH on respiratory control have been described. In this chapter, we examine the evidence that chronic intermittent hypoxia (CIH) has adverse effects on respiratory muscle structure and function and cranial motor control of the upper airway. Several groups have now demonstrated that CIH increases upper airway muscle fatigue. Furthermore, long-term exposure to IH impairs upper airway motor control and increases airway collapsibility. From these studies, it is concluded that CIH triggers a vicious cycle of respiratory muscle dysfunction and impaired respiratory homeostasis and as such is implicated in the pathophysiology of OSAS. Studies aimed at identifying the underlying mechanism(s) and strategies designed to interrupt or break the cycle of IH-induced respiratory impairment will have important implications for the treatment of patients with OSAS. In this regard, oxidative and nitrosative stress are likely culprits in the development of key morbidities in OSAS and animal models of the disorder. Encouragingly, in animal models of sleep apnoea, antioxidant treatments are effective in blocking or ameliorating the deleterious effects of IH on the respiratory control system. Therefore, might antioxidant therapies yet prove effective as adjunct treatments in OSAS? These and future studies employing preventative strategies may have significant implications for therapies in patients with OSAS