The human upper airway: more than a floppy tube.

THE MULTIFUNCTIONAL UPPER AIRWAY, its mechanical properties, and the muscles that control its shape and size are complex (Fig. 1). As highlighted by Fregosi and Ludlow (7) in their mini-review on activation of upper airway muscles during breathing and swallowing, precise coordination of the upper airway is essential for efficient swallowing. Sleep and the supine posture place additional demands on it, especially in humans. Reductions in neural drive to the upper airway dilator muscles promote upper airway narrowing and closure [i.e., obstructive sleep apnea (OSA)]. However, major gaps in the physiological understanding of upper airway control and function remain. This series of mini-reviews on upper airway control and function comprises five reviews on upper airway neurophysiological control, biomechanical properties of the upper airway, and the potential role of arousal and electrical stimulation in the pathophysiology and treatment of OSA (1, 6, 7, 9, 13). These articles cover key recent findings and unresolved aspects of upper airway physiology and the potential for much needed new therapies to treat OSA. Upper airway anatomy and neuromuscular control in quadrupeds and bipeds is unique (7, 12). Genioglossus, the largest extrinsic tongue muscle, is the most extensively studied upper airway muscle, yet the tongue is comprised of four intrinsic and four extrinsic muscles (7). Ultimately, many factors influence neural control and the mechanical properties of the upper airway. These factors alter upper airway size, shape, and dynamic function (see Fig. 1). At sleep onset and during rapid-eye-movement (REM) sleep, particularly when active eye movements are present, there is a profound loss of drive to the upper airway muscles. Not surprisingly, upper airway closure is common during these periods. As discussed in the mini-review on state-dependent and reflex drives to the upper airway (9), recent work by Horner and others has provided insight into the mechanisms mediating genioglossus muscle inhibition during REM sleep, the source of inspiratory drive to hypoglossal motoneurons, and the possibility that motor suppression in sleep and drug-induced sedation share common neural pathways and cellular mechanisms. Approximately one-third of OSA patients generate minimal or no neural activation of genioglossus during non-REM sleep in response to experimentally induced apneas and hypopneas (5, 6). One therapeutic approach to overcome major reductions Address for reprint requests and other correspondence: D. Eckert, Neuroscience Research Australia (NeuRA), PO Box 1165, Randwick, Sydney NSW, Australia 2031 (e-mail: [email protected]).