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Pathophysiology of Obstructive Sleep Apnoea/Hypopnoea Syndrome

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Pathophysiology of Obstructive Sleep Apnoea/Hypopnoea Syndrome 159 REVIEW SERIES Thorax: first published as 10.1136/thorax.2003.015859 on 3 February 2004. Downloaded from Sleep ? 2: Pathophysiology of obstructive sleep apnoea/hypopnoea syndrome R B Fogel, A Malhotra, D P White ............................................................................................................................... Thorax 2004;59:159–163. doi: 10.1136/thx.2003.015859 The pathogenesis of airway obstruction in patients with airway. When pharyngeal collapse does occur, it generally does so in the velopharynx (behind the obstructive sleep apnoea/hypopnoea syndrome is soft palate), the oropharynx (from the tip of the reviewed. The primary defect is probably an anatomically soft palate to the epiglottis), or both.45 small or collapsible pharyngeal airway, in combination The human pharynx can be modelled as a collapsible tube, the patency of which can be with a sleep induced fall in upper airway muscle activity. described using a ‘‘balance of pressures’’ con- ........................................................................... cept.26The size of the upper airway depends on the balance between those forces that would collapse the airway (such as negative intralum- bstructive sleep apnoea/hypopnoea syn- inal pressure and increased tissue (extraluminal) drome (OSAHS) is a common disorder pressure) and those that maintain airway which affects 2–4% of middle aged patency (contraction of pharyngeal dilator mus- O 1 cles, see below). The transmural pressure of the women and men in the United States. This disorder is characterised by recurrent sleep pharynx (Ptm) is thus equal to the pressure in the induced collapse of the pharyngeal airway2 lumen (Pl) minus the surrounding pressure in leading to hypoxaemia and hypercapnia, with the tissue (Pti), with the airway lumen becoming arousal from sleep being required to re-establish smaller as Ptm decreases. The change in area for a airway patency. While the pathophysiology of given change in pressure describes the effective this disorder remains incompletely understood, elastance of the pharynx. The Ptm at which the much progress has been made since the last area of the pharynx equals zero is the closing review of this topic was published in this pressure of the pharynx. A number of studies journal.3 We believe that most evidence supports have used this model of pharyngeal mechanics to the concept that patients with OSAHS have an look at differences in the mechanical properties anatomical predisposition to airway collapse. of the pharynx in normal controls and subjects with OSAHS, and generally report a higher (less However, during wakefulness, protective http://thorax.bmj.com/ mechanisms maintain the patency of the phar- negative or even positive) closing pressure in yngeal airway by increasing the activity of those with OSAHS. Schwartz and colleagues pharyngeal dilator muscles. These protective measured the critical closing pressure (Pcrit, mechanisms fail during sleep, with subsequent pressure at zero flow) during sleep in patients 7 8 collapse of the pharyngeal airway behind the with OSAHS and controls. These studies have palate, tongue, or both. In this review we shown that normal subjects typically have Pcrit consider the current state of knowledge regard- values below 28cmH2O while those with mild ing the pathogenesis of airway obstruction OSAHS/snoring have a slightly negative Pcrit in patients with OSAHS, emphasising those value and those with severe disease have a Pcrit on September 23, 2021 by guest. Protected copyright. theories that have the most experimental of .0. This again suggests an anatomically support. smaller airway in patients with apnoea that is more collapsible during sleep when muscle activity may be low. MECHANICS OF THE PHARYNX The pharyngeal airway is a complex structure (fig 1) whose functions include respiration, ANATOMY OF THE PHARYNX speech, and swallowing. Thus, the evolution of There is abundant evidence to suggest anatomi- the structure and function of the pharynx has cal differences in the pharyngeal airway between required ‘‘trade offs’’ between these competing patients with OSAHS and controls. functions. It is hypothesised that the evolution of Cephalometric x rays were among the earliest speech in man, which requires substantial techniques used to image the pharyngeal airway mobility of the larynx, led to the loss of rigid and showed that patients with OSAHS have a See end of article for support of the hyoid bone which is present in reduction in the length of the mandible, an authors’ affiliations most mammals. The human pharyngeal airway inferiorly positioned hyoid bone, and a retro- ....................... is therefore largely dependent on muscle activity position of the maxilla.9 Using more sophisti- Correspondence to: to maintain its patency. However, the depen- cated imaging techniques including CT scanning, Dr R B Fogel, Division of dence of individual subjects on this pharyngeal acoustic reflection and, most recently, MRI, a Sleep Medicine, Brigham dilator muscle activity is probably a product of number of investigators have shown that and Women’s Hospital, the intrinsic anatomy and collapsibility of their patients with apnoea have a smaller airway Harvard Medical School, airway. Individuals with an anatomically large lumen than controls.5 10–13 Studies by Schwab Boston, MA 02115, USA; [email protected] airway may be less dependent on muscles to et al have also indicated a number of soft tissue ....................... maintain airway patency than those with a small abnormalities in patients with apnoea including www.thoraxjnl.com 160 Fogel, Malhotra, White PHARYNGEAL MUSCLE FUNCTION AND THE EFFECT Thorax: first published as 10.1136/thorax.2003.015859 on 3 February 2004. Downloaded from OF SLEEP Although the muscles responsible for maintaining patency of Tensor palatini the upper airway and the mechanisms controlling their function are incompletely understood, certain generalisations Levator palatini Nasopharynx can be made. The muscles of primary importance fall into three groups: (1) muscles influencing hyoid bone position Genioglossus Velopharynx (geniohyoid, sternohyoid), (2) the muscle of the tongue (genioglossus), and (3) the muscles of the palate (tensor Epiglottis palatini, levator palatini). The activity of many of these Oropharynx muscles is increased during inspiration, thus stiffening and Genu of mandible dilating the upper airway and acting to counteract the collapsing influence of negative airway pressure.19 These are Geniohyoid Hypopharynx referred to as inspiratory phasic upper airway muscles, with the genioglossus being the one best studied. The activity of Hyoid bone these muscles is substantially reduced (although not elimi- nated) during expiration (tonic activation) when pressure Thyrohyoid inside the airway becomes positive and there is less tendency Thyroid cartilage for collapse. Other muscles such as the tensor palatini do not consistently have inspiratory phasic activity but, instead, maintain a relatively constant level of activity throughout the Figure 1 Anatomical representation of the upper airway and the respiratory cycle.20 These are called tonic or postural muscles important muscles controlling airway patency. In patients with apnoea, airway collapse typically occurs behind the palate (velopharynx), the and are also thought to play a role in the maintenance of tongue (oropharynx), or both. airway patency. These two types of pharyngeal muscles are probably controlled by groups of neurones within the brainstem that have different firing patterns relative to the respiratory cycle. an increase in the volume of the tongue, soft palate, The activity of the pharyngeal dilator muscles is carefully parapharyngeal fat pads, and the lateral walls surrounding controlled by a number of variables (fig 2). Firstly, motor the pharynx.13 In addition to a difference in size, a number of nuclei controlling these muscles receive input from central studies have shown a difference in airway shape, with respiratory pattern generating neurones located in the ventral apnoeic subjects having an airway with its long axis directed medulla. It is probably these neurones that lead to the anterior-posterior rather than laterally. Some have suggested previously described pattern of activation of the genioglossus that this airway orientation in patients with apnoea may (inspiratory phasic activation) as this muscle becomes active place pharyngeal dilator muscles at a relative mechanical before the onset of diaphragmatic contraction or inspiratory disadvantage, decreasing their ability to maintain pharyngeal airflow, thus ‘‘preparing’’ the upper airway for negative patency.14 Recent data also suggest that airway length may be pressure. Secondly, standard respiratory stimuli (rising PCO an important anatomical variable in determining patency. 2 and falling PO ) can augment the activity of these muscles, 2 http://thorax.bmj.com/ Sforza et al found that the distance between the hyoid bone probably working through the respiratory premotor neu- and the mandibular plane predicted collapsing pressure rones. Thirdly, as in other components of the respiratory 15 (Pcrit) in a group of men with OSAHS. Verin et al found system, a ‘‘wakefulness’’ drive to these muscles may exist this cephalometric variable to be the best predictor of upper and may well be mediated through the state sensitive 16 airway resistance in awake apnoea patients and controls. (decreased activity during sleep) neural systems discussed Data from our
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