Moving beyond an empiric trial to using combined physiology and anatomy to predict success of oral appliances in obstructive sleep apnoea

D. Rapoport
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引用次数: 2

Abstract

Both diagnosis and severity of obstructive sleep apnoea (OSA) have traditionally been assessed through the apnoea–hypopnoea index, a simple count of how often obstruction occurs. However, it is now widely accepted that this metric performs poorly in predicting the success of various non-continuous positive airway pressure (CPAP) therapies; the rate of obstructive events appears to be insensitive to the cause(s) of obstruction in a particular patient. This failure has led several groups to propose that an interaction of multiple pathophysiological factors underlie OSA and that specific therapies may work best in a subset of patients. The ‘holy grail’ has been to define such subsets using this ‘phenotypic’ approach. The problem is exemplified by response to oral appliances, as there is a substantial failure rate in unselected patients. As the time to titration is often prolonged and cost of an empiric therapeutic trial is non-trivial because of needing multiple titration visits and sleep studies, it would be advantageous to be able to select patients with a higher than average success rate. The simplest, but so far unsuccessful, approach to estimating the chance of success has been to use clinical, polysomnographic (PSG) and/or anthropomorphic measures of the patient at baseline. This assumes that anatomy drives OSA and that a relatively linear relation exists between external features, e.g. body mass index, neck size and awake visual assessment of the upper airway, and the causes of obstruction. The lack of success of these predictions in most published trials supports a competing assumption that sleep, airway mechanics and neural reflexes are as important as anatomy, and that their relative contribution is not evident without explicit testing. In this issue of The Journal of Physiology, Marques and colleagues test one such approach (Marques et al. 2019). Previous evidence, quoted by the authors, suggests that tongue position and measurement of collapsibility of the airway may individually modestly predict success of oral appliances, but their combined value has not been explored. In recent years, research techniques have been developed to assess the ‘phenotype’ of a given patient’s OSA. This is variably defined, and a recent trend is to focus on combinations of physiological ‘traits’ to define such a ‘phenotype’. Because the tools to measure the traits that contribute to the pathophysiology of obstruction require methodologies that are difficult and not suited to the clinical PSG environment, surrogates of the major components (anatomy, airway collapsibility or Pcrit, upper airway responsiveness and loop gain) are also being developed and tested for their ability to predict clinical outcomes. In their study Marques and colleagues test the utility of tongue position and Pcrit individually to predict the outcome of oral appliance therapy using state of the art techniques (sleep endoscopy and determination of Pcrit using CPAP drops). More importantly than the individual utility of these traits, they show that when combined in a prediction equation, an accuracy of 19/22 cases was achieved, with high positive and negative predictive value. If confirmed, this implies that it is possible to select patients prior to trying the therapy and predict success and failure of an oral appliance. However, as they themselves point out, the tools used – sleep endoscopy to define the role of the tongue in obstruction, and Pcrit determination using CPAP drops during a sleep study – are invasive, expensive and not well suited to clinical use. It remains to be tested if, as the authors suggest, non-invasive surrogates of these determinations, that are becoming available, will be equally predictive. The major contribution of this paper is the demonstration that it is possible to predict success of therapy from pre-therapy physiology, and thus there is reinforcement for trying to simplify the testing. Clinicians should anxiously await the follow-up data showing that parameters from the clinical PSG or other readily available clinical tests can perform equally well.
从经验性试验到结合生理学和解剖学来预测口腔器械在阻塞性睡眠呼吸暂停中的成功
阻塞性睡眠呼吸暂停(OSA)的诊断和严重程度传统上都是通过呼吸暂停-低通气指数来评估的,这是一种简单的阻塞发生频率计数。然而,现在被广泛接受的是,该指标在预测各种非持续气道正压(CPAP)治疗的成功方面表现不佳;在一个特定的病人中,梗阻事件的发生率似乎对梗阻的原因不敏感。这一失败导致一些研究小组提出,多种病理生理因素的相互作用是OSA的基础,特定的治疗方法可能对一部分患者最有效。“圣杯”一直是使用这种“表型”方法来定义这些子集。这个问题体现在对口腔器械的反应上,因为在未选择的患者中有很大的失败率。由于滴定的时间通常会延长,而且经验性治疗试验的成本不菲,因为需要多次滴定访问和睡眠研究,因此能够选择成功率高于平均水平的患者将是有利的。估计成功几率的最简单方法是使用临床、多导睡眠图(PSG)和/或基线患者的拟人化测量。这假设解剖驱动OSA,并且外部特征(如体重指数、颈部大小和上呼吸道清醒时的视觉评估)与阻塞原因之间存在相对线性的关系。在大多数已发表的试验中,这些预测都没有成功,这支持了一种与之相反的假设,即睡眠、气道力学和神经反射与解剖学一样重要,如果没有明确的测试,它们的相对贡献是不明显的。在本期的《生理学杂志》上,Marques及其同事测试了一种这样的方法(Marques et al. 2019)。作者引用的先前证据表明,舌头位置和气道可折叠性的测量可以单独适度地预测口腔矫形器的成功,但它们的综合价值尚未得到探讨。近年来,研究技术已经发展到评估特定患者的OSA的“表型”。这是可变的定义,最近的趋势是关注生理“特征”的组合来定义这种“表型”。由于测量导致梗阻病理生理特征的工具需要的方法困难且不适合临床PSG环境,因此也正在开发和测试主要组成部分(解剖学,气道可折叠性或Pcrit,上呼吸道反应性和环路增加)的替代品,以预测临床结果。在他们的研究中,Marques和同事分别测试了舌头位置和Pcrit的效用,以预测使用最先进技术(睡眠内窥镜和使用CPAP滴剂测定Pcrit)的口腔器械治疗的结果。比这些特征的个人效用更重要的是,它们表明,当组合在一个预测方程中时,达到了19/22的准确率,具有很高的正负预测值。如果得到证实,这意味着有可能在尝试治疗之前选择患者并预测口腔矫治器的成功和失败。然而,正如他们自己指出的那样,所使用的工具——睡眠内窥镜来确定舌头在阻塞中的作用,以及在睡眠研究中使用CPAP滴液来确定Pcrit——是侵入性的,昂贵的,不太适合临床使用。正如作者所建议的那样,这些检测方法的非侵入性替代方法是否同样具有预测性,还有待检验。本文的主要贡献是证明了从治疗前生理学预测治疗的成功是可能的,因此有了试图简化测试的强化。临床医生应该焦急地等待随访数据,表明临床PSG或其他现成的临床测试的参数也能表现良好。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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