Auto-PEEP to treat obstructive sleep apnea.

In this issue of the Journal of Clinical Sleep Medicine, Rosenthal et al.1 describe the results of a study assessing the ability of nasal expiratory resistors (PROVENT™) to reduce sleep disordered breathing in a group of OSA patients with a relatively wide range of apnea severity. A study such as this raises a number of fundamental questions: First: How do expiratory nasal resistors improve sleep apnea? Such resistors likely affect respiratory physiology in a number of ways. Expiratory airway pressure almost certainly becomes more positive while expiratory time (Te) increases. If the expiratory resistance is great enough, the expiratory time will extend through until the start of inspiration with no end expiratory pause. Thus airway and alveolar pressure at the start of inspiration will be positive, which is the definition of auto-PEEP (positive end expiratory pressure). The question becomes why will auto-PEEP reduce apnea severity? There are likely several mechanisms. First, auto-PEEP leads to increased lung volume which augments longitudinal traction on the upper airway making the pharynx less collapsible. There is a substantial literature to support this concept.2 In addition, most evidence suggests that pharyngeal airway collapse, complete or partial, occurs at end expiration when airway pressure is generally zero and upper airway dilator muscle activity is at its nadir.3,4 However, with auto-PEEP, as stated above, airway pressure is positive at end expiration which would dilate the airway thereby preventing this collapse. With the onset of inspiration, airway pressure will quickly become negative. This collapsing force may, however, be counteracted to some extent by the rapid onset of pharyngeal dilator muscle activity generally seen during inspiration and the fact that the airway is relatively large when negative pressure develops which may allow for some collapse before a critical airway dimension is reached. Thus auto-PEEP will likely improve pharyngeal airway patency during sleep thereby reducing apnea severity. Second: How effective is this form of therapy? The data from the current study would suggest that expiratory nasal resistors do reduce apnea severity although this effect was variable and modest. The overall AHI fell from 24.5 to 15.5 at 30 days with only 10 of 24 patients with an AHI >10 off therapy having an AHI of <10 on therapy. In addition, there was not a statistically significant decrement in ODI (3% or greater falls in SaO2), minimum SaO2 level, or a change in sleep architecture. If we believe that obstructive sleep apnea leads to its adverse consequences as a product of either sleep disruption or intermittent hypoxia, neither seem to improve with this form of therapy. Thus we need to interpret decrements in AHI with caution. Third: Why do some patients respond so well to this therapy while others do not respond at all? If you look at Table 2, subject #203 started with an AHI of 35.7 (severe sleep apnea) and consistently had an AHI <10 with PROVENT in place. On the other hand, subject #316 at baseline had an AHI of 9 (mild sleep apnea) which increased to 20.2 after 30 days on therapy. Although some of this can be explained by night to night variability in apnea severity, this is unlikely to be the total explanation. There are several other possibilities. First, how an individual responds to increments in expiratory resistance is likely to vary considerably. Some patients will lengthen Te as described above with all the expected consequences thereby reducing apnea severity. Others are likely to more aggressively activate expiratory muscles such that end expiratory pressure is not positive and lung volume does not increase. Individuals such as this will not likely respond to this form of therapy. In addition, how much lung volume increases in response to rising end expiratory pressure will likely vary substantially depending on chest wall and pulmonary compliance. Second, PROVENT assumes that patients will switch to nasal breathing during sleep despite the extraordinarily high expiratory resistance. Although the nasal route of breathing seems to be generally preferred during sleep,5 it is unlikely that everyone will make this transition when the work of breathing is potentially so high. If oral breathing persists during sleep, then PROVENT is not likely to be a successful approach. Finally, obstructive sleep apnea does not have the same cause in all individuals with ventilatory control instability and low arousal threshold having a greater role in some patients than others. Thus, depending on the mechanisms leading to apnea, PROVENT may simply be more effective in some patients than others. Finally, where do we go from here? Obviously we need more data to put the current information regarding PROVENT into perspective. However, I do not simply mean larger trials although these are certainly needed. We must know: What percentage of patients will breathe through the nose when the expiratory resistance is substantially elevated? What is the effect of PROVENT on lung volume and does this vary based on simple measures such as weight or BMI? What happens to Te when PROVENT is applied and how variable is this between individuals? Do decrements in RDI correlate with any of the variables described above? There is no question we need new and improved ways to effectively treat sleep apnea, and PROVENT may well be one such approach. However, we need to understand it better before we can determine how it fits into our algorithms of care for these patients.