The Next Era of PAP

Around 430 BCE, Hippocrates—who is generally considered the father of modern medicine—used the Greek word kairos to describe the “right or precise time” of therapy in one of his many treatises on medicine. The ancient Greeks had two words for time: chronos, which referred to chronological time, and kairos, which translated to the opportune moment. It’s a different concept of time, and no similar word exists in the English language.

Nearly 2,500 years later, Kairos is now the name of a new therapy for obstructive sleep apnea (OSA) that could revolutionize the way treatment is delivered. Kairos positive airway pressure (KPAP), or Kairos PAP^™ for short, provides pressure only at the “precise” time it’s needed. KPAP uses a new algorithm that substantially reduces airway pressure during both inspiration and much of expiration, only returning pressure to the optimal treatment level towards the end of expiration. A recent landmark article in the journal Sleep Medicine showed that “Kairos PAP (KPAP) equals continuous PAP (CPAP) in efficacy and offers superior comfort for OSA treatment”.¹ KPAP provides the same therapy as traditional CPAP despite up to 5 cm H₂O less pressure and 50% less unintentional air leak, and 93% to 95% of new patients (n=150) overall chose KPAP over CPAP for comfort.¹

“Let’s face it, CPAP is difficult for many to tolerate, and pressure is usually the biggest obstacle,” says lead study author David P. White, MD, professor of medicine at Harvard Medical School. “KPAP may be the first real solution to this obstacle. We are in the process of collecting more data, but I have breathed KPAP, and the difference is not subtle. I find the increase in comfort remarkable.”

The Limitations of Traditional PAP Therapy

Most of the complaints about CPAP revolve around the pressure and leak. Typically, each patient with OSA needs a certain level of pressure (therapy) to keep their airway open during sleep, some more and some less.

For the past 40 years, patients have had to tolerate a single therapy pressure continuously (thus CPAP) throughout the breathing cycle, and historically only 30% to 50% of patients use CPAP long term.^2-3

Then 30 years ago, the first bilevel devices with two pressures were introduced.⁴ A higher inspiratory positive airway pressure (IPAP) when breathing in and a lower expiratory pressure (EPAP) when breathing out. The hope was providing two pressures would be more comfortable and increase long-term usage, but that never happened.⁵ Despite the markedly increased expense of bilevel devices, adherence with these devices did not improve.

Bilevel devices not only failed to increase adherence rates, but they were also less effective at preventing airway obstruction and more likely to cause the side effect of central sleep apnea (CSA).^6-8 Despite these findings, bilevel devices have been widely used to treat OSA and with the development of expiratory pressure reduction algorithms (EPRA), today almost all CPAP devices have bilevel features. However, just like bilevel devices, CPAP devices with EPRA have also failed to increase rates of adherence, likely destabilize the upper airway, and may increase CSA.^5,7,9-10

“It just didn’t make sense to me,” says William H. Noah, MD, the inventor of both the V-Com^® and KPAP algorithms. “We were all taught that we must maintain inspiratory pressure to stabilize the airway, but studies from the 1990s and how we naturally breathe, made me think we were backwards. It was the opposite of kairos. We were giving the pressure at the wrong time.”

Rethinking Pressure: The Kairos Approach

During COVID, Dr. Noah became determined to find a better way. He built a PAP research lab on his farm outside of Nashville, Tenn., and began experiments. He theorized that reducing IPAP (inspiratory pressure) below EPAP (expiratory pressure) could be the solution, but because no bilevel device on the market could do that, Dr. Noah had to invent a way. He first developed and released a non-compensated resistor (V-Com^®) on the market in 2022.

When added to the CPAP circuit, V-Com reduced inspiratory pressure and yet still maintained therapy while adding comfort and reducing leak.¹¹ This added considerable weight to Dr. Noah’s theory, which went even further.

Dr. Noah also hypothesized that since higher inspiratory pressures increased central apneas (likely from augmented tidal volumes), then reducing inspiratory pressure would reduce central apneas emerging from PAP treatment—treatment emergent central sleep apnea, or TECSA. In a study recently accepted by the Journal of Clinical Sleep Medicine, Dr. Noah and colleagues at the University of Utah and Harvard found that reducing inspiratory pressure with the V-Com resolved TECSA.¹²

“I don’t think it’s a coincidence that TECSA only became an issue after C-Flex^® was introduced. I believe the higher inspiratory pressure made central apnea much more common,” says Dr. Noah. “And as KPAP replaces CPAP, TECSA should return to obscurity.”

After releasing V-Com, Dr. Noah recruited leading engineers from the field to build prototype PAP devices that could modulate pressure in ways never conceived to test his theory of KairosPAP.

“During my 30 years at Respironics and then Philips, maintaining or increasing inspiratory pressure above expiratory pressure to treat OSA was sacred dogma,” says Bernard Hete, PhD, chief technology officer at SleepRes. “But I base my world on physics, and when Dr. Noah first presented the physics behind his theory, I immediately knew he was right. Now after two and a half years of research and development on KPAP, it appears traditional CPAP will soon be obsolete. If the pressure is unnecessary, and can lead to side effects, why would we continue to force it on patients?”

KPAP supplies the therapy pressure only towards the end of expiration—the crucial time (kairos). Upon breathing in, the pressure immediately drops 1-2 cm H₂O (Figure 1) and at peak inspiratory flow, the pressure drops another 1-3 cm H₂O. Therefore, as the patient begins to exhale, the pressure is already reduced by as much as 5 cm H₂O, making expiration more natural and passive. Once the patient reaches their peak expiratory flow, the pressure begins to return to the therapy pressure to stabilize the airway and maintain end-expiratory lung volume. Each of these parameters may be modified individually for comfort.

The algorithm does not allow airway pressure to fall below 5 cm H₂O so patients on less than 10 cm H₂O CPAP would experience lesser drops.

“I tried KPAP and found it more comfortable to breathe on than CPAP,” says Richard Berry, MD, professor of medicine at the University of Florida. “Combining my experience with the results of their recent randomized trial, I am excited about [KPAP’s] potential to improve PAP treatment for patients with OSA.”

Fig. 1. Visual representation of the Kairos positive airway pressure (KPAP) algorithm. Pressure is dropped at the beginning of inspiration and again at peak inspiratory flow (arrows in red). Pressure starts to return to baseline levels about halfway through expiration. By contrast, continuous PAP (CPAP) has constant pressure throughout the entire respiratory cycle.

Engineering Airflow for Maximum Comfort

Both Dr. Noah and Dr. Hete credit long-time PAP engineer Michael Knepper for creating a new way that the pressure adjusts almost instantaneously to a patient’s individual airflow. This provides additional comfort. Dr. Hete says even those trying to purposely vary their breathing to fool the device are surprised by the responsiveness.

Dr. Hete also credits SleepRes’ rapid progress to commercialization to the synergy of their team. “My experience is that PAP manufacturers are very siloed and have little physician input. But our physicians and engineers work together and learn from each other every day,” says Dr. Hete. “Our physicians think like experienced engineers, and as engineers, we are now building with the right physiology. KPAP is a whole new paradigm, but it is just the beginning.”

SleepRes plans to release their own CPAP devices with KPAP in the U.S. in 2025. They also plan to release their new mask line with some surprising new technology as well. At the time of this writing, SleepRes devices with KPAP and masks are not yet cleared by the FDA But the question is when they receive clearance and are commercially available, what impact willKPAP have on the market? “Two years from now, with KPAP fully available, I can’t imagine why any patient would be using standard CPAP,” Dr. White says.

“It is simple to me. If over 90% of patients prefer KPAP, why would I consider prescribing a device without KPAP once available,” says Nancy H. Stewart, DO, assistant professor of medicine at University of Kansas Medical Center. “I compared breathing on KPAP and CPAP for myself. The difference is huge.”

Dr. Noah is working hard to provide that option for patients. “What really drives me each day is that I want to first provide KPAP to my own patients in Tennessee, and then to patients around the world,” he says. “I get to wear KPAP each night. Soon everyone else will too.”

Source: SleepWorld Magazine

References

5. White DP, Messineo L, Thompson E, Hughes B, Lannom WD, Hete B, Joshi A, Noah WH. Kairos positive airway pressure (KPAP) equals continuous PAP in effectiveness, and offers superior comfort for obstructive sleep apnea treatment. Sleep Med. 2024 Sep 18;124:268-275. doi: 10.1016/j.sleep.2024.09.028. Epub ahead of print.
6. Rotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over twenty years of data collection: a flattened curve. J Otolaryngol Head Neck Surg. 2016;45(1):43. doi: 10.1186/s40463-016-0156-0.
7. Andry JM Jr, Toban G, Chafin C, Noah W. Positive airway pressure therapy supplied by an integrated sleep practice associated with greater adherence among pre-Medicare-aged patients with sleep-disordered breathing. J Clin Sleep Med. 2021;17(1):31-6. doi: 10.5664/jcsm.8786.
8. Sanders MH, Kern N. Obstructive sleep apnea treated by independently adjusted inspiratory and expiratory positive airway pressures via nasal mask. Physiologic and clinical implications. Chest. 1990;98(2):317-24. doi: 10.1378/chest.98.2.317.
9. Smith I, Lasserson TJ. Pressure modification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2009;(4):CD003531. doi: 10.1002/14651858.CD003531.pub3.
10. Gugger M, Vock P. Effect of reduced expiratory pressure on pharyngeal size during nasal positive airway pressure in patients with sleep apnoea: evaluation by continuous computed tomography. Thorax. 1992;47(10):809-13. doi: 10.1136/thx.47.10.809.
11. Sériès F, Marc I. Effects of inspiratory and expiratory positive pressure difference on airflow dynamics during sleep. J Appl Physiol. 1998;85(5):1855-62. doi: 10.1152/jappl.1998.85.5.1855.
12. Johnson KG, Johnson DC. Bilevel positive airway pressure worsens central apneas during sleep. Chest. 2005;128(4):2141-50. doi: 10.1378/chest.128.4.2141.
13. Zhu K, Aouf S, Roisman G, Escourrou P. Pressure-relief features of fixed and autotitrating continuous positive airway pressure may impair their efficacy: evaluation with a respiratory bench model. J Clin Sleep Med. 2016;12(3):385-92. doi: 10.5664/jcsm.5590.
14. Loh G, Shiekh K, Hostler J, et al. Flex-settings increase central apneas and reduce mask leak but have no effect on overall compliance. Chest. 2014;146(4):954A. doi:10.1378/chest.1995089
15. Farney RJ, Hete B, White DP, et al. Reducing inspiratory positive airway pressure (IPAP) to treat obstructive sleep apnea provides equivalent therapy, improves comfort, and reduces unintentional leak. J Sleep Disord Ther. 2024;13(4):1-7.
16. Noah WH, Messineo L, Hete B, et al. Treatment-emergent central sleep apnea resolves with lower inspiratory pressure. J Sleep Disord Ther. In press.