We have just completed the 27th Annual Advances in Diagnosis and Treatment of Sleep Apnea and Snoring course in San Francisco, California. It has been wonderful to be a co-director for about 15 years, and I learn so much myself in every course. This year we did something different: a virtual format! We can thank the Omicron variant of the SARS-CoV-2 virus and the surge in cases that made us concerned about bringing people together in an indoor setting for full days of . Although we missed the chance to see everyone in person, it had the advantage of allowing many to attend from other countries without the need to travel. I wanted to share some interesting topics and research discussed at the course, similar to what I have done for previous courses, such as those in 2020 and 2019. As always, I gave some of the surgery talks and have a chance to discuss surgical topics in other blog posts, so I will focus on those not directly related to surgery.
Sleep Deprivation and Insomnia
The couse focuses on sleep apnea and snoring, but this year we incorporated more speakers to discuss sleep deprivation and insomnia. Sleep apnea can interfere with high-quality, restful sleep, but sleep deprivation and insomnia are also extremely common, interfering with sleep quantity. Unfortunately, many patients suffer from problems with both sleep quality and sleep quantity. Aric Prather, PhD from the University of California, San Francisco (UCSF) spoke about sleep deprivation, primarily sleeping less than 6 hours per night. He presented the substantial research showing the negative impacts on emotional health (depression, coping with stress), appetite (decreased leptin and increased ghrelin hormones), health (important risk factor for development of type 2 diabetes, cardiovascular events, and death as well as increased susceptibility to colds).
Andrew Krystal, MD from UCSF spoke about personalizing insomnia therapy based on their activities on specific neurotransmitters. Normally, any lecture involving neurotransmitters can be extremely dry, but his talk was fascinating to me as someone unfamiliar with the subtleties of insomnia treatment. He explained why some insomnia medications (what have previously been called benzodiazepine receptor agonists) have greater effects on anxiety vs. balance, based on their differential binding to the alpha subunit of the GABA receptors in the brain. The available evidence indicates that eszopiclone may have greater benefits in treating insomnia that coexists with mental health disorders or chronic pain. Also, histamine-blocker medications like doxepin are not as helpful for difficulty falling asleep but can be more helpful in preventing awakening at the end of the sleep period when histamine is so important in promoting wakefulness. Finally, the orexin antagonists can be particularly helpful for those with difficulties with sleep onset and maintenance (will not decrease awakenings but will decrease the time to fall back asleep), especially in those who need to be awake and functioning normally in the middle of the night (parents of infants or young children).
Personalized Approaches to OSA Treatment
Allan Pack, MBChB, PhD from the University of Pennsylvania has been a long-time proponent of personalized medicine or precision medicine in obstructive sleep apnea. His most active research relates to two areas. He shared results of work in the genetic causes of sleep apnea in collaborative efforts throughout the US and around the world, indicating clearly that there are interesting findings but more work that needs to be done. He also discussed the 3 clinical clusters or subtypes (different types of patients with sleep apnea) first identified through the Icelandic Sleep Apnea Cohort and now shown in other groups of patients: disturbed sleep (insomnia, frequent awakenings during sleep), medical comorbidities (hypertension, diabetes, cardiovascular disease) without symptoms, and excessively sleepy (sleepiness and related symptoms), although there may be 1-2 additional clusters (my experience would agree with that).
These differences may be important in examining treatment outcomes, as the improvement with sleep apnea treatment will be different, for example there would be more improvements in daytime sleepiness in the last group (excessively sleepy) but not those without symptoms. What is interesting is that the cardiovascular risk from sleep apnea comes primarily in those who are excessively sleepy, based on studies from the US and Chile. In another lecture later in the course, he spoke about how sleep apnea research studies need to understand these differences, especially for studies of sleep apnea treatment that have always excluded those with excessive sleepiness (who would be most likely to have an improvement in cardiovascular disease risk). In that same talk, he also singled out two studies from Ali Azarbarzin, PhD from Brigham and Women’s Hospital identifying two markers that appear to be associated with cardiovascular risk from sleep apnea. These were the hypoxic burden (how low and how long the oxygen levels drop during sleep apnea events) and heart rate response (increases) to sleep apnea events.
Andrew Goldberg, MD, MSc from UCSF spoke about the microbiome, the combination of microorganisms in our body that has been most closely studied for the intestinal tract. For obstructive sleep apnea, there appears to be a bidirectional association, in that animal research shows that some sleep changes like drops in oxygen levels and disruption of sleep can adversely affect the microbiome. Interestingly, pre/probiotics can reduce neuroinflammation and cardiovascular disease in animal models of sleep apnea. It is always great to hear Andy’s talks and the growing number of research papers in this field that are relevant to sleep apnea.
OSA and the Brain
Liza Ashbrook, MD from UCSF spoke about brain health, especially the glymphatics system of waste removal in the brain that has been studied mostly in non-human animals but which has some human studies with similar findings. Waste in the brain includes abnormally-folded protein like beta-amyloid whose accumulation is implicated in Alzheimer’s Disease (AD). Importantly, studies show that the glymphatic system primarily functions during sleep, with aging associated with decreased function. Sleep deprivation (especially less slow-wave sleep) impairs clearance of beta-amyloid in the brain.
Dr. Pack followed this with a discussion of AD and sleep apnea. Based on brain PET scans, amyloid-beta and tau levels in the brain rise many years before the development of AD, offering hope for initiating treatment to prevent disease. The challenge is that sleep time is reduced early in the disease process, especially for slow-wave sleep. He then discussed the idea that sleep apnea may be an environmental factor that combines with genetic susceptibility (the APOE4 gene), with studies showing that moderate to severe sleep apnea is associated with the development of cognitive impairment. Furthermore, the limited evidence indicates that treatment of sleep apnea can reduce the accumulation of amyloid-beta and tau proteins. Overall, Dr. Pack recommends evaluation for possible sleep apnea of those undergoing evaluation for AD and, furthermore, treatment of the sleep apnea, although we do not have high-quality evidence yet to show definitively that treatment will reverse or slow progression of disease.
Richard Schwab, MD from the University of Pennsylvania shared his team’s research on the importance of tongue fat in obstructive sleep apnea, including work that I have discussed previously on this blog. He also shared more-recent research showing that the improvement in sleep apnea after weight loss appears to occur specifically because of the decrease in fat within the tongue and other soft tissue structures. He concluded by agreeing with a theory proposed by Dr. Pack earlier in the course, suggesting that there might be a genetic basis for fat deposition in the tongue (this occurs in some but not all people when they gain fat weight.
Robert Baron, MD, MS from UCSF spoke about obesity and sleep apnea. He shared the fact that high-quality studies show that dietary composition of macronutrients (protein/fat/carbohydrate) produce no differences in weight loss for obese individuals; all diets that lower calorie consumption produce the same weight loss, with differences based on whether someone can adhere to the diet. That being said, it is good to eliminate added sugars and refined calories. He indicated that randomized trials show no weight loss benefit with intermittent fasting. Dr. Baron was not as enthusiastic as some of his own colleagues (by his own admission) about weight loss medications, as these should generally only be used in patients who are losing weight with lifestyle modifications over a 12-week period. Surprising to me was that exercise is not specifically helpful for weight loss, but it can help maintain weight loss (in addition to many other health benefits, including lowering mortality). He shared a great saying of “fitness trumps fatness” as fit patients who have a body mass index in the obese range actually tend not to have an increased risk of death, meaning that fitness is much more important than body mass index. This reminds me…I need to go for a run!
Positive Airway Pressure
Atul Malhotra, MD from the University of California, San Diego discussed numerous studies utilizing large databases (aka, big data). He has collaborated with other experts on numerous such studies, showing some of the following findings:
- Worldwide prevalence of obstructive sleep apnea is more than 900 million adults, with over 400 million having moderate to severe obstructive sleep apnea
- For patients not tolerating CPAP, a switch to bilevel positive airway pressure (BPAP) can be associated with an improvement in usage of approximately 1 hour
- For patients who are using CPAP but still having residual sleep apnea (at least 15 events/hour) a switch to another type of positive airway pressure therapy (ASV) can improve the control of sleep apnea and increase positive airway pressure therapy usage by about 1 hour
I learned so much myself during the course and am looking forward to next year!