As the surgical treatment of snoring and obstructive sleep apnea are relatively new fields, Dr. Kezirian uses the latest research advances to improve the care of his patients and to teach patients as well other physicians about new developments.

Dr. Kezirian is actively engaged in a wide variety of research efforts, and he is recognized nationally and internationally for this work. His research has been sponsored by the National Institutes of Health, the American Academy of Otolaryngology—Head and Neck Surgery Foundation, and the American Laryngological, Rhinological, and Otological Society (aka Triological Society). Based on his expertise, Dr. Kezirian works with several established and startup health care companies (and has his own patents) in work developing new treatments for snoring and obstructive sleep apnea. Although the research involved in these projects is confidential in the early stages, Dr. Kezirian is committed to making these available as soon as they have demonstrated clear benefits.

A full list of Dr. Kezirian’s research publications is available on his curriculum vitae or the National Library of Medicine website. Using the National Library of Medicine link, you will find some of these publications available free of charge. They are noted as “Free PMC Article” or “Free Article”. Dr. Kezirian often discusses his previous research in more detail on his blog. Here are some highlights of some of Dr. Kezirian’s snoring and sleep apnea surgery research.

Drug-Induced Sleep Endoscopy

There are many snoring and sleep apnea procedures available to treat patients. These procedure address the different structures of the nose and throat that can play important roles in causing snoring and obstructive sleep apnea. Successful surgical treatment is based on accurately identifying where the snoring and blockage in breathing is occurring and developing targeted, effective treatment. Dr. Kezirian jokes that he could come to each patients’ home and look inside their throat with a flexible fiberoptic telescope to watch the areas where blockage in breathing occurs as they sleep, all night, every night. Of course, this would be a little challenging, so we have to look for other options.

Drug-induced sleep endoscopy was developed in Europe as an evaluation for patients with snoring and sleep apnea who are considering surgery. During the procedure, surgeons look inside the throat with a flexible fiberoptic endoscope while a patient is sedated in the operating room. Dr. Kezirian is one of the world’s leaders in evaluation techniques that are essential to selecting surgical procedures, including drug-induced sleep endoscopy. His research has evaluated important characteristics of drug-induced sleep endoscopy, compared it to other evaluations, and examined surgical results. For additional information about this ongoing research, please see the National Institutes of Health’s ClinicalTrials.gov website.

Dr. Kezirian’s research on drug-induced sleep endoscopy has evolved from focusing only on his own patients’ experience to leading major research collaborations across multiple centers from around the world through the International Surgical Sleep Society. This research has used a more-rigorous approach to show exactly how drug-induced sleep endoscopy can improve sleep apnea surgery results and how drug-induced sleep endoscopy findings are associated with results of Inspire Upper Airway Stimulation. Using these same databases, the team has shown that specific features of the shape of the palate (roof of the mouth) are associated with outcomes of soft palate surgery and Upper Airway Stimulation outcomes. The studies have been supported by the American Academy of Otolaryngology—Head and Neck Surgery Foundation and the American Sleep Medicine Foundation, the foundation arm of the American Academy of Sleep Medicine.

Combining Surgery and Medications to Treat Obstructive Sleep Apnea

Research over the past couple of decades has suggested that multiple factors contribute to obstructive sleep apnea. The most important factor is anatomy, meaning that there are structural issues causing blockage in breathing during sleep. Surgery treats anatomy, and the goal of evaluations like drug-induced sleep endoscopy is to identify the abnormal anatomy and select the right surgical treatment for each patient.

While surgery can work very well on its own, there are other factors that appear to be important in sleep apnea, such that treatment of them may enhance the results of surgery. Some of these other factors include unstable control of breathing patterns (also called unstable ventilatory control or high loop gain) or a tendency to wake up too easily (also called low arousal threshold).

The good news is that these other factors can be treated, including with medications. The research examining the role of these other factors has relied on single medications to treat obstructive sleep apnea, but the results have been poor, on average. What is interesting, however, is that some patients will respond very well to single medications.

Dr. Kezirian believes that these limited results are due to the fact that the medications on their own are not treating the anatomy, the key cause of obstructive sleep apnea in most patients. While some patients may have these other factors as their most important cause of sleep apnea, the typical patient needs treatment of their anatomy first and foremost, with medications to provide additional benefit if the anatomic treatment has not been successful.

Dr. Kezirian is conducting research with the support of a major grant from the National Institutes of Health to study evaluation procedures like drug-induced sleep endoscopy for their ability to guide surgical treatment and select patients who might respond well to soft palate surgery. For those who appear to be good candidates based on their anatomy but who do NOT have sufficient improvement in their sleep apnea, the study will include treatment with medications to address these two other common factors causing sleep apnea (abnormal control of breathing and waking up too easily). The work involves collaboration with internationally-recognized scientists: Scott Sands, PhD and Andrew Wellman, MD, PhD from Brigham Women’s Hospital in Boston and Michael Khoo, PhD at the USC Viterbi School of Engineering. They will examine the complex breathing patterns on sleep studies, potentially determining who might benefit from soft palate surgery, without and then with the use of specific medications.

Examining Results for Inspire Medical’s Upper Airway Stimulation

Inspire Medical’s Upper Airway Stimulation system remains one of the most exciting recent breakthroughs in the treatment of obstructive sleep apnea. Dr. Kezirian was the first surgeon in the western United States to offer this therapy after FDA approval in 2014. Our continued enthusiasm for Upper Airway Stimulation as an important sleep apnea treatment is based on the excellent results we have seen in our patients. We believe that our results reflect the combination of:

• the Upper Airway Stimulation technology and the support of Inspire Medical personnel

• careful selection of appropriate patients, relying heavily on drug-induced sleep endoscopy

• shared commitment to patient care from the entire surgical and sleep medicine teams

With this foundation to deliver the best results for patients, Dr. Kezirian led one of just a few centers in the country that were part of two studies supported by Inspire Medical. The first study is what is called a post-FDA approval study. Inspire Medical was asked to conduct this study as part of the approval for sale in the United States. The purpose is to evaluate the results in patients receiving the treatment after approval, just to confirm that the excellent results of their STAR Trial remain consistent in another group of patients.

The second study is a registry study that looks at all patients who have received the device, without the same number of sleep studies and other evaluations that are part of the post-FDA approval study.

Dr. Kezirian has substantial experience with the approach of hypoglossal nerve stimulation. He was a key researcher in the work of a company called Apnex Medical, examining their results at 6 months and then 12 months after surgical implantation of their device. These studies were important in showing the value of hypoglossal nerve stimulation in the treatment of obstructive sleep apnea, including its role in treating blockage in breathing in both the Tongue Region and the Palate Region.

Sleep Apnea Surgery Practice Patterns and Procedure Selection

A first study examined national obstructive sleep apnea surgical treatment patterns using large databases developed by the Agency for Healthcare Research and Quality. This work characterized the number, types, and costs of surgeries performed in the United States. An estimated 35,000 procedures were performed nationally to treat obstructive sleep apnea in 2006, but only 20% included procedures to treat blockage in breathing in the tongue region. Over time, surgeons have learned more about the importance of treating the tongue region, including the use of technologies like the Inspire Upper Airway Stimulation system.

Dr. Kezirian is now working with a team to update the analysis for 2019, the latest year for which reliable national data are available.

To explore the factors involved in procedure selection, Dr. Kezirian conducted another study, finding that insufficient training in these techniques is a major barrier to performing tongue region procedures for many surgeons. As many of these procedures are relatively new, technically more difficult, and associated with a higher risk of complications, Dr. Kezirian is committed to the training of surgeons across the country and around the world in the techniques and the avoidance of complications.

The findings of this research are presented in more detail on a posting on Dr. Kezirian’s blog.

Measuring the Effectiveness of Sleep Apnea Surgery

Obstructive sleep apnea is treated because it has important adverse effects on health and daytime function (sleepiness, quality of life, and alertness). Surgical outcomes are measured by comparing the preoperative and postoperative sleep studies to determine the improvement in breathing patterns. While this is essential, this research considered the potential benefits on health and daytime function with a combination of blood tests and questionnaires. This published study showed that patients who achieve resolution of significant sleep apnea also have marked improvement in health and daytime function, but some patients whose sleep apnea did not resolve can also improve in daytime function. For additional information, please see the description at the National Institutes of Health website.

Obstructive Sleep Apnea in Older Adults

Most of the research describing the impact of obstructive sleep apnea has focused on young and middle-aged adults. Two large, national studies have allowed researchers to examine the impacts in older women and men. Dr. Kezirian has worked with the lead investigators from these studies to examine the quality of life and health consequences of obstructive sleep apnea in older adults. Researchers have wondered for many years whether sleep symptoms like sleepiness or decreased quality of life due to sleep issues were related to sleep apnea or the fact that adults over 60 years of age generally get less sleep than young and middle-aged adults. Dr. Kezirian’s research was the first to show that these symptoms are more closely related to sleep time rather than sleep apnea. In fact, this work has led to changes in the way that older adults with mild to moderate sleep apnea are treated.

Another research study evaluated one of many possible reasons why snoring and sleep apnea are more common in people as they age. This study suggested that collagen and elastin decrease over time in the hyoepiglottic ligament. These changes are similar to those that occur in the skin, providing one reason to explain the greater likelihood of airway airway related to the epiglottis in older patients that Dr. Kezirian sees in drug-induced sleep endoscopy. These patients with epiglottis-related obstruction are often candidates for hyoid suspension or epiglottis surgery.