USC researcher Michael Khoo uses mathematical modeling and control engineering to better understand the interaction of respiratory, cardiovascular and sleep regulation systems.

Photo by Irene Fertik

With that characterization, Dickens provided one of the earliest accurate descriptions of someone with severe obstructive sleep apnea syndrome (OSAS).

Some of the most recent findings about this life-threatening condition come from Michael Khoo, professor of biomedical engineering, in the USC School of Engineering.

“Imagine if throughout the night someone were to block your nose and mouth for 10 to 60 seconds every couple of minutes,” said Khoo.

The airflow blockage occurs when the pharynx (throat) collapses from the negative pressure during inward breathing, said Khoo. Blood oxygen levels decrease, carbon dioxide levels increase and the individual makes greater efforts to draw a breath.

But the stronger negative airway pressures heighten the collapse of the pharynx. It’s like trying to breathe through a collapsed straw.

While the brain keeps signaling respiratory muscles to work harder, no air gets into the lungs. Then the struggling subject briefly awakens and breathes. When sleep resumes, the entire apnea cycle repeats.

An estimated 18 million Americans suffer from sleep apnea. It is twice as common in African Americans as in whites, and the incidence in professional football players may be as high as 34 percent.

It should surprise no one that people with sleep apnea experience excessive daytime sleepiness, frequently falling asleep.

Other characters in Dickens’ yarn called Joe “young dropsy,” a 19th-century term for people with swelling in the legs, a common symptom of congestive heart failure.

Dickens was right on the mark. There is a link between sleep apnea and various forms of cardiovascular disease, including hypertension, stroke, coronary heart disease and congestive heart failure.

The relationship between sleep apnea and cardiovascular disease is the primary focus of Khoo’s research.

“During an apnea, blood oxygen concentrations can plunge to alarmingly low levels,” said Khoo.

Activity surges in the sympathetic nervous system, the network of nerves that mediate the “fight or flight” reflexes. Arousal from sleep contributes to a further increase. Blood pressure and heart-rate rise.

“We believe that long-term exposure to these repetitive surges leads the sympathetic nervous system to operate in a mode of permanent overdrive, which wreaks havoc on the cardiovascular system.”

Physicians treat hypertensive sleep apnea patients with a mask-like medical device that administers continuous positive airway pressure (CPAP). The treatment lowers blood pressure, suggesting that sleep apnea is the cause, not the consequence of, high blood pressure.

Sleep apnea involves the dynamic interaction of three major physiological control systems — respiratory, cardiovascular and sleep regulation. Khoo uses mathematical modeling and control engineering to better understand the interaction.

“We developed a computer-controlled ventilator system that delivers a sequence of breaths with randomly modulated volumes,” said Khoo. “We then subjected normal and OSAS volunteers to this test protocol during wakefulness and different sleep states, at the same time recording measurements of respiration, heart rate and blood pressure.”.

In the January 2003 issue of the American Journal of Respiratory and Critical Care Medicine, Khoo catalogued the dynamic characteristics of the major components responsible for regulating heart rate and blood pressure in sleep apnea patients and in a control group during wakefulness and sleep.

This study, the first of its kind, was done at L.A. County/USC Medical Center in collaboration with physicians Ricardo Juarez and Ahmet Baydur.

In a previous study, conducted with physician Richard Berry of the Long Beach V.A. Medical Center, Khoo applied similar techniques to a group of sleep apnea patients receiving home CPAP therapy.

“We found a substantial treatment-related improvement,” said Khoo. “But only in those patients who, on average, used CPAP for at least three hours per night.”

In another study published in the February 2003 issue of Sleep, Khoo analyzed data recorded while the subjects were breathing spontaneously, without any external interventions. All were assessed using conventional noninvasive methods of cardiovascular function testing.

Khoo believes he has shown that a short, simple and noninvasive test can detect the harmful cardiovascular effects of sleep apnea and assess how well these effects are reduced during long-term treatment.

Currently, the severity of a patient’s sleep apnea is assessed through a sleep study allowing a physician to choose a suitable individual therapy. Usually, there is no follow-up to determine effectiveness on cardiovascular function.

“It is our hope,” said Khoo, “that the future availability of a convenient and economical means of testing can fill this gap in the treatment of sleep apnea.”