Obstructive Sleep Apnea Significantly Increases Risk of Sever Asthma

by Annette Boyle

March 10, 2014
Mihaela Teodorescu, MD

MADISON, WI — For older patients, obstructive sleep apnea (OSA) appears to increase the risk of severe asthma sevenfold, which could be especially significant for veterans because of their high rates of sleep apnea.

The study led by VA researchers suggests that assessment of obstructive sleep apnea risk might provide important guidance for treatment.

“We know from several studies that there is a bidirectional relationship between obstructive sleep apnea and asthma,” said Mihaela Teodorescu, MD, director, James B. Skatrud Pulmonary/Sleep Research Laboratory at the William S. Middleton Memorial VA Hospital in Madison, WI, and associate professor, allergy, pulmonary and critical care medicine at the University of Wisconsin School of Medicine and Public Health. “Current literature in adults seems to favor that asthma comes first and sleep apnea develops later, but once obstructive sleep apnea is established, it seems to worsen asthma.”

“We posed the question in asthma patients: Does age increase the impact of sleep apnea? We found that elderly patients have more severe asthma and that OSA is more prevalent. For them, this link between the two conditions is even tighter,” Teodorescu said.

Last year, Tricia Harris, a nurse at the Houston VAMC, showed Marine Corps veteran Christy Simmons how to use the Positive Airway Pressure machine.
Photo by Deborah Williams.

Teodorescu and her colleagues found that obstructive sleep apnea was associated with a nearly 700% increase in the likelihood of severe asthma in older subjects. In younger patients, OSA doubled the likelihood of severe asthma.1

Veterans have four to five times the risk of sleep apnea compared with the general population. Up to half of veterans seeking outpatient care at VA medical centers have a high risk for OSA and about 1 in 5 has a diagnosis of OSA. Factors that put individuals at risk include male gender, obesity and older age, all common characteristic of the majority of veterans in VHA care.2

The exact mechanism that makes OSA a risk factor for asthma exacerbations in this cohort remains unknown, but Teodorescu and her colleagues have some hypotheses. “There could be changes in the inflammatory milieu in the systemic circulation or mechanical properties of OSA could influence upper airway patency,” Teodorescu told U.S. Medicine. Further, research the group published recently in the Journal of Clinical Sleep shows that inhaled corticosteroids also can reduce upper airway patency.3

“We are trying to separate the features of OSA, such as chronic interim apnea and disruption of sleep, to study their individual effects on lower airways. That’s challenging because they occur concomitantly in humans, so we’ve been conducting mechanistic studies on rats,” she noted.

The association of OSA and asthma might be driven by specific characteristics of the type of asthma these patients have.

“Some researchers think that OSA with asthma may represent a different phenotype. The vast majority of asthmatics have allergic-type inflammation, while those who have sleep apnea and asthma tend to have neutrophil-type inflammation,” Teodorescu said.

The difference has important clinical implications; neutrophil-type inflammation typically does not respond to inhaled corticosteroids, which is a central element of current asthma treatment. These patients often have increased levels of systemic inflammation and worse clinical outcomes, according to research in the last few years. 4

While steroids appear to be less effective in these patients, continuous positive airway pressure (CPAP) device use improves both the OSA for which the machines are typically prescribed and asthma symptoms, particularly in older patients, according to the research by Teodorescu and colleagues recently published in Sleep Disorders. CPAP use attenuated the risk of severe asthma in the older patient group by 91%.

The study enrolled 813 subjects with asthma who were patients at outpatient pulmonary and asthma/allergy clinics affiliated with the University of Michigan and University of Wisconsin, 154 (19%) of whom were age 60 to 75; 659 (81%) patients were ages 18-59.

“CPAP use may reduce the oxygen stress that develops in OSA and reduce inflammation, but the specific effect on the lower airway isn’t known,” Teodorescu said.

For older patients, the presence of OSA was the factor most predictive of poorly controlled asthma, according to the researchers. “In marked contrast to OSA symptoms, traditionally recognized risk factors for asthma such as BMI [body mass index], female gender, African-American race, rhinitis, and GERD [gastroesophageal reflux disease] showed little or no independent predictive value for asthma control among older persons,” they concluded.

Older patients with OSA typically had more nighttime asthma symptoms, while younger patients experienced more asthma symptoms during the day, research has shown.

Consequently, “if an older asthma patient doesn’t sleep well, providers should screen for OSA, as unrecognized sleep apnea is may be a factor in poor asthma control. Further, for older patients, OSA is associated with higher mortality rates among asthma patients,” Teodorescu said. Despite growing awareness, OSA remains frequently undiagnosed, even in the VA system.

More research is needed to determine the precise nature of the relationship between OSA and sleep apnea and how CPAP mediates their interplay. “We’re still looking at the impact of CPAP use on neutrophils, but it’s been hard to recruit enough patients who have asthma and OSA from a single center. With the increasing clinical burden of OSA, obesity and asthma, we need multiple centers to conduct a randomized controlled trial of CPAP use,” she said.

Providers or veterans interested in learning more about obstructive sleep apnea and asthma can contact the research team for information or to participate in a larger trial at [email protected] or (608) 256-1901, Ext. 11902.

1 Teodorescu M, Polomis DA, Gangnon RE, Fedie JE, Consens FB, Chervin RD, Teodorescu MC. Asthma Control and Its Relationship with Obstructive Sleep Apnea(OSA) in Older Adults. Sleep Disord. 2013:251567.

2Samson P, Casey KR, Knepler J, Panos RJ. Clinical characteristics, comorbidities, and response to treatment of veterans with obstructive sleep apnea, Cincinnati Veterans Affairs Medical Center, 2005-2007. Prev Chronic Dis. 2012;9:110117.

3Teodorescu M, Xie A, Sorkness CA, Robbins J, Reeder S, et al. Effects of Inhaled Fluticasone on Upper Airway during Sleep and Wakefulness in Asthma—A Pilot Study. Journal of Sleep Medicine. Not yet published.

4Wood LG, Baines KJ, Fu J, Scott HA, Gibson PG. The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma. Chest. 2012 Jul;142(1):86-93

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