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THE
IMPACT OF SLEEP-DISORDERED BREATHING ON OTHER AIRWAY DISEASES
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Key Point
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| Treatments for sleep-disordered breathing in patients with asthma, Cheyne-Stokes respiration, and obesity hypoventilation syndrome are currently being investigated. |
MONTREAL—After seeing major improvement in the nocturnal asthma symptoms of a patient receiving continuous positive airway pressure (CPAP) for obstructive sleep apnea, James M. Parish, MD, had to ask, Are sleep apnea and asthma related?
He reviewed the literature on the topic and determined that there are some observational and case-control studies supporting a sleep apnea/asthma relationship. Although these studies are by no means conclusive, further investigation of the relationship is warranted, said Dr. Parish during a symposium on sleep-disordered breathing at the annual meeting of the American College of Chest Physicians.1
Studies of sleep apnea and asthma date back to 1988, Dr. Parish noted, when Sullivan et al found that CPAP reduced nocturnal asthma symptoms in nine patients with difficult-to-control asthma and sleep apnea. "Their peak expiratory flow rates improved, and their subjective symptoms [of asthma] improved markedly as well," added Dr. Parish, Chair of the Division of Thoracic Diseases and Critical Care at the Mayo Clinic in Scottsdale, Arizona.
Another study in 1988 looked at 10 patients with severe sleep apnea—their mean apnea-hypopnea index was 51/h—and secondary asthma symptoms.2 "They were treated with CPAP, and they all had resolution of their asthma symptoms," said Dr. Parish.
This study included a second group that presented with asthma and later reported symptoms suggesting sleep apnea, particularly snoring. Although sleep studies failed to detect significant sleep apnea in these patients, they revealed what was later described as upper airway resistance syndrome—markedly negative respiratory pressures during sleep. Both the snoring and nocturnal asthma symptoms resolved with CPAP.
More recently, Turkish investigators reported improvement in persistent nighttime asthma symptoms after two months of CPAP in a study of 43 asthma patients3; CPAP was initiated in 16 of the 19 patients who had significant sleep apnea, as shown by an apnea-hypopnea index of 15/h (CPAP could not be tolerated in three cases). No significant change in pulmonary function studies was observed with CPAP.
From a molecular standpoint, both asthma and sleep apnea have been associated with elevations in a variety of inflammatory mediators such as interleukin-6, tumor necrosis factor, and C-reactive protein. In obese persons, there is also evidence of increased inflammatory mediators, a risk factor for asthma and sleep-disordered breathing.
A potential relationship between nasal congestion/allergies and sleep-disordered breathing is worth further investigation, too, said Dr. Parish.
CHEYNE-STROKES RESPIRATION
Although much about Cheyne-Stokes respiration is still unknown, it is not quite the mystery it once was. "When I was in medical school, it was sort of an anomaly, just something to look at that had no consequences," recalled Brian A. Boehlecke, MD, Professor in the Division of Pulmonary and Critical Care Medicine at the University of North Carolina at Chapel Hill.
Now there are data suggesting that Cheyne-Stokes respiration can have serious consequences during sleep, including hypoxemia and reduced cardiac function. Cheyne-Stokes respiration has also been associated with arrhythmias—such as a twofold rise in the incidence of ventricular premature beats during slow-wave sleep and other forms of stable sleep—and some studies have shown that it increases mortality in patients with heart failure, Dr. Boehlecke related.
Daytime sleepiness appears to be another potential result of Cheyne-Stokes respiration, suggested a comparison of heart failure patients with and without Cheyne-Stokes respiration. The patients with Cheyne-Stokes respiration reported being sleepy when they underwent multiple sleep latency tests, pointed out Dr. Boehlecke. Thus, he reasoned that sleepiness in these patients was from sleep disruption related to abnormal respiration, whereas fatigue reported by the patients without Cheyne-Stokes respiration was due to low cardiac output.
Notably, a recent study has challenged the notion that Cheyne-Stokes respiration raises mortality risk. Among 78 potential heart transplant candidates with low left ventricular ejection fractions, mortality after 52 months of follow-up was no different between those with and without Cheyne-Stokes respiration. Of these patients, 42% had Cheyne-Stokes respiration or central sleep apnea, 28% had obstructive sleep apnea, and 29% had no form of sleep-disordered breathing.
Cardiac resynchronization with an implantable pacer is a promising therapy for heart failure patients with Cheyne-Stokes respiration. In small studies of this population, it has been shown to reduce the apnea-hypopnea index, improve sleep quality, decrease Cheyne-Stokes events, and slightly increase the left ventricular ejection fraction. The available data on supplemental oxygen suggest that oxygen can dramatically reduce the apnea-hypopnea index of patients with Cheyne-Stokes respiration after one month, although it does not seem to affect the left ventricular ejection fraction or sleep architecture of these patients.
In addition to relieving airway obstruction, nasal CPAP seems to increase the functional residual capacity of patients with Cheyne-Stokes respiration and heart failure. Investigators have also reported that mortality was significantly lower among these patients 48 months after they started CPAP. More recently, bilevel positive airway pressure (BiPAP) in a small number of patients with Cheyne-Stokes respiration was found to improve sleep architecture, measures of respiratory function, left ventricular ejection fraction, and New York Heart Association functional class after several months.
Effective novel therapies for Cheyne-Stokes respiration may eventually include adaptive servo ventilation with the mechanical ventilator and CPAP with carbon dioxide. In a small comparative study, adaptive servo ventilation was as effective as CPAP in reducing the apnea-hypopnea index after three and six months in patients with Cheyne-Stokes respiration and heart failure. Furthermore, adaptive servo ventilation "seemed to have an advantage in terms of quality-of-life scores and left ventricular ejection fraction," Dr. Boehlecke observed.
The addition of 0.5% to 1.0% carbon dioxide to CPAP dramatically reduced the apnea-hypopnea index of a small group of patients with refractory mixed central and obstructive sleep-disordered breathing in a recent study.4 In these patients, the apnea-hypopnea index fell from 66/h to 32/h when CPAP was started and to 4.5/h after carbon dioxide was added, said Dr. Boehlecke.
ALVEOLAR HYPOVENTILATION DURING SLEEP
Although sleep-related arterial hypoventilation is usually encountered in patients with lung parenchymal, airway, or pulmonary vascular disease, it can also occur secondary to neuromuscular disease or to chest wall deformity such as that seen in the obese. Focusing her remarks on the latter scenario, Nancy A. Collop, MD, said that the medical literature defines obesity hypoventilation syndrome as a body mass index of 30 or greater and a Pco2 exceeding 45 mm Hg in the absence of another explainable cause for hypoventilation.
Unlike obstructive sleep apnea, which is more common in men, obesity hypoventilation syndrome appears to have similar prevalence between the sexes. "I believe that all of these patients need polysomnography," stressed Dr. Collop, Director of the Johns Hopkins Hospital Sleep Disorders Center in Baltimore.
The breathing patterns that may be present in obesity hypoventilation syndrome are obstructive sleep apnea, flow limitation with obstructive hypoventilation, central sleep hypoventilation, and paradoxical ventilation. Like patients with neuromuscular disease, obese patients with sleep-related arterial hypoventilation often have respiratory muscle weakness and fatigue, diaphragm dysfunction, pulmonary microatelectasis, and altered respiratory drive.
There are no prospective, randomized, controlled trials to guide the treatment of obesity hypoventilation syndrome. "But obviously, you would use CPAP to treat the obstructive events and any flow limitation that you see," said Dr. Collop. She advised initiating BiPAP if the obstructive events and flow limitation persist and the patient continues to have episodes of desaturation.
"If you get to that point, and the patient continues to have either central apnea or persistent desaturation, I think it is reasonable to add a backup rate to your BiPAP," maintained Dr. Collop. "Set the rate close to the patient’s baseline." Supplemental oxygen can then be added if necessary, she said.
—Timothy Begany
Reference
1. Collop NA, Parish JM, Lee-Chiong TL Jr, Boehlecke BA. Management of different and difficult sleep-disordered breathing syndromes. Presented at: annual meeting of the American College of Chest Physicians; October 31, 2005; Montreal, Quebec.
2. Chan CS, Woodcock AJ, Sullivan CE. Nocturnal asthma: role of snoring and obstructive sleep apnea. Am Rev Respir Dis. 1988;137:1502-1504.
3. Ciftci TU, Ciftci B, Guven SF, et al. Effect of nasal continuous positive airway pressure in uncontrolled nocturnal asthmatic patients with obstructive sleep apnea syndrome. Respir Med. 2005;99:529-534.
4. Thomas RJ, Daly RW, Weiss JW. Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing. Sleep. 2005;28:69-77.
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