COPD and mood disorders, part 2:Sleep problems

Chronic obstructive pulmonary disease (COPD) is a common and costly condition that is usually diagnosed in older adults with a history of smoke exposure or a₁-antitrypsin deficiency. Therefore, COPD is seldom the patient's only condition requiring medical evaluation, management, and follow-up.

Among the multiple morbidities that are common in persons with COPD are mood disorders, including anxiety and depression, and sleep disorders. Like COPD, these conditions are often under-recognized and under-treated. Few specialists are prepared to deal with the wide range of comorbidities, especially those related to mood and sleep. Therefore, primary care physicians need to be prepared to recognize, treat, and monitor these conditions.

In the March 2007 issue of The Journal of Respiratory Diseases, we discussed the impact of depression and anxiety in patients with COPD. In this article, we focus on sleep problems.

COPD AND SLEEP

While the quality of sleep is often disturbed in persons with anxiety and depression, COPD adds another layer of complexity. In patients who have COPD, sleep produces pathophysiological disturbances that may have important implications for sleep quality, functional status, and quality of life. Despite the fact that sleep is commonly impaired in patients with COPD, physician awareness of sleep impairment or of the physiological factors that predispose to poor sleep quality is limited; as a result, recognition and treatment are inadequate.

Epidemiology

Subjective sleep complaints are common in patients with COPD; 38% of those who are older than 65 years complain of morning tiredness, and 35% complain of early awakenings.¹ In addition, many patients complain of difficulty in falling asleep, restlessness, the need to take sleep hypnotics, and daytime sleepiness.²

In COPD patients with cough or wheezing, 39% report insomnia and 12% report daytime sleepiness; in those who have both cough and wheezing, 52% complain of insomnia and 22% complain of daytime sleepiness.³ Several studies have confirmed these common problems, with polysomnography showing increases in sleep latency and arousals and reductions in sleep efficiency, total sleep time, and slow-wave and rapid eye movement (REM) sleep phases.^4-7

Poor sleep has been found to directly correlate not only with fatigue but also with the development of anxiety and depressed mood states.⁸ Impaired sleep has been considered by some to be instrumental in the development of a chronic fatigue state that in conjunction with dyspnea leads to impaired functional status in patients who have COPD (Figure).

Etiology

Nocturnal hypoxemia, airflow obstruction, hyperinflation, and the combination of obstructive sleep apnea (OSA) and COPD--known as the overlap syndrome--have all been reported as important factors contributing to impaired sleep. In patients with COPD, mean falls in PaO₂ of 13.5 mm Hg, and increases in PaCO₂ of 8.3 mm Hg have been reported during REM sleep.⁹ The prevalence of nocturnal desaturation in persons with COPD is not entirely clear, but one study of 135 patients found that 27% had nocturnal desaturation below 88% despite having a PaO₂ of greater than 60 mm Hg while awake.¹⁰

Clinical phenotype may be important in predicting the frequency and magnitude of nocturnal desaturation. Patients with the "blue bloater" clinical phenotype desaturate more frequently and to a greater extent during sleep than do those with the "pink puffer" types.¹¹ Predicting which patients may desaturate during sleep is not always easy, however. Daytime measurements of gas exchange (PaO₂ and PaCO₂) have variably been reported to indicate which patients will desaturate during sleep.^10-13

The degree of airflow obstruction, however, may be a better indicator; a ratio of forced expiratory volume in 1 second to forced vital capacity of less than 60% is associated with increased risk of having an arterial oxygen saturation (SaO₂) of less than 90% for more than 5% of total sleep time (odds ratio, greater than 3.31).¹⁴

In normal sleep, hypoventilation occurs because of reduced metabolic rate, reticular activating system activity, and chemosensitivity and increased upper airway resistance. Because of these changes, SaO₂ may be decreased by about 2% during normal sleep. In COPD patients, however, hypoventilation is more pronounced, especially during REM sleep. In one study, ventilation decreased by 32% in COPD patients during REM sleep and by 16% during non-REM sleep; this was attributed to a decreased recruitment of accessory respiratory muscle activation during REM sleep.¹⁵

Hypoventilation-induced gas exchange disturbances during sleep may adversely affect pulmonary hemodynamics in patients who have COPD. Stage 4 and REM-related decreases in oxygenation, with or without increased PaCO₂ (and consequent decreases in pH), have been associated with increased pulmonary artery pressures¹⁶ and even a reduction in survival.¹⁷ However, these findings have not been consistently demonstrated, and the effects of treatment with nocturnal supplemental oxygen on survival and the development of pulmonary hypertension are unclear.

The coexistence of obstructive airways disease has been reported in about 11% of patients with OSA.¹⁸ Compared with patients who have OSA alone, patients who have both COPD and OSA have lower PaO₂ and higher PaCO₂ levels, higher pulmonary artery pressures, and greater decreases in central drive, but there is not a significant difference in the apnea-hypopnea index.

The mortality rate also may be greater in patients with this overlap syndrome; older age, more severe airflow obstruction, and a greater than 30 pack-year smoking history may be additional confounding factors that contribute to the higher mortality.¹⁹

Recognition of sleep problems

Several recommendations have been made concerning the use of sleep studies in patients with COPD. A recent American Thoracic Society/European Respiratory Society joint position paper recommends that COPD patients should undergo a sleep study when sleep apnea is clinically suspected, when there are complications of hypoxemia that are not explained by the patient's PaO₂ while awake, and when the patient has pulmonary arterial hypertension that is out of proportion to the severity of pulmonary function derangement.²⁰

A thorough history and physical examination that reveals nocturnal symptoms indicative of poor sleep quality (insomnia, early awakening) and sleep-associated complaints (enuresis, choking, witnessed apnea) or finds morbid obesity with large neck circumference should raise suspicion for the presence of sleep-associated abnormalities.

Treatment

The British Medical Research Council Long-Term Domiciliary Oxygen Treatment Trial showed that nocturnal oxygen improved survival, compared with no oxygen administration, in patients with COPD and severe hypoxemia.²¹ The Nocturnal Oxygen Treatment Trial found that continuous oxygen improved survival more than nocturnal oxygen.²²

However, the data demonstrating the effects of supplemental oxygen in patients who desaturate only during sleep are contradictory. Chaouat and associates²³ found that nocturnal oxygen administration did not improve survival or pulmonary hemodynamics at 2 years or affect the need for long-term oxygen therapy in COPD patients who had nocturnal desaturation.

Fletcher and colleagues²⁴ compared 36 months of supplementary oxygen with placebo in COPD patients with nocturnal desaturation and found a mild decrease in pulmonary pressure and resistance but no difference in survival. Calverley and associates⁵ reported that oxygen administration increased total sleep time and the amount of time spent in stages 3 and 4 and REM sleep, with a decrease in arousals and interrupted sleep.

In contrast, Fleetham and associates⁶ reported no effect of oxygen treatment on these parameters. Thus, the effects of oxygen administration on sleep function and physiological parameters in patients with COPD are unclear and merit further investigation.

The effects of bronchodilators on sleep have also been studied, with variable results. Theophylline, albuterol, and tiotropium have been reported to have no effect on sleep, while ipratropium has been reported to reduce nocturnal desaturation and increase the percentage of REM sleep.²⁵

Noninvasive positive pressure ventilation (NPPV) and lung volume reduction surgery (LVRS) have also been examined for their effects on sleep. NPPV has been reported to improve gas exchange, reduce the number of sleep abnormalities, and increase the percentage of total sleep time and REM sleep in several studies.^26,27 However, others report no beneficial effect on sleep function, mortality, or any aspect of lung function.^28,29

A consensus conference of experts in the use of NPPV has recommended that NPPV be considered in patients with COPD when they exhibit the characteristics found in the Table.³⁰ However, these recommendations have not been validated by prospective controlled studies.

In one study, patients with COPD who had undergone LVRS had greater improvement in sleep parameters, such as total sleep time and sleep efficiency, than did those who received medical treatment.⁷ These improvements in sleep parameters were coupled with reductions in static lung volumes and airflow obstruction. The durability of these effects over time remains to be reported.

In patients with diagnosed sleep apnea, weight loss and nocturnal administration of continuous positive airway pressure or bilevel airway pressure may be indicated. The pressure levels used should be those shown to effectively alleviate the central and obstructive apneas during polysomnography.

Insomnia in COPD patients must be viewed for the physiological disturbances that occur with COPD. Worsening airflow obstruction, nocturnal hypoxemia and hypercapnia, secretions, and postural-induced increases in the work of breathing may all contribute to insomnia in this patient group. When these physiological abnormalities have been excluded as the cause of insomnia, the judicious use of short-acting hypnotic agents may have a role in carefully selected patients.

SUMMARY

Primary care physicians who care for patients with COPD must address the common mood disorders and sleep problems that these patients experience, in addition to managing their respiratory symptoms. During the limited amount of time available for each visit, only a few problems can be evaluated; however, over the course of many visits in a year, all of these issues can be addressed. Considering the relative importance and treatability of depression, anxiety, and sleep disorders, these conditions should be among the first that are assessed in any person with COPD.

References:

REFERENCES

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