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9. sleep disorders &copd

Chapter: 9
Kimberly A. Hardin MD, MS, MCR, FAASM

COPD affects 24 million people in the USA and is projected to be the 3rd leading cause of
death worldwide by the year 2020. COPD is the 7th leading cause of disability in the USA
resulting in significant morbidity and impaired quality of life (QOL). Little is known
regarding the sleep patterns in patients with COPD or how altered sleep may impact
clinical outcomes. I will review the data on sleep quality in COPD patients, factors that
disturb sleep, the effect of normal sleep on respiratory function and how this can impact
the patient with COPD, and suggest sleep improving strategies.
Sleep Quality in COPD
Approximately 40% of patients with severe COPD complain of difficulty initiating and
maintaining sleep or other sleep disturbance. Additionally, polysomnography (PSG) has
demonstrated increased sleep latency, decreased total sleep time (TST), poor sleep
efficiency, decreased slow wave sleep (SWS) and REM sleep, as well as an increase in
the number of arousals and early morning awakenings causing fragmented sleep (NETT
trial). COPD patients are also shown to have more nocturnal wakefulness (30%) than
control subjects.
Factors that Contribute to Sleep Disruption
Insomnia and daytime sleepiness is more prevalent in COPD patients with nighttime
cough, dyspnea, or wheezing. Other factors that may cause sleep fragmentation include
pain, frequent urination, inability to lie flat, or other co-morbid condition. Co-existent
sleep disorders are present in 10-20% of individuals with COPD, such as snoring,
periodic leg movement (PLMD) and restless leg syndrome (RLS) that are often un-
diagnosed or un-treated.
Medications used to treat COPD can affect sleep quality. Beta-adrenergics if taken in
higher dosage may cause insomnia. However, if bronchoconstriction is present, then a
beta-agonist improves sleep. Long-acting anticholinergic, tiotropium, improves sleep
quality, but the effect may diminish over time. Oxygen therapy can have a positive effect
on sleep quality.
All these abnormalities contribute to COPD patient’s complaints of excessive daytime
sleepiness (72%), impaired daytime concentration (32%) and fatigue, which can interfere
with performing daily activities, QOL, and are associated with more pronounced

Normal Respiratory Changes during Sleep
Normal sleep is associated with the loss of voluntary respiratory control and breathing
becomes dependent on metabolic or gas exchange components. Ventilatory responses to
both hypercapnia and hypoxemia are decreased due to decreased medullary chemo-
responsiveness. This becomes more pronounced during REM sleep when there is a loss
of intercostal and accessory muscles activity leaving the diaphragm to maintain adequate
work of breathing and minute ventilation. Minute ventilation decreases by ~10% in
healthy subjects during NREM and Pa02 may decrease by 2-8mm Hg with an increase in
PaC02 by 3-10mm Hg. Additionally there is increased upper airway resistance due to
decreased pharyngeal dilator muscle activity. Airflow obstruction and hypoventilation
result in ventilation/perfusion abnormalities that do not impact overall respiratory
function or gas exchange in healthy individuals.
Effect of Respiratory Function during Sleep in COPD Patients
Nocturnal hypoxemia and impaired gas exchange are known to cause significant
morbidity and mortality in COPD. Indeed, to date, only oxygen therapy has been shown
to improve mortality and exercise tolerance (NOTT trial). Hypoventilation, altered
neuromuscular function, and changes in breathing patterns that are expected during
normal sleep can cause profound respiratory impairment in patients with COPD (1).
Normal alterations in respiratory mechanics and gas exchange that occur during sleep can
result in substantial nocturnal oxygen desaturation in patients with COPD. Koo et al
studied 15 patients with severe COPD (FEV1 0.96 liters) and found a mean decrease in
nocturnal Pa02 of 13.5mm Hg, despite a lack of daytime hypoxemia (Pa02 >60mm Hg)
reflecting the potential deleterious effects that can occur during sleep. Forced expiratory
volume in one second (FEV1) correlates poorly with the degree of oxygen desaturation
that may occur during sleep. Daytime oxygen saturation is the best predictor of sleep
desaturation. Individuals with lower baseline daytime oxygenation are more susceptible
to developing sustained nocturnal oxygen desaturation. Those with impaired
diaphragmatic function (emphysema) are especially vulnerable during REM sleep where
minute ventilation has been shown to drop by 32% resulting in hypoxemia and
hypercapnia. These factors may lead to the same sequelae that occur in patients with
obstructive sleep apnea (OSA): impaired sleep quality, arrhythmias, vascular endothelial
injury, myocardial ischemia, pulmonary hypertension and cor pulmonale with possible
decreased survival.

The Overlap Syndrome
Obstructive sleep apnea (OSA) is present in 10-15% of COPD patients and is known as
the “Overlap Syndrome”. Patients with Overlap Syndrome (COPD + OSA) have a
compounded affect on respiratory mechanics and oxygenation that can result in profound
intermittent oxygen desaturation and/or sustained hypoxemia that would not be as severe
with each disease process alone. Patients with only OSA may have severe oxygen
desaturation with apneic episodes, but usually are able to restore oxygenation in between
the apneas. Patients with Overlap Syndrome, even if the OSA component is milder, are
often incapable of regaining oxygenation in between apneas due to pre-existing lung
Alternatively, patients with chronic daytime hypoxemia and/or hypercapnia may have a
less sensitive arousal threshold to oxygen desaturation associated with snoring or apneic
episodes and sleep through these more severe oxygen desaturations. This can create
greater daytime gas exchange abnormalities.
Medical management with long-acting bronchodilators is the mainstay of therapy for
COPD. Tiotropium has been shown to improve sleep duration and decrease awakenings,
and patients have fewer excerbations. Oxygen therapy is indicated for daytime
hypoxemia following the ATS/ERS recommendations. The potential benefit of nocturnal
oxygen is to reduce the profound decrease in oxygenation that occurs during sleep that
create arousals and sleep fragmentation. Continuous positive airway pressure
(CPAP/BIAPAP™) may improve daytime function in patients who have daytime carbon
dioxide retention, Overlap Syndrome, and sleep respiratory failure that is not corrected by
oxygen therapy, congestive heart failure, and patients with nocturnal asthma. Studies
have been small with inconsistent results in measuring sleep quality. No controlled
studies have been conducted on the effect of positive pressure in patients with Overlap
Additional strategies to improve sleep include promoting sleep hygiene by advising
patients to go to bed and get up at the same time each day in order to facilitate a circadian
rhythm. Exercise should be in the morning. The bedroom should be only for sleep and
sex, not eating or watching television. Medications, such as diuretics, should be taken
early in the daytime. More frequent, light meals should be eaten instead of heavier
evening meals. Avoid alcohol and sedatives if possible. Underlying sleep disorders
described above should be treatment. Lastly, short term use of a non-GABA agent, such
as melatonin agonist may be tried and has been shown to improve sleep initiation and
does not suppress respiration in COPD patients.

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