Asthma is an inflammatory disease of the airways that occurs in about 5% of the population. It is characterized by episodic dyspnea and wheezing, reversible episodes of bronchoconstriction, and airway hyperreactivity to a variety of specific and nonspecific stimuli.

In a survey of asthmatic patients, 74% of subjects reported nocturnal awakenings at least once weekly, and 64% had one at least three times a week (1). In another group of asthmatic patients, nocturnal symptoms occurred less than once a week in 16% to 23% and at least once a week in 5% to 15% of subjects (2).

Patients with nocturnal asthma experience poor sleep quality and frequent arousals, resulting in sleep deprivation, irritability, and fatigue (1). Worsening of asthma at night or in the early morning occurs in over two-thirds of asthmatics, indicating nighttime bronchoconstriction (3). Besides normal sleep-related decreases in functional residual capacity (FRC), minute ventilation, and tidal volume, asthmatics have further abnormal reductions in these parameters during sleep that are attributed to increased airway responsiveness, increased airway secretions, and circadian changes in vagal tone, body temperature, cortisol, epinephrine, and inflammatory mediators (4, 5). Bronchoalveolar lavage fluid in patients with nocturnal asthma may show an increase in total leukocyte count, neutrophils, and eosinophils (6).

Polysomnographic (PSG) features of asthmatic subjects demonstrate increased wake time, less total sleep time, reduced sleep efficiency, increased number of awakenings, and greater wake time after sleep onset compared with normal subjects (7, 8). Nocturnal asthmatics who snore or have obstructive sleep apnea (OSA) show increased frequency of nocturnal asthma attacks. Although they are two distinct disease processes, nocturnal asthma and OSA often share overlapping symptoms of choking, coughing, and dyspnea. Continuous positive airway pressure (CPAP) therapy has been shown to improve asthma control and increase peak expiratory flow rate in this group of patients (9, 10).

Chronic obstructive pulmonary disease (COPD) (also called “chronic obstructive lung disease”) is a disease state characterized by airflow limitation that is relatively irreversible. The airflow limitation is usually associated with an abnormal inflammatory response of the lungs to noxious particles or gases and is progressive in nature (11). The inflammatory response of the lungs results in pathologic changes in the small airways and alveoli. Emphysema results when there is a predominance of alveolar destruction, whereas chronic bronchitis is the result of progressive airway narrowing because of excessive secretions blocking the lumen of the airways. Dyspnea and chronic cough are the chief complaints with which COPD patients usually present. Respiratory failure can complicate advanced cases, with hypoxemia and hypercapnia occurring during both wakefulness and sleep. The World Health Organization predicts that COPD will be the fifth most prevalent disease (currently 12th)
and the third most common cause of death (currently sixth) by 2020 (12).

Clinicians distinguish between two subtypes of COPD patients: blue bloaters and pink puffers. Blue bloaters have lower baseline arterial oxygen saturation (SaO₂), hence their blood will be bluer and they will experience larger falls in SaO₂ (especially during rapid eye movement [REM] sleep), more episodes of oxygen desaturation, and longer durations of oxygen desaturation while asleep than will pink puffers.

Patients with COPD sleep poorly compared with healthy subjects (13, 14, 15). The incidence of sleep complaints is related to the rates of respiratory symptoms in COPD patients. In the Tucson Epidemiologic Study of Chronic Lung Diseases, 28% of asymptomatic COPD subjects reported insomnia and 9% reported daytime sleepiness. Among subjects with one respiratory symptom, either cough or wheezing, 39% reported insomnia and 12% reported daytime sleepiness. When both cough and wheezing were present as respiratory symptoms, sleep complaints increased in patients, with 52% of them reporting insomnia and 22% reporting daytime sleepiness (16).

PSG features show reduced total sleep time, increased sleep stage changes, and increased arousal frequency. Arousals may or may not be related to hypoxemia. Fleetham et al. showed that reversal of hypoxemia with supplemental oxygen did not diminish arousal frequency. Oxygen therapy may or may not affect sleep quality (17, 18).

During sleep, COPD patients may develop significant oxygen desaturation, with the most severe desaturations occurring during REM sleep (14, 19, 20, 21). Sleep-related hypoxemic episodes are more common among blue bloaters than among pink puffers and occur during periods of hypoventilation, typically during REM sleep, because of the relative atonia of the intercostal muscles that occurs during REM sleep (20, 22, 23). Ventilatory abnormalities associated with decreased lung volumes (because, for instance, of obesity) also contribute to hypoxemia during sleep (24).

Overlap syndrome, also referred to as OLDOSA (obstructive lung disease and obstructive sleep apnea), is a term used for patients with coexisting COPD and/or asthma and OSA. A more severe course of sleep-disordered breathing is noted in subjects with coexisting COPD (25). Sleep studies are usually indicated in COPD when there is a possibility of sleep apnea or obesity-hypoventilation syndrome (26, 27, 28). A triad of respiratory alterations contributes to the physiologic derangements seen in overlap syndrome:

Several studies have shown that patients with COPD and OSA have more profound nocturnal oxygen desaturations and sleep disturbances compared with either disease alone. Additionally, reports from observational studies suggest increased mortality in overlap syndrome compared with COPD and OSA alone (Table 23-1) (30).

Although supplemental oxygen is the mainstay for COPD and sleep-associated desaturation alone, positive airway pressure, either CPAP or bilevel positive airway pressure (BPAP), combined with supplemental oxygen, is required for the overlap syndrome (31, 32). Some patients may respond better to BPAP than to CPAP (33).

Cystic fibrosis (CF) is a multisystem genetic disorder that primarily affects Caucasian infants, children, and young adults. It is characterized by abnormal transport of sodium and chloride across the epithelium in all exocrine tissues, leading to an increase in sweat sodium and chloride concentration. This inability to move salt and chloride in and out of cells results in thick viscous secretions in the lungs, pancreas, intestine, liver, and reproductive tract. Consequently, CF patients develop bronchiectasis and progressive lung disease, exocrine pancreatic insufficiency, intestinal dysfunction, abnormal sweat gland function, and urogenital dysfunction (34, 35, 36, 37, 38).

CF patients have poor sleep quality (39). Nonetheless, sleep latency and sleep efficiency are often normal in CF patients despite poor sleep quality (39). Exacerbations of lung disease in adults with CF adversely affect sleep and neurobehavioral performance regardless of underlying disease severity (40). A study of 40 children with CF in stable condition showed an early occurrence of OSA associated with a mild level of sleep disruption. Early routine nocturnal respiratory monitoring is advised in children with CF (41).

Cough, sleep fragmentation, medication side effects such as β-agonists, increased work of breathing, and hypoxemia have all been documented during sleep in CF patients. Episodic nocturnal hypoxia may lead to the development of pulmonary hypertension and cor pulmonale. Poor daytime function and quality of life have also been reported (42, 43). Noninvasive ventilation has been proposed as a means to temporarily reverse or slow the progression of worsening respiratory failure in CF (44).

Restrictive lung diseases are characterized by reduced lung volumes, either because of an alteration in the lung parenchyma or because of diseases of the chest wall, pleura, or neuromuscular apparatus. In the early stages, the patient may be totally asymptomatic, but with disease progression, exertional dyspnea, followed by dyspnea at rest, is commonly encountered. Restrictive lung diseases commonly associated with sleep-disordered breathing are obesity, kyphoscoliosis, interstitial lung disease, and pregnancy (45).

Patients with restrictive lung disease exhibit a wide range of respiratory and oxygenation abnormalities during sleep. The combination of restrictive severity (intrapulmonary as well as extrapulmonary) and confounding factors, such as obesity, age, and gender, determines the degree of disturbed nocturnal physiology (46). These patients often complain of disrupted sleep and excessive daytime sleepiness, often even before waking respiratory symptoms become discernible. Other sleep-related symptoms include apneas, awakenings, choking, unrefreshing sleep, and morning headaches (47).

PSG suggests that OSA is present in more than 50% of patients with restrictive lung diseases and nocturnal hypoventilation in more than 29% of severely obese individuals (48, 49, 50). REM sleep percentage and sleep efficiency are decreased in obese patients, but sleep-onset latency and REM latency can remain normal (48).

In patients with kyphoscoliosis, a spectrum of breathing abnormalities can be found, ranging from no abnormalities to obstructive apneas/hypopneas and central apneas (51, 52, 53). Patients with interstitial lung disease often demonstrate transient or sustained nocturnal desaturation during REM sleep, disturbances in sleep quality, increase in stage N1 sleep, reduction in REM sleep, and an increase in the number of arousals (54, 55, 56, 57). During pregnancy, sleep quality is poor, with reduced sleep efficiency, increased nocturnal awakenings, increased stage N1 sleep, reduced REM sleep, increased daytime fatigue, and louder or more frequent snoring (58, 59, 60, 61, 62).

The diaphragm is the primary muscle of ventilation. When contracted, the diaphragm descends downward, increasing thoracic volume while decreasing intrapleural pressure. The change in intrapleural pressure creates a pressure gradient and allows air to flow into the lungs. A single anatomic structure, the diaphragm has two halves individually innervated by branches of the phrenic nerve. The individual nerve supply allows each half to function independently of the other, although in normal diaphragmatic function, both halves move synchronously.

The most common causes of bilateral diaphragmatic paralysis are high spinal cord injury, thoracic trauma, multiple sclerosis, anterior horn disease, and MD. Unilateral paralysis of the diaphragm is much more common
than is bilateral paralysis and may be caused by phrenic nerve damage because of trauma, surgery, radiation, tumor, or neuropathy. Unilateral diaphragmatic paralysis is associated with nocturnal hypoxemia but, in the absence of systemic lung disease, it does not generally lead to chronic respiratory failure or cor pulmonale (88).

During REM sleep in normal persons, ventilation depends primarily on diaphragm function. In patients with diaphragm dysfunction, during both REM sleep and wakefulness, electromyographic activity of the extradiaphragmatic respiratory muscles is higher than normal as a compensation for diaphragm weakness (89). Patients with diaphragmatic paralysis have reduced REM and stage N3 sleep. Patients with unilateral diaphragm dysfunction are at risk of developing sleep-disordered breathing during REM sleep (89). Bilateral diaphragmatic paralysis can be associated with sleep apnea (90). Watanabe et al. (91) reported a case of central sleep apnea (CSA) accompanied by bilateral paralysis of the diaphragm after pediatric cardiac surgery. Hoffstein and Taylor described a rapid development of OSA following hemidiaphragmatic and unilateral vocal cord paralysis as a complication of mediastinal surgery (92).

It had been hypothesized that patients with bilateral diaphragmatic paralysis might not be able to sustain REM sleep. However, Bennett et al. (93) observed that patients with bilateral diaphragmatic paralysis had a normal quantity of REM sleep achieved by inspiratory recruitment of extradiaphragmatic muscles in both tonic and phasic REM, suggesting brainstem reorganization.

Gastroesophageal reflux (GER) is caused by a backflow of gastric acid and other gastric contents into the esophagus because of incompetent barriers at the gastroesophageal junction. The pathogenesis of GER is multifactorial, involving transient lower esophageal sphincter (LES) relaxation as well as other LES pressure abnormalities. Other factors contributing to the pathophysiology of GER include the presence of a hiatal hernia, poor esophageal clearance, delayed gastric emptying, and impaired mucosal defensive factors (94).

Regurgitation of gastric contents into the mouth and heartburn are the characteristic symptoms of GER. Reflux of acidic stomach contents into the pharynx, larynx, and tracheobronchial tree can cause chronic cough, bronchoconstriction, pharyngitis, laryngitis, bronchitis, or pneumonia. Morning hoarseness may be noted. Recurrent pulmonary aspiration can cause aspiration pneumonia, pulmonary fibrosis, or chronic asthma. Reflux in the sleeping horizontal person is exacerbated by delayed acid clearance secondary to decreased esophageal motility, and reduced salivation and swallowing.

Several studies have reported an association between OSA and GERD. On the one hand, GERD may play a role in the development of OSA by causing upper airway inflammation and obstruction. Acid suppression with proton pump inhibitors resulted in improvement of the apnea index in OSA patients in a small nonrandomized study. On the other hand, OSA may lead to GERD because of increased intrathoracic pressure, and treatment with CPAP has been shown to improve nocturnal heartburn and regurgitation, as well as distal esophageal acid exposure and frequency of acid reflux episodes (95).

The negative impact on quality of life may be greater in nocturnal GER than in daytime GER. In a large nationwide telephone survey in the United States, 79% of respondents reported having heartburn symptoms at night, of which 75% stated that their sleep was affected by heartburn, and 63% noted that heartburn had an impact on their ability to sleep well (96). Farup et al. (97) found a prevalence of 10% for nocturnal GER, with 74% of respondents who reported frequent GER symptoms having nocturnal GER.

GER is estimated to be present in 50% to 60% of asthmatic children and 60% to 80% of adult asthmatics (98). A study conducted by Wasilewska and colleagues reported a possible association between nocturnal GER and sleep-related breathing disorders in children. Higher numbers of apneas and hypopneas during REM sleep were found in children with nocturnal GER (99). Demeter et al. (100, 101, 102) noted that in patients with severe OSA, erosive reflux disease is more frequent, and a positive correlation between severity of reflux disease and sleep apnea has been reported by some, but not all, investigators.

PSG findings in GERD patients include an increased arousal index and decreased duration spent in the deeper stages of sleep (103).

Functional bowel disorders are characterized by chronic gastrointestinal tract symptoms without significant anatomic, metabolic, or infectious abnormalities. They can affect the entire digestive tract. These disorders include functional dyspepsia (FD), diarrhea, constipation, abdominal bloating, abdominal pain syndrome, and irritable bowel syndrome (IBS).

Patients with functional bowel disorders have a high incidence of sleep complaints as well as abnormalities of autonomic functioning. The measurement of autonomic functioning during sleep can differentiate the patients with functional bowel disorders from normal controls (104, 105). Patients reported significantly more dissatisfaction with their sleep quality and increased
daytime fatigue as a result of both insomnia-type symptomatology and nonrestful sleep (106, 107).