Current Respiratory Medicine Reviews - Volume 5, Issue 4, 2009

Patients with a variety of pulmonary disorders commonly have distinct abnormalities related to sleep. These include poor sleep quality [1] and the development of nocturnal oxygen desaturation [2]. Patients with lung disease commonly develop insomnia - either manifesting as difficultywith initiating or maintaining sleep or both [3]. Sleep is associated with physiologic changes in ventilatory behavior which include changes in ventilatory control and thoracoabdominal muscle activity that are sleep stage specific [4], besides also influencing upper airway dilator muscle activity, resulting in changes in upper airway resistance with sleep onset [5]. These alterations, coupled with the effects of supine body position and its effects on lung volume, [6] become especially significant in patients with chronic lung disease and with limited pulmonary reserve and manifest with distinctive clinical presentations. Patients with co morbid obesity present with a unique set of manifestations commonly related to the presence of obstructive sleep apnea, [7] and in a subset of these patients hypoventilation syndromes characterized by daytime hypercapnea and cor pulmonale [8]. Circadian factors also play a role in determining pulmonary function and this effect is most commonly observed and clinically very relevant in patients with chronic asthma [9]. Nocturnal oxygen desaturation may be either intermittent in relation to sleep-disordered breathing or sustained. A variety of mechanisms contribute to the latter process, and it is especially relevant in patients with parenchymal lung disease such as emphysema [10] as well as in patients with pulmonary vascular disease and pulmonary hypertension [11]. Besides, patients with end-stage lung disease develop chronic hypercapneic respiratory failure and require non-invasive positive pressure ventilation [12] - newer modalities of providing such ventilatory support are gaining ground including average volume assured pressure support ventilation [13]. A variety of factors including low oxygen levels, and ventilatory disturbances, may lead to poor sleep quality in patients with chronic lung disease. Medications used to treat common pulmonary diseases are also seen to have important effects on sleep [14]. Sleep disturbances may lead to daytime fatigue and this in turn may lead patients to adopt poor sleep habits characterized as poor sleep hygiene and thus setting up a vicious cycle that may lead to chronic sleep onset as well as sleep maintenance insomnia. A number of unanswered important questions remain, including determining which factors contribute most, and are best predictive of nocturnal desaturation, and poor sleep quality in patients with chronic pulmonary disease. In addition, it is yet to be determined to what extent poor sleep quality in these patients affects daytime function, including mood, neuro-cognitive function, and overall quality of life, whether interventions such as NPPV are able to predictably improve these parameters, and what is the optimal strategy specific to improving sleep health in patients with pulmonary disease.

Nocturnal asthma is a significant clinical problem in asthmatics that can lead to sleep disruption, daytime fatigue and hypersomnolence. There is increased sleep latency, reduced sleep efficiency and reduction in slow wave sleep. Circadian changes in airway lumen are exaggerated in nocturnal asthma. Hormonal variations at night, increased airway hyperreactivity with inflammation, decreased lung volume and increased intrathoracic blood volume contribute to the pathophysiology. Nocturnal asthmatics demonstrate a reduction in glucocorticoid receptor binding affinity at night as well as an increase in the glucocorticoid receptor splice variant which reduces the efficacy of steroids. Both the number and physiologic function of beta-2 receptors are significantly decreased from 4 PM to 4 AM in asthmatics with nocturnal worsening compared to non-nocturnal asthmatics and normal controls. Chronotherapeutically administered steroids may have an additional role in control of nocturnal asthma. There is a high prevalence of OSA in patients with asthma. This appears to be bidirectional relationship. Females are affected with both concomitantly more often than males. OSA augments asthmatic inflammation at night. Treatment with CPAP improves asthma control without affecting lung functions or airway hyperreactivity.

Chronic obstructive pulmonary disease is one of the most common disease affecting millions of people worldwide. It is a multicomponent disease which beside airflow obstruction causes airway inflammation, structural changes, mucociliary dysfunction and systemic dysfunction. Airway responsiveness is altered during sleep along with decrease in ventilation due to reduction in tidal volume. Patients with COPD also develop significant nocturnal desaturation despite adequate oxygenation during the wake state. Almost 14% of patients with COPD also have concurrent obstructive sleep apnea, which in turn can lead to more desaturation, hypoxia and hypercarbia. The COPD can affect the quality of life by causing insomnia, excessive day time sleepiness, fatigue, morning awakening, and poor sleep quality. In the current article we will address the issues of oxygenation during sleep, effects of combination of COPD and OSA, quality of sleep in COPD patients and different therapeutic options to counter the effects of COPD on sleep.

Patients with interstitial lung disease (ILD) suffer from poor quality of life and increased mortality. The poor quality of life is multifactorial, attributable in large part to respiratory symptoms and limitations, medication side effects, and the psychiatric effects of chronic illness. Sleep is affected by these same stresses, resulting in poor sleep quality and sleep disordered breathing. Sleep fragmentation, arousals, and Stage N1 sleep are all increased in patients with ILD. Sleep disordered breathing, in the form of nocturnal hypoxia and obstructive sleep apnea, is common in these patients as well. These sleep disorders are associated with indices of poor quality of life and excessive daytime sleepiness, and may be targets of therapy for the overall management of patients with ILD.

Pulmonary hypertension in obstructive sleep apnea syndrome is common and under recognized. Although more common in patients with OSA associated with chronic lung disease, it is still present in about 20% of patient without co morbid lung or heart disease. Various pathophysiologic changes in OSA especially nocturnal oxygen desaturation, intrathoracic pressure swings, abnormalities in lung mechanics, alteration in ventricular function and rheological changes can contribute to the presence and severity of pulmonary hypertension. The clinical profile in individuals with OSA and pulmonary hypertension are different than in patients with OSA who do not have pulmonary hypertension. Effective treatment of OSA with n CPAP for 12 weeks results in improvement in pulmonary artery pressure.

Sleep problems are common in pediatric patients with chronic respiratory disorders. Nocturnal awakenings are frequent in children with asthma. Chronobiologic rhythms impact the pathophysiology of nocturnal asthma. Poor sleep quality can lead to impaired school performance, neurocognitive defects and attention problems in children. As lung function worsens sleep disruption becomes more prominent in patients with cystic fibrosis. Bronchopulmonary dyplasia has been associated with hypoxia during sleep. These infants have been reported to have reduced total sleep time, sleep fragmentation and reduced REM sleep. Nocturnal respiratory variations are exaggerated at night in children with sickle cell disease and the nocturnal hypoxia has been associated with painful crisis. Adenotonsillar hypertrophy with attendant obstructive sleep apnea worsen these episodes in sickle cell disease. In children with kyphoscoliosis hypoventilation at night worsens during REM sleep. Nocturnal hypoventilation generally precedes respiratory failure. Sleep-disordered breathing with excessive daytime sleepiness has been well described in pediatric neuromuscular disorders. Abnormal sleep patterns including sleep-disordered breathing occur in infants with apnea of prematurity and sudden infant death syndrome. Further research in this diverse group of sleep disorders in children exploring the pathophysiology and treatment is essential.

Sleep disturbances due to medications is a common problem. The effects can vary from mild insomnia to major alterations in sleep architecture. The factors affecting the sleep disturbances can be related to the patient or the drug. In this review article we have focused on the side effects due to medication commonly used in pulmonary medicine. The group of drugs discussed are corticosteroids, bronchodilators, leukotriene antagonists, methylxanthines, antihistamines, immunosuppressive medications and prostaglandins. Most evidence comes from studies involving small number of healthy volunteers, retrospective reports, or sleep disturbance reported during clinical trials. Though most of these medications have the potential to cause sleep disturbances, they may actually promote better sleep by improving the respiratory symptoms, especially in asthmatics and COPD patients. It is important that the clinician needs to be aware of these side effects so that the effects can be minimized by making appropriate adjustments to the drugs, making the patient aware of the side effects, counseling on good sleep hygiene and behavioral changes.

Cystic Fibrosis (CF) is a chronic, multi-system disorder that primarily affects the lungs, and pancreas, and leads to significant and progressive bronchiectasis, and subsequently end-stage lung disease. Sleep disturbances in cystic fibrosis include nocturnal hypoxemia due to a variety of physiologic changes including ventilation-perfusion mismatch, changes in mechanics of breathing. Derecruitment of ventilatory muscles, particularly during REM sleep and resultant hypoventilation may also be contributory, and may also lead to sleep-disordered breathing in these patients. Other potential causes of sleep disruption in CF patients include nocturnal wheezing and cough, as well as side effects of medications such as β-agonists, as well as chronic pain syndromes. It is likely that sleep fragmentation contributes significantly to impaired quality of life in CF patients. Nocturnal ventilation has been shown to improve symptoms, reverse hypoventilation and increase exercise capacity in CF patients.

Sleep disturbances are very common in cancer patients. They are part of a symptom cluster with fatigue and pain that greatly affect quality of life in these patients. Lung cancer patients are found to have the highest prevalence of sleep disturbances. However, these disturbances have not been as well-studied in the lung cancer patients. Though insomnia is the most common disorder seen in these patients, other sleep disorders like excessive daytime sleepiness, limb movement disorders and circadian rhythm disorders have also been described. Treatment of these disorders may affect the prognosis of patients with lung cancer. More studies should be done to elucidate the details of sleep disturbances in lung cancer patients.

One of the first devices to successfully employ the principles essential to rocket flight was a wooden bird. Somewhere around the year 400 B.C., Archytas mystified and amused the citizens of Tarentum by flying a pigeon made of wood. Escaping steam propelled the bird suspended on wires. The pigeon used the action-reaction principle, which was not to be stated as a scientific law until the 17th century. During the latter part of the 17th century, the great English scientist Sir Isaac Newton laid the scientific foundations for modern rocketry. In 1926, an American, Robert H Goddard, launched the first liquid propellant rocket, and discussed the possibility of a rocket reaching the moon. On October 1957, the Soviet Union stunned the world by launching an Earth-orbiting artificial satellite. Physiological studies in microgravity are young. It is clearly essential to have long-term studies of physiology in microgravity if further space exploration is to take place. For example, a Mars mission will take of the order of 1,000 days, which is about three times longer than anybody has been in space so far.

The association of malignant lymphoma with subsequent development of a solitary chest wall mass is uncommon. Diffuse large B-cell lymphoma is a subcategory of non-Hodgkin's lymphoma that commonly affects the stomach, thyroid, parotid glands, and lungs. There is a defined association between preexisting inflammation and the development of these lymphomas. It is also well known to have a predilection to disseminate to extranodal sites in a noncontiguous manner and has been previously reported to affect the chest wall in less than 100 cases. We present the case of an enlarging chest wall mass with an associated lymphomatous pleural effusion found to be an unusual presentation of diffuse large B-cell lymphoma.

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder, characterized by repeated disruptions of breathing during sleep. This disease has many potential consequences including excessive daytime sleepiness, neurocognitive deterioration, endocrinologic and metabolic effects and decreased quality of life. Patients with OSAS experience repetitive episodes of hypoxia and reoxygenation during transient cessation of breathing that provoke systemic effects. Furthermore, there may be increased levels of biomarkers linked to endocrine-metabolic and cardiovascular alterations. Epidemiological studies have identified OSAS as an independent comorbid factor in cardiovascular and cerebrovascular diseases and physiopathological links may exist with onset and progression of heart failure. In addition, OSAS is associated to other disorders and comorbities which worsen cardiovascular consequences, such as obesity, diabetes, and metabolic syndrome. Metabolic syndrome is an emerging public health problem that represents a constellation of cardiovascular risk factors. Each single component of the cluster increases total cardiovascular risk, but the combination of factors is even more significant. Both OSAS and metabolic syndrome may exert negative synergistic effects on the cardiovascular system through multiple mechanisms (eg., hypoxemia, sleep disruption, activation of the sympathetic nervous system, inflammatory activation). Continue positive airway pressure (CPAP) therapy for OSAS provides an objective improvement in symptoms and cardiac function, decreases cardiovascular risk, improves insulin sensitivity and normalizes biomarkers. OSAS contributes to the pathogenesis of cardiovascular disease independently and by the interaction with comorbities. The present review focuses on indirect and direct evidence regarding mechanisms implicated in cardiovascular disease among OSAS patients.