SECTION 4 - SLEEP AND HEALTH

Sleep in Medical Conditions

Background

Individuals with a variety of common medical illnesses—including adult and juvenile arthritis , asthma , cancer , cardiopulmonary diseases, chronic fatigue syndrome (CFS), diabetes , end-stage renal disease (ESRD ), fibromyalgia (FM) , human immunodeficiency virus (HIV ), irritable bowel syndrome (IBS), obesity , and temporomandibular joint disorders (TMJD) — frequently experience sleep disturbances. It is recognized that medical illnesses can adversely affect sleep quality , and that pain , infection, and inflammation can induce symptoms of excessive daytime sleepiness and fatigue. It is less clear, however, how sleep quality affects disease progression and morbidity. In addition, patients with these medical illnesses may also have a primary sleep disorder (see Section V) that further contributes to significant morbidity. The role of sleep disturbances and sleep disorders in the morbidity of most chronic conditions is understudied in children and adults and, as a result, is poorly understood. Similarly, how sleep disturbances affect responses and adherence to medical therapy for the primary illness and the best ways to manage disturbed sleep in most chronic conditions is understudied. The relationship between sleep processes and the development, progression, and management of chronic diseases, therefore, requires further study.

Insomnia associated with abnormal sleep architecture is most evident in disorders characterized by known structural pathology, e.g., arthritis , cancer , heart failure, and ESRD. In chronic pain-related conditions without known structural pathology (e.g., FM, CFS, IBS), the most striking observation in these “unexplained disorders”, is a self-report of poor and nonrestorative sleep that is often out of proportion to modest changes in objective measures of sleep. This discrepancy between subjective and objective sleep indicators has been studied extensively in FM and is most evident when patients are selected on the basis of appropriate case definition, compared to women of similar age, and screened for psychiatric disorders, particularly depression . Insomnia in these chronic conditions is known to exacerbate symptoms of pain, fatigue , and daytime sleepiness , negatively impact work performance, social and family relationships, quality of life , and increase use of health care services. Controversy still exists, however, regarding the clinical significance and diagnostic value of abnormal sleep physiology in these unexplained disorders.

Sleep is considered restorative and important for illness recovery. It remains unknown, however, whether sleep actually facilitates recovery processes. Clinicians advise patients to “get plenty of sleep” during an acute febrile illness or following surgery or trauma , but sleep is often fragmented and disrupted. These sleep disturbances are considered “incident” or “transient” forms of insomnia that are treated readily with hypnotic medications and often resolve with recovery. However, mutually exacerbating effects of disturbed sleep and primary illness may be a significant barrier to full recovery. The role of acute illness-related insomnia in the development and pathogenesis of chronic conditions both in children and adults is understudied and perhaps underestimated. In addition, the impact of acute care environments in exacerbating sleep disruption and further limiting successful implementation of medical or behavioral regimens is understudied.

Progress in the Last 5 Years

•  Asthma and other pulmonary diseases commonly exacerbate during sleep, but the mechanisms involved are poorly understood.

•  There is an association between daytime sleepiness and cardiovascular disease-related morbidity and mortality (e.g., hypertension , myocardial infarction, and congestive heart failure ).

•  Severity of diabetes is directly associated with severity of distur bed sleep, and partial sleep deprivation of healthy adults increases insulin resistance .

•  Patients with ESRD have disrupted nocturnal sleep with excessive daytime sleepiness and the timing of dialysis treatment affects mortality. ESRD patients on dialysis have among the highest incidence of both SDB and periodic leg movements (PLMs) in sleep, and PLMs are a significant predictor of survival and mortality in this population.

•  Sleep disturbance and fatigue are highly prevalent and disabling symptoms in a majority of individuals infected with HIV . Recent findings suggest that symptoms of sleep disturbance and fatigue are independently associated with survival among people with HIV infection. However, sleep disturbances in children and adults with HIV remains understudied, underdiagnosed, and, therefore, undertreated.

•  “Unexplained disorders” are more prevalent in females than in males, but the biologic basis of this sex difference is poorly understood. Failure to identify a structural basis for these disorders has led some researchers and clinicians to embrace sociocultural explanations that can bias research and care.

•  Altered timing and reduced nocturnal concentrations of sleep-dependent hormones (e.g., growth hormone, prolactin , melatonin ) have been described in a number of chronic conditions and are possibly linked with altered sleep physiology and reduced sleep continuity.

•  Lack of altered circadian rhythms observed in FM patients coupled with lower concentrations of sleep-dependent hormones (growth hormone and prolactin ) in other studies, underscores the possibility of dysfunctional homeostatic sleep regulation as a basis for symptoms of poor sleep and fatigue .

•  Pain is a major factor associated with disrupted sleep in many chronic conditions. Experimental studies in healthy young men and in animals show reduced responsiveness to noxious stimuli during sleep, but the mechanisms involved in sleep-related pain modulation are unknown.

•  Neuroimaging studies have identified areas of the thalamus and basal ganglia that may be hypofunctional in women with FM and hence may contribute to abnormal sleep physiology.

Research Recommendations

•  As the United States ' population ages, the number of people living with chronic medical illnesses will increase dramatically in the next two decades. It will be important to identify chronically ill populations at highest risk for sleep disturbances, determine the factors most associated with disturbed sleep, and the best ways to improve such sleep disturbances. There is also a need to understand how sleep disturbances affect adherence to treatments for chronic disease and ways that improving sleep may improve treatment outcomes.

•  Study the bidirectional relationship between sleep processes and disease development, progression, and morbidity. Determine identifiable, measurable characteristics of sleep quality that could serve as potential indicators of primary disease diagnosis, progression, and severity. Such markers might indicate how sleep regulation and timing are reciprocally coupled to disease pathophysiology.

•  Epidemiological and clinical research is needed in children and adults to elucidate the benefits of sleep, the risks associated with insufficient sleep during an acute illness, and the extent of unresolved acute illness-related insomnia. The beneficial outcomes associated with improved sleep during illness using behavioral , pharmacological, and environmental approaches need to be explored.

•  Conduct interdisciplinary basic science studies of the effects of pain and inflammation on sleep physiology both in animals and in humans.

•  Conduct experimental challenge studies using sleep delay or partial sleep deprivation to assess the extent of homeostatic sleep regulation dysfunction in chronic illnesses.

•  Study sleep, neuroendocrine and autonomic functioning in newly diagnosed patients with FM compared to patients with CFS and with primary insomnia. Studies of children, adolescents, and young women should be particularly informative.

•  In patients with chronic illness, determine the effectiveness of self-management strategies (e.g., cognitive -behavioral and sleep hygiene) designed for treating primary insomnia, in relieving symptoms and improving clinical outcomes.