Sleep Deficiency: A Symptoms Perspective: Exemplars from Chronic Heart Failure, Inflammatory Bowel Disease, and Breast Cancer

Introduction

Excessive daytime sleepiness (EDS) and fatigue are important and disabling consequences of sleep deficiency. Sleep deficiency includes short, prolonged, fragmented, mistimed, and/or irregular sleep, as well as specific sleep disorders. Both fatigue and EDS are common in the general population and have multiple demographic, social, clinical, environmental, and behavioral determinants, in addition to sleep deficiency.^1–7 Sleep deficiency and sleep disorders, such as sleep disordered breathing and insomnia, are also prevalent among people with common chronic medical and psychiatric conditions (e.g., cancer, heart disease, metabolic disease, depression) and may contribute to EDS and fatigue, as well as disease pathology (e.g., worsening heart failure, immune function). In turn, EDS⁵ and fatigue contribute to decrements in quality of life, cognition, performance, safety, and other aspects of daily function, including the ability to perform self-care, adhere to treatment and self-manage chronic conditions^5,8 – all of which are important to health and quality of life outcomes among people with chronic conditions. Thus, these symptoms warrant attention to predict risk of negative health outcomes and serve as targets for intervention. The purpose of this paper is to discuss the contributions of sleep deficiency and sleep disorders to fatigue and EDS among people with chronic conditions. We use exemplars from the literature on chronic heart failure (HF), inflammatory bowel disease (IBD), and breast cancer (BC) to (1) describe the prevalence of fatigue and EDS and their consequences; (2) examine the evidence for the contributions of sleep deficiency and sleep disorders to these symptoms; and (3) recommend implications for future research and practice to address sleep-deficiency and sleep-related daytime symptoms.

Fatigue and EDS are highly prevalent and separate, but often overlapping, phenomena that are both consequences of sleep deficiency and sleep disorders, although sleepiness is thought to be a more specific response than fatigue to sleep loss. These symptoms are often conflated in clinical practice and research. However, differentiating them is critical to accurate diagnosis and treatment^9–11 and to addressing their negative effects. For example, people with insomnia are often not sleepy, but may report fatigue.^1,10 EDS is considered a cardinal sign of sleep apnea but people with sleep apnea also report fatigue.¹⁰ Interventions for both fatigue and sleepiness may include a focus on sleep deficiency and specific sleep disorders, as well as attention to disease characteristics and other determinants.

Fatigue is a patient-reported outcome that has been defined in various ways (e.g., “vital exhaustion,” “tiredness”) and levels of fatigue do not consistently track with the severity of pathophysiology. The Patient Reported Outcome System group defined it as “an overwhelming, debilitating and sustained sense of exhaustion that decreases the ability to function and carry out daily activities.”¹² However, fatigue may also be characterized by both physical and psychological dimensions and distinguished by its acute versus chronic nature. Fatigue has also been described as central (arising from the central nervous system) and peripheral (arising from the peripheral nervous system or musculature), although there are variations within these conceptualizations.¹³ As a patient-reported phenomenon, fatigue is measured with a variety of self-report formats, including questionnaires, visual analog scales, and other methods that use various time frames and dimensions (e.g., severity, impact, frequency).

Although data are conflicting due to the wide variety of measurement methods and populations studied, the prevalence of fatigue ranges from about 22% to 32% in adults and older adults in the general population ^1,4 Fatigue is more frequently reported by women than men and more prevalent among people with chronic medical and psychiatric conditions. Fatigue also depends on the severity of the disease, trajectory of the condition (e.g., remissions vs. exacerbations), treatment phase, and other factors, although these physical characteristics do not always correspond with fatigue severity. Chronic fatigue and cancer fatigue are generally considered to be a pathological phenomenon that are not relieved by rest or sleep. However, increasing evidence suggests that sleep deficiency is an important and often modifiable contributor to multiple aspects of fatigue, and sleep extension has been shown to improve it.¹⁴

The International Classification of Sleep Disorders (ICSD)¹⁵ defines EDS as difficulty staying awake and alert during the major waking period. EDS has been operationalized as both a symptom (based on self-report) and a sign (measured with objective testing, such as the multiple sleep latency test), and these measures often are often discrepant.^11,13,16 Disorders of hypersomnolence that are primarily characterized by sleepiness represent a separate class of sleep disorders in the ICSD and do not explain the EDS that is a consequence of other forms of sleep deficiency.¹⁷ EDS may also be a disorder of altered consciousness.¹⁸ Sleepiness has been measured as both an acute and chronic phenomenon. It is responsive to acute sleep loss, but also a chronic symptom. Measurement includes both objective (i.e., multiple sleep latency test, maintenance of wakefulness test, and psychomotor vigilance) and acute (i.e., Stanford Sleepiness test) and chronic (Epworth Sleepiness Scale) self-report approaches. Each may elicit different attributes.¹¹ EDS is only resolved by obtaining adequate sleep¹⁸ and is considered a specific response to sleep loss, with the exception of sleepiness associated with the use of sedating medications.

EDS is estimated to occur in between 9 and 28% of adults.^3,7 This wide range may be due to the use of a variety of measurement methods and specific characteristics of the populations studied. A recently completed population-based study of over 2000 community-residing adults that used the Epworth Sleepiness Scale, a well-validated self-report measure, revealed that 33% of participants reported EDS at baseline. Short sleep, sleep apnea, insomnia, and chronic medical conditions were statistically significant predictors of EDS. Prevalent EDS, described as “difficulty staying awake and alert during the major waking period,” was reported in 23%⁵ to 33%² of participants in separate studies; 28% of participants had incident sleepiness over 5 years.²

Sleep Disturbance, Fatigue, and Sleepiness among People with Chronic Heart Failure

People with chronic heart failure (HF), a group of almost 6.5 million Americans¹⁹ and over 26 million people worldwide,²⁰ often report sleep disturbance, fatigue, and EDS. As many as 75% of people with HF report poor global sleep quality;^6,21 people with HF also have more fragmented sleep and wake after sleep onset, but no shorter sleep duration than a healthy comparison group.²¹ About half of people with HF reported difficulties initiating and maintaining sleep, and wakening too early²² – symptoms suggestive of insomnia,²³ and from 40–81% of people with HF have significant sleep disordered breathing, including both central and obstructive sleep apnea, with rates varying between those with reduced ejection fraction compared with preserved ejection fraction and depending on measures and cut-offs for levels of the apnea hypopnea index,²⁴ as well as stable versus exacerbated HF.

Fatigue is a classic symptom of HF, with rates between 28 and 90%.^25–28 This broad range is likely attributable to differences in measurement, severity, and etiology of HF, uncompensated versus stable disease, comorbidity, medications, and the presence of depression,²⁹ among other factors. Fatigue often occurs as a component of clustered symptoms^30–32 and may be either central or peripheral.³³ Although it has received less attention than fatigue among people with HF, EDS is also common and experienced by 21% and 44% of people with HF.^{6,21,22,28,34} However, these data are generally limited to studies that focused on groups with sleep disorders, and many studies of symptoms among people with HF have not measured EDS because it has not been considered a classic symptom of HF.

Sleep deficiency, insomnia, and sleep disordered breathing contribute to both fatigue and EDS among people with HF, although the contributions of sleep deficiency to fatigue and EDS are often conflicting. For example, self-reported sleep disturbance, poor sleep quality,²⁸ and insomnia symptoms were associated with both fatigue and EDS.²³ In addition to sleep quality, functional class, non-adherence to diuretics, and lack of physical activity explained EDS, but only sleep quality was associated with fatigue (p <0.001).²⁸ Notably, despite high rates of EDS in people in the general population who have sleep disordered breathing, SDB did not explain EDS in several studies of people with HF,^6,35–37 and self-reported EDS is lower among people with HF when compared with other groups with a similar severity of sleep disordered breathing.³⁸ Although the reasons for this discrepancy are not completely known, it may be explained by the alerting effects of sympathetic arousal associated with both HF and sleep disorders.^39,40 These findings may also be explained, by discrepancies between self-reported EDS and objective measures of alertness, such as the psychomotor vigilance test. HF patients may not be aware of objective decrements in behavioral alertness.^16,41 Each of these measures may elicit different dimensions of sleepiness,¹¹ and people with objective decrements may not self-report sleepiness.

Sleep-related fatigue and EDS are important concerns for people with HF as they may signal the presence of sleep disorders, but they also contribute to other HF outcomes, including daytime function, cognition, medication adherence and self-care related to HF. EDS was associated with physical function, measured with the Kansas City Cardiomyopathy Scale and the Medical Outcomes Study SF-12.⁴² A latent variable consisting of sleepiness, fatigue and depressive symptoms mediated the effects of insomnia and sleep quality on self-report functional performance and six-minute walk distance among people with stable HF. This relationship was not explained by sleep disordered breathing, comorbidity, or HF severity.⁴³ However, the cross-sectional nature of these data preclude understanding of the causal or temporal relationships among these phenomena.

EDS was also associated with self-care among people with HF in a small study.⁴⁴ Although EDS was associated with cognitive impairment, an important influence on self-care, in middle aged adults with HF.⁴⁵ EDS was independently associated with medication adherence, an important self-care behavior.⁴⁶ In contrast, fatigue, but not sleep disturbance, was also associated with self-care behavior in two studies,^29,47 and despite the frequent association of depression with fatigue symptoms, depression did not explain this relationship.⁴⁷

Given the prevalence and consequences of both EDS and sleep-related fatigue and the influence of sleep deficiency and specific sleep disorders on these outcomes, treatment of sleep deficiency, including sleep apnea, insomnia, and short sleep, may improve fatigue and sleepiness. However, the data are somewhat conflicting. Among people with HF and central sleep apnea, adaptive servo-ventilation did not improve daytime sleepiness,⁴⁸ while both exercise and CPAP improved the apnea hypopnea index and daytime sleepiness in people with HF and obstructive sleep apnea. However, the effects of exercise were larger than CPAP on function.⁴⁹ Auto-titrating CPAP also improved EDS, but not other outcomes among people with chronic HF and obstructive sleep apnea.⁵⁰

There is also evidence that treatment of insomnia may also improve EDS, fatigue, and functional outcomes in HF. Cognitive behavioral therapy (CBT-I) had large effects on fatigue, but not EDS among people with insomnia.⁵¹ Pharmacological treatment of insomnia may also improve insomnia and in, turn, EDS and fatigue, but benzodiazepines were associated with adverse prognosis in HF,⁵² and HF patients expressed concern about their potential addictive effects.⁵³ In addition, the negative effects of polypharmacy and drug interactions are important to consider, given the large number of prescribed medications taken by people with HF. A small group of HF patients with insomnia also reported frequent use of over-the-counter diphenhydramine containing products that produced daytime sedation and functional impairment. Administration of melatonin has beneficial cardiovascular effects⁵⁴ and may be cardioprotective for ischemic HF.⁵⁵ Although data are not conclusive, melatonin has been effective for sleep onset insomnia and sleep disturbance,⁵⁶ including among older adults.⁵⁷ Newer insomnia drugs and wake-promoting agents may also play a role in treatment of insomnia among people with HF, but data on their safety in this population are not consistently available. Give the widespread efficacy of CBT-I in other groups, including those with chronic conditions, CBT-I alone or in combination with melatonin or other agents may be efficacious.

Considerable attention has been focused by the sleep disorders community on sleep disordered breathing among people with HF. However, increasing evidence suggests that insomnia is also common,⁵⁸ frequently comorbid with,^23,51 and not explained by²³ sleep disordered breathing. These findings suggest the importance of treating both conditions together. However, to our knowledge, there has not been a randomized controlled trial among people with HF. This may be beneficial in improving cardiovascular function, as well as EDS, fatigue, and daytime function.

Sleep Disturbance, Excessive Daytime Sleepiness and Fatigue among People with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), a chronic progressive immune-mediated disease that includes Crohn’s disease and ulcerative colitis, afflicts 1.6 million people in the US.⁵⁹ IBD is characterized by intestinal inflammation and follows an unpredictable course of active and inactive disease. The disease burden in people with IBD is high as most people with IBD are diagnosed in adolescence and young adulthood. People with IBD experience significant life disruptions to education and careers and poor quality of life.^60,61

Self-reported sleep disturbance is highly prevalent in adults with IBD, with between 55% and 78% reporting poor sleep quality during active disease and 33% to 64% during inactive disease.^62–64 While fewer data are available on objectively measured sleep characteristics in IBD, polysomnographic and wrist actigraph studies demonstrate that sleep is short and highly fragmented, further supporting that this population faces substantial sleep deficiency.^65–68

Self-reported sleep disturbance is associated with increased risk for clinically active disease over 6 and 12 months^69,70 and increased risk of hospitalizations and IBD-related surgery over one year.⁷¹ These results are supported by mouse models of colitis, in which intermittent sleep deprivation and shifting of sleep timing cause worsening of colonic inflammation.^72,73 Worsening of disease activity may result from the negative effects of sleep deficiency on the immune system as chronic sleep deprivation increases proinflammatory cytokines (e.g., IL-6 and IL-1β) in healthy adults. These cytokines are key in regulating the immune response of the gastrointestinal tract.⁷⁴ These results suggest that interventions that target sleep deficiency in this population may not only improve sleep but may also improve gastrointestinal and systemic inflammation and possibly daytime consequences, including bowel symptoms and fatigue.

Fatigue continues to be an unmet need for people with IBD, and a key patient-reported outcome.⁷⁵ Fatigue is severe and prevalent symptom in people with IBD and about 55% of people with IBD experience substantial fatigue.^76,77 Although fatigue is often worse during active disease, it persists during inactive phases of IBD.⁶² Both self-reported sleep disturbance and evening chronotype were associated with fatigue among people with IBD.^62,78,79 However, how specific aspects of sleep deficiency (e.g., duration, timing, fragmentation) are associated with fatigue is unknown.

Despite the apparent high levels of sleep deficiency and fatigue among people with IBD, they do not report substantial EDS measured by the Epworth Sleepiness Scale even during active disease.^66,68 These findings may reflect the conceptual distinction between EDS and fatigue, but it is also possible that objective measurement of EDS may reveal decreased alertness given the high levels of sleep deficiency in this population. Future studies with objective measurements are needed to address this possibility.

As in some other groups with chronic conditions (e.g., heart failure, cancer, chronic obstructive pulmonary disease), fatigue often co-occurs with symptoms of pain, sleep disturbance, and mood disturbance, with symptoms persisting for as long as a year or more.⁸⁰ Despite evidence from several studies of self-reported sleep disturbance, little is known about the contributions of specific objective measures of sleep fragmentation, sleep timing, or sleep disorders to fatigue in IBD. Likewise, there are no studies that examined the biological mechanisms that may explain the relationships between sleep deficiency and fatigue, such as potentially common inflammatory pathways (e.g., cytokines, gut microbiome) in co-occurring fatigue and sleep deficiency in people with IBD. These foundational studies are needed to illuminate the type and timing of sleep intervention needed to improve sleep deficiency ad sleep-related fatigue in this population.

Despite the prevalence of sleep disturbance among people with IBD, there have been few studies of interventions to improve sleep deficiency and sleep-related fatigue. A four-week stepped care brief behavioral therapy (BBT) for IBD, with the addition of bupropion for some individuals, improved both fatigue and sleep disturbance in young adults ages 15 to 30 years with IBD.⁸¹ However, while fatigue improved, it did not fully resolve for any of the participants and the addition of the bupropion did not improve on BBT alone. The follow-up for this study was only 12 weeks, and improvements in fatigue may require a longer duration follow-up duration to be seen. Additionally, while sleep disturbance improved, objective sleep characteristics were not elicited; thus, it is unclear which specific characteristics of sleep may have improved after the intervention. A second study of an 8-week aerobic exercise intervention for children and adolescents with IBD improved polysomnographic- measured deep sleep and wake after sleep onset but not self-report sleep disturbance.⁸² Notably, fatigue outcomes were not assessed. These studies suggest the importance of symptom management among people with IBD, but studies are needed that examine the extent to which improvements in sleep lead to improved daytime symptoms, such as EDS and fatigue.

Biologic therapy for IBD with vedolizumab and anti-tumor necrosis factor α agents (anti-TNF) also improved sleep disturbance over 6 weeks.⁸³ However, the effects on sleep may be related to improvement in disease activity, reduction of systemic cytokines, and/or nighttime symptoms (e.g., nocturnal diarrhea) rather than direct effects on sleep. While these interventions show promise, additional research is needed to determine the types and timing of sleep interventions that improve not only sleep deficiency but also reduce the risk of active disease, and fatigue.

Sleep Disturbance, Fatigue and Excessive Daytime Sleepiness Among Women with Breast Cancer

Breast cancer is the most common cancer in women around the world. In the United States, there are 3.8 million women with a history of breast cancer.⁸⁴ Women treated for breast cancer are at risk for persistent physical and psychological comorbid symptoms before, during, and after cancer treatment, including sleep disturbance, fatigue, and EDS. These symptoms may vary over the trajectory of treatment, but they persist long after treatment for many women.

Fatigue is the most common, persistent symptom in adults with cancer in general, and cancer-related fatigue is distinguished from the broader concept of fatigue as it does not improve with sleep or rest. It is characterized by long duration and high severity and a consequence of cancer or its treatment.^85,86 Prior to adjuvant chemotherapy, 72% of patients report mild fatigue and 27% reported moderate fatigue.⁸⁷ As many as 99% of women undergoing chemotherapy and/or radiation therapy report some degree of fatigue.⁸⁵ A meta-analysis of 68 studies involving 12,125 women revealed that the prevalence of severe self-reported fatigue is 27% in women with breast cancer across stages 0 – IIII.⁸⁸ While studies suggest that fatigue improves after the first 6 months following the last cancer treatment, ^88,89 approximately 34% of women with breast cancer report fatigue after 10 years of cancer survivorship.⁹⁰

Breast cancer patients frequently report sleepiness with fatigue, but these terms are not well differentiated.⁸⁵ During chemotherapy, 38% of women reported EDS measured by the Epworth Sleepiness Scale.⁹¹ Among recently diagnosed women, physical and attentional fatigue predicted the trajectory of daytime sleepiness, assessed by the General Sleep Disturbance Scale, over the continuum of treatment.⁹² Women with more education and those who did not receive neo-adjuvant chemotherapy had higher levels of EDS over time.⁹² Younger age and more acute pain were also significantly associated with EDS.⁹³ Future studies are needed to investigate the relationship between fatigue and EDS to better distinguish these symptoms and to focus interventions among oncology patients.⁹⁴

Sleep deficiency is closely associated with fatigue through inflammatory processes in cancer patients.⁹⁵ Prior to breast surgery, interleukin-6, interleukin-13, and tumor necrosis factor-alpha (TNF-α) were associated with greater level of a symptom cluster of self-reported sleep disturbance, fatigue, pain, and depressive mood.⁹⁶ However, the exact mechanism has not been clearly determined,^97,98 and more studies are needed to confirm the underlying mechanisms that explain these linkages, as well as the causal directions as sleep deficiency may also contribute to inflammation.

While fatigue and EDS have multiple determinants, self-reported sleep disturbance is among the most common debilitating symptoms in women with breast cancer⁹⁹ and contributes to these outcomes. Self-reported sleep disturbance refers to a symptom caused by sleep deficiency defined as deficiency in the quantity or quality of sleep to maintain optimal health.¹⁰⁰ Sleep disorders, insufficient sleep duration, and fragmented sleep can cause sleep deficiency.¹⁰⁰ Overall, 67 to 90% of women report sleep disturbance and up to 70% of women experience insomnia symptoms (e.g., difficulty falling asleep, staying asleep).^92,101,102 Prior to adjuvant chemotherapy, 36 to 66% report sleep disturbance as measured with the Pittsburgh Sleep Quality (PSQI),^87,103–106 and these rates may change over the course of treatment and recovery. During chemotherapy, 49 to 58% report sleep disturbance.^103,105 Sleep disturbance persists after completion of cancer treatment, with 38% report poor sleep quality assessed by the PSQI at five years after cancer treatment and continues to worsen over the course of cancer survivorship.^{92,103,107,108}

While symptoms of sleep disturbance, as a result of sleep deficiency are widely studied in women with breast cancer, few studies specifically determined the presence of specific sleep disorders, with the exception of insomnia.¹⁰⁹ The prevalence rate of insomnia in breast cancer patients is over 30% and it is higher than patients of other cancer types.^110,111 Possible contributing factors to insomnia in women with breast cancer include female sex, stress related to the cancer diagnosis and treatment, psychological symptoms of anxiety and depression, and chronic maladaptive sleep behaviors that may lead to chronic insomnia.⁹⁵ In post-treatment women diagnosed with stage 0 to III breast cancer, 98% reported symptoms of chronic insomnia and 79% reported symptoms suggestive of SDB.¹¹² Although the reasons for risk for SDB are not completely clear, weight gain is common in breast cancer patients,^113–115 and the relationship between high body mass index (BMI) and SDB is well established.¹¹⁶ There is also evidence of positive relationship between BMI and daytime sleepiness and difficulty falling asleep in women with breast cancer.^117,118 Given that EDS is one of the common symptoms reported with SDB, the increased incidence of SDB with menopause, and the high prevalence of chemotherapy-induced menopause following breast cancer treatment, there is a need for more study on SDB in breast cancer patients, given the limited body of research or consideration of SDB in this population.

Numerous studies assessed the effects of physical exercise and mind-body interventions on sleep deficiency and cognitive-behavioral therapy for insomnia (CBT-I) among women with breast cancer.^119–121 Based on a meta-analysis of 14 randomized controlled trials of CBT-I on insomnia in breast cancer patients, CBT-I has medium to large intervention effects on improving insomnia symptoms among women with breast cancer.¹¹⁹ Although this meta-analysis did not report the pooled effect size of CBT-I on fatigue, 9 out of 14 studies measured fatigue with various fatigue measures (e.g., Multidimensional Fatigue Symptom Inventory, Piper Fatigue Scale) in addition to insomnia symptoms.¹¹⁹ There is evidence that CBT-I also improves fatigue in post-treatment breast cancer patients.^122,123 CBT-I also significantly improved daytime sleepiness, assessed by the Epworth Sleepiness Scale, among post -treatment patients with various cancer types (70% or more breast cancer).¹²⁴

Mind-body interventions, such as mindfulness-based stress reduction intervention, improve sleep and fatigue in women with breast cancer, although effects were small and measured only over the short term.¹²¹ With regards to cancer-related fatigue, physical exercise and psychological interventions are clinical recommendations in practice because they have shown a significant benefit over pharmaceutical interventions in improving fatigue.¹²⁵ These interventions may also improve sleep, although the extent to which improvements in fatigue are associated with reducing sleep deficiency is under-studied. Although the results of studies were not consistent, a meta-analysis suggested that oral administration of melatonin may also improve insomnia and sleep disturbance in cancer.¹²⁶ Taken together, these studies suggest that intervention may be effective in improving sleep deficiency and fatigue – significant problems in the breast cancer population. However, future research is needed.

There is a need for research to assess the relationship between sleep deficiency and sleep-related daytime symptoms and shared underlying biological and behavioral mechanisms, as well as the differential effects of interventions over the course of treatment, recovery, and survivorship. The relationship between fatigue and EDS needs to be clearly defined and investigated to develop effective interventions. In addition, identifying sleep disorders, such as SDB, and their associations with EDS would enhance our understanding of sleep deficiency in breast cancer patients. The effect of CBT-I and mind-body interventions on sleep deficiency and sleep-related daytime symptoms requires further investigation.

Implications for Practice and Future Research

Sleep deficiency, EDS, and fatigue are important phenomena experienced by people with chronic conditions that influence quality of life, function, safety, and the ability to self-manage. Sleep deficiency also contributes to pathophysiologic processes that may also lead to fatigue, EDS, and poor function. We discussed exemplars from three specific chronic conditions, but adults with other chronic conditions also suffer from the negative effects of sleep deficiency, fatigue, and EDS.^127,128 As with the other exemplars provided, these people demonstrate improvement in symptoms and function with appropriate treatment of sleep deficiency, including insomnia¹²⁹, sleep disordered breathing,¹³⁰ and fragmented or irregular sleep. Thus, focused assessment and intervention for sleep deficiency and associated daytime symptoms should be an important component of chronic disease management. Although this may seem obvious, patients have reported that despite their high levels of concern about their sleep quality and its negative daytime effects, non-sleep specialist clinicians often do not elicit this information.⁵³ Although the reasons for this are likely factorial, inclusion of specific questions in the health history regarding sleep and providing referral for sleep assessment and treatment may improve chronic disease management for these patients and should be an important component of the standard of care, especially for people at high risk for sleep deficiency.

Despite growing reports of the contributions of sleep disturbance to fatigue and EDS among people with chronic conditions, additional research is needed to define the contributions of specific sleep characteristics and disorders to daytime symptoms, as well as disease pathology, given that many studies focused on global self-reported sleep quality. This measure does not provide information to guide understanding of specific sleep mechanisms or targets for interventions focused on specific sleep characteristics (e.g., duration, timing, regularity, fragmentation, or specific sleep disorders).

While interventions such as cognitive behavioral therapy for insomnia have shown efficacy for some chronic conditions, others might focus on sleep variability or circadian regulation but have seldom been considered in these populations. Given the close interrelationships between sleep deficiency, EDS and fatigue, sleep promoting interventions for people with chronic conditions should also address these outcomes. Mechanistic studies that address multiple levels, including biological, psychological, clinical, psychological, and environmental factors are also needed to improve understanding of the contributions of sleep deficiency to EDS and fatigue. For example, studies of inflammation,¹³¹ and the microbiome¹³² are beginning to provide useful information.

Conclusion

Fatigue and EDS are often consequences of sleep deficiency, and these phenomena are common among people with chronic conditions among whom sleep deficiency and sleep disorders are prevalent. There is a need for careful clinical assessment and intervention for these phenomena due to their influences on health outcomes in this large and growing population of adults. While research remains needed, efficacious interventions are available to improve these disabling symptoms.

Synopsis:

Sleep deficiency is associated with disabling daytime symptoms, including excessive daytime sleepiness (EDS) and fatigue. The purpose of this paper is to discuss the contributions of sleep deficiency and sleep disorders to fatigue and EDS among people with chronic conditions. We use exemplars from the literature on chronic heart failure (HF), inflammatory bowel disease (IBD), and breast cancer (BC) to (1) describe the prevalence of fatigue and EDS and their consequences; (2) examine the evidence for the contributions of sleep deficiency and sleep disorders to these symptoms; and (3) recommend implications for future research and practice.

Key points:

1. Multiple aspects of sleep deficiency contribute to symptoms of excessive daytime sleepiness and fatigue.

2. These sleep-deficiency related symptoms are highly prevalent and associated with poor quality of life and function, and difficulty with cognition and self-management

3. There is a critical need for efficacious sleep interventions that improve sleep deficiency, fatigue and excessive daytime sleepiness.