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• W2158982485 abstract "The best bridge between despair and hope is a good night's sleep.—E. Joseph CossmanThe worst thing in the world is to try to sleep and not to.—F. Scott Fitzgerald Sleep, the long-recognized victim of obstructive sleep apnea, also suffers in patients with asthma, atopic dermatitis, and allergic rhinitis. As many as 75% of patients with asthma awaken weekly with symptoms of their disease, and about half of these awaken nightly.1Turner-Warwick M. Epidemiology of nocturnal asthma.Am J Med. 1988; 85: 6-8Abstract Full Text PDF PubMed Scopus (273) Google Scholar Rhinitis sufferers also tend to sleep poorly, often because of sleep-disordered breathing secondary to nasal obstruction2Young T. Finn L. Kim H. Nasal obstruction as a risk factor for sleep-disordered breathing.J Allergy Clin Immunol. 1997; 99: S757-S762Abstract Full Text Full Text PDF PubMed Scopus (408) Google Scholar, 3Craig T.J. McCann J.L. Gurevich F. Davies M.J. The correlation between allergic rhinitis and sleep disturbance.J Allergy Clin Immunol. 2004; 114: S139-S145Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar and with the consequence of decreased quality of life and increased daytime somnolence.4Blaiss M, Reigel T, Philpot E. A study to determine the impact of rhinitis on sufferers' sleep and daily routine. J Allergy Clin Immunol 2005;115(suppl 2):S197Google Scholar, 5Stuck B.A. Czajkowski J. Hagner A. Klimek L. Verse T. Hörmann K. et al.Changes in daytime sleepiness, quality of life, and objective sleep patterns in seasonal allergic rhinitis: a controlled clinical trial.J Allergy Clin Immunol. 2004; 113: 663-668Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar Adults6Bender B. Leung S.B. Leung D. Actigraphy assessment of sleep disturbance in patients with atopic dermatitis: an objective life quality measure.J Allergy Clin Immunol. 2003; 111: 598-602Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar and children7Reuveni H. Chapnick G. Tal A. Tarsiuk A. Sleep fragmentation in children with atopic dermatitis.Arch Pediatr Adolesc Med. 1999; 153: 249-253Crossref PubMed Scopus (91) Google Scholar with atopic dermatitis are more restless in their sleep, awaken more often, spend fewer minutes in sleep, and report more daytime fatigue than those without. In this issue of the Journal, 4 contributions help advance our understanding of the relationships among sleep, immune function, and respiratory disease. Madje and Krueger8Majde J.A. Krueger J.M. Links between the innate immune system and sleep.J Allergy Clin Immunol. 2005; 116: 1188-1198Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar integrate a large literature that examines immune function in normal and abnormal sleep. Bergeron et al9Bergeron C. Kimoff J. Hamid Q. Obstructive sleep apnea syndrome and inflammation.J Allergy Clin Immunol. 2005; 116: 1393-1396Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar cite recent evidence that systemic and airway inflammation may contribute to daytime sleepiness associated with obstructive sleep apnea syndrome. It follows that implementing appropriate anti-inflammatory treatment may facilitate improved sleep. The substantial evidence for airway changes and differential response to β2-receptor agonists and glucocorticoids at night is reviewed by Sutherland.10Sutherland E.R. Nocturnal asthma.J Allergy Clin Immunol. 2005; 116: 1179-1186Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar Combining data from 3 studies of perennial rhinitis, Craig et al11Craig T.J. Hanks C.D. Fisher L.H. How do topical nasal corticosteroids improve sleep and daytime somnolence in allergic rhinitis?.J Allergy Clin Immunol. 2005; 116: 1264-1266Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar demonstrate that treatment with intranasal corticosteroids reduces nasal congestion, sleep disturbance, and daytime somnolence. These collective contributions remind the reader that both sleep and immunology are governed by complex circadian patterns, and that the treatment of patients with respiratory, allergic, and immune disorders must take into account the quality of their sleep. Sleep disruption can bring significant daytime consequences. Poor sleep has a well documented deleterious effect on mood, cognition, and motor performance. Further, individuals deprived of sufficient sleep are at markedly increased risk of causing a motor vehicle accident. Crashes or near-crashes are increased among truck drivers,12McCartt A.T. Rohrbaugh J.W. Hammer M.C. Fuller S.Z. Factors associated with falling asleep at the wheel among long-distance truck drivers.Accid Anal Prev. 2000; 32: 493-504Crossref PubMed Scopus (184) Google Scholar airline pilots,13Bourgeois-Bougrine S. Casrbon P. Gounelle C. Mollard R. Coblentz A. Perceived fatigue for short- and long-haul flights: a survey of 739 airline pilots.Aviat Space Environ Med. 2003; 74: 1072-1077PubMed Google Scholar shift workers,14Folkard S. Monk T.H. Shiftwork and performance.Hum Factors. 1979; 21: 483-492Google Scholar and medical residents,15Steele M.T. Ma O.J. Watson W.A. Thomas H.A. Muelleman R.L. The occupational risk of motor vehicle collisions for emergency medicine residents.Acad Emerg Med. 1999; 6: 1050-1053Crossref PubMed Scopus (146) Google Scholar all of whom are exposed to irregular and reduced sleep. While sleep science has long recognized the dramatic changes in human performance that accompany multiple nights of total sleep deprivation,16Kleitman N. Sleep and wakefulness. University of Chicago Press, Chicago1963Google Scholar more recent research has provided insight into the consequences of partial sleep deprivation, or the poor night's sleep often accompanying atopic and respiratory diseases, but also commonly associated with the stress and demands of daily life. Even as little as 4 nights of partial sleep restriction resulting in less than 7 hours of sleep causes measurable increases in daytime sleepiness and impaired cognitive performance.17Drake C.L. Roehrs T.A. Burduvali E. Bonahoom A. Rosekind J. Roth T. Effects of rapid versus slow accumulation of eight hours of sleep loss.Psychophysiology. 2001; 38: 979-987Crossref PubMed Scopus (151) Google Scholar, 18Belenky G. Wesensten N.J. Thorne D.R. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study.J Sleep Res. 2003; 12: 1-12Crossref PubMed Scopus (980) Google Scholar In a comprehensive study of sleep deprivation, 2 weeks of sleep restricted to 4 hours created deficits in attention and memory equivalent to 2 nights of total sleep deprivation.19Van Dongen H. Maislin G. Mullington J.M. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation.Sleep. 2003; 26: 117-126Crossref PubMed Scopus (2130) Google Scholar A systematic review of intermittent hypoxia in children concluded that even at mild levels of desaturation, children with sleep-disordered breathing demonstrate lower levels of performance on tests of attention and verbal intelligence.20Bass J.L. Corwin M. Gozal D. Moore C. Nishida H. Parker S. et al.The effect of chronic or intermittent hypoxia on cognition in childhood: a review of evidence.Pediatrics. 2004; 114: 805-816Crossref PubMed Scopus (344) Google Scholar Readers interested in learning more about neurocognitive consequences of sleep deprivation are directed to an excellent review by Durmer and Dinges.21Durmer J.S. Dinges D.F. Neurocognitive consequences of sleep.Semin Neurol. 2005; 25: 117-129Crossref PubMed Scopus (1111) Google Scholar The causes of poor sleep in these patients may not be as obvious as they first appear. The discomforts experienced by patients with asthma, allergic rhinitis, and atopic dermatitis are clear, and the implications for sleep seem evident. The increased nasal airway resistance accompanying allergic rhinitis nearly triples when a patient lies down,22Lavie P. Gertner R. Zomer J. Podoshin L. Breathing disorders in sleep associated with “microarousals” in patients with allergic rhinitis.Acta Otolaryngol. 1981; 92: 529-533Crossref PubMed Scopus (137) Google Scholar and many with atopic dermatitis report unbearable itching at night. For some with asthma, circadian variations in airway physiology deliver a marked increase in sleep-disordered breathing between midnight and 8:00 am. Yet the origins of disordered sleep in these patients may also be traced to altered inflammatory processes. Studies of individuals with diseases causing systemic inflammation23Majde J.A. Krueger J.M. Neuroimmunology of sleep.in: D'haenen H. Textbook of biological psychiatry. John Wiley & Sons, Ltd, London2002: 1247-1257Google Scholar and healthy volunteers in sleep deprivation studies24Redwine L. Hauger R.L. Christian G.J. Irwin M. Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans.J Clin Endocrinol Metab. 2000; 85: 3597-3603Crossref PubMed Scopus (313) Google Scholar, 25Sutherland E.R. Ellison M.C. Kraft M. Martin R.J. Elevated serum melatonin is associated with the nocturnal worsening of asthma.J Allergy Clin Immunol. 2003; 112: 513-517Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar reveal that a variety of cytokines are implicated in sleep regulation. Majde and Krueger23Majde J.A. Krueger J.M. Neuroimmunology of sleep.in: D'haenen H. Textbook of biological psychiatry. John Wiley & Sons, Ltd, London2002: 1247-1257Google Scholar cite some that include IL-4, IL-6, IL-1β, and TNF-α. For example, IL-4 and IL-1β, both of which are elevated in patients with allergy, are associated with increased latency to rapid eye movement sleep and lower overall quality of sleep.26Krouse H.J. Davis J.E. Krouse J.H. Immune mediators in allergic rhinitis and sleep.Otolaryngol Head Neck Surg. 2002; 126: 607-613Crossref PubMed Scopus (84) Google Scholar The causal pathway may be that cytokine changes resulting from these diseases contribute to sleep changes by affecting the role of these substances in the brain neurochemistry of sleep regulation. Equally plausible is the possibility that sleep disturbance resulting from the discomfort of allergic rhinitis or atopic dermatitis promotes further changes in cytokines, hormones, or other neuropeptides, which in turn influence the course of the disease. Majde and Krueger23 review studies demonstrating that sleep deprivation alters IL-6 and growth hormone production and increases susceptibility to infection. A growing body of electrophysiological, biochemical, and genetic evidence indicates that IL-1 and TNF-α play a role in supporting sleep.27Krueger J.M. Ferenc O.J. Fang J. The role of cytokines in physiological sleep regulation.Acad Sci. 2001; 933: 211-221Crossref PubMed Scopus (321) Google Scholar, 28Opp M.R. Cytokines and sleep.Sleep Med Rev. 2005; 9: 355-364Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar When injected into animals peripherally, or microinjected directly into the brain, IL-1 and TNF-α increase nonrapid eye movement sleep while suppressing rapid eye movement sleep.29Manfridi A. Grambilla D. Bianchi S. Mariotti M. Opp M.R. Imeri L. Interleukin enhances non-rapid eye movement sleep when microinjected into the dorsal raphe nucleus and inhibits serotonergic neurons in vitro.Eur J Neurosci. 2003; 18: 1041-1049Crossref PubMed Scopus (80) Google Scholar, 30Kubota T. Li N. Guan Z. Brown R.A. Krueger J.M. Intrapreoptic microinjection of TNF-alpha enhances non-REM sleep in rats.Brain Res. 2002; 932: 37-44Crossref PubMed Scopus (72) Google Scholar, 31Alam M. McGinty D. Bashir T. Kumar S. Imeri L. Opp M.R. Interleukin-1 beta modulates state-dependent discharge activity of preoptic area and basal forebrain neurons: role in sleep regulation.Eur J Neurosci. 2004; 20: 207-216Crossref PubMed Scopus (82) Google Scholar Daytime sleepiness is decreased in patients with sleep apnea given intravenous TNF-α receptor antagonist.32Vgontzas A. Zoumakis E. Lin H.M. Bixler E.O. Trakada G. Chrousos G.P. Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-{alpha} antagonist.J Clin Endocrinol Metab. 2004; 89: 4409-4413Crossref PubMed Scopus (280) Google Scholar In healthy volunteers, injection of IL-1 or TNF-α alters rapid eye movement sleep.27Krueger J.M. Ferenc O.J. Fang J. The role of cytokines in physiological sleep regulation.Acad Sci. 2001; 933: 211-221Crossref PubMed Scopus (321) Google Scholar Disease, inflammation, and sleep are thus linked in a complex set of relationships. The possibilities are intriguing, and the continuing task of teasing apart the causal sequences promises important discoveries. Treatments for asthma, allergic rhinitis, and atopic dermatitis should slow or stop the interaction between disease and sleep while improving both. For example, a group of children with atopic dermatitis treated with pimecrolimus cream demonstrated improvement in their skin that in turn was correlated with improvement in sleep.33Leo H.L. Bender B. Leung S. Vu Tran Z. Leung D. Effect of pimecrolimus cream 1% on skin condition and sleep disturbance in children with atopic dermatitis.J Allergy Clin Immunol. 2004; 114: 691-693Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar As Sutherland and colleagues25Sutherland E.R. Ellison M.C. Kraft M. Martin R.J. Elevated serum melatonin is associated with the nocturnal worsening of asthma.J Allergy Clin Immunol. 2003; 112: 513-517Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar note, understanding the circadian cycles of inflammation and symptoms may direct choice and timing of specific treatments. In the case of asthma, this includes dosing strategies to optimize therapeutic effects during periods of nocturnal worsening. The role of sleep-promoting medications for these groups of patients is unclear and should be approached cautiously. In the case of atopic dermatitis, the possibility of treating sleep with such medications as a way to interrupt the itch-scratch-itch cycle is a strategy that warrants further exploration." @default.
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