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Sleep Snippets Newsletter – October 2017

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Dementia, Alzheimer’s Disease & Sleep Disorders


The older patient population is growing rapidly around the world and in the USA. Almost half of seniors over age 65 who live at home are dissatisfied with their sleep, and nearly two-thirds of those residing in nursing home facilities suffer from sleep disorders. Chronic and pervasive sleep complaints and disturbances are frequently associated with excessive daytime sleepiness and may result in impaired cognition, diminished intellect, poor memory, confusion, and psychomotor retardation all of which may be misinterpreted as dementia.

The key sleep disorders impacting patients with dementia include insomnia, hypersomnolence, circadian rhythm misalignment, sleep disordered breathing, motor disturbances of sleep such as periodic leg movement disorder of sleep and restless leg syndrome, and parasomnias, mostly in the form of rapid eye movement (REM) sleep behavior disorder (RBD). RBD is a pre-clinical marker for a class of neurodegenerative diseases, the “synucleinopathies”, and requires formal polysomnographic evaluation. Untreated sleep disorders may exacerbate cognitive and behavioral symptoms in patients with dementia and are a source of considerable stress for bed partners and family members. When left untreated, sleep disturbances may also increase the risk of injury at night, compromise health-related quality of life, and precipitate and accelerate social and economic burdens for caregivers.

Sleep, Cognition and Dementia. Curr Psychiatry Rep. 2015 Dec;17(12):97.Porter VR1, Buxton WG2, Avidan AY3.

Obstructive Sleep Apnea Syndrome: An Emerging Risk Factor for Dementia.

CNS Neurol Disord Drug Targets. 2016;15(6):678-82. Buratti L, Luzzi S, Petrelli C, Baldinelli S, Viticchi G, Provinciali L, Altamura C, Vernieri F, Silvestrini M

studies have suggested that obstructive sleep apnea syndrome (OSAS) may increase the risk of developing cognitive impairment. In patients with Alzheimer’s disease (AD), the prevalence of OSAS is much higher than that expected in cognitively healthy subjects. A deeper knowledge of the pathophysiological link between OSAS and AD and the demonstration that OSAS may directly influence the development of cognitive alterations, would increase prevention and treatment strategies for AD patients. In this article, we discuss the evidence of the association between OSAS and dementia. Moreover, we present data about the functional and anatomic cerebral changes induced by OSAS and the possible effects on cognitive activities and on AD pathogenesis. The possibility to positively influence cognitive impairment by OSAS treatment will be also discussed.

Sleep characteristics and risk of dementia and Alzheimer’s disease: The Atherosclerosis Risk in Communities Study

Alzheimers Dement. 2017 Jul 21. pii: S1552-5260(17)32522-0. doi: 10.1016/j.jalz.2017.06.2269. Lutsey PL1, Misialek JR2, Mosley TH3, Gottesman RF4, Punjabi NM5, Shahar E6, MacLehose R7, Ogilvie RP7, Knopman D8, Alonso A9.

INTRODUCTION: This study tested the hypotheses that late-midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia over 15 years of follow-up.

METHODS: A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in-home polysomnography (1996-1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996-2012) and (2) a comprehensive neurocognitive examination (2011-2013) with adjudication.

RESULTS:OSA and sleep duration were not associated with risk of incident dementia. When using adjudicated outcomes, severe OSA (≥30 vs. <5 apnea-hypopnea events/hour) was associated with higher risk of all-cause dementia (risk ratio [95% confidence interval], 2.35 [1.06-5.18]) and Alzheimer’s disease dementia (1.66 [1.03-2.68]); associations were attenuated with cardiovascular risk factor adjustment. Sleeping <7 versus 8 to ≤9 hours was associated with higher risk of all-cause dementia.

DISCUSSION: When adjudicated outcome definitions were used, late-midlife OSA and short sleep duration were associated with all-cause and Alzheimer’s disease dementia in later life.

Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer’s Disease Biomarkers Changes.

Sleep. 2017 May 1;40(5). doi: 10.1093/sleep/zsx011. Liguori C1, Mercuri NB1,2,3, Izzi F1, Romigi A4, Cordella A2, Sancesario G3, Placidi F1.

Study Objectives: Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer’s Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid42, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP).

Methods: We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis.

Results: OSA patients showed lower CSF Aβ42 concentrations, higher CSF lactate levels, and higher t-tau/Aβ42 ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ42 levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients.

Conclusions: We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ42 levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes.

Impact of sleep on the risk of cognitive decline and dementia.

Curr Opin Psychiatry. 2014 Nov;27(6)Spira AP1, Chen-Edinboro LP, Wu MN, Yaffe K.

PURPOSE OF REVIEW: Trouble falling or staying asleep, poor sleep quality, and short or long sleep duration are gaining attention as potential risk factors for cognitive decline and dementia, including Alzheimer’s disease. Sleep-disordered breathing has also been linked to these outcomes. Here, we review recent observational and experimental studies investigating the effect of poor sleep on cognitive outcomes and Alzheimer’s disease, and discuss possible mechanisms.

RECENT FINDINGS: Observational studies with self-report and objective sleep measures (e.g. wrist actigraphy, polysomnography) support links between disturbed sleep and cognitive decline. Several recently published studies demonstrate associations between sleep variables and measures of Alzheimer’s disease pathology, including cerebrospinal fluid measures of Aβ and PET measures of Aβ deposition. In addition, experimental studies suggest that sleep loss alters cerebrospinal fluid Aβ dynamics, decrements in slow-wave sleep may decrease the clearance of Aβ from the brain, and hypoxemia characteristic of sleep-disordered breathing increases Aβ production.

SUMMARY: Findings indicate that poor sleep is a risk factor for cognitive decline and Alzheimer’s disease. Although mechanisms underlying these associations are not yet clear, healthy sleep appears to play an important role in maintaining brain health with age, and may play a key role in Alzheimer’s disease prevention.

Changes in Neurocognitive Architecture in Patients with Obstructive Sleep Apnea Treated with Continuous Positive Airway Pressure.

EBioMedicine. 2016 May;7:221-9.Rosenzweig I1, Glasser M2, Crum WR3, Kempton MJ3, Milosevic M4, McMillan A2, Leschziner GD5, Kumari V6, Goadsby P7, Simonds AK2, Williams SC3, Morrell MJ8.

BACKGROUND: Obstructive sleep apnea (OSA) is a chronic, multisystem disorder that has a bidirectional relationship with several major neurological disorders, including Alzheimer’s dementia. Treatment with Continuous Positive Airway Pressure (CPAP) offers some protection from the effects of OSA, although it is still unclear which populations should be targeted, for how long, and what the effects of treatment are on different organ systems. We investigated whether cognitive improvements can be achieved as early as one month into CPAP treatment in patients with OSA.

METHODS: 55 patients (mean (SD) age: 47.6 (11.1) years) with newly diagnosed moderate-severe OSA (Oxygen Desaturation Index: 36.6 (25.2) events/hour; Epworth sleepiness score (ESS): 12.8 (4.9)) and 35 matched healthy volunteers were studied. All participants underwent neurocognitive testing, neuroimaging and polysomnography. Patients were randomized into parallel groups: CPAP with best supportive care (BSC), or BSC alone for one month, after which they were re-tested.

FINDINGS: One month of CPAP with BSC resulted in a hypertrophic trend in the right thalamus [mean difference (%): 4.04, 95% CI: 1.47 to 6.61], which was absent in the BSC group [-2.29, 95% CI: -4.34 to -0.24]. Significant improvement was also recorded in ESS, in the CPAP plus BSC group, following treatment [mean difference (%): -27.97, 95% CI: -36.75 to -19.19 vs 2.46, 95% CI: -5.23 to 10.15; P=0.012], correlated to neuroplastic changes in brainstem (r=-0.37; P=0.05), and improvements in delayed logical memory scores [57.20, 95% CI: 42.94 to 71.46 vs 23.41, 95% CI: 17.17 to 29.65; P=0.037].

INTERPRETATION: One month of CPAP treatment can lead to adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness, and improved verbal episodic memory in patients with OSA. We propose that partial neural recovery occurs during short periods of treatment with CPAP.

Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis.

Sleep Med Rev. 2017 Jul 6. pii: S1087-0792(17)30011-4. Shi L1, Chen SJ2, Ma MY3, Bao YP4, Han Y4, Wang YM5, Shi J4, Vitiello MV6, Lu L7.

Sleep disturbances and dementia are two common and significant health problems in older adults. Investigations suggest that sleepdisturbances might increase the risk of dementia. The aim of the present study was to systematically review and meta-analyze the predictive roles of overall sleep disturbances, their subtypes (e.g., insomnia, sleep disordered breathing [SDB]), and other sleep problems (e.g., excessive daytime sleepiness, sleep-related movement disorder, circadian rhythm sleep disorder, and nonspecific sleep problems) in incident all-cause dementia and Alzheimer’s disease (AD) and vascular dementia subtypes.

We performed a systematic search of the PubMed, EMBase, ISI Web of Science, and PsycINFO databases for longitudinal studies that were published up to October 28, 2016. A total of 12,926 papers were retrieved. Eighteen longitudinal studies that included 246,786 subjects at baseline and 25,847 dementia cases after an average 9.49 y of follow-up were eligible for inclusion. Compared with individuals without sleep disturbances, subjects who reported sleepdisturbances had a higher risk of incident all-cause dementia, AD, and vascular dementia.

The subgroup analysis showed that insomnia increased the risk of AD but not vascular or all-cause dementia. In contrast, SDB was associated with a higher incidence of all-cause dementia, AD, and vascular dementia. This meta-analysis suggests that sleep disturbances may predict the risk of incident dementia. Moreover, insomnia was associated only with incident AD, and SDB was a risk factor of all-cause dementia, AD, and vascular dementia. However, sleep disturbances were evaluated mainly based on self-reports, and some confounders may mediate the relationship between sleep disturbances and dementia. Therefore, the results should be further validated. In summary, these findings may help identify individuals who are at risk for dementia and optimize early prevention strategies.

Sleep, Cognitive impairment, and Alzheimer’s disease: A Systematic Review and Meta-Analysis.

Sleep. 2017 Jan 1;40(1). Bubu OM1, Brannick M2, Mortimer J1, Umasabor-Bubu O1, Sebastião YV1, Wen Y3, Schwartz S1, Borenstein AR1, Wu Y1, Morgan D4,5, Anderson WM6.

STUDY OBJECTIVES: Mounting evidence implicates disturbed sleep or lack of sleep as one of the risk factors for Alzheimer’s disease (AD), but the extent of the risk is uncertain. We conducted a broad systematic review and meta-analysis to quantify the effect of sleepproblems/disorders on cognitive impairment and AD.

METHODS: Original published literature assessing any association of sleep problems or disorders with cognitive impairment or AD was identified by searching PubMed, Embase, Web of Science, and the Cochrane library. Effect estimates of individual studies were pooled and relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. We also estimated the population attributable risk.

RESULTS: Twenty-seven observational studies (n = 69216 participants) that provided 52 RR estimates were included in the meta-analysis. Individuals with sleep problems had a 1.55 (95% CI: 1.25-1.93), 1.65 (95% CI: 1.45-1.86), and 3.78 (95% CI: 2.27-6.30) times higher risk of AD, cognitive impairment, and preclinical AD than individuals without sleep problems, respectively. The overall meta-analysis revealed that individuals with sleep problems had a 1.68 (95% CI: 1.51-1.87) times higher risk for the combined outcome of cognitive impairment and/or AD. Approximately 15% of AD in the population may be attributed to sleep problems.

CONCLUSION: This meta-analysis confirmed the association between sleep and cognitive impairment or AD and, for the first time, consolidated the evidence to provide an “average” magnitude of effect. As sleep problems are of a growing concern in the population, these findings are of interest for potential prevention of AD.

Sleep Snippets Newsletter – July 2017

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Epilepsy & Sleep Disorders


The comorbidity of epilepsy and sleep apnea is not uncommon. The diagnosis and treatment of obstructive sleep apneas will improve the prognosis and the quality of life in patients with epilepsy.

Diagnosis and treatment of epilepsy and sleep apnea comorbidity. Expert Rev Neurother. 2017 May;17(5):475-485. doi: 10.1080/14737175.2017.1262259. Epub 2016 Nov 28.Liu F1, Wang X1.a Department of Neurology , The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology , Chongqing , China.

Diagnosis and treatment of epilepsy and sleep apnea comorbidity.

Expert Rev Neurother. 2017 May;17(5):475-485. doi: 10.1080/14737175.2017.1262259. Epub 2016 Nov 28.Liu F1, Wang X1.a Department of Neurology , The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology , Chongqing , China.

The comorbidity of epilepsy and sleep apnea is not uncommon. The diagnosis and treatment of obstructive sleep apneas will improve the prognosis and the quality of life in patients with epilepsy. Areas covered: In this paper, the authors review the pathological link between sleep apnea and epilepsy and systematically analyze the current literature on the diagnosis and treatment of obstructive sleep apnea in patients with epilepsy. This review includes studies retrieved from the PubMed, Embase and Google Scholar databases. Expert commentary: A variety of treatments are available for OSA and epilepsy independently but there are no standards or guidelines for how to implement these treatments for patients who suffer from both disorders. The authors expect that alternative efficient therapies for comorbidity will be explored, which may change the current clinical practice for the management of epileptic patients.

Obstructive sleep apnoea in patients with epilepsy: a meta-analysis.

Sleep Breath. 2017 May;21(2):263-270. doi: 10.1007/s11325-016-1391-3. Epub 2016 Jul 30.Lin Z1, Si Q2, Xiaoyi Z3. 1Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China. 2School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.3Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China. xiaoyizou@scu.edu.cn.

PURPOSE: The aim of this study was to accurately determine the prevalence of obstructive sleep apnoea (OSA) in patients with epilepsy (PWE) and to evaluate the efficacy of seizure control after treating OSA.

METHODS: Articles were identified through a search of both MEDLINE and Embase. The articles were collected and data were extracted independently by two authors. OSA was described using the following terms: Apnoea/hypopnoea index (AHI) and respiratory disturbance index (RDI). The variables were calculated using DerSimonian and Laird’s random-effects model and odds ratio (OR).

RESULTS: The prevalence of mild-to-severe OSA in PWE was determined to be 33.4 % (95 % CI 20.8-46.1 %), and PWE are more susceptible to OSA as compared to healthy controls (OR 2.36; 95 % CI 1.33-4.18). Males were shown to be more susceptible to OSA than females (OR 3.00; 95 % CI 2.25-3.99). The results also indicated that the prevalence of OSA in patients with refractory epilepsy is not higher than the prevalence of OSA in PWE overall (17.5 vs 33.4 %). The prevalence of OSA was not found to be significantly different for different seizure types or in the number of antiepileptic drugs (AEDs). Patients that had been treated with continuous positive airway pressure (CPAP) were shown to have better seizure control than those untreated (OR 5.26; 95 % CI 2.04-13.5).

CONCLUSIONS: The prevalence of OSA in PWE is higher than in the general population. Additionally, the results of our study suggest that CPAP treatment results in a reduction of seizures.

High risk of developing subsequent epilepsy in patients with sleep-disordered breathing.

PLoS One. 2017 Mar 14;12(3):e0173491. doi: 10.1371/journal.pone.0173491.

Harnod T1,2, Wang YC3,4, Lin CL3,4, Tseng CH5,6.
1Department of Neurosurgery, Hualien Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.2College of Medicine, Tzu Chi University, Hualien, Taiwan.
3Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
4College of Medicine, China Medical University, Taichung, Taiwan.
5Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.6Department of Neurology, China Medical University Hospital, Taichung, Taiwan.p PURPOSE: Several reports have demonstrated an association between glaucoma and obstructive sleep apnea (OSA), though the origin of this association remains unknown. In the present study, the influence of OSA and continuous positive airway pressure (CPAP) therapy on intraocular pressure (IOP) and ocular perfusion pressure (OPP) was examined.

PURPOSE: Sleep-disordered breathing (SDB) is often associated with other medical disorders. Whether SDB interacts with other factors for developing subsequent epilepsy remains unclear.

METHODS: This population-based cohort study was conducted using the National Health Insurance Research Database of Taiwan. Patients aged >20 years and diagnosed with SDB between 2000 and 2010 comprised the SDB cohort (n = 138,507), and their data were compared with those of the comparison cohort (n = 138,507). The adjusted hazard ratio (aHR) for epilepsy was calculated using a multivariate Cox proportional hazards model.

RESULTS: The SDB cohort had an increased risk of epilepsy (aHR = 1.50, 95% confidence interval [CI] = 1.36-1.66). The sex-stratified analysis revealed a significant adjusted hazard ratio (aHR) for epilepsy with a 1.51-fold higher risk for female patients, and also a significantly 1.49-fold higher risk for male patients in the SDB cohort. Although epilepsy incidence increased with age in both cohorts, different age groups in the SDB cohort all had a significantly higher risk of developing epilepsy than comparison cohort.

CONCLUSION: This population-based cohort study indicates that patients with SDB are at a high risk of developing subsequent epilepsy, in both sexes and all age groups.

Sleep-disordered breathing and excessive daytime sleepiness in patients with epilepsy – a polysomnographic study. p.reference Harrison W, Pence N, Kovacich S. Indiana University School of Optometry, Cornea and Contact Lens Research Clinic, Bloomington, Indiana, USA. Optometry. 2007 Jul;78(7):352-5.

Neuro Endocrinol Lett. 2016 Sep;37(4):313-317.

Klobucnikova K1, Siarnik P1, Sivakova M1, Kollar B1.11st Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.

OBJECTIVES: Epilepsy and sleep-disordered breathing (SDB) are relatively common disorders. SDB induces repetitive arousals and sleep fragmentation and may cause symptomatic epileptic seizures or hypoxic encephalopathy. Epileptic seizures change sleep architecture with increase of light sleep and reduction of REM sleep, which may lead to central apneas. The aim of this study was to evaluate the relationship between SDB and daytime sleepiness in patients with epilepsy, who underwent polysomnography (PSG) due to problems with breathing during sleep or due to excessive daytime sleepiness.

METHODS: We enrolled 40 patients with epilepsy. Type, etiology of epilepsy and actual antiepileptic therapy was recorded. All of them underwent overnight PSG. Excessive daytime sleepiness (EDS) was assessed by Epworth Sleepiness Scale (ESS).

RESULTS: SDB (apnea-hypopnea index [AHI]<5) was present in 25 patients, 15 patients had no SDB (AHI≥5). EDS was present in 16 patients (40%). ESS significantly correlated with presence of symptomatic epilepsy (r=0.385, p=0.014), presence of SDB (r=0.524, p=0.001), AHI (r=0.416, p=0.003) and duration of REM sleep (r=-0.476, p=0.002). The presence of SDB (beta=0.447, p=0.002) and duration of REM sleep (beta=-0.308, p=0.029) were the only independent variables significantly associated with ESS in regression analysis.

CONCLUSION: SDB has negative influence on quality of sleep and daytime vigility in patients with epilepsy. Sleep fragmentation with the reduction of the REM sleep seems to be the most important mechanism leading to EDS. We suppose that PSG could be beneficial in all patients with epilepsy and EDS.

Temporal lobe epilepsy is a predisposing factor for sleep apnea: A questionnaire study in video-EEG monitoring unit.

Yildiz FG1, Tezer FI2, Saygi S2.

1Institute of Neurological Sciences and Psychiatry, Hacettepe University, Turkey. Electronic address: gokcemy@yahoo.com.
2Department of Neurology, School of Medicine, Hacettepe University, Turkey.

OBJECTIVE: The interaction between epilepsy and sleep is known. It has been shown that patients with epilepsy have more sleep problems than the general population. However, there is no recent study that compares the frequency of sleep disorders in groups with medically refractory temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). The main purpose of this study was to investigate the occurrence of sleep disorders in two subtypes of epilepsy by using sleep questionnaire forms.

METHODS: One hundred and eighty-nine patients, out of 215 who were monitored for refractory epilepsy and were followed by the video-EEG monitoring unit, were divided into a group with TLE and a group with ETLE. The medical outcome study-sleep scale (MOS-SS), Epworth sleepiness scale (ESS), and sleep apnea scale of the sleep disorders questionnaire (SD-SDQ) were completed after admission to the video-EEG monitoring unit. The total scores in the group with TLE and group with ETLE were compared.

RESULTS: Of the patients, TLE was diagnosed in 101 (53.4%) (45 females), and ETLE was diagnosed in 88 (46.6%) (44 females). Comparison of MOS-SS and Epworth sleepiness scale scores in the two subgroups did not reveal significant differences. In the group with TLE, SD-SDQ scores were significantly higher compared to that in the group with ETLE.

CONCLUSION: Patients with temporal lobe epilepsy have higher risk of obstructive sleep apnea (OSA) according to their reported symptoms. Detection of OSA in patients with epilepsy by using questionnaire forms may decrease the risk of ictal or postictal respiratory-related ‘Sudden Unexpected Death in Epilepsy’.

Excessive daytime sleepiness and obstructive sleep apnea in Thai epileptic patients.

J Med Assoc Thai. 2014 Feb;97 Suppl 2:S175-80.

Ruangkana P, Chinvarun Y, Udommongkol C, Chairungsaris P, Nidhinandana S, Suwantamee J, Sithinamsuwan P. p OBJECTIVES: Previous studies suggested that obstructive sleep apnea (OSA) was associated with glaucoma. However, data on this issue are controversial. This study aims to use meta-analysis to determine whether OSA is related to glaucoma.

BACKGROUND: Sleepiness is a common complaint in epilepsy. Also obstructive sleep apnea (OSA) is increasingly detected and would affect the epilepsy prognosis. We aimed to determine the frequency and predictors of sleepiness and OSA in epileptic patients.

MATERIAL AND METHOD: This was a cross-sectional descriptive study using Epworth Sleepiness Scale questionnaire (ESS) and Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) to identify excessive daytime sleepiness and OSA in our consecutive epileptic patients in Neurology out-patient clinic.

RESULTS: Overall 113 patients (male 55%) answered a personal survey and completed ESS and SA-SDQ. Mean age was 47 years (range 15-93). Average body mass index (BMI) was 24. Excessive daytime sleepiness (ESS 10) was demonstrated in 37%, and the prevalence of OSA diagnosed by using SA-SDQ was 20% (male 18%, female 22%). OSA were identified 68% among individuals whose BMI of more than 25, which was significant higherfi-equency than in the nomnnal BMI group (32%). The predictors of having OSA were older age and higher BMI. Epworth Sleepiness Scale score was also higher in the OSA group than in non-OSA group.

CONCLUSION: Excessive daytime sleepiness was identified around one third of our epileptic individuals. Twenty percent had met the questionnaire criteria of having OSA. Overweight was the most important and modifiable risk factor of OSA.


Sleep Snippets Newsletter – April 2017

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OSA & Eye Health


During the past decade, associations between sleep disorders and certain ophthalmologic disorders have been increasingly recognized. To review the literature on these important associations, we conducted a PubMed search using combinations of the following terms: sleep disorders, sleep apnea, circadian rhythm disorder, continuous positive airway pressure, eye disease, floppy eyelid syndrome, glaucoma, ischemic optic neuropathy, papilledema, nocturnal lagophthalmos, and vision loss.

We limited our search to articles published in English that involved human participants. All available dates were included. One of the most common sleep disorders, obstructive sleep apnea, has been associated with a variety of eye diseases, including glaucoma, nonarteritic anterior ischemic optic neuropathy, floppy eyelid syndrome, papilledema, and continuous positive airway pressure-associated eye complications. Nocturnal lagophthalmos manifests during sleep and is defined as the failure to fully close the eyelids at night. Finally, blindness is associated with increased risk of circadian rhythm disorders.

On the basis of the existing published literature, we discuss these rarely recognized associations, potential pathophysiologic mechanisms, and the effect these associations have on the clinical management of patients. The knowledge of these associations is important for the primary care physician, ophthalmologist, and sleep physician so that underlying sleep disorders or ophthalmologic disorders can be detected.

Sleep disorders and the eye.Waller EA(1), Bendel RE, Kaplan J.Mayo Clin Proc. 2008 Nov;83(11):1251-61.

Eye disorders associated with obstructive sleep apnoea.

West SD1, Turnbull C. Curr Opin Pulm Med. 2016 Nov;22(6):595-601.

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. Public awareness is also growing. Although OSA is a disorder primarily of the upper airway during sleep, its physiological impact on other parts of the body is now well recognized. There is increasing interest in the association of OSA with various eye disorders. Work in this field has been directed predominantly to OSA prevalence and association studies, but some authors have tried to elucidate the effect of OSA therapies on eye diseases, including continuous positive airway pressure, upper airway surgery or bariatric surgery. This review discusses the publications in this area from the past year.

RECENT FINDINGS: The key ocular disorders featured in the studies and meta-analayses include glaucoma, floppy eyelid syndrome, nonarteritic ischaemic optic neuropathy, keratoconus, age-related macular degeneration and diabetic retinopathy. Associations with OSA were found with all these conditions, but aspects of the studies still leave gaps in our knowledge.

SUMMARY: This review highlights the need for ophthalmologists to consider OSA in their patients and also makes recommendations for future research studies, especially whether therapies for OSA can be effective for ocular disorders also.

The effect of nocturnal CPAP therapy on the intraocular pressure of patients with sleep apnea syndrome.

Cohen Y(1), Ben-Mair E(2), Rosenzweig E(2), Shechter-Amir D(2), Solomon AS(3). Graefes Arch Clin Exp Ophthalmol. 2015 Dec;253(12):2263-71

PURPOSE: Few studies have documented that nocturnal continuous positive airway pressure (CPAP) therapy is associated with an increase in intraocular pressure (IOP) in patients with severe obstructive sleep apnea syndrome (OSAS). We re-examined the effect of CPAP therapy on the IOP of OSAS patients.

METHODS: The IOP of two different groups of newly diagnosed OSAS patients was compared at their first sleep lab exam without CPAP treatment (non-CPAP treated group; n = 20) and at the second sleep lab exam with CPAP treatment (CPAP treated group; n = 31). The sleep lab exam (sleep period: from 11:00 p.m. until 6:00 a.m.) included IOP measurements, a complete ophthalmologic exam, and nocturnal hemodynamic recordings. The IOP was measured serially using rebound tonometer (IOP; ICARE® PRO) performed while in sitting and supine positions before, during, and after the sleep period. We compared the difference in IOP of CPAP and non-CPAP groups.

RESULTS: The mean IOP of the CPAP and non-CPAP groups measured in sitting position before the sleep period was 13.33 ± 2.04 mmHg and 14.02 ± 2.44 mmHg, respectively (p = 0.9). Assuming a supine position for 1 minute significantly increased the IOP by 1.93 mmHg and 2.13 mmHg for both the non-CPAP and CPAP groups (paired t-test; p = 0.02, p = 0.001 respectively), but this IOP rise showed no difference between the two groups. The IOP increased significantly further after 7 hours of sleep in the supine position, and the mean IOP of the CPAP and non-CPAP groups was 19.2 ± 5.68 mmHg and 19.69 ± 5.61 mmHg respectively (independent t-test; p = 0.74). The rise in IOP for both groups was not correlated with any hemodynamic parameters. Three OSAS patients with glaucoma treated with CPAP had mean IOP of 23.75 mmHg after 7 hours of sleep.

CONCLUSIONS: OSAS patients have a significant rise in IOP during the sleep period when comparing measurements before and after the sleep period; however, CPAP therapy did not affect the measured IOP. The presented findings suggest that in terms of IOP, CPAP is safe for non-glaucomatous patients, but this may not hold true for glaucomatous patients.

Continuous positive airway pressure therapy is associated with an increase in intraocular pressure in obstructive sleep apnea.

Kiekens S(1), Veva De Groot, Coeckelbergh T, Tassignon MJ, van de Heyning P, Wilfried De Backer, Verbraecken J. Invest Ophthalmol Vis Sci. 2008 Mar;49(3):934-40.

PURPOSE: Several reports have demonstrated an association between glaucoma and obstructive sleep apnea (OSA), though the origin of this association remains unknown. In the present study, the influence of OSA and continuous positive airway pressure (CPAP) therapy on intraocular pressure (IOP) and ocular perfusion pressure (OPP) was examined.

METHODS: IOP, blood pressure, and pulse rate were measured every 2 hours during 24-hour sessions in 21 patients with newly diagnosed OSA. A first series of measurements was performed before CPAP therapy, and a second series was performed 1 month after the initiation of CPAP therapy. OPP was then calculated.

RESULTS: Baseline measurements showed a significant nycththemeral fluctuation in the average IOP, with the highest IOPs at night. After 1 month of CPAP therapy, the average IOP was significantly higher than baseline. The increase in overnight IOP was also significantly higher. A 24-hour IOP fluctuation of > or =8 mm Hg was found in 7 patients at baseline and in 12 patients during CPAP therapy. The mean difference between trough and peak IOP was 6.7 +/- 1.5 mm Hg at baseline and 9.0 +/- 2.0 mm Hg during CPAP therapy. Thirty minutes after CPAP cessation a significant decrease in IOP was recorded. There was a statistically significant decrease in mean OPP during CPAP therapy.

CONCLUSIONS: Patients with OSA demonstrated significant 24-hour IOP fluctuations, with the highest values at night. CPAP therapy causes an additional IOP increase, especially at night. Regular screening of visual fields and the optic disc is warranted for all patients with OSA, especially those treated with CPAP.

Anterior segment complications secondary to continuous positive airway pressure machine treatment in patients with obstructive sleep apnea.

Harrison W, Pence N, Kovacich S. Indiana University School of Optometry, Cornea and Contact Lens Research Clinic, Bloomington, Indiana, USA. Optometry. 2007 Jul;78(7):352-5.

BACKGROUND: Obstructive sleep apnea (OSA) is a disorder that, when left untreated, can have serious complications, mainly cardiovascular. OSA is commonly treated with a continuous positive airflow pressure (CPAP) machine. Patients using CPAPs routinely complain of dryness of the nose and eyes.

CASES: Case 1: A keratoconic woman, wearing gas-permeable lenses began therapy with a CPAP, and vascularized limbal keratitis (VLK) developed. She now wears soft lenses, compromising visual acuity, but preventing the VLK.

Case 2: A man with 20/20 visual acuity in the right eye (O.D.) and hand motion in the left eye (O.S.), presented with recurring corneal ulcers O.D. after starting treatment with a CPAP.

Case 3: A man with pellucid degeneration started using a CPAP, which increased his complaint of dryness with his lenses. He subsequently had 2 occurrences of bacterial conjunctivitis.

CONCLUSION: It is unclear if the complications seen in these cases come from leakage of air into the eyes causing drying, from bacteria trapped under the mask being forced up into the eyes, or from air passing from the nose into the eye via the nasolacrimal duct. In the care of these patients, being aware of complications, suggesting nighttime lubricants, and knowing the alternatives to CPAP could help maintain ocular health and successful lens wear.

Eyelid hyperlaxity and obstructive sleep apnea (O.S.A.) syndrome.

Robert PY1, Adenis JP, Tapie P, Melloni B. Eur J Ophthalmol. 1997 Jul-Sep;7(3):211-5.

PURPOSE: An association between the floppy eyelid syndrome and the obstructive sleep apnea syndrome (O.S.A.) has been reported. We studied eyelid tissue elasticity and other ophthalmologic findings in a large number of patients with sleep disorders.

MATERIAL AND METHODS:Sixty-nine patients with sleep disorders were evaluated. Two thirds were found to have O.S.A., and one third was treated at night by nasal continuous positive airway pressure(nasal C.P.A.P.). Slit lamp examination, eyelid measurements and Schirmer test were performed.

RESULTS: Eyelid hyperlaxity was increased in patients with O.S.A. The floppy eyelid syndrome (associated papillary conjunctivitis), however, was rare. Associated corneal lesions were rare, and most patients were asymptomatic. In some cases, ocular irritation was due to air leaks from nasal C.P.A.P. A significant proportion of patients required treatment for primary open angle glaucoma.

CONCLUSIONS: Our study of 69 patients found an association between O.S.A. and eyelid hyperlaxity.

Eyelid hyperlaxity and obstructive sleep apnea (O.S.A.) syndrome.

Glaucoma

Meta-Analysis of Association of Obstructive Sleep Apnea With Glaucoma.

Liu S, Lin Y, Liu X. Chongqing Key Laboratory of Ophthalmology, The First Affiliated Hospital of Chongqing, China J Glaucoma. 2016 Jan;25(1):1-7.

OBJECTIVES: Previous studies suggested that obstructive sleep apnea (OSA) was associated with glaucoma. However, data on this issue are controversial. This study aims to use meta-analysis to determine whether OSA is related to glaucoma.

MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane library, the Web of Science, and the Chinese BioMedical Literature Database disk databases up to November 20, 2014 for related literature. The association of OSA with glaucoma was assessed by odds ratio (OR) with 95% confidence interval (CI) as the effect size. Then subgroup analysis was performed according to area and glaucoma type.

RESULTS: Six primary studies (3 cohort study and 3 case-control studies) were included in this meta-analysis involving 2,288,701 participants. There was a significant association between OSA and glaucoma (adjusted-effect summary for case-control studies OR=2.46; 95% CI, 1.32-4.59, P=0.005) (adjusted-effect summary for cohort studies OR=1.43; 95% CI, 1.21-1.69, P=0.000). There was no significant publication bias.

CONCLUSION: OSA was a risk factor for glaucoma. A large number of studies is needed to explore the mechanisms that link OSA with glaucoma.

Prevalence of glaucoma in patients with moderate to severe OSA: ocular morbidity and outcomes in a 3 year follow-up study.

Hashim SP, Al Mansouri FA, Farouk M, Al Hashemi AA, Singh R. Ophthalmology Section, Hamad Medical Corporation, Doha, Qatar. Eye (Lond). 2014 Nov;28(11):1304-9. Erratum in Eye (Lond). 2014 Nov;28(11):1393.

PURPOSE: This study was conducted to investigate the prevalence and progressionof glaucoma in patients receiving treatment for obstructive sleep apnea (OSA). Wealso investigated whether there is an association between severity of OSA and theincidence of glaucoma.

METHODS: A total of 39 patients aged >30 years who had been diagnosed withmoderate and severe OSA in the sleep clinic at Hamad General Hospital wereassessed for the presence of glaucoma. The severity of OSA was graded as mild,moderate, or severe based on American Association of Sleep Medicine (AASM)criteria using the apnea hypopnea index. Before enrollment, all patientsunderwent a complete ophthalmic examination including serial visual field tests, optical coherence tomography (OCT) with fundus photographs, and pachymetry.Enrolled patients were followed up in the ophthalmology outpatient clinic andsleep clinic for a period of 3 years.

RESULTS: Examinations found that 8 (20.5%; 95% confidence interval (CI) 9.9-37%) of the 39 patients with OSA had glaucoma. Six (75%; 95% CI 36-96%) of thesepatients had normal-tension glaucoma (NTG) and two (25%; 95% CI 4.5-64.4%)patients had high-tension glaucoma. Among the 27 patients with severe OSA, 7(25.9%; 95% CI 8-34%) had glaucoma, and among 12 patients with moderate OSA, 1(8.3%; 95% CI 0.1-15%) had glaucoma. During the course of follow-up, two patientswho previously did not have glaucoma were reclassified as NTG and two patients with glaucoma deteriorated. A higher prevalence of glaucoma in the severe OSA group compared with the moderate OSA group was found, albeit a statistically significant difference could not be attained (P=0.4).

CONCLUSIONS: Our study showed that severe OSA is an important risk factor for developing glaucoma. Adequate treatment of OSA, along with optimal ophthalmiccare, resulted in better control of glaucoma.

Obstructive sleep apnoea syndrome in patients with primary open-angle glaucoma.

Balbay EG, Balbay O, Annakkaya AN, Suner KO, Yuksel H, Tunç M, Arbak P. Department of Chest Diseases, Faculty of Medicine, Düzce University, 81620 Düzce, Turkey. Hong Kong Med J. 2014 Oct;20(5):379-85.

OBJECTIVE: To investigate the prevalence of obstructive sleep apnoea syndrome in patients with primary open-angle glaucoma.

DESIGN: Case series.

SETTING: School of Medicine, Düzce University, Turkey.

PATIENTS: Twenty-one consecutive primary open-angle glaucoma patients (12 females and 9 males) who attended the out-patient clinic of the Department of Ophthalmology between July 2007 and February 2008 were included in this study. All patients underwent polysomnographic examination.

RESULTS: The prevalence of obstructive sleep apnoea syndrome was 33.3% inpatients with primary open-angle glaucoma; the severity of the condition was mild in 14.3% and moderate in 19.0% of the subjects. The age (P=0.047) and neck circumference (P=0.024) in patients with obstructive sleep apnoea syndrome were significantly greater than those without the syndrome. Triceps skinfold thickness in glaucomatous obstructive sleep apnoea syndrome patients reached near significance versus those without the syndrome (P=0.078). Snoring was observed in all glaucoma cases with obstructive sleep apnoea syndrome. The intra-ocular pressure of patients with primary open-angle glaucoma with obstructive sleep apnoea syndrome was significantly lower than those without obstructive sleep apnoea syndrome (P=0.006 and P=0.035 for the right and left eyes, respectively). There was no significant difference in the cup/disc ratio and visual acuity, except visual field defect, between primary open-angle glaucoma patients with and without obstructive sleep apnoea syndrome.

CONCLUSIONS: Although it does not provide evidence for a cause-effect relationship, high prevalence of obstructive sleep apnoea syndrome in patients with primary open-angle glaucoma in this study suggests the need to explore the long-term results of coincidence, relationship, and cross-interaction of these two common disorders.

Nasal CPAP during wakefulness increases intraocular pressure in glaucoma.

Alvarez-Sala R(1), García IT, García F, Moriche J, Prados C, Díaz S, Villasante C, Alvarez-Sala JL, Villamor J. Monaldi Arch Chest Dis. 1994 Dec;49(5):394-5.

Few important side-effects of nasal continuous positive airway pressure (nCPAP) have been reported. No increase of intraocular pressure (IOP) complicating this treatment has previously been described. The goal of our study was to analyse the influence of nCPAP on IOP. We evaluated 18 patients previously diagnosed as having glaucoma and 22 normal subjects. nCPAP was used during wakefulness, at +12 cmH2O for 15 min.

The results showed that nCPAP significantly increases IOP in patients with glaucoma (before nCPAP 20.3 +/- 6.3 mmHg) (mean +/- SEM); after nCPAP 22.3 +/- 5.7 mmHg. We believe that nCPAP might be relatively contraindicated in difficult to manage glaucoma patients, if these results are corroborated.

Obstructive sleep apnea patients having surgery are less associated with glaucoma.

Chen HY(1), Chang YC(2), Lin CC(3), Sung FC(4), Chen WC(5). J Ophthalmol. 2014;2014:838912. Epub 2014 Jul 24.

Objective. To investigate if different treatment strategy of obstructive sleep apnea (OSA) was associated glaucoma risk in Taiwanese population.

Methods. Population-based retrospective cohort study was conducted using data sourced from the Longitudinal Health Insurance Database 2000. We included 2528 OSA patients and randomly selected and matched 10112 subjects without OSA as the control cohort. The risk of glaucoma in OSA patients was investigated based on the managements of OSA (without treatment, with surgery, with continuous positive airway pressure (CPAP) treatment, and with multiple modalities).

The multivariable Cox regression was used to estimate hazard ratio (HR) after adjusting for sex, age, hypertension, diabetes, hyperlipidemia, and coronary artery disease. Results. The adjusted HR of glaucoma for OSA patients was 1.88 (95% CI: 1.46-2.42), compared with controls. For patients without treatment, the adjusted HR was 2.15 (95% CI: 1.60-2.88). For patients with treatments, the adjusted HRs of glaucoma were not significantly different from controls, except for those with CPAP (adjusted HR = 1.65, 95% CI = 1.09-2.49).

Conclusions. OSA is associated with an increased risk of glaucoma. However, surgery reduces slightly the glaucoma hazard for OSA patients.

Effects of Use of a Continuous Positive Airway Pressure Device on Glaucoma.

Ulusoy S(1), Erden M(2), Dinc ME(1), Yavuz N(3), Caglar E(4), Dalgic A(1), Erdogan C(5). Med Sci Monit. 2015 Nov 8;21:3415-9.

BACKGROUND: The aim of this study was to investigate the prevalence of glaucoma in obstructive sleep apnea syndrome (OSAS) and to determine the efficacy of the equipment used in the treatment of this disease.

MATERIAL AND METHODS: In this cross-sectional study, 38 patients with OSAS used the continuous positive airway pressure (CPAP) device (Group 1) and 32 patients with OSAS refused CPAP device (Group 2). Thirty-six patients did not have OSAS (Group 3).

RESULTS: Patient age, gender, height, weight, and neck circumference did not differ among groups (p>0.05); and the apnea-hypopnea index (AHI) and respiratory disturbance index (RDI) values did not differ between Groups 1 and 2 (p>0.05). Vision and pachymetric values did not differ among groups (p>0.05). The IOP was significantly higher in Group 2 than in Group 1 (p<0.05) but did not differ between Groups 1 and 3 (p>0.05). The fundus C/D ratio was significantly higher (p<0.05) in Group 2 than in the other groups but did not differ between Groups 1 and 3 (p>0.05). In Group 1, 2, and 3, 5.2%, 12.5%, and 0%, respectively, of patients had glaucoma.

CONCLUSIONS: OSAS should be considered a significant risk factor for glaucoma. Eye tests may help to identify individuals with undiagnosed OSAS, and such testing of patients with diagnosed OSAS may allow early detection of glaucoma and referral of such patients for CPAP therapy to prevent development of complications.

Normal tension glaucoma, sleep apnea syndrome and nasal continuous positive airway pressure therapy–case report with a review of literature.

Kremmer S(1), Selbach JM, Ayertey HD, Steuhl KP. Klin Monbl Augenheilkd. 2001 Apr;218(4):263-8.

BACKGROUND: In the pathogenesis of glaucoma, besides an elevated intraocular pressure (IOP), cardiovascular risk factors, such as arterial hypotension and hypertension, vasospasms, autoregulatory defects, atherosclerosis, and diabetes mellitus are of increasing importance, especially in normal tension glaucoma. Recently, there have been several reports of an additional risk factor: obstructive sleep apnea syndrome.

METHODS: Literature review (Medline) and case report.

RESULTS: The authors report on a 8 1/2 years follow-up of a 60-year-old patient with normal tension glaucoma. Despite successful pharmacological and surgical lowering of intraocular pressure a progressive glaucomatous damage with optic nerve atrophy and increasing visual field defects occurred. As a result of intensive investigations of possible cardiovascular risk factors, an obstructive sleep apnea syndrome was diagnosed. Since the beginning of therapy with nCPAP (nasal continuous positive airway pressure) more than 3 1/2 years ago, no further progression of glaucomatous optic nerve damage or visual field defects have been observed.

CONCLUSIONS: In clinical practice, obstructive sleep apnea syndrome often is underdiagnosed. In patients suffering from glaucoma and obstructive sleep apnea syndrome, intraocular pressure lowering therapy may not be enough, whereas an additional nCPAP-therapy potentially could prevent the beginning/progression of glaucomatous optic nerve damage.

 

Sleep Snippets Newsletter – November 2016

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Sleep Apnea and Cancer


Obstructive sleep apnea promotes cancer development and progression: a concise review.

Cao J1, Feng J, Li L, Chen B. Sleep Breath. 2015 May;19(2):453-7

BACKGROUND: Obstructive sleep apnoea-hypopnoea (OSA) is an increasingly common sleep disorder which is widely accepted to be associated with high rates of morbidity and mortality. OSA is an independent risk factor for cardiovascular diseases, cerebrovascular disease, and metabolic disease. Recently, several studies have demonstrated that patients with OSA have a higher prevalence of cancer and cancer-related mortality. The epidemiological surveys suggest that patients with OSA had a higher incidence of cancer and cancer-related mortality than patients without OSA. Animal studies indicate that the activation of HIF-1 and VEGF pathways in response to intermittent hypoxia may promote the blood supply which supports tumor growth. In addition, tumor-associated macrophages may be altered by intermittent hypoxia (or sleep fragmentation) to a tumor-promoting phenotype yielding more aggressive cancer behaviour.

CONCLUSIONS: The relationship between OSA and cancer has been confirmed, in which patients with OSA have a relative high prevalence of cancer and cancer-related mortality. The mechanism of OSA promoting cancer development and progression may be related with intermittent hypoxia and possibly sleep fragmentation. The activation of several cancer-related pathways may play an important role in tumor growth and metastasis. More clinical data and basic studies are needed to explain and confirm the relationship between OSA and cancer.

Obstructive sleep apnea and cancer: effects of intermittent hypoxia?

Kukwa W1, Migacz E1, Druc K2, Grzesiuk E3, Czarnecka AM2. Future Oncol. 2015;11(24):3285-98.

Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that intermittent hypoxia in OSA may influence tumorigenesis. This review presents recent articles on the potential role of OSA in cancer development. Relevant research has focused on: molecular pathways mediating the influence of intermittent hypoxia on tumor physiology, animal and epidemiological human studies linking OSA and cancer. Current data relating OSA to risk of neoplastic disease remain scarce, but recent studies reveal the potential for a strong relation. More work is, therefore, needed on the impact of OSA on many cancer-related aspects. Results may offer enlightenment for improved cancer diagnosis and treatment.

Cancer and OSA: Current Evidence From Human Studies.

Martínez-García MÁ1, Campos-Rodriguez F2, Barbé F3. Chest. 2016 Aug;150(2):451-63.

Despite the undeniable medical advances achieved in recent decades, cancer remains one of the main causes of mortality. It is thus extremely important to make every effort to discover new risk factors for this disease, particularly ones that can be treated or modified. Various pathophysiologic pathways have been postulated as possible causes of cancer or its increased aggressiveness, and also of greater resistance to antitumoral treatment, in the presence of both intermittent hypoxia and sleep fragmentation (both inherent to sleep apnea).

Thus far, these biological hypotheses have been supported by various experimental studies in animals. Meanwhile, recent human studies drawing on preexisting databases have observed an increase in cancer incidence and mortality in patients with a greater severity of sleep-disordered breathing. However, the methodologic limitations of these studies (which are mostly retrospective and lack any measurement of direct markers of intermittent hypoxia or sleep fragmentation) highlight the need for controlled, prospective studies that would provide stronger scientific evidence regarding the existence of this association and its main characteristics, as well as explore its nature and origin in greater depth. The great epidemiologic impact of both cancer and sleep apnea and the potential for clinical treatment make this field of research an exciting challenge.

Sleep and Breathing… and Cancer?: A report from the University of California San Diego Sleep and Cancer Symposium, January 5- 6th, 2016 in La Jolla, CA.

Owens RL1, Gold K2, Gozal D3, Peppard PE4, Jun J5, Lippman SM6, Malhotra A7. Cancer Prev Res (Phila). 2016 Sep 7

Sleep, like eating and breathing, is an essential part of the daily life cycle. Although the science is still emerging, sleep plays an important role in immune, cardiovascular, and neurocognitive function. Despite its great importance, nearly 40% of US Adults experience problems with sleep ranging from insufficient total sleep time, trouble initiating or maintaining sleep (Insomnia), Circadian Rhythm Disorders, Sleep-Related Movement Disorders, and Sleep-Related Breathing Disorders such as obstructive sleep apnea (OSA). Herein, we discuss new evidence that suggests that sleep may also impact carcinogenesis. Specifically, we review recent epidemiological data suggesting links between cancer and OSA.

As OSA is a common, underdiagnosed, and undertreated condition, this has public health implications. Intriguing animal model data support a link between cancer and sleep/OSA, although mechanisms are not yet clear. Leaders in the fields of Sleep Medicine, Pulmonology and Oncology recently met to review and discuss these data, as well as to outline future directions of study. We propose a multidisciplinary, three-pronged approach to studying the associations between cancer and sleep, utilizing mutually interactive epidemiologic studies, pre-clinical models, and early-phase clinical trials.

Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study.

Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farré R. University of Wisconsin-Madison, Madison, WI, USA. Am J Respir Crit Care Med. 2012 Jul 15;186(2):190-4.

RATIONALE: Sleep-disordered breathing (SDB) has been associated with total and cardiovascular mortality, but an association with cancer mortality has not been studied. Results from in vitro and animal studies suggest that intermittent hypoxia promotes cancer tumor growth.

OBJECTIVES: The goal of the present study was to examine whether SDB is associated with cancer mortality in a community-based sample.

METHODS: We used 22-year mortality follow-up data from the Wisconsin Sleep Cohort sample (n = 1,522). SDB was assessed at baseline with full polysomnography. SDB was categorized using the apnea-hypopnea index (AHI) and the hypoxemia index (percent sleep time below 90% oxyhemoglobin saturation). The hazards of cancer mortality across levels of SDB severity were compared using crude and multivariate analyses.

MEASUREMENTS AND MAIN RESULTS: Adjusting for age, sex, body mass index, and smoking, SDB was associated with total and cancer mortality in a dose-response fashion. Compared with normal subjects, the adjusted relative hazards of cancer mortality were 1.1 (95% confidence interval [CI], 0.5-2.7) for mild SDB (AHI, 5-14.9), 2.0 (95% CI, 0.7-5.5) for moderate SDB (AHI, 15-29.9), and 4.8 (95% CI, 1.7-13.2) for severe SDB (AHI ≥ 30) (P-trend = 0.0052). For categories of increasing severity of the hypoxemia index, the corresponding relative hazards were 1.6 (95% CI, 0.6-4.4), 2.9 (95% CI, 0.9-9.8), and 8.6 (95% CI, 2.6-28.7).

CONCLUSIONS: Our study suggests that baseline SDB is associated with increased cancer mortality in a community-based sample. Future studies that replicate our findings and look at the association between sleep apnea and survival after cancer diagnosis are needed.

Tumor Cell Malignant Properties Are Enhanced by Circulating Exosomes in Sleep Apnea.

Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farré R. University of Wisconsin-Madison, Madison, WI, USA. Am J Respir Crit Care Med. 2012 Jul 15;186(2):190-4.

BACKGROUND:Obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. Exosomes are vesicles secreted by most cells, are released into the bloodstream, and play a role in tumor progression and metastasis. Here, we evaluated whether the chronic intermittent hypoxia (IH) that characterizes OSA leads to release of tumor-promoting exosomes in circulation.

METHODS: C57/B6 male mice were randomized to 6 weeks of IH or room air (RA). A subgroup of the mice was injected with TC1 lung carcinoma cells in the left flank after 2 weeks of IH. Exosomes from mouse plasma and from 10 adult human patients with OSA before (Pre) and after adherent treatment for 6 wks (Post) were co-cultured with mouse TC1 and human adenocarcinoma cells lines. Malignant tumor properties such as proliferation, migration, invasion and endothelial monolayer disruption were assessed, as well as miRNA exosomal content and transcriptomic effects of exosomes on TC1 cells in vitro to identify target genes.

RESULTS: Application of IH-induced exosomes from either IH-exposed tumor bearing (IH (+) or non-bearing mice IH (-) significantly promoted TC1 malignant properties. Similarly, Pre exosomes from OSA patients significantly enhanced proliferation and migration of human adenocarcinoma cells compared to Post. 11 distinct miRNAs emerged in IH (-) mice and their gene targets in TC1 cells were identified.

CONCLUSION: Circulating exosomes released under IH conditions in vivo selectively enhance specific properties of lung tumor cell cultures. Thus, plasma exosomes participate in the increased tumor aggressiveness observed in OSA patients.

Obstructive sleep apnea is associated with an increased risk of colorectal neoplasia.

Lee S1, Kim BG1, Kim JW1, Lee KL1, Koo DL2, Nam HW2, Im JP3, Kim JS3, Koh SJ4. Gastrointest Endosc. 2016 Aug 6.

BACKGROUND AND AIMS: A recent meta-analysis showed that obstructive sleep apnea (OSA) is associated with a higher prevalence of cancer and cancer-related mortality; however, little information is available on the association between OSA and colorectal neoplasia.

METHODS: We identified consecutive patients who underwent overnight polysomnography (PSG) and subsequent colonoscopy. We compared the prevalence of colorectal neoplasia between patients with or without OSA according to the results of PSG. For each OSA case, 1 or 2 age-matched (± 5 years), sex-matched, body mass index (BMI), and smoking-matched controls who had undergone first-time screening colonoscopy were selected.

RESULTS: Of the 163 patients, 111 patients were diagnosed with OSA and 52 patients showed normal range of apnea-hypopnea index. Of the 111 patients with OSA, 18 patients (16.2%) had advanced colorectal neoplasia, including 4 (3.6%) colorectal cancers. In the multivariate analyses, OSA was associated with an increased risk of advanced colorectal neoplasia after adjusting for factors including age and sex (mild, odds ratio [OR], 14.09; 95% confidence interval [CI], 1.55-127.83; P = 0.019; moderate or severe, OR, 14.12; 95% CI, 1.52-131.25; P = 0.020). Our case-control study revealed that the odds of detecting advanced colorectal neoplasia among patients with OSA were approximately 3.03 times greater than in the age-, sex-, BMI-, and smoking-matched controls (OR, 3.03; 95% CI, 1.44-6.34; P = 0.002).

CONCLUSION: Physicians should be aware of the association between OSA and the development of colorectal neoplasia and explain the need for colonoscopy to patients with OSA.

Associations of self-reported sleep duration and snoring with colorectal cancer risk in men and women.

Zhang X, Giovannucci EL, Wu K, Gao X, Hu F, Ogino S, Schernhammer ES, Fuchs CS, Redline S, Willett WC, Ma J. Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. Sleep. 2013 May 1;36(5):681-8.

STUDY OBJECTIVES: We assessed the relationship between sleep duration, snoring and colorectal cancer risk. DESIGN: Prospective cohort studies.

SETTING: United States.

PARTICIPANTS: A total of 30,121 men aged 41 to 79 years in the Health Professionals Follow-up Study and 76,368 women aged 40 to 73 years in the Nurses’ Health Study.

INTERVENTIONS: None.

MEASUREMENTS AND RESULTS: We queried information on sleep duration and snoring in 1986/87. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs, 95% CIs). We documented 1,973 incident colorectal cancer cases (709 men and 1,264 women) over a 22-year follow-up period. Compared to sleep an average 7 h, ≥ 9 h of sleep was significantly associated with a higher risk of colorectal cancer among men (HR = 1.35, 95% CI: 1.00, 1.82), and to a lesser degree, among women (HR = 1.11, 95% CI: 0.85, 1.44). The risk associated with longer sleep was restricted to individuals who regularly snored (men: HR = 1.80, 95% CI: 1.14, 2.84; women: HR = 2.32, 95% CI: 1.24, 4.36) and to overweight individuals (i.e., BMI ≥ 25 kg/m2) (men: HR = 1.52, 95% CI: 1.04, 2.21; women: HR = 1.37, 95% CI: 0.97, 1.94). Short sleep duration (≤ 5 h) was not associated with an increased risk of colorectal cancer in the entire sample or in subgroups stratified by snoring or BMI.

CONCLUSIONS: Longer sleep duration was associated with an increased risk of developing colorectal cancer among individuals who were overweight or snored regularly. This observation raises the possibility that sleep apnea and its attendant intermittent hypoxemia may contribute to cancer risk.

Sleep Apnea and Cancer: Analysis of a Nationwide Population Sample.

Gozal D1, Ham SA2, Mokhlesi B3. Sleep. 2016 Aug 1;39(8):1493-500

STUDY OBJECTIVES: Epidemiological evidence from relatively small cohorts suggests that obstructive sleep apnea (OSA) is associated with higher cancer incidence and mortality. Here we aimed to determine whether cancer incidence for major cancer types and risk of metastases or mortality from cancer are increased in the presence of OSA.

METHODS: All OSA diagnoses included in an employee-sponsored health insurance database spanning the years 2003-2012 were identified and 1:1 matched demographically based on age, gender, and state of residence, or alternatively matched by comorbidities. The incidence of 12 types of cancer was assessed. In addition, another cohort of patients with a primary diagnosis of cancer was retrieved, and the risk of metastatic disease or cancer mortality was determined as a function of the presence or absence of OSA. Multivariate Cox proportional hazards regression models were fitted to assess the independent associations between OSA and outcomes of interest.

RESULTS: Based on a cohort of ∼5.6 million individuals, the incidence of all cancer diagnoses combined was similar in OSA and retrospectively matched cases. However, the adjusted risk of pancreatic and kidney cancer and melanoma were significantly higher in patients with OSA, while the risk of colorectal, breast, and prostate cancers appeared to be lower. Among individuals with a diagnosis of cancer, the presence of OSA was not associated with an increased risk for metastasis or death.

CONCLUSIONS: In a large nationally representative health insurance database, OSA appears to increase the risk for only a very selective number of cancer types, and does not appear to be associated with an increased risk of metastatic cancer or cancer-related deaths.

Association between sleep-disordered breathing, obstructive sleep apnea, and cancer incidence: a systematic review and meta-analysis.

Palamaner Subash Shantha G1, Kumar AA2, Cheskin LJ3, Pancholy SB4. Sleep Med. 2015 Oct;16(10):1289-94.

OBJECTIVE/BACKGROUND: Via this systematic review and meta-analysis, we assessed the associatio between sleep-disordered breathing (SDB)/obstructive sleep apnea (OSA) and cancer incidence.

METHOD: Medline, Embase, Cochrane Central, and electronic databases were searched for relevant studies in any language. Studies were included based on the following criteria: (1) those on patients with SDB/OSA, (2) those reporting cancer incidence rates specific to patients with SDB/OSA, and (3) those defining SDB/OSA using sleep-study-based objective measures. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOQA).

RESULTS: Of the 8766 retrieved citations, five studies that defined SDB/OSA using the apnea-hypopnea index (AHI) or the respiratory disturbance index (RDI) totaling 34,848 patients with SDB and 77,380 patients without SDB were pooled into a meta-analysis. All five studies were of good quality (NOQA ≥ 6). A total of 574 (1.6%) and 290 (0.37%) incident cancers were reported in patients with and without SDB, respectively. In the unadjusted analysis, patients with SDB/OSA were at an increased risk of incident cancer (relative risk [RR]: 1.53, 95% confidence interval [CI]: 1.31-1.79, P <0.001, I(2): 0, five included studies). When adjusted for traditional cancer risk factors, the association between SDB/OSA and cancer incidence, although attenuated (RR: 1.40, 95% CI: 1.01-1.95, P = 0.04, I(2): 60%, five included studies), remains significant.

CONCLUSIONS: SDB/OSA may increase the risk of incident cancer. Inferring an independent association is not possible from our analysis considering the retrospective cohort design of the included studies and high inter-study heterogeneity. An individual patient data meta-analysis would help validate our findings.

Obstructive sleep apnea is associated with cancer mortality in younger patients.

Martínez-García MA, Campos-Rodriguez F, Durán-Cantolla J, de la Peña M, Masdeu MJ, González M, Del Campo F, Serra PC, Valero-Sánchez I, Ferrer MJ, Marín JM, Barbé F, Martínez M, Farré R, Montserrat JM; Spanish Sleep Network. Sleep Med. 2014 Jul;15(7):742-8.

OBJECTIVE: The association between obstructive sleep apnea (OSA) and cancer mortality has scarcely been studied. The objective of this study was to investigate whether OSA is associated with increased cancer mortality in a large cohort of patients with OSA suspicion.

METHODS: This was a multicenter study in consecutive patients investigated for suspected OSA. OSA severity was measured by the apnea-hypopnea index (AHI) and the hypoxemia index (% night-time spent with oxygen saturation <90%, TSat90). The association between OSA severity and cancer mortality was assessed using Cox’s proportional regression analyses after adjusting for relevant confounders.

RESULTS: In all, 5427 patients with median follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with cancer. Log-transformed TSat90 was independently associated with increased cancer mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.42), as well as in the group of patients with cancer (HR, 1.19; 95% CI, 1.02-1.41). The closest association was shown in patients <65years in both the AHI (continuous log-transformed AHI: HR, 1.87; 95% CI, 1.1-3.2; upper vs lower AHI tertile: HR, 3.98; 95% CI, 1.14-3.64) and the TSat90 (continuous log-transformed TSat90: HR, 1.73; 95% CI, 1.23-2.4; upper vs. lower TSat90 tertile: HR, 14.4; 95% CI, 1.85-111.6). CONCLUSIONS: OSA severity was associated with increased cancer mortality, particularly in patients aged <65 years.

Risk of Cancer in Patients with Insomnia, Parasomnia, and Obstructive Sleep Apnea: A Nationwide Nested Case-Control Study.

Fang HF1, Miao NF2, Chen CD3, Sithole T4, Chung MH5. J Cancer. 2015 Sep 15;6(11):1140-7.

PURPOSE: Insomnia, parasomnia, and obstructive sleep apnea have been associated with a number of disease pathologies, but little is known about the relationship of these sleep disorders and cancer. The study explored the risk of sleep disorder (SD)-induced cancer using nationwide population data. Two million data from the National Health Insurance system of Taiwan was used to assess for the relationship.

PATIENTS AND METHODS: Patients with cancer as our cases and patients without cancer as our control group in 2001-20011. The study patients were traced back to seek the exposure risk factor of sleep disorders, which was divided into three categories: insomnia, obstructive sleep apnea (OSA) and parasomnia. Patients were selected excluding patients who had cancer prior to presenting with the sleep disorder and the person-year is less than 2 years. Each case was randomly matched with two cases with the same age, gender, and index year.

RESULTS: There were significantly increased risks of breast cancer in the patients with insomnia (AHR=1.73; 95% CI: 1.57-1.90), patients with parasomnia (AHR=2.76; 95% CI: 1.53-5.00), and patients with OSA (AHR=2.10; 95% CI: 1.16-3.80). Moreover, patients with parasomnia had significantly higher risk of developing oral cancer (AHR=2.71; 95% CI: 1.02-7.24) compared with patients without parasomnia. The risk of suffering from nasal cancer (AHR=5.96, 95% CI: 2.96-11.99) and prostate cancer (AHR=3.69, 95% CI: 1.98- 6.89) in patients with OSA was significantly higher than that of patients without OSA.

CONCLUSIONS: Our findings provided the evidence that people diagnosed with insomnia, parasomnia and OSA are at a higher risk of developing cancers to remind people to improve sleep quality.

Sleep apnea and the subsequent risk of breast cancer in women: a nationwide population-based cohort study.

Chang WP, Liu ME, Chang WC, Yang AC, Ku YC, Pai JT, Lin YW, Tsai SJ. Yuanpei University, HsinChu, Taiwan. Sleep Med. 2014 Sep;15(9):1016-20.

BACKGROUND: Hypoxia plays an important role in the development of solid tumors. Intermittent hypoxia is the hallmark of sleep apnea (SA). We tested the hypothesis that SA may increase the risk of breast cancer in Taiwan by using a population-based data set.

METHODS: Our study cohort consisted of women diagnosed with SA between January 2003 and December 2005 (n = 846). For each SA patient, five age-matched control women were randomly selected as the comparison cohort (n = 4230). All participant cases were followed for 5 years from the index date to identify the development of breast cancer. Cox proportional-hazards regression was performed to evaluate the 5-year breast-cancer-free survival rates.

RESULTS: Forty-four women developed breast cancer during the 5-year follow-up period, among whom 12 were SA patients and 32 were in the comparison cohort. The adjusted hazard ratio (HR) of breast cancer in patients with SA was higher HR, 2.09; 95% confidence interval (CI), 1.06-4.12; P < 0.05] than that of the controls during the 5-year follow-up. Despite not meeting statistical significance, we found increases in the risk of breast cancer in women aged 30-59 years (HR, 2.06; 95% CI, 0.90-4.70) and ≥60 years (HR, 3.05; 95% CI, 0.90-10.32) compared with those aged 0-29 years.

CONCLUSION: The findings of our population-based study suggest an association between SA and an increased risk of breast cancer in women.

Sleep Snippets Newsletter – March 2016

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Sleepiness and Driving Risk

Dr Geoff Eather

Dr Geoff Eather
Respiratory and Sleep Physician
Telephone: 07 3846 7955 | Facsimile: 07 3217 2523 | Website: www.qsdu.com.au

Well recognised risk factors for motor vehicle accidents include driving under the influence of alcohol and other drugs and excessive speed. It has been estimated however that 15 to 20% of all crashes are related to sleepiness. Many factors, including sleep deprivation, shift work, sedative drugs or medication, contribute to this, but underlying sleep disorders are an important treatable cause that should be considered.

Motor vehicle accidents can occur due to dozing behind the wheel, but risk is also associated with reduced vigilance and impaired concentration, akin to the effects of excessive alcohol.

In patients complaining of tiredness and somnolence it is important to assess driving risk, and to take a thorough medical history, including an assessment of medical disorders, medications, sleep habit and sleep duration. Sleep restriction is a common and important factor. For example, sleep duration of <5 hours has been shown to significantly increase crash risk, similar to the effects of a blood alcohol level above the legal limit.

It is also important to identify risk factors for sleep apnoea. Drivers with known obstructive sleep apnoea have been demonstrated to have up to 15 times higher likelihood of having a motor vehicle accident, with the highest risk being in those with the most severe and symptomatic disease. Patients with untreated sleep apnoea are at a cumulative increased risk if other factors such as sleep deprivation, shift work or other conditions are also present.

The difficulty is identifying those with sleep apnoea who are at most risk, as the reality is that the majority of people with sleep apnoea do not have accidents.

Those at highest driving risk are those that have: severe obstructive sleep apnoea; a history of crash or near-miss episode attributable to drowsiness or inattention and; severe sleepiness (as defined by a score on the Epworth Sleepiness Scale of ≥15).

Those who fit into this high risk category should be advised to restrict their driving as appropriate until adequate assessment and management can be obtained. Ideally a sleep physician should be involved, particularly in those who are commercial licence holders where it is mandated.

The good news is that treatment of sleep apnoea with CPAP can significantly reduce the crash risk and enable people with sleep apnoea to drive safely provided they are on effective therapy. The trick is to identify those most at risk and to promptly diagnose and treat sleep apnoea, while being mindful of managing other contributing factors.

Summary:

Drowsiness-associated motor vehicle accidents are related to many factors, including sleep deprivation, poor sleep habit, medical conditions, sedating medications and sleep disorders. Obstructive sleep apnoea is a common condition associated with increased risk if untreated and this diagnosis should always be considered. Assessment and treatment of sleep apnoea is essential to help reduce avoidable, life-threatening accidents caused by drowsy driving.

Elevated risk of sleepiness-related motor vehicle accidents in patients with OSAS: a case-control study.

Basoglu OK, Tasbakan MS.

Department of Chest Diseases, Ege University School of Medicine, Izmir, Turkey.

Traffic Inj Prev. 2014;15(5):470-6.

OBJECTIVES: The present case-control study aimed to determine whether obstructive sleep apnea syndrome (OSAS) patients are at an increased risk for sleepiness-related motor vehicle accidents (MVAs) than controls and to identify disease-related factors associated with accident risk.

METHODS: Demographic, anthropometric, clinical, and polysomnographic parameters of 312 OSAS patients were compared with 156 age- and sex-matched primary snoring subjects.

RESULTS: The rate of OSAS patients reporting accident was higher than snoring subjects (21.2% vs. 11.5%, P = .011), and OSAS was associated with an increase in accident risk (odds ratio = 2.06, 95% confidence interval [CI], 1.17 to 3.61, P =.012). Younger OSAS patients (P = .001) and those who were male (P = .001), had greater neck circumference (P = .002), had a higher Epworth sleepiness score(ESS; P < .0001), and had a higher apnea-hypopnea index (AHI; p = .039) had more MVAs than OSAS patients. Daytime sleepiness was associated with a 2.74-foldincrease (95% CI, 1.54 to 4.87, P = .001) in accident risk. In multiple logistic regression analysis, accident risk was associated with neck circumference (P <.031) and ESS (P < .0001). In addition, accident risk could be excluded in OSAS patients with neck circumference < 43 cm and ESS < 11 (sensitivity 33.3%,specificity 85.8%).

CONCLUSIONS: The present results show that OSAS patients have a twofold higher risk of traffic accidents than control subjects, and increased neck circumference and excessive daytime sleepiness are useful in predicting OSAS patients at higher risk of having accidents.

Excessive daytime sleepiness increases the risk of motor vehicle crash in obstructive sleep apnea.

Ward KL, Hillman DR, James A, Bremner AP, Simpson L, Cooper MN, Palmer LJ,Fedson AC, Mukherjee S.

University of WA, Western Australian Sleep Disorders ResearchInstitute, Queen Elizabeth II Medical Centre, Australia.

J Clin Sleep Med. 2013 Oct 15;9(10):1013-21.

STUDY OBJECTIVES: (1) To describe the incidence rate of motor vehicle crashes (MVCs) in patients with obstructive sleep apnea (OSA); and (2) to investigate MVC risk factors in OSA patients.

METHODS: A retrospective case-series observational study was conducted using data from the West Australian Sleep Health Study at a tertiary hospital-based sleep clinic. Participants were patients (N = 2,673) referred for assessment of suspected sleep disordered breathing. Questionnaire data were collected including age, sex, years of driving, near-misses and MVCs, sleepiness, and consumption of alcohol and caffeinated drinks. Overnight laboratory-based polysomnography was performed using standard methodology.(1) Poisson univariate and negative binomialmultivariable regression models were used to investigate associations between risk factors and MVC and near-miss risk in patients with untreated OSA.

RESULTS: In patients with untreated OSA, the crash rate was 0.06 MVC/person-year compared with the general community crash rate of 0.02 MVC/person-year. The rate ratio comparing very sleepy men with normal men was 4.68 (95% CI 3.07, 7.14) for near-misses and 1.27 (95% CI 1.00, 1.61) for crashes, after adjusting for confounders. In women there was a significant association with sleepiness score (p = 0.02) but no dose effect across quartiles.

CONCLUSIONS: Untreated OSA is associated with an increased risk of near-misses in men and women and an increased risk of MVCs in very sleepy men. There is a strong association between excessive daytime sleepiness and increased report of near-misses. Our data support the observation that it is those patients with increased sleepiness regardless of OSA severity who are most at risk.

Impact of sleep deprivation and OSAS on daytime vigilance and driving performance: a lab perspective.

Pizza F; Contardi S; Mondini S; Cirignotta F

IRCCS Istituto delle Scienze Neurologiche, Universita di Bologna, Italy. fpizza@gmail.com

Giornale italiano di medicina del lavoro ed ergonomia (Italy) Jul-Sep 2012, 34 (3 Suppl) p375-7

INTRODUCTION: To study the impact of sleepiness, a well-established cause of car accidents, on driving ability, we designed a 30-min monotonous simulated driving task. MATERIALS AND

METHODS: Our simulated driving task encompasses both primary vehicle control (standard deviation of lane position, crash occurrence) and secondary tasks (type and reaction times to divided attention tasks). Driving simulator data were correlated to subjective (state/trait) and objective (MSLT/MWT) sleepiness measures in healthy subjects undergoing sleep deprivation (SD) and in obstructive sleep apnea (OSAS) patients.

RESULTS: SD induced severe sleepiness during night time, when state sleepiness increased while primary vehicle control ability worsened. After SD, driving ability decreased and was inversely correlated to subjective and objective sleepiness at MSLT. OSAS patients driving ability was well correlated to objective sleepiness, with inverse correlation to sleep propensity at the MSLT and even more strict relation with the ability to maintain wakefulness at the MWT.

CONCLUSIONS: Sleepiness worsens driving ability in healthy subjects after SD and in OSAS patients. Driving ability correlates with subjective and objective sleepiness measures, in particular to the ability to maintain wakefulness.

Employer-mandated sleep apnea screening and diagnosis in commercial drivers.

Berger Mark; Varvarigou Vasileia; Rielly Albert; Czeisler Charles A; Malhotra Atul; Kales Stefanos N

Precision Pulmonary Diagnostics, Houston, TX, USA.

Journal of occupational and environmental medicine Aug 2012, 54 (8) p1017-25

INTRODUCTION: Obstructive sleep apnea (OSA) is common among commercial drivers and associated with health/safety risks, leading several trucking firms to mandate OSA screening.

METHODS: A total of 19,371 commercial drivers were screened for OSA with an online questionnaire (Somni-Sage reg) through employer mandates. Questionnaire and polysomnography results were analyzed retrospectively.

RESULTS: Screening categorized 5908 drivers (30%) as higher risk. To date, employers have sent 2103 higher-risk drivers for polysomnography, demonstrating that 68% of high-risk drivers tested had an apnea-hypopnea index (AHI) greater than 10 and 80% had an AHI of 5 or more. A conservative prevalence estimate for OSA (AHI > 10) was 21% among the drivers studied.

CONCLUSIONS: Online screening followed by polysomnography for high-risk drivers demonstrates as many as 21% of commercial drivers may have OSA. Mandatory screening can have a high yield among commercial drivers.

One night’s CPAP withdrawal in otherwise compliant OSA patients: marked driving impairment but good awareness of increased sleepiness.

Filtness Ashleigh J; Reyner Louise A; Horne James A

Sleep Research Centre, Loughborough University, Leicestershire, UK. ashleigh.filtness@monash.edu

Sleep & breathing = Schlaf & Atmung (Germany) Sep 2012, 16 (3) p865-71

PURPOSE: Obstructive sleep apnoea (OSA) patients effectively treated by and compliant with continuous positive air pressure (CPAP) occasionally miss a night’s treatment. The purpose of this study was to use a real car interactive driving simulator to assess the effects of such an occurrence on the next day’s driving, including the extent to which these drivers are aware of increased sleepiness.

METHODS: Eleven long-term compliant CPAP-treated 50-75-year-old male OSA participants completed a 2-h afternoon, simulated, realistic monotonous drive in an instrumented car, twice, following one

night: (1) normal sleep with CPAP and (2) nil CPAP. Drifting out of road lane (‘incidents’), subjective sleepiness every 200 s and continuous electroencephalogram (EEG) activities indicative of sleepiness and compensatory effort were monitored.

RESULTS: Withdrawal of CPAP markedly increased sleep disturbance and led to significantly more incidents, a shorter ‘safe’ driving duration, increased alpha and theta EEG power and greater subjective sleepiness. However, increased EEG beta activity indicated that more compensatory effort was being applied. Importantly, under both conditions, there was a highly significant correlation between subjective and EEG measures of sleepiness, to the extent that participants were well aware of the effects of nil CPAP.

CONCLUSIONS: Patients should be aware that compliance with treatment every night is crucial for safe driving.

Sleep Snippets Newsletter – December 2015

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COPD and OSA Overlap Syndrome

Dr Katherine Semple

Dr Katherine Semple | MBBS (Hons) MPhil FRACP
Thoracic and Sleep Physician
Pulmedica, Greenslopes Private Hospital | t: 07 3847 8890 | f: 07 3847 8891
VMO Mater Adult Hospital

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are both common diseases. Almost 20% of COPD patients also have OSA. The combination is associated with a poor prognosis. Sleep difficulties are common in COPD. Up to 70% of patients with COPD without significant daytime hypoxaemia can have significant oxygen desaturation at night, especially during REM sleep. A high daytime pCO2 is a predictor of nocturnal hypoxaemia and increased mortality.

Patients with a combination of OSA and COPD have more severe hypoxaemia, than if either disease is present in isolation. This is associated with pulmonary hypertension, right heart failure, cardiac arrhythmias and a much higher risk of dying.

Oxygen alone is not sufficient treatment for these patients. COPD patients with untreated OSA have a relative risk of death of 1.8, compared with matched COPD patients who do not have OSA. Overlap syndrome patients also have a higher incidence of COPD admissions. Effective treatment of OSA with CPAP improves survival and reduces hospital admissions. In some patients bilevel non-invasive ventilation (NIV) is required.

Summary

COPD and OSA commonly overlap
and this is associated with a much worse survival. Consider screening patients with moderate to severe COPD for OSA, especially if they have hypercapnoea or pulmonary hypertension. CPAP mitigates the excess morbidity and mortality risk.

Obstructive sleep apnea and asthma.

Salles C(1), Terse-Ramos R, Souza-Machado A, Cruz ÁA. Federal University of Bahia, Salvador, Brazil. J Bras Pneumol. 2013 Sep-Oct;39(5):604-12.

Symptoms of sleep-disordered breathing, especially obstructive sleep apnea syndrome (OSAS), are common in asthma patients and have been associated with asthma severity. It is known that asthma symptoms tend to be more severe at night and that asthma-related deaths are most likely to occur during the night or early morning. Nocturnal symptoms occur in 60-74% of asthma patients and are
markers of inadequate control of the disease. Various pathophysiological mechanisms are related to the worsening of asthma symptoms, OSAS being one of the most important factors.

In patients with asthma, OSAS should be investigated whenever there is inadequate control of symptoms of nocturnal asthma despite the treatment recommended by guidelines having been administered. There is evidence in the literature that the use of continuous positive airway pressure contributes to asthma control in asthma patients with obstructive sleep apnea and uncontrolled asthma.

Patients with a combination of OSA and COPD

The prevalence of obstructive sleep apnea in patients with difficult-to-treat asthma.

Guven SF, Dursun AB, Ciftci B, Erkekol FO, Kurt OK. Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital, SleepDisorders Center Ankara, Turkey. Asian Pac J Allergy Immunol. 2014 Jun;32(2):153-9.

OBJECTIVES: Obstructive sleep apnea (OSA) occurs more commonly in asthma patients than in the general population and can complicate asthma management. The aim oft his study was to evaluate the presence of OSA in patients with difficult-to-treat asthma (DTA) and to investigate the sleep quality in these patients.

METHODS: Patients with DTA were recruited from the adult allergy clinic of atertiary care hospital. After completing the Sleep Questionnaire and Epworth Sleepiness Scale, all participants underwent overnight polysomnography. The demographic and asthma severity assessments included the following measures: the age at diagnosis, duration of illness, smoking and atopy status, results of pulmonary function tests, number of asthma control medications used, and number of
hospitalizations and emergency room visits because of asthma and analgesic hypersensitivity according to apnea-hypopnea index (AHI) scores.

RESULTS: We analyzed 47 (M:9/F:38) DTA patients with a mean age of 48.74±9.45years. The mean duration of asthma was 9.17±6.5 years. Twenty-four (51.1%) patients were atopic. The analgesic hypersensitivity rate was 27.7%. Fourteen patients (29.8%) were former smokers and 2 patients were current smokers. Sleep quality was impaired in all patients. Thirty-five patients (74.5%) had OSA, 11 of whom had mild OSA, and 24 patients had moderate-severe OSA. The presence of OSA was not statistically correlated with asthma characteristics.

CONCLUSION: The study showed that there is a remarkably high prevalence of OSA in DTA. Although no statistically significant relationship between the presence of OSA and clinical asthma characteristics was identified, all DTA patients should be assessed for OSA.

Sleep disorders in asthma and chronic obstructive pulmonary disease (COPD)

Böing S(1), Randerath WJ(2). Institut für Pneumologie an der Universität Witten Herdecke, Germany Ther Umsch. 2014 May;71(5):301-8.

Sleep disturbances (SD) are a frequent finding in patients with asthma and chronic obstructive pulmonary disease (COPD) and have a negative impact on quality of life and the clinical course of the disease. The causes of SD are multiple and include for example respiratory symptoms and comorbidities. On the other hand sleep goes along with multiple physiological changes in respiration, so that sleep itself interacts with asthma and COPD. This interaction favours respiratory symptoms and may lead to hypoxemia and hypercapnia.

A further complication of the respiratory situation and the clinical course can be found in asthma and COPD patients with coexisting obstructive sleep apnea syndrome (OSAS). Due to the heterogeneity of SD in asthma and COPD, a detailed patient survey is the most important diagnostical tool. Based on the survey further technical examinations should be considered.

Treatment strategies for the reduction of SD in asthma and COPD include an optimized medication and treatment of comorbidities. If indicated oxygen therapy, positive pressure breathing and pulmonary rehabilitation can contribute.

Sleep disorders in asthma and chronic obstructive pulmonary disease (COPD)

Obstructive sleep apnoea and atopy among middle aged COPD and bronchial asthma patients.

Kumar R, Nagar D, Mallick A, Kumar M, Tarke CR, Goel N. Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. J Assoc Physicians India. 2013 Sep;61(9):615-8.

BACKGROUND: Obstructive sleep apnoea syndrome is associated with significant morbidity. A high prevalence of obstructive sleep apnoea (OSA) symptoms has been reported in patients with asthma and chronic obstructive pulmonary disease (COPD). There are limited studies regarding relationship between atopy and OSA.

OBJECTIVE: To study the risk of obstructive sleep apnoea among middle aged chronic obstructive pulmonary disease and asthma patients by a home based sleep study and its association with atopy.

METHODS: Patients with asthma and COPD were evaluated for OSA symptoms by Epworth sleepiness scale (ESS) and Berlin questionnaire (BQ). ESS score > or = 9 was considered as high risk for OSA. Patients having high risk for OSA by ESS and BQ were further evaluated for OSA by home based sleep study. Skin prick test against common allergens was done to diagnose atopy in these patients.

RESULTS: Among 400 patients (229, 57.25% male and 171, 42.75% female) 328 were asthmatics and 72 were COPD patients. ESS and BQ was positive in 11.25% (45/400) and 18.25% (73/400) patients respectively. ESS was positive in 10.67% (35/328) of asthma and 13.88% (10/72) of COPD patients. BQ was positive in 18.29% (60/328) of asthmatic and 18.05% (13/72) of COPD patients. Skin prick test was positive in74.16% patients. The maximum positivity was found in asthmatics (139/155, 89.68%) compared to COPD patients (16/155, 10.32%). Skin prick test was done for 40patients out of 73 of Asthma and COPD patients who were found positive by ESS and BQ. 72.5% patients were found to be atopic. Out of 19 patients in whom home polysomnography was done, 13 patients consented for skin prick test with common aeroallergens and 9 (69.23%) patients were found to be atopic.

CONCLUSIONS: There is an increased risk of obstructive sleep apnoea among middle aged chronic obstructive pulmonary disease and asthma patients. Atopy could be associated with OSA.
The association needs to be proved in a larger study.

Associations of moderate to severe asthma with obstructive sleep apnea.

Byun MK, Park SC, Chang YS, Kim YS, Kim SK, Kim HJ, Chang J, Ahn CM, Park MS. Div of Pulm, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Korea. Yonsei Med J. 2013 Jul;54(4):942-8.

PURPOSE: This study aimed to evaluate the correlation between associating factors of moderate to severe asthma with obstructive sleep apnea (OSA).

MATERIALS AND METHODS: One hundred and sixty-seven patients who visited the pulmonary and sleep clinic in Severance Hospital presenting with symptoms of sleep-disordered breathing were evaluated. All subjects were screened with Apnea Link. Thirty-two subjects with a high likelihood of having OSA were assessed with full polysomnography (PSG).

RESULTS: The mean age was 58.8±12.0 years and 58.7% of subjects were male. The mean Apnea Link apnea-hypopnea index (AHI) was 12.7±13.0/hr. The mean Apnea Link AHI for the 32 selected high risk patients of OSA was 22.3±13.2/hr, which was lower than the sleep laboratory-based PSG AHI of 39.1±20.5/hr. When OSA was defined at an Apnea Link AHI≥5/hr, the positive correlating factors for OSA were age, male gender, and moderate to severe asthma.

CONCLUSION: Moderate to severe asthma showed strong correlation with OSA when defined at an Apnea Link AHI≥5/hr

The effect of continuous positive airway pressure on stair-climbing performance in severe COPD patients.

Walterspacher S, Walker DJ, Kabitz HJ, Windisch W, Dreher M. University Hospital of Freiburg, Freiburg, Germany. COPD. 2013 Apr;10(2):193-9.

Stair climbing is associated with dynamic pulmonary hyperinflation and the development of severe dyspnea in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess whether (i) continuous positive airway pressure (CPAP) applied during stair climbing prevents dynamic hyperinflation and thereby reduces exercise-induced dyspnea in oxygen-dependent COPD-patients, and (ii) the CPAP-device and oxygen tank can be carried in a hip belt.

In a
randomised cross-over design, oxygen-dependent COPD patients performed two stair-climbing tests (44 steps): with supplemental oxygen only, then with the addition of CPAP (7 mbar). The oxygen tank and CPAP-device were carried in a hip belt during both trials. Eighteen COPD patients were included in the study. Although all patients could tolerate stair climbing with oxygen alone, 4 patients were unable to perform stair climbing while using CPAP.

Fourteen COPD patients (mean FEV1 36 ± 14% pred.) completed the trial and were analyzed. The mean flow rate of supplemental oxygen was 3 ± 2 l/min during stair climbing. Lung hyperinflation, deoxygenation, hypoventilation, blood lactate production, dyspnea and the time needed to manage stair climbing were not improved by the application of CPAP (all p > 0.05). However, in comparison to climbing with oxygen alone, limb discomfort was reduced when oxygen was supplemented with CPAP (p = 0.008).

In conclusion, very severe COPD patients are able to carry supporting devices such as oxygen tanks or CPAP-devices in a hip belt during stair climbing. However, the application of CPAP in addition to supplemental oxygen during stair climbing prevents neither exercise-induced dynamic hyperinflation, nor dyspnea.

The effect of continuous positive airway pressure on stair-climbing performance in severe COPD patients

Sleep Snippets Newsletter – September 2015

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Obstructive sleep apnoea and heart disease

Dr Andrew Rosenstengel
Sleep/Respiratory Physician
Holy Spirit Northside

Obstructive sleep apnoea (OSA) is a common disorder associated with repetitive episodes of reduced airflow through the upper airway (hypopnoeas) or complete upper airway obstruction (apneas) associated with reduced blood oxygen levels (desaturations). This condition is more prevalent in obese patients. These patients are in turn more likely to suffer from cardiovascular disease as well as diseases that increase cardiac risk, such as diabetes and hypertension. A large number of observational studies have displayed an association between OSA and cardiovascular disease, independent of obesity. Accumulating evidence suggests that treating sleep apnoea, especially severe sleep apnoea, in these patients with continuous positive airway pressure (CPAP) may mitigate cardiac risk.

Recurrent hypoxemia, sympathetic nervous system stimulation, increased inflammation and metabolic change can all be seen in OSA. These changes are thought to be triggers for increased cardiovascular risk. Sympathetic nervous stimulation can increase heart rate and blood pressure, with severe sleep apnoea provoking the greatest changes.

Hypertension is prevalent inpatients with obstructive sleep apnoea, with the prevalence increasing with the severity of sleep apnoea. CPAP has been shown to induce modest but real and significant reductions in blood pressure. A much higher incidence of atrial fibrillation is seen in patients with obstructive sleep apnoea and patients with atrial fibrillation are more likely to have OSA. Limited data suggest that treatment for atrial fibrillation in the form of cardioversion or ablation may be more successful if co-morbid OSA is effectively treated. Other rhythm disturbances such as bradycardia or asystole can be seen in OSA due to increased vagal tone. These abnormal rhythms often resolve with effective CPAP therapy.

Pulmonary hypertension is also commonly seen in patients with severe OSA, and heart failure has an increased incidence in this group as well.

Summary:

There is a strong association between sleep apnoea, especially severe sleep apnoea, and cardiac disease. Patients with known cardiac disease may benefit from questioning about symptoms of sleep apnoea and may prompt investigation for sleep disordered breathing. Treatment of obstructive sleep apnoea with CPAP therapy has been shown to be effective in improving cardiac outcomes and reducing risk in certain populations with cardiac disease.

Impact of OSA on cardiovascular events after coronary artery bypass surgery.

Uchôa CH, Danzi-Soares Nde J, Nunes FS, de Souza AA, Nerbass FB, Pedrosa RP, César LA, Lorenzi-Filho G, Drager LF. University of São Paulo, Sao Paulo, Brazil.Chest. 2015 May;147(5):1352-60.

BACKGROUND: The impact of OSA on new cardiovascular events in patients under going coronary artery bypass graft (CABG) surgery is poorly explored.

METHODS: Consecutive patients referred for CABG underwent clinical evaluation and standard polysomnography in the preoperative period. CABG surgery data, including percentage of off-pump and on-pump CABG, number of grafts, and intraoperative complications, were collected. The primary end point was major adverse cardiac or cerebrovascular events (MACCEs) (combined events of all-cause death, myocardial infarction, repeated revascularization, and cerebrovascular events). Secondary end points included individual MACCEs, typical angina, and arrhythmias. Patients were evaluated at 30 days (short-term) and up to 6.1 years (long term) after CABG.

RESULTS: We studied 67 patients (50 men; mean age, 58 ± 8 years; mean BMI, 28.5 ±4.1 kg/m2). OSA (apnea-hypopnea index ≥ 15 events/h) was present in 56% of the population. The patients were followed for a mean of 4.5 years (range, 3.2-6.1years). No differences were observed in the short-term follow-up. In contrast, MACCE (35% vs 16%, P = .02), new revascularization
(19% vs 0%, P = .01), episodes of typical angina (30% vs 7%, P = .02), and atrial fibrillation (22% vs 0%, P =.0068) were more common in patients with than without OSA in the long-term follow-up. OSA was an independent factor associated with the occurrence of MACCE, repeated revascularization, typical angina, and atrial fibrillation in the multivariate analysis.

CONCLUSIONS: OSA is independently associated with a higher rate of long-term cardiovascular events after CABG and may have prognostic and economic significance in CABG surgery.

Obstructive sleep apnoea and heart disease

Sleep apnea and asymptomatic carotid stenosis: a complex interaction.

Ehrhardt J, Schwab M, Finn S, Guenther A, Schultze T, Witte OW, Rupprecht S. Jena University Hospital, Germany Chest. 2015 Apr;147(4):1029-36.

BACKGROUND: Carotid arteriosclerosis and sleep apnea are considered as independent risk factors for stroke. Whether sleep apnea mediates severity of carotid stenosis remains unclear. Sleep apnea comprises two pathophysiologic conditions: OSA and central sleep apnea (CSA). Although OSA results from upper airway occlusion, CSA reflects enhanced ventilatory drive mainly due to carotid chemoreceptor dysfunction.

METHODS: Ninety-six patients with
asymptomatic extracranial carotid stenosis of ≥50% underwent polysomnography to (1) determine prevalence and severity of sleep apnea for different degrees of carotid stenosis and (2) analyze associations between OSA and CSA, carotid stenosis severity, and other arteriosclerotic risk factors.

RESULTS: Sleep apnea was present in 68.8% of patients with carotid stenosis. Prevalence and severity of sleep apnea increased with degree of stenosis (P ≤.05) because of a rise in CSA (P ≤ .01) but not in OSA. Sleep apnea (OR, 3.8; P ≤.03) and arterial hypertension (OR, 4.1; P ≤ .05) were associated with stenosis severity, whereas diabetes, smoking, dyslipidemia, BMI, age, and sex were not. Stenosis severity was related to CSA (P ≤ .06) but not to OSA. In addition, CSA but not OSA showed a strong association with arterial hypertension (OR, 12.5; P ≤.02) and diabetes (OR, 4.5; P ≤ .04).

CONCLUSIONS: Sleep apnea is highly prevalent in asymptomatic carotid
stenosis. Further, it is associated with arteriosclerotic disease severity as well as presence of hypertension and diabetes. This vascular risk constellation seems to be more strongly connected with CSA than with OSA, possibly attributable to carotid chemoreceptor dysfunction. Because sleep apnea is well treatable, screening should be embedded in stroke prevention strategies.

Hypertension

Association of severe OSA and elevated blood pressure despite antihypertensive medication use.

Walia HK, Li H, Rueschman M, Bhatt DL, Patel SR, Quan SF, Gottlieb DJ, Punjabi NM, et al Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USAJ Clin Sleep Med. 2014 Aug 15;10(8):835-43. Comment in J Clin Sleep Med. 2014 Aug 15;10(8):845-6.

RATIONALE: We hypothesized that untreated severe obstructive sleep apnea (OSA) is associated with elevated ambulatory blood pressure (BP) in subjects with high cardiovascular disease (CVD) risk despite medical management.

METHODS: Data from the baseline examination of the Heart Biomarker Evaluation in Apnea Treatment (Heart BEAT) study, a 4-site randomized controlled trial were analyzed. Individuals with moderate-severe OSA (apnea hypopnea index, AHI =15-50) and cardiovascular risk were recruited from cardiology practices. Those with hypertension were included. Intensive antihypertensive regimen (IAR) was defined as ≥ 3 anti hypertensives including a diuretic. Definitions were controlled BP (BP < 130/80), uncontrolled elevated BP (BP ≥ 130/80 not on IAR) and resistant elevated BP (BP ≥ 130/80 mm Hg despite IAR). Associations of untreated severe OSA (AHI ≥ 30) and uncontrolled and resistant elevated BP were evaluated using logistic regression analyses adjusted for age, sex, race, body mass index, smoking status, diabetes, and CVD.

RESULTS: Among the 284 participants (mean age 63.1 ± 7.2 years, 23.6% with severe OSA), 61.6% had controlled BP, 28.5% had uncontrolled elevated BP, and 9.9% had resistant elevated BP. Among participants prescribed IAR, resistant elevated BP was more prevalent in those with severe compared to moderate OSA (58.3% vs.28.6%, p = 0.01). Participants with severe OSA had a 4-fold higher adjusted odds of resistant elevated BP (OR 4.1, 95% CI: 1.7-10.2), a finding not reproduced in the absence of IAR use.

CONCLUSIONS: Among patients with increased cardiovascular risk and moderate to severe OSA, untreated severe compared to moderate OSA was associated with elevated BP despite IAR suggesting untreated severe OSA contributes to poor BP control despite aggressive medication use.

Association of severe OSA and elevated blood pressure despite antihypertensive medication use

Influence of sleep apnea severity on blood pressure variability of patients with hypertension.

Steinhorst AP, Gonçalves SC, Oliveira AT, Massierer D, Gus M, Fuchs SC, Moreira LB, Martinez D, Fuchs FD. Graduate Program in Medicine: Cardiology, School of Medicine, Universidade Federal do Rio Grande do Sul, Brazil. Sleep Breath. 2014 May;18(2):397-401.

PURPOSE: Obstructive sleep apnea (OSA) is a risk factor for the development of hypertension and cardiovascular disease. Apnea overloads the autonomic cardiovascular control system and may influence blood pressure variability, a risk for vascular damage independent of blood pressure levels. This study investigates the hypothesis that blood pressure variability is associated with OSA.

METHODS: In a cross-sectional study, 107 patients with hypertension underwent24-h ambulatory blood pressure monitoring and level III polysomnography to detect sleep apnea. Pressure variability was assessed by the first derivative of blood pressure over time, the time rate index, and by the standard deviation of blood pressure measurements. The association between the apnea-hypopnea index and blood pressure variability was tested by univariate and multivariate methods.

RESULTS: The 57 patients with apnea were older, had higher blood pressure, and had longer duration of hypertension than the 50 patients without apnea.
Patients with apnea-hypopnea index (AHI) ≥ 10 had higher blood pressure variability assessed by the standard deviation than patients with AHI < 10 during sleep (10.4 ± 0.7 versus 8.0 ± 0.7, P = 0.02) after adjustment for age, body mass, and blood pressure. Blood pressure variability assessed by the time rate index presented a trend for association during sleep (P = 0.07). Daytime blood pressure variability was not associated with the severity of sleep apnea.

CONCLUSION: Sleep apnea increases nighttime blood pressure variability inpatients with hypertension and may be another pathway linking sleep abnormalities to cardiovascular disease.

Arrhythmias

Positive pressure therapy in patients with cardiac arrhythmias and obstructive sleep apnea.

Dediu GN, Dumitrache-Rujinski S, Lungu R, Frunz S, Diaconu C, Barto D, Bogdan MA. Romania Pneumologia. 2015 Jan-Mar;64(1):18-22.

BACKGROUND: Positive pressure therapy (CPAP) in patients with cardiac arrhythmias and obstructive sleep apnea (OSAS) may have favorable effects by correcting intermittent hypoxemia and sympathetic activation.

OBJECTIVE: To assess the effect of CPAP added to pharmacological treatment in the rate control and prevention of arrhythmias recurrence in patients with OSA.

MATERIALS AND METHODS: Prospective, interventional study study which included patients diagnosed with OSAS (cardio respiratorypolygraphy, AHI>5/hour), and arrhythmias (ECG, Holter ECG), divided in two groups: group A (pharmacological therapy only) and group B (pharmacological therapy and CPAP). The patients were evaluated at enrollment (T0), at 3 and 6 months (T3 and T6) regarding the type, severity and recurrence of cardiac arrhythmias.

RESULTS: 36 patients (31 men), mean age: 63.2 ± 12 years were enrolled. In group A: 7 patients with ventricular extra systoles, 8 with permanent atrial fibrillation, 1 patient with atrial flutter and 2 patients with paroxystic supraventricular tachycardia. In group B: 8 patients with ventricular extra systoles, 5 with permanent atrial fibrillation, 2 patients with recurrent episodes of atrial fibrillation and 3 with paroxystic supraventricular tachycardia. A positive correlation (r: 0.74, p < 0.001) between Oxygen Desaturation Index and AHI was found. At T6, 12 patients from group B, and 18from group A were evaluated. In group B, the mean heart rate in patients with atrial fibrillation was 69/min., lower than in group A (82/min.), no cases with recurrent atrial fibrillation were found, and more patients with class II Lown ventricular extra systoles passed in class I Lown, compared to group A. In group B, heart rate statistically correlated with AHI (r: 0.53, p < 0.005).

CONCLUSION: In patients with OSAS, adding CPAP to pharmacological therapy has favorable effects on preventing recurrences, heart rate control in patients with atrial fibrillation and in reducing frequency and/or severity of ventricular extra systoles.

Positive pressure therapy in patients with cardiac arrhythmias and obstructive sleep apnea

Incidence and risk of atrial fibrillation in sleep-disordered breathing without coexistent systemic disease.

Chao TF, Liu CJ, Chen SJ, Wang KL, Lin YJ, Chang SL, Lo LW, Hu YF, Tuan TC, Chen TJ, Chiou CW, Chen SA.Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan Circ J. 2014;78(9):2182-7. Epub 2014 Jul 23.

BACKGROUND: Although the link between sleep-disordered breathing (SDB) and atrial fibrillation (AF) has been reported, a population-based longitudinal cohort study was lacking. The goal of the present study was to investigate the AF risk carried by SDB, using the National Health Insurance Research Database in Taiwan.

METHODS AND RESULTS: From 2000 to 2001, a total of 579,521 patients who had no history of cardiac arrhythmias or significant comorbidities were identified. Among them, 4,082 subjects with the diagnosis of SDB were selected as the study group, and the remaining 575,439 subjects constituted the control group. The study endpoint was the occurrence of new-onset AF. During a follow-up of 9.2±2.0 years, there were 4,023 patients (0.7%) experiencing new-onset AF. The occurrence rate of AF was higher in patients with SDB compared to those without it (1.3% vs.0.7%, P<0.001). The AF incidences were 1.38 and 0.76 per 1,000 person-years for patients with and without SDB, respectively. After an adjustment for age and sex, SDB was a significant risk factor of AF with a hazard ratio of 1.536. The AF risk increased with increasing clinical severity of SDB, represented by the requirement of continuous positive airway pressure use.

CONCLUSIONS: SDB itself, without the coexistence of other systemic diseases, was a risk factor of AF.

Sleep Snippets Newsletter – June 2015

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Obstructive Sleep Apnoea in Children

by Dr Sadasivam Suresh.

In children Snoring and Obstructive Sleep Apnoea is an outstanding example of the seamless transition from normal phenomenon to an abnormal pathology. Snoring is noted in at least 15% of paediatric population at any one stage and is considered benign when it is not associated with any other sleep symptomatology. The main clinical presentation in OSA are: snoring, witnessed pauses, sleep disturbance and poor performance at school. Detailed sleep history supplemented by clinical examination and assessment of breathing during sleep will help in diagnosing OSA. Full polysomnography remains the gold standard for diagnosis, however overnight oximetry when performed and analyzed by experienced staff is a useful screening tool. The mainstay of treatment in children is adenotonsillectomy and the resolution rate is close to 90%. Treatment of underlying medical condition and control of weight gain contribute significantly in reducing the severity of OSA. Supportive therapy during sleep in the form of continuous positive airway pressure [CPAP] has been proven to be beneficial and well tolerated in children.

Complications of untreated OSA:

Over the last decade there has been increased understanding of the morbidity from untreated OSA, even when the OSA is in the mild to moderate category. Neurocognitive and learning deficits have been associated with OSA and early diagnosis and appropriate treatment appears to reverse some of the deficits. Also, it is postulated that older the child at the age of treatment the lesser the chance of reversing the deficits. Untreated OSA in adulthood is associated with increased cardiovascular, cerebrovascular morbidity and it is likely that some of the changes have their origins in childhood.

Summary:

  • Snoring is very common symptom in childhood with 10-15% prevalence
  • Obstructive sleep apnea occurs in 2-5% of children
  • When recognized and treated early can have an impact on sleep quality, growth and neurocognitive development.

Guest Author

Dr Scott Burgess (left) and Dr Sadasivam Suresh.

Lessons Learned from Sleep Education in Schools: A Review of Dos and Don’ts

Journal of Clinical Sleep Medicine by Dr Sarah Blunden who is a well know researcher in adolescent sleep problems.

There is strong evidence that sleep is important for children and young people. Insufficient or poor quality sleep has been associated with inattention, poorer memory, behavioural problems and poorer academic performance. Other problems such as anxiety, depression, stress, weight gain and obesity have also been seen in teens who are having inadequate sleep.

There is growing evidence than many children and a greater percentage of teenagers are not having sufficient sleep. With the increasing popularity of small screens and social media this is becoming a growing problem.

In this months Journal of Clinical Sleep Medicine, Dr Sarah Blunden from Central Queensland University, has published a meta-analysis of the 12 studies conducted in schools to educate and improve sleep habits in children and young people.

The conclusion is that we still have a lot to learn. Providing information alone is not enough. Programs will need to better engage parents and peers as children’s homes and friends play a big role in determining sleep habits.

Programs will need to include components designed to drive behavioural change as many teens lack motivation or self-efficacy to change their sleep habits. Although incorporation into the curriculum and engaging teachers is important, programs lead by non-teaching experts had greater appeal and impact on students.

Finally working with electronic devices may be necessary as bland didactic lectures did little to engage students.

National Sleep Foundation’s sleep time duration recommendations: methodology and results summary

Max Hirshkowitz,PhD, KaitlynWhiton,MHS , Steven M. Albert, PhD , Cathy Alessi,MD,
Oliviero Bruni, MD, Lydia DonCarlos, PhD, Nancy Hazen, PhD, John Herman, PhD, Eliot S. Katz, MD,Leila Kheirandish-Gozal, MD, MSc, David N. Neubauer, MD, Anne E. O’Donnell, MD,
Maurice Ohayon, MD, DSc, PhD, John Peever, PhD, Robert Rawding, PhD,Ramesh C. Sachdeva, MD, PhD, JD, Belinda Setters, MD, Michael V. Vitiello, PhD . Catesby Ware, PhD, Paula J. Adams Hillard, MD

Objective: The objective was to conduct a scientifically rigorous update to the National Sleep Foundation’s sleep duration recommendations.

Methods: The National Sleep Foundation convened an 18-member multidisciplinary expert panel, representing 12 stakeholder organizations, to evaluate scientific literature concerning sleep duration recommendations.We determined expert recommendations for sufficient sleep durations across the lifespanusing the RAND/UCLA Appropriateness Method.

Results: The panel agreed that, for healthy individuals with normal sleep, the appropriate sleep duration fornewborns is between 14 and 17 hours, infants between 12 and 15 hours, toddlers between 11 and 14 hours, preschoolers between 10 and 13 hours, and school-aged children between 9 and 11 hours. For teenagers, 8 to 10 hours was considered appropriate, 7 to 9 hours for young adults and adults, and 7 to 8 hours of sleep for older adults.

Conclusions: Sufficient sleep duration requirements vary across the lifespan and from person to person. The recommendations reported here represent guidelines for healthy individuals and those not suffering from a sleep disorder. Sleep durations outside the recommended range may be appropriate, but deviating far from the normal range is rare. Individuals who habitually sleep outside the normal range may be exhibiting signs or symptoms of serious health problems or, if done volitionally, may be compromising their health and well-being.

Education in children’s sleep hygiene: which approaches are effective?

J Atten Disord. 2013 Oct;17(7):550-64. doi: 10.1177/1087054712457992. Epub 2012 Sep 13.

Aim: To analyze the interventions aimed at the practice of sleep hygiene, as well as their applicability and effectiveness in the clinical scenario, so that they may be used by pediatricians and family physicians for parental advice.

Source of data: A search of the PubMed database was performed using the following descriptors: sleep hygiene OR sleep education AND children or school-aged. In the LILACS and SciELO databases, the descriptors in Portuguese were: higiene E sono, educação E sono, educação E sono E crianças, e higiene E sono Einfância, with no limitations of the publication period.

Summary: In total, ten articles were reviewed, in which the main objectives were to analyze the effectiveness of behavioral approaches and sleep hygiene techniques on children’s sleep quality and parents’ quality of life. The techniques used were one or more of the following: positive routines; controlled comforting and gradual extinction or sleep remodeling; as well as written diaries to monitor children’s sleep patterns. All of the approaches yielded positive results.

Conclusions: Although behavioral approaches to pediatric sleep hygiene are easy to apply and adhere to, there have been very few studies evaluating the effectiveness of the available techniques. This review demonstrated that these methods are effective in providing sleep hygiene for children, thus reflecting on parents’ improved quality of life. It is of utmost importance that pediatricians and family physicians are aware of such methods in order to adequately advise patients and their families.

Future research directions in sleep and ADHD: report of a consensus working group.

Owens J(1), Gruber R, Brown T, Corkum P, Cortese S, O’Brien L, Stein M, Weiss M.
Author information: (1)1George Washington School of Medicine and Health Sciences, Washington, DC,USA.

Objective: To explore relationships between basic and translational science research regarding sleep and ADHD in children.

Method: A multidisciplinary group of experts in pediatric sleep medicine and ADHD convened in November 2010 to summarize the current literature, delineate knowledge gaps, and formulate recommendations regarding future research directions and priorities.

Results: Six major research areas of interest were identified: (a) brain centers regulating sleep, arousal, and attention; (b) neurotransmitter systems involved in both sleep and attention regulation; (c) alterations of neural systems regulating sleep in ADHD; (d) phenotypic similarities between behavioral, mood, and cognitive manifestations of insufficient/disrupted sleep and ADHD; (e) hypoarousal and sleepiness in ADHD; and (f) external sleep-wake signals that affect sleep regulation in ADHD.

Conclusion: An enhanced understanding of the complex mechanisms regulating sleep
promotion, wakefulness, and attention may contribute to new insights regarding
the core impairments in ADHD and lead to the development of new therapies.

Sleep Snippets Newsletter – February 2015

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Men’s Issues & Obstructive Sleep Apnoea

Men's Issues and Obstructive Sleep Apnoea

Gender difference in snoring and how it changes with age: systematic review and meta-regression.

Chan Chung-Hong; Wong Billy M; Tang Jin-Ling; Ng Daniel K
Department of Paediatrics, Kwong Wah Hospital, Kowloon, Hong Kong, China. chainsawtiney@gmail.com
Sleep & breathing = Schlaf & Atmung ( Germany ) Dec 2012 , 16 (4) p977-86

PURPOSE: The aim of this study was to study the interactions among age, gender, and snoring across all age groups

METHODS: All cross-sectional study reporting gender-specific prevalence of snoring in general population published from 1966 through July 2008 were included and were meta-analyzed. The sources of heterogeneity among primary studies were studied by meta-regression.

RESULTS: From a total of 1,593 citations reviewed, 63 were included in the analysis of snoring. These 63 studies were comprised 104,337 and 110,474, respectively. A combined odds ratio of 1.89 with a 95% confidence interval of 1.75-2.03 for male versus female was found. The heterogeneity was significant with an estimated between-study variance, tau (2) being 0.065 and 95% confidence interval of 0.0397-0.0941. Multiple meta-regression showed that age were the significant effect modifier of the relationship between snoring and gender.

CONCLUSION: This study found a consistent male predominance in snoring among the general population, and the heterogeneity in the risk of snoring between two genders can be partly explained by age.

Roles of gender, age, race/ethnicity, and residential socioeconomics in obstructive sleep apnea syndromes.

Ralls Frank M; Grigg-Damberger Madeleine
Uni of New Mexico School of Med, Uni of New Mexico Hospital Sleep Disorders Center, USA. fralls@salud.unm.edu
Current opinion in pulmonary medicine ( United States ) Nov 2012 , 18 (6) p568-73

PURPOSE OF REVIEW: Review recent research on the roles of gender, race/ethnicity, residential socioeconomics and age in obstructive sleep apnea syndromes (OSA) and their treatment.

RECENT FINDINGS: Men have a higher prevalence of OSA than women and require higher continuous positive airway pressure (CPAP) pressures for treatment, given similar severity of OSA. When comparing age, women have less severe apnea at all ages. Menopause, pregnancy and polycystic ovarian syndrome increase the risk for OSA in women. Neck fat and BMI influence apnea-hypopnea index (AHI) severity in women; abdominal fat and neck-to-waist ratio do so in men. Obesity, craniofacial structure, lower socioeconomic status and neighborhood disadvantage may better explain ethnic/racial differences in the prevalence and severity of OSA. Ethnicity was no longer significantly associated with OSA severity when WHO criteria for obesity were used.

SUMMARY: OSA has a male predominance; women have a lower AHI than men during certain stages of sleep; women require less CPAP pressure for treatment of similar severity of OSA, and there are ethnic/racial differences in the prevalence and severity of OSA but these may be due to environmental factors, such as living in disadvantaged neighbourhoods.

Obstructive sleep apnea syndrome is associated with higher diastolic blood pressure in men but not in women.

Lee YJ, Jeong DU.
Seoul NationalUniversity College of Medicine and Hospital, Seoul, Republic of Korea.
Am J Hypertens. 2014 Mar;27(3):325-30.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) and poor sleep quality both increase blood pressure (BP). This study aimed to find the sex effects and the role of poor sleep quality on systolic BP (SBP) and diastolic BP (DBP) in OSAS patients.

METHODS: Polysomnographic findings, morning BP values, and clinical data of 460subjects (348 men; 112 women) diagnosed with OSAS were analyzed. Analyses were performed separately in each sex to examine the association of the apnea-hypopneaindex (AHI) with BP, SBP, DBP, and sleep quality.

RESULTS: In male subjects, AHI predicted the high BP and high DBP groups but not the high SBP group. In female subjects, AHI did not predict any of the high BP,DBP, or SBP groups. Poor sleep quality, in the absence of AHI effect, weakly correlated with BP in both sexes, but the association between poor sleep quality and high AHI was stronger in male subjects than in females.

CONCLUSIONS: In male subjects only, OSAS was associated with DBP but not SBP. The significant association between OSAS and DBP may be responsible for the BP elevations in OSAS. It could be speculated that the stronger association between poor sleep quality and OSAS in male subjects compared with females may have partly contributed to the sex effect on BP.

Severity of nocturnal cardiac arrhythmias correlates with intensity of sleep apnea in men.

Szaboova E; Holoubek D; Tomori Z; Szabo P; Donic V; Stancak B
Faculty of Medicine, PJ Safarik University, Kosice, Slovakia. angiolog@ipower.sk
Advances in experimental medicine and biology ( United States ) 2013 , 755 p155-68

Various cardiac arrhythmias frequently occur in patients with sleep apnea, but complex analysis of the relationship between their severity and the probable arrhythmogenic risk factors is conflicting. The question is what cardiovascular risk factors and how strongly they are associated with the severity of cardiac arrhythmias in sleep apnea. Adult males (33 with and 16 without sleep apnea), matched for cardiovascular co-morbidity were studied by polysomnography with simultaneous ECG monitoring. Arrhythmia severity was evaluated for each subject by a special 7-degree scoring system. Laboratory, clinical, echocardiographic, carotid ultrasonographic, ambulatory blood pressure, and baroreflex sensitivity values were also assessed. Moderate sleep apnea patients had benign, but more exaggerated cardiac arrhythmias than control subjects (2.53 +/- 2.49 vs. 1.13 +/- 1.64 degrees of cumulative severity, p < 0.05). We confirmed strong correlations between the arrhythmia severity and known arrhythmogenic risk factors (left ventricular ejection fraction and dimensions, right ventricular diameter, baroreflex sensitivity, carotid intima-media thickness, age, previous myocardial infarction, and also apnea-hypopnea index). In multivariate modelling only the apnea-hypopnea index indicating the sleep apnea intensity remained highly significantly correlated with the cumulative arrhythmia severity (beta = 0.548, p < 0.005).

In conclusion, sleep apnea modifying cardiovascular risk factors and structures or functions provoked various nocturnal arrhythmias. The proposed scoring system allowed a complex analysis of the contribution of various triggers to arrhythmogenesis and confirmed the apnea-hypopnea index as an independent risk for nocturnal cardiac arrhythmia severity in sleep apnea.

Obstructive sleep apnea in young lean men: impact on insulin sensitivity and secretion.

Pamidi Sushmita; Wroblewski Kristen; Broussard Josiane; Day Andrew; Hanlon Erin C; Abraham V; Tasali Esra
Department of Medicine, University of Chicago, Chicago, IL, USA. sushmita.pamidi@mail.mcgill.ca
Diabetes care ( United States ) Nov 2012 , 35 (11) p2384-9 ,

OBJECTIVE: To assess whether the presence of obstructive sleep apnea (OSA) affects glucose metabolism in young, lean individuals who are healthy and free of cardiometabolic disease.

RESEARCH DESIGN AND METHODS: In a prospective design, 52 healthy men (age 18-30 years; BMI 18-25 kg/m(2)) underwent laboratory polysomnogram followed by a morning oral glucose tolerance test (OGTT). We stratified all subjects according to the presence or absence of ethnicity-based diabetes risk and family history of diabetes. We then used a frequency-matching approach and randomly selected individuals without OSA, yielding a total of 20 control men without OSA and 12 men with OSA. Indices of glucose tolerance, insulin sensitivity, and insulin secretion (early phase and total) were compared between men with OSA and control subjects. The incremental areas under the glucose (incAUC(glu)) and insulin (incAUC(ins)) curves were calculated using the trapezoidal method from 0 to 120 min during the OGTT.

RESULTS: Men with OSA and control subjects were similar in terms of age, BMI, ethnicity-based diabetes risk, family history of diabetes, and level of exercise. Both groups had normal systolic and diastolic blood pressure and fasting lipid levels. After ingestion of a glucose load, men with OSA had 27% lower insulin sensitivity (estimated by Matsuda index) and 37% higher total insulin secretion (incAUC(ins)) than the control subjects, despite comparable glucose levels (incAUC(glu)).

CONCLUSIONS: In young, lean, and healthy men who are free of cardiometabolic disease, the presence of OSA is associated with insulin resistance and a compensatory rise in insulin secretion to maintain normal glucose tolerance. Thus, OSA may increase the risk of type 2 diabetes independently of traditional cardiometabolic risk factors.

C-reactive protein and heart rate recovery in middle-aged men with severe obstructive sleep apnea.

Chien Meng-Yueh; Lee Peilin; Tsai Yuan-Feen; Yang Pan-Chyr; Wu Ying-Tai
School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Sleep & breathing = Schlaf & Atmung ( Germany ) Sep 2012 , 16 (3) p629-37
Comment in Sleep Breath. 2012 Sep;16(3):593-4

OBJECTIVE: The study aimed to evaluate whether the inflammatory marker “high-sensitivity C-reactive protein (hsCRP)” level was associated with impaired heart rate recovery at 1 min after exercise termination (HRR-1) in middle-aged patients with severe obstructive sleep apnea (OSA). METHODS: Thirty middle-aged male patients (40-64 years old) with severe OSA (apnea-hypopnea index [AHI] >= 30 h(-1)) and 30 subjects without OSA (AHI < 5 h(-1)), matched with age and body mass index (BMI), were recruited. All subjects underwent an overnight polysomnography and completed a symptom-limited maximal exercise test. Cardiopulmonary parameters included peak oxygen consumption (VO(2peak)) and heart rate response during and immediately after exercise. Fasting blood samples were drawn for hsCRP analysis. RESULT: Patients with severe OSA had significantly higher hsCRP levels (0.18 vs. 0.07 mg/dl, P < 0.01), lower reduced HRR-1, peak heart rate, and VO(2peak) values than those in the controls. The hsCRP levels significantly correlated with HRR-1 in the OSA group (r = -0.69, P < 0.01) after adjustment for VO(2peak) (r = -0.66, P < 0.01). Furthermore, stepwise multiple regression analysis showed that HRR-1 and AHI were significant predictors of hsCRP levels in all participants (adjusted R(2) = 0.53, P < 0.01).

CONCLUSIONS: Blunted HRR was shown in middle-aged men with severe OSA, and it was associated with high hsCRP levels significantly.

Mortality in middle-aged men with obstructive sleep apnea in Finland.

Muraja-Murro A, Eskola K, Kolari T, Tiihonen P, Hukkanen T, Tuomilehto H,Peltonen M, Mervaala E, Töyräs J.
Department of Clinical Neurophysiology, Kuopio University Hospital, POB 1777,Kuopio, Finland. anu.muraja-murro@kuh.fi
Sleep Breath. 2013 Sep;17(3):1047-53.

INTRODUCTION: Obstructive sleep apnea (OSA) has been associated with an elevated rate of cardiovascular mortality. However, this issue has not been investigatedin patients with elevated proneness to cardiovascular diseases. Our hypothesiswas that OSA would have an especially adverse effect on the risk ofcardiovascular mortality in Finnish individuals exhibiting elevated proneness forcoronary heart diseases.

METHODS: Ambulatory polygraphic recordings from 405 men having suspected OSA wereretrospectively analyzed. The patients were categorized regarding sleepdisordered breathing into a normal group (apnea hypopnea index (AHI) < 5, n =104), mild OSA group (5 ≤ AHI < 15, n = 100), and moderate to severe OSA group(AHI ≥ 15, n = 201). In addition, basic anthropometric and health data werecollected. In patients who died during the follow-up period (at least 12 years and 10 months), the primary and secondary causes of death were recorded.

RESULTS: After adjustment for age, BMI, and smoking, the patients with moderate to severe OSA suffered significantly (p < 0.05) higher mortality (hazard ratio3.13) than their counterparts with normal recordings. The overall mortality in the moderate to severe OSA group was 26.4 %, while in the normal group it was 9.7%. Hazard ratio for cardiovascular mortality was 4.04 in the moderate to severe OSA and 1.87 in the mild OSA group.

CONCLUSIONS: OSA seems to have an especially adverse effect on the cardiovascular mortality of patients with an elevated genetic susceptibility to coronary heart diseases. When considering that all our patients had possibility of continuous positive airway pressure treatment and our reference group consisted of patients suffering from daytime somnolence, the hazard ratio of 4.04 for cardiovascular mortality in patients with moderate to severe disease is disturbingly high.

Long-term changes of sexual function in men with obstructive sleep apnea after initiation of CPAP.

Long-term changes of sexual function in men with obstructive sleep apnea after initiation of CPAP

Budweiser Stephan; Luigart Ruth; Jorres Rudolf A; Kollert Florian; Kleemann Yannick; Wieland Wolf F; et al
Div of Pulmonary and Resp Medicine, RoMed Clinical Center Rosenheim, Germany. stephan.budweiser@ro-med.de
journal of sexual medicine ( United States ) Feb 2013 , 10 (2) p524-31

INTRODUCTION: Obstructive sleep apnea (OSA), particularly intermittent nocturnal hypoxemia, is associated with erectile dysfunction (ED). AIM: We investigated in patients with OSA whether continuous positive airway pressure (CPAP) therapy has a long-term effect on sexual function, including ED, in the presence of other risk factors for ED.

METHODS: Within a long-term observational design, we reassessed 401 male patients who had been referred for polysomnography, with respect to erectile and overall sexual function. Mean +/- standard deviation follow-up time was 36.5 +/- 3.7 months. Patients with moderate to severe ED were stratified according to the regular use of CPAP.

MAIN OUTCOME MEASURE: Changes of sexual function were assessed by the 15-item International Index of Erectile Function (IIEF-15) questionnaire, including the domains erectile function (EF), intercourse satisfaction, orgasmic function (OF), sexual desire (SD), and overall satisfaction (OS). RESULTS: Of the 401 patients, 91 returned a valid IIEF-15 questionnaire at follow-up. Their baseline characteristics were not different from those of the total study group. OSA (apnea-hypopnea index >5/hour) had been diagnosed in 91.2% of patients. In patients with moderate to severe ED (EF domain <17), CPAP users (N=21) experienced an improvement in overall sexual function (IIEF-15 summary score; P=0.014) compared with CPAP non-users (N=18), as well as in the subdomains OF (P=0.012), SD (P=0.007), and OS (P=0.033). Similar results were obtained in patients with poor overall sexual dysfunction (IIEF-15 summary score <44). In patients with moderate to severe ED and low mean nocturnal oxygen saturation (<=93%, median), also the EF subdomain improved in CPAP users vs. non-users (P=0.047).

CONCLUSIONS: These data indicate that long-term CPAP treatment of OSA and the related intermittent hypoxia can improve or preserve sexual function in men with OSA and moderate to severe erectile or sexual dysfunction, suggesting a certain reversibility of OSA-induced sexual dysfunctions. (c) 2012 International Society for Sexual Medicine.

Association between sleep apnea, sleep duration, and serum lipid profile in an urban, male, working population in Japan.

Toyama Yoshiro; Chin Kazuo; Chihara Yuichi; Takegami Misa; Takahashi Ken-Ichi; Sumi Kensuke; et al
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Chest ( United States ) Mar 2013 , 143 (3) p720-8
Comment in Chest. 2013 Apr;143(4):1188-9
Comment in Chest. 2013 Apr;143(4):1187-8

BACKGROUND: Dyslipidemia is often comorbid with obstructive sleep apnea (OSA), but few population-based studies have investigated their relationship. Short sleep duration is associated with hypertension and diabetes; however, its association with dyslipidemia is not well known. We investigated relationships among OSA, sleep duration, and the lipid profile in a community-based study. METHODS: We measured the respiratory disturbance index (RDI) and sleep duration by a type 3 portable device and actigraph in 275 men in a Japanese company. Fasting blood parameters were obtained from periodic inspection data.

RESULTS: According to Japanese criteria, 143 subjects had dyslipidemia. Percent sleep time of oxygen saturation as measured by pulse oximetry (SpO2) < 90% and prevalence of severe OSA were greater and sleep duration and mean SpO2 during sleep were lower in subjects with dyslipidemia than in those without. Univariate analysis showed that the RDI was positively correlated with serum triglyceride (TG) levels (rho = 0.20, P < .01), and sleep duration was negatively correlated with serum total cholesterol (TC) levels (gamma = -0.13, P = .03) and serum low-density lipoprotein cholesterol levels (gamma = -0.12, P = .04). Stepwise multiple regression analysis revealed that TG was correlated with RDI (beta = 0.14, P = .02), BMI (beta = 0.20, P < .01), and alcohol intake (beta = 0.20, P < .01), and that TC was correlated with sleep duration (beta = -0.13, P = .03), age (beta = 0.15, P = .02), and waist/hip ratio (beta = 0.15, P = .02).

CONCLUSIONS: Short sleep duration was associated with TC levels and RDI was positively associated with TG levels among working-aged men in an urban Japanese company. Correcting the status of OSA and/or short sleep duration might improve the lipid profile and cardiovascular consequences.

Sleep disturbances and risk of frailty and mortality in older men.

Ensrud Kristine E; Blackwell Terri L; Ancoli-Israel Sonia; Redline Susan; Cawthon Peggy M; Paudel Misti L; et al
Center for Chronic Disease Outcomes Research, Veterans Affairs Health Care System, USA. ensru001@umn.edu
Sleep medicine ( Netherlands ) Dec 2012 , 13 (10) p1217-25
Comment in Sleep Med. 2012 Dec;13(10):1211-2

OBJECTIVE: To test the hypothesis that non-frail older men with poorer sleep at baseline are at increased risk of frailty and death at follow-up.

METHODS: In this prospective cohort study, subjective (questionnaires) and objective sleep parameters (actigraphy, in-home overnight polysomnography) were measured at baseline in 2505 non-frail men aged >=67years. Repeat frailty status assessment performed an average of 3.4 years later; vital status assessed every four months. Sleep parameters expressed as dichotomized predictors using clinical cut-points. Status at follow-up exam classified as robust, intermediate (pre-frail) stage, frail, or died in interim.

RESULTS: None of the sleep disturbances were associated with the odds of being intermediate/frail/dead (vs. robust) at follow-up. Poor subjective sleep quality (multivariable odds ratio [MOR] 1.26, 95% CI 1.01-1.58), greater nighttime wakefulness (MOR 1.31, 95% CI 1.04-1.66), and greater nocturnal hypoxemia (MOR 1.47, 95% CI 1.02-2.10) were associated with a higher odds of frailty/death at follow-up (vs. robust/intermediate). Excessive daytime sleepiness (MOR 1.60, 95% CI 1.03-2.47), greater nighttime wakefulness (MOR 1.57, 95% CI 1.12-2.20), severe sleep apnea (MOR 1.74, 95% CI 1.04-2.89), and nocturnal hypoxemia (MOR 2.28, 95% CI 1.45-3.58) were associated with higher odds of death (vs. robust/intermediate/frail at follow-up). The association between poor sleep efficiency and mortality nearly reached significance (MOR 1.48, 95% CI 0.99-2.22). Short sleep duration and prolonged sleep latency were not associated with frailty/death or death at follow-up.

CONCLUSIONS: Among non-frail older men, poor subjective sleep quality, greater nighttime wakefulness, and greater nocturnal hypoxemia were independently associated with higher odds of frailty or death at follow-up, while excessive daytime sleepiness, greater nighttime wakefulness, severe sleep apnea and greater nocturnal hypoxemia were independently associated with an increased risk of mortality.

Sleep Snippets Newsletter – Winter/Spring 2014

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Insomnia: A sleep physician’s perspective

Michael Fanning

The next time a patient complains of insomnia, before you reach for a prescription pad to write temazepam, consider the following… apart from poor sleep hygiene and psychophysiologic insomnia (whereby the patient’s anxiety about insomnia exacerbates the insomnia), insomnia is frequently secondary to circadian rhythm disorders and sleep disordered breathing. Sorting it out requires a thorough sleep history including time to bed, sleep latency, night-time awakenings, time out of bed and details about day time naps.

A common mistake that patients make is trying to force themselves to sleep (rather than going to bed when sleepy), getting out of bed at variable times (rather than getting out of bed at the same time each day, which helps reset our ~25 hour circadian rhythm back to a 24 hour cycle) and lying in bed awake for prolonged periods (which tends to teach the body that being awake in bed is desirable).

Sleep disordered breathing such as obstructive sleep apnoea is a common cause of sleep maintenance insomnia (where the patient can’t stay asleep) and restless sleep. It is the obstructive breathing that wakes them from sleep but patients are rarely able to recall breathing difficulties.


Type 2 Diabetes

Risk of obstructive sleep apnea in patients with type 2 diabetes mellitus.

PMID: 23846968

Cass AR, Alonso WJ, Islam J, Weller SC.
University of Texas Medical Branch, Galveston, TX 77555-1123, USA. acass@utmb.edu
Fam Med. 2013 Jul-Aug;45(7):492-500.

Diabetes

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (DM) and obstructive sleep apnea (OSA) share several clinical findings: obesity, hypertension, and impaired glucose tolerance. OSA may be an under-recognized comorbidity of DM. The purpose of this study is to estimate the proportion of patients with type 2 DM at risk for OSA and describe factors associated with that risk.

METHODS: This cross-sectional study enrolled 297 adults, ages 18 years and older, with type 2 DM from a university-based Family Medicine Center. Participants completed a research questionnaire recording socio-demographic information, medical history, and clinical data including medications and hemoglobin A1C. OSA risk was determined using the Berlin Questionnaire. Relationships between risk of OSA and socio-demographic and clinical variables were evaluated using bivariate analyses and covariate adjusted logistic regression models.

RESULTS: Thirty-seven participants (12.5%) had a prior diagnosis of OSA. Based on the Berlin Questionnaire, 124 (48.6%) of the remaining patients were classified as high risk for OSA. Patients less than age 60 years were at increased risk for OSA, adjusted OR=2.67 (1.57, 4.54; 95% CI). Non-Hispanic whites, adjusted OR=1.76(1.01, 3.06; 95% CI), and patients with symptoms of depression, adjusted OR=2.64 (1.60, 4.52; 95% CI), were also at higher risk. Gender and hemoglobin A1C were not associated with increased risk of OSA.

CONCLUSION: Nearly half of adults with type 2 DM may be at high risk for OSA, and many may be undiagnosed. In a primary care setting, the Berlin Questionnaire is an easily applied screening instrument that identifies patients at increased risk of OSA who may benefit from further diagnostic studies and treatment of OSA.

OSA is associated with impaired glucose metabolism in Han Chinese subjects.

PMID: 23286469

Gu CJ, Li M, Li QY, Li N, Shi GC, Wan HY.
Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chin Med J (Engl). 2013 Jan;126(1):5-10.

BACKGROUND: Increasingly, evidence from population, clinic-based and laboratory studies supports an independent association between obstructive sleep apnea syndrome (OSAS) and an increased risk of type 2 diabetes; however, this observation has yet to be replicated in China and the potential mechanisms that link these two conditions are not clear.

METHODS: A total of 179 Han Chinese subjects were enrolled in this study. All subjects underwent polysomnography, the oral glucose tolerance-insulin releasing test (OGTT-IRT) and serum HbA(1)c measurement. Indexes including homeostasis model assessment-IR (HOMA-IR), Matsuda index, HOMA-β, early phase insulinogenic index (ΔI(30)/ΔG(30)), AUC-I(180) and oral disposition index (DIo) were calculated for the assessment of insulin resistance and pancreatic β-cellfunction.

RESULTS: Based on OGTT, 25.4%, 44.6% and 54.5% subjects were diagnosed having glucose metabolic disorders respectively in control, mild to moderate and severe OSAS groups (P < 0.05). Serum HbA(1)c levels were highest in subjects with severe OSAS (P < 0.05). In contrast, compared with normal subjects, HOMA-β,ΔI(30)/Δ(G30) and DIO were lower in severe OSAS group (P < 0.05). In stepwise multiple linear regressions, 0-min glucose and HbA(1)c were positively correlated with the percentage of total sleep time below an oxyhemoglobin saturation of 90% (T90) (Beta = 0.215 and 0.368, P < 0.05); 30-min and 60-min glucose was negatively correlated with the lowest SpOO(2) (LSpO(2)) (Beta = -0.214 and-0.241, P < 0.05). HOMA-β and DI(O) were negatively correlated with T90 (Beta =-0.153 and -0.169, P < 0.05) while body mass index (BMI) was the only determinant of HOMA-IR and Matsuda index.

CONCLUSION: OSAS is associated with impairment in glucose tolerance and pancreatic β-cell function in Han Chinese subjects while insulin sensitivity is mainly determined by obesity.

Decreased nocturnal glucose variability in non-diabetic patients with sleep apnea: a pilot study.

Elizur A, Maliar A, Shpirer I, Buchs AE, Shiloah E, Rapoport MJ.
Dept of Pediatrics, Assaf Harofeh Medical Center, Sackler Faculty of Med, Tel Aviv University, Israel. elizura@gmail.com
Isr Med Assoc J. 2013 Sep;15(9):465-9.
Comment inIsr Med Assoc J. 2013 Sep;15(9):510-1.

BACKGROUND: Obstructive sleep apnea has been should be associated with impaired glucose metabolism and overt diabetes mellitus. However, the effect of hypoxic episodes on nocturnal glucose regulation in non-diabetic patients is unknown.

OBJECTIVES: To investigate the effect of hypoxemia and nocturnal glucose homeostasis in non-diabetic patients with sleep apnea.

METHODS: Seven non-diabetic patients with moderate to severe sleep apnea were connected to a continuous glucose-monitoring sensor while undergoing overnight polysomnography. Mean SpO2 and percentage of time spent at SpO2 90% were recorded. The correlation between mean glucose levels, the difference between consecutive mean glucose measurements (glucose variability) and the corresponding oxygen saturation variables were determined in each patient during REM and non-REM sleep.

RESULTS: No consistent correlation was found for the individual patient between oxygen saturation variables and glucose levels during sleep. However, a lower mean SpO2 correlated with decreased glucose variability during sleep (r = 0.79, P= 0.034). This effect was primarily evident during REM sleep in patients with significant, compared to those with mild, oxygen desaturations during sleep (>30% vs. < 10% of sleeping time spent with SpO2 < 90%) (P = 0.03).

CONCLUSION: Severe nocturnal hypoxemia in non-diabetic patients with moderate to severe sleep apnea might affect glucose regulation primarily during REM sleep.


Hypertension

Predictors of blood pressure reduction with nocturnal CPAP therapy in patients with OSA and prehypertension.

PMID: 23427278

Yorgun H, Kabakçi G, Canpolat U, Kirmizigül E, Sahiner L, Ates AH, Sendur MA, et al
Department of Cardiology, Hacettepe University, Ankara, Turkey.
Comment in Angiology. 2014 Feb;65(2):93-4.
Angiology. 2014 Feb;65(2):98-103

HypertensionPrevious studies showed that treatment of obstructive sleep apnea syndrome (OSAS) with continuous positive airway pressure (CPAP) significantly reduced the blood pressure (BP) in hypertensive patients. We investigated the predictors of BP change in normotensive patients with OSAS who underwent CPAP. A total of 24patients with OSAS (19 male; age: 48.7 ± 10.4 years) were enrolled. The 24-hour mean BP (24 hMBP), subjective sleepiness, fasting venous blood samples, and anthropometric measurements were assessed at baseline, 6th week and 12th week of CPAP treatment. The 24 hMBP fell at 12 weeks from 89.2 ± 8.4 to 82.9 ± 7.3 mm Hg (P < .0001) irrespective of the severity of disease. Also, both daytime and nighttime BP showed significant reduction after CPAP. Male gender, Epworthsleepiness scale, body mass index, smoking, alcohol use, and baseline 24 hMPB were the independent predictors of a fall in 24 hMBP.

CONCLUSION: CPAP therapy may provide benefit even in the absence of overt hypertension by reducing both daytime and nighttime BP.

The relationship between morning hypertension and sleep quality in patients with OSAS.

PMID: 23530964

Sasaki N, Ozono R, Yamauchi R, Teramen K, Edahiro Y, Ishii K, Seto A, Kihara Y.
Department of Internal Medicine, Mitsubishi Mihara Hospital, Mihara, Japan. fm2khdz3@384.jp
Clin Exp Hypertens. 2013;35(4):250-6.

This study aimed to investigate the prevalence of abnormal diurnal blood pressure(BP) profiles in patients with obstructive sleep apnea syndrome (OSAS) in relation to the data of a sleep study. Total 103 patients newly diagnosed with OSAS underwent overnight polysomnography and 24-hour ambulatory BP measurements. Patients without morning or nocturnal hypertension (control group), patients with morning hypertension but not nocturnal hypertension (surge-type group), and patients with both morning and nocturnal hypertension (sustained-type group) were compared. Morning hypertension was present in 54 patients (16 surge-type and 38sustained-type). The apnea-hypopnea index and sleep efficiency were higher and lower, respectively, in the sustained-type group than in the other groups. Slow-wave sleep incidence was significantly lower in the sustained-type and surge-type groups than in the control group.

CONCLUSION: These results suggest that approximately half the OSAS patients displayed morning hypertension, the sustained-type being more common than the surge-type. Poor sleep quality plays an important role in the pathogenesis of morning hypertension in both the sustained-and the surge-type group.


Gastro-oesophageal Reflux (GOR)

Nocturnal gastro-oesophageal reflux, asthma and symptoms of OSA: a longitudinal, general population study.

PMID: 23018910

Emilsson ÖI, Bengtsson A, Franklin KA, Torén K, Benediktsdóttir B, Farkhooy A, Weyler J, Dom S, De Backer W, et al.
Faculty of Medicine, University of Iceland, Landspitali University Hospital, Reykjavik, Iceland. ossuri@landspitali.is
Eur Respir J. 2013 Jun;41(6):1347-54.

GOR

Nocturnal gastro-oesophageal reflux (nGOR) is associated with asthma and obstructive sleep apnoea (OSA). Our aim was to investigate whether nGOR is a risk factor for onset of asthma and onset of respiratory and OSA symptoms in a prospective population-based study. We invited 2640 subjects from Iceland, Sweden and Belgium for two evaluations over a 9-year interval. They participated in structured interviews, answered questionnaires, and underwent spirometries and methacholine challenge testing. nGOR was defined by reported symptoms. Subjects with persistent nGOR (n=123) had an independent increased risk of new asthma at follow-up (OR 2.3, 95% CI 1.1-4.9). Persistent nGOR was independently related to onset of respiratory symptoms (OR 3.0, 95% CI 1.6-5.6). The risk of developing symptoms of OSA was increased in subjects with new and persistent nGOR (OR 2.2,95% CI 1.3-1.6, and OR 2.0, 95% CI 1.0-3.7, respectively).

CONCLUSION: No significant association was found between nGOR and lung function or bronchial responsiveness. Persistent symptoms of nGOR contribute to the development of asthma andrespiratory symptoms. New onset of OSA symptoms is higher among subjects with symptoms of nGOR. These findings provide evidence that nGOR may play a role in the genesis of respiratory symptoms and diseases.

Nocturnal gastro-oesophageal reflux and sleep apnea: what relationship?

Emilsson ÖI, Bengtsson A, Franklin KA, Torén K, Benediktsdóttir B, Farkhooy A, Weyler J, Reflux gastro-oesophagien nocturne et syndrome d’apnees du sommeil : Quelles relations ?
Romdhane Hayfa; Ben Abdallah Hatem; Abdelli Mohamed Nabil
Hospital militaire principal d’instruction de Tunis, Universitd Tunis-El Manar, Tunisie.
La Tunisie medicale ( Tunisia ) Aug-Sep 2012 , 90 (8-9) p598-601

BACKGROUND: Gastro-oesophageal reflux disease and nocturnal sleep disturbances are frequently encountered in clinical practice and are often associated. However, the combination of these two syndromes does not necessarily imply a cause and effect. In a more precise, the relationship between nocturnal gastro-oesophageal reflux and sleep apnea syndrome has been debated since even if their respective prevalences are high in the presence of one or the other syndrome, it is difficult to eliminate mutual induction.

AIM: To determine the pathophysiological relations, the frequency of the association between nocturnal gastro-oesophageal reflux and sleep apnea syndrome and the impact of specific therapies to each of these two syndromes on the other. METHODS: Review of the literature.

RESULTS: On the relationship between these two entities, it seems obvious that nocturnal gastro-oesophageal reflux affects the normal physiology of sleep and alters its quality and that the sleep apnea syndrome can aggravate reflux. On the frequency of their association, gastro-oesophageal reflux was observed in the presence of sleep apnea syndrome; in 27 to 75% of patients in studies that do not include pH-metric and polysomnographic recording simultaneously. Regarding treatment, continuous positive airway pressure seems to improve night time gastro-oesophageal reflux both in terms of symptoms that pH-metric results. Similarly, inhibitors of proton pump inhibitors have demonstrated their effectiveness in combination with specific treatment, in improving symptoms caused by sleep apnea syndrome.

CONCLUSION: we can confirm that there is a strong link between nocturnal gastro-oesophageal reflux and sleep apnea syndrome but causality is hard to be confirmed. Moreover, it seems useful to look for sleep disorders in patients with nocturnal gastro-oesophageal reflux also to suggest the diagnosis of gastro-oesophageal reflux in patients with sleep apnea syndrome.


Depression

Obstructive sleep apnea and the subsequent risk of depressive disorder: a population-based follow-up study.

Chen YH, Keller JK, Kang JH, Hsieh HJ, Lin HC.
School of Public Health, Taipei Medical University, Taipei, Taiwan.
J Clin Sleep Med. 2013 May 15;9(5):417-23.
Comment in J Clin Sleep Med. 2013 May 15;9(5):425-6.

DepressionSTUDY OBJECTIVES: Empirical findings on the prospective link between obstructive sleep apnea (OSA) and subsequent depression are mixed. This nationwide, population-based study thus aimed at assessing the risk of depressive disorder within the first year following a diagnosis with OSA. Gender effects were further examined.

DESIGN: Cohort study.

SETTING: Taiwan.

PATIENTS: This study used data from the Longitudinal Health Insurance Database2000. A total of 2,818 patients diagnosed with OSA between 2002 and 2008 were evaluated, and 14,090 matched non-OSA enrolees used as a comparison cohort.

MEASUREMENTS AND RESULTS: Each patient was followed for one year to identify subsequent depressive disorder. We found that during the one-year follow-up, the incidence of depressive disorder per thousand person-years was about twice as high among patients with OSA (18.10, 95% CI = 13.62-23.61) as those without OSA(8.23, 95% CI = 6.83-9.84). The Cox proportional hazards model revealed that patients with OSA were independently associated with a 2.18 times (95% CI =1.55-3.08) increased risk of subsequent depressive disorder within a year, compared to those without OSA. As epidemiological studies have consistently documented an increased risk for depression in women, we hypothesized and confirmed higher risks of depressive disorder among female patients with OSA(2.72, 95% CI = 1.68-4.40) than their male counterparts (1.81, 95% CI =1.09-3.01).

CONCLUSION: A prospective link between OSA and subsequent depressive disorder within one year was confirmed by the current study. The risk was particularly evident among women. Regular psychiatric screening among patients with OSA is suggested to prompt the timely detection of depression.


Image attributions:

“Diabetic Lancet Device In Hand” Image courtesy of pat138241 / FreeDigitalPhotos.net

“Doctor Measuring Blood Pressure” Image courtesy of Ambro / FreeDigitalPhotos.net

Sleep Snippets Newsletter – November 2014

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Message from Dr Zoe Scounos

Dr Zoe Scounos
Thoracic & Sleep Physician

It is fitting for this issues newsletter that focuses on Women’s issues to discuss the gender differences that exist for one of the most common sleep disorders, that being Obstructive Sleep Apnoea. Population studies show that OSA affects approximately 10% of adult females and 25% of adult males, although most have few or no symptoms. Put another way, it is well recognized that the male sex contributes a particularly strong risk factor and confers a 2 to 3 fold increase of sleep apnoea in the general population at large. This increased risk may be related to the difference in adipose tissue distribution in men, who exhibit a predominantly central fat deposition pattern around the neck, trunk, and abdominal viscera compared to women. In addition to obesity, hormonal status may impact on sleep apnoea susceptibility, particularly in women. Post-menopausal women demonstrate increases in sleep apnoea prevalence and severity compared with pre-menopausal women. Importantly, a substantial proportion of obese women are protected from the development and/or progression of sleep apnoea, although the humoral mechanisms conferring the protection remain largely unknown.

Regardless of the gender differences of this condition, it is important to focus on the relevance of identifying its severity, as this has an impact on risk stratification for long term complications. It is well established that severe OSA is strongly associated with increased mortality, stroke and cardiovascular disease in the middle aged population. The cardiovascular risk from moderate OSA is uncertain, although the data suggest an increased risk for stroke (particularly in men). There is no evidence of increased cardiovascular risk from mild OSA. Despite the high prevalence of this condition, most patients are minimally symptomatic. Furthermore, 15% of patients have moderate to severe sleep apnoea. Hence, the vital issue in clinical practice is to identify those with OSA who have clinically important disease.

The question therefore arises, who should be investigated? clearly, all patients with obvious risk factors and symptoms. However, patients with cardiovascular disease, stroke and diabetes or poorly controlled hypertension are at risk of OSA and should be questioned for symptoms of the like, which if present, may warrant further investigation and treatment.

In summary, the major goals of the management of OSA should be what is currently recommended, that being: to identify and offer treatment to symptomatic patients, regardless of disease severity, whose safety and quality of life is affected; to identify and offer treatment to patients with severe OSA determined by polysomnogram, regardless of symptoms, who may be at risk of adverse health outcomes; to modify adverse lifestyle factors that contribute to OSA pathogenesis and other poor health outcomes. This may include advice on diet and exercise to lose weight, and encouragement to reduce alcohol intake along with smoking cessation.


Women’s Issues & Obstructive Sleep Apnoea

Woman lying in bed sleeping

Sleep apnoea is a common occurrence in females.

Franklin Karl A; Sahlin Carin; Stenlund Hans; Lindberg Eva

Dept. of Surgical and Perioperative Sciences, Surgery, Umea University, Sweden. karl.franklin@surgery.umu.se

European respiratory journal ( Switzerland ) Mar 2013 , 41 (3) p610-5

Obstructive sleep apnoea (OSA) is primarily regarded as a male disorder, presenting with snoring, daytime sleepiness and cardiovascular disease. We aimed to determine the frequency of sleep apnoea among females in the general population. We investigated 400 females from a population-based random sample of 10,000 females aged 20-70 yrs. They answered a questionnaire and performed overnight polysomnography.

OSA (apnoea/hypopnoea index (AHI) >=5) was found in 50% (95% CI 45-55%) of females aged 20-70 yrs. Sleep apnoea was related to age, obesity and hypertension, but not to daytime sleepiness. Severe sleep apnoea (AHI >=30) was present in 14% (95% CI 8.1-21%) of females aged 55-70 yrs and in 31% (95% CI 12-50%) of obese females with a body mass index of >=30 kg.m(-2) aged 55-70 yrs. Sleep apnoea with daytime sleepiness and sleep apnoea with hypertension were observed as two different phenotypes of OSA.

OSA occurs in 50% of females aged 20-70 yrs. 20% of females have moderate and 6% severe sleep apnoea. Sleep apnoea in females is related to age, obesity and hypertension, but not to daytime sleepiness. When searching for sleep apnoea in females, females with hypertension or obesity should be investigated.

Role of sleep apnea and CPAP therapy in the incidence of stroke or coronary heart disease in women.

Campos-Rodriguez F(1), Martinez-Garcia MA, Reyes-Nuñez N, Caballero-Martinez I,Catalan-Serra P, et al

Hospital Universitario y Politecnico La Fe, Valencia, Spain

Am J Respir Crit Care Med. 2014 Jun 15;189(12):1544-50.

Comment in Am J Respir Crit Care Med. 2014 Jun 15;189(12):1459-60.

RATIONALE: It is unknown whether obstructive sleep apnea (OSA) may be a risk factor for incident cardiovascular events in women.

OBJECTIVES: We sought to investigate whether OSA increases the incidence of acomposite of stroke or coronary heart disease (CHD) in women, and the role of continuous positive airway pressure (CPAP) treatment on this association.

METHODS: This was a prospective, observational study conducted in two Spanish teaching hospitals between 1998 and 2007. Consecutive women referred for suspected OSA and free of previous stroke and CHD were analyzed. Women with anapnea-hypopnea index (AHI) less than 10 comprised the control group, and those with an AHI greater than or equal to 10 were diagnosed with OSA and classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). The follow-up ended in December 2010.

MEASUREMENTS AND MAIN RESULTS: A total of 967 women were studied (median follow-up, 6.8 yr; interquartile range, 5.2-8.2). The untreated OSA group showed a greater incidence rate of the composite outcome than the control group (2.19vs. 0.54 per 100 person-years; P < 0.0005). Compared with the control group, the fully adjusted hazard ratios for the composite outcome incidence were 2.76 (95%confidence interval [CI], 1.35-5.62) for the untreated OSA group, and 0.91 (95%CI, 0.43-1.95) for the CPAP-treated group. When the type of cardiovascular event was separately assessed, untreated OSA showed a stronger association with incident stroke (adjusted hazard ratio, 6.44; 95% CI, 1.46-28.3) than with CHD(adjusted hazard ratio, 1.77; 95% CI, 0.76-4.09).

CONCLUSIONS: In women, untreated OSA is associated with increased incidence of serious cardiovascular outcomes, particularly incident stroke. Adequate CPAP treatment seems to reduce this risk.

Glucose tolerance and weight loss in obese women with obstructive sleep apnea.

Gilardini L, Lombardi C, Redaelli G, Vallone L, Faini A, Mattaliano P, Parati G, Invitti C.

Department of Medical Sciences and Rehabilitation, Istituto Auxologico Italiano, Milan, Italy.

PLoS One. 2013 Apr 17;8(4):e61382.

BACKGROUND: The association of obstructive sleep apnea (OSA) with glucose intolerance and the beneficial effect of lifestyle intervention have been poorly investigated in women particularly before menopausal status. The study explored 1) whether OSA is associated with impaired glucose homeostasis in obese non diabetic premenopausal and menopausal women and 2) the effects of a 3- month lifestyle intervention on glucose homeostasis in OSA women.

DESIGN AND METHODS: We consecutively recruited 98 obese women (39 premenopausal) from those referred for a weight loss intervention. Ambulatory nocturnal polysomnography, body composition, oral glucose tolerance test, insulin sensitivity and β cell function were assessed before and after intervention.

RESULTS: 41% of premenopausal and 64% of menopausal women had OSA which was associated with worse glucose homeostasis before menopausal status. Mean and minimal nocturnal oxygen saturation (SaO2) was associated with neck/height ratio (NHR), independently of total and central obesity. Mean and minimal nocturnal SaO2 and NHR were correlated with insulin sensitivity and fasting glucose. In multivariate analyses, nocturnal mean SaO2 was negatively and independently correlated with fasting glucose (p<.0001) and nhr with insulin sensitivity (p<0.0001). in osa women, the intervention induced a 5% weight reduction significant increase minimal nocturnal sao2, β cell function. changes fasting glucose were associated those sao2 (p<0.05) not loss.<>p>

CONCLUSIONS: In obese women, glucose homeostasis worsens due to nocturnal hypoxia and increased neck circumference through mechanisms partially independent of obesity. OSA is more clearly associated with glucose intolerance in premenopausal than in menopausal women. In OSA women, the improvement of nocturnal hypoxia induced by lifestyle modifications is associated with that of glucose homeostasis.

Sleep and sleep disorders in menopausal women.

Guidozzi F

Dept of Obstetrics and Gynaecology, Charlotte Maxeke Johannesburg Acad Hosp, Uni of Witwatersrand, Climacteric – the journal of the International Menopause Society ( England ) Apr 2013 , 16 (2) p214-9

Sleep disorders in the menopause are common. Although these disorders may be due to the menopause itself and/or the associated vasomotor symptoms, the etiology is multifactorial and includes a number of other associated conditions. They may simply arise as part of the aging process and not be specifically related to the decrease in estrogen levels or, alternatively, because of breathing or limb movement syndromes, depression, anxiety, co-morbid medical diseases, medication, pain and/or psychosocial factors. The most commonly encountered sleep disorders in menopausal women include insomnia, nocturnal breathing disturbances and the associated sleep disorders that accompany the restless leg syndrome, periodic leg movement syndrome, depression and anxiety. This review article addresses sleep and the sleep disorders associated with menopause and briefly the role that hormone therapy may play in alleviating these disorders.

Cross-sectional assessment of the roles of comorbidities in resting and activity-related dyspnea in severely obese women.

Essalhi Mohamed; Gillaizeau Florence; Chevallier Jean-Marc; Ducloux Roxane; Chevalier-Bidaud Brigitte; et al

AP-HP, Hopital Europeen Georges-Pompidou, Service de Physiologie – Clinique de la Dyspnee, Paris, France.

Journal of asthma – official journal of the Association for the Care of Asthma ( England ) Aug 2013 , 50 (6) p565-72

OBJECTIVES: Obesity has been associated with a lesser degree of asthma control that may be biased by other comorbidities. The objectives of this cross-sectional study were to describe resting and activity-related dyspnea complaints according to the presence of obesity-related comorbidities (asymptomatic airway hyperresponsiveness (AHR), asthma, gastroesophageal reflux disease (GERD) and sleep-disordered breathing (SDB)). We hypothesized that obese women can exhibit both resting and activity-related dyspnea, independently of the presence of asthma.

METHODS: Severely obese (body mass index (BMI) > 35 kg m(-2)) women prospectively underwent description of resting and activity-related dyspnea (verbal descriptors and Medical Research Council (MRC) scale), pulmonary function testing (spirometry, absolute lung volumes, and methacholine challenge test), oesogastro-duodenal fibroscopy, and overnight polygraphy. Thirty healthy lean women without airway hyperresponsiveness were enrolled. RESULTS: Resting dyspnea complaints were significantly more prevalent in obesity (prevalence 41%) than in healthy lean women (prevalence 3%). Chest tightness and the need for deep inspirations were independently associated with both asthma and GERD while wheezing and cough were related to asthma only in obese women. Activity-related dyspnea was very prevalent (MRC score > 1, 75%), associated with obesity, with the exception of wheezing on exertion due to asthma. Asymptomatic AHR and SDB did not affect dyspneic complaints.

CONCLUSIONS: In severely obese women referred for bariatric surgery, resting dyspnea complaints are observed in association with asthma or GERD, while activity-related dyspnea was mainly related to obesity only. Consequently, asthma does not explain all respiratory complaints of obese women.


Pregnancy

Stress at the pregnant woman at home

The prevalence and correlates of habitual snoring during pregnancy.

Frederick IO, Qiu C, Sorensen TK, Enquobahrie DA, Williams MA.

Center for Perinatal Studies, Swedish Medical Center, USA. Ihunnaya.Frederick@swedish.org

Sleep Breath. 2013 May;17(2):541-7.

PURPOSE: Mounting evidence implicate habitual snoring, a prominent symptom of sleep-disordered breathing, as an important risk factor for adverse pregnancy outcomes including preeclampsia and gestational diabetes. Little, however, is known about the determinants of habitual snoring among pregnant women. We sought to assess its prevalence and to identify maternal characteristics associated with habitual snoring during pregnancy.

METHODS: Pregnant women (N = 1,303) receiving prenatal care provided information about habitual snoring before and during pregnancy in in-person interviews completed in early pregnancy. We calculated adjusted odds ratios (aOR) and 95 %confidence intervals (95 % CI) from multivariable models designed to identify factors associated with snoring during pregnancy.

RESULTS: Approximately 7.3 % of pregnant women reported habitual snoring during early pregnancy. The odds of habitual snoring during pregnancy was strongly related with maternal reports of habitual snoring prior to the index pregnancy(aOR = 24.32; 95 % CI, 14.30-41.51). Advanced maternal age (≥35 years)(aOR = 2.02; 95 % CI, 1.11-3.68), history of pregestational diabetes (aOR = 3.61;95 % CI, 1.07-12.2), history of mood and anxiety disorders (aOR = 1.81; 95 % CI, 1.02-3.20), and prepregnancy overweight (25-29.9 kg/m(2)) (aOR = 2.31; 95 % CI,1.41-3.77) and obesity (≥30 kg/m(2)) (aOR = 2.81; 95 % CI, 1.44-5.48) status were statistically significant risk factors for habitual snoring during pregnancy. In addition, maternal smoking during pregnancy (aOR = 2.70; 95 % CI, 1.17-6.26) was associated with habitual snoring during pregnancy.

CONCLUSIONS: Identification of risk factors for habitual snoring during pregnancy has important implications for developing strategies aimed at reducing the prevalence of sleep-disordered breathing, promoting improved sleep hygiene and improved pregnancy outcomes among reproductive-age women.

Effects of maternal obstructive sleep apnoea on fetal growth: a prospective cohort study.

Fung AM, Wilson DL, Lappas M, Howard M, Barnes M, O’Donoghue F, Tong S, Esdale

Department of Perinatal Medicine, Mercy Hospital for Women, Melbourne, Australia.

PLoS One. 2013 Jul 24;8(7):e68057.

OBJECTIVE: The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes.

STUDY DESIGN: We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth.

RESULTS: Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA(cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1-13.8) for cases and 2.2 (1.3-3.5) for controls (p<.001). impaired fetal growth was observed in 43% (6>14) of cases, vs11% (3/27) of controls (RR 2.67; 1.25-5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2-29.7, p = 0.03) and body mass index (OR 2.52; 1.09-5.80,p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93-30.34,p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, andIGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different.

CONCLUSION: OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth.

Sleep disordered breathing and gestational hypertension: postpartum follow-up study.

Reid J, Glew RA, Skomro R, Fenton M, Cotton D, Olatunbosun F, Gjevre J, Guilleminault C.

Division of Respiratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada

Sleep. 2013 May 1;36(5):717-721B.

BACKGROUND: Gestational hypertension (GH) is a newly recognized risk factor for adverse cardiovascular events later in life. Sleep disordered breathing (SDB) is an established risk factor for adverse cardiovascular events. Recent research has suggested that women with GH may have an increased rate of SDB during pregnancy, but it is not known if this higher rate of SDB persists into the postpartum state.

OBJECTIVE: To assess whether women with GH continue to have an increased rate of SDB compared to healthy pregnant women, after the physiologic changes of pregnancy resolve.

METHODS: We previously studied women with GH and uncomplicated pregnancies with sleep questionnaires and level 1 polysomnography. Participants were invited to participate in repeat testing 1-2 years postpartum. Respiratory disturbance index(RDI) differences were assessed.

RESULTS: Eighteen subjects (11 GH and 7 healthy) had complete follow-up data available for comparison with antepartum data. This group was representative oft he initial antepartum cohort. Women with GH experienced a decrease in mean RDI from antepartum to postpartum (12.0 ± 12.3 vs. 2.9 ± 2.9; P = 0.02). Healthy women did not experience the same change (2.8 ± 5.3 vs. 2.1 ± 3.2; P = 0.81).Postpartum comparisons showed the mean RDI of women with GH had decreased to be similar to that of healthy women (P = 0.75).

CONCLUSIONS: SDB in women with gestational hypertension improved in the postpartum state to levels indistinguishable from our healthy subjects. This suggests that the physiologic effects of pregnancy may have had a pathologic rolein the development of antepartum SDB in women with GH.

SDB and gestational diabetes mellitus: a meta-analysis of 9,795 participants enrolled in epidemiological observational studies.

Luque-Fernandez MA, Bain PA, Gelaye B, Redline S, Williams MA.

Harvard University, USA mluquefe@hsph.harvard.edu

Diabetes Care. 2013 Oct;36(10):3353-60.

OBJECTIVE: Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM.

RESEARCH DESIGN AND METHODS: We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed.

RESULTS: Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89-4.96).

CONCLUSIONS: These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy.