Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present

The Different Facets of Heart Rate Variability in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA), a heterogeneous and multifactorial sleep related breathing disorder with high prevalence, is a recognized risk factor for cardiovascular morbidity and mortality. Autonomic dysfunction leads to adverse cardiovascular outcomes in diverse pathways. Heart rate is a complex physiological process involving neurovisceral networks and relative regulatory mechanisms such as thermoregulation, renin-angiotensin-aldosterone mechanisms, and metabolic mechanisms. Heart rate variability (HRV) is considered as a reliable and non-invasive measure of autonomic modulation response and adaptation to endogenous and exogenous stimuli. HRV measures may add a new dimension to help understand the interplay between cardiac and nervous system involvement in OSA. The aim of this review is to introduce the various applications of HRV in different aspects of OSA to examine the impaired neuro-cardiac modulation. More specifically, the topics covered include: HRV time windows, sleep staging, arousal, sleepiness, hypoxia, mental illness, and mortality and morbidity. All of these aspects show pathways in the clinical implementation of HRV to screen, diagnose, classify, and predict patients as a reasonable and more convenient alternative to current measures.Peer Reviewe

Arousal, Sleep and Cardiovascular Responses to Intermittent Hypercapnic Hypoxia in Piglets

Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon

Arousal, Sleep and Cardiovascular Responses to Intermittent Hypercapnic Hypoxia in Piglets

Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon

Gender Differences in Obstructive Sleep Apnea

The overall aim of this thesis was to understand gender differences in obstructive sleep apnea (OSA) and use this information to develop a tailored therapy for female patients. Specific aims were to determine whether gender differences commonly reported in the literature are present in mild OSA and upper airway resistance syndrome (UARS) patient groups, and whether symptoms could be linked to respiratory parameters in these groups. The final aim was to develop, test and validate a new AutoSet treatment for female OSA patients. CHAPTER 1 of this thesis provides a detailed review of gender differences in the prevalence, symptoms, clinical experience, and health outcomes of OSA and UARS patients, with a focus on the implications of different scoring rules. CHAPTER 2 reviews of quality of life questionnaires from 259 untreated patients with mild OSA. Females reported statistically significantly higher levels of sleepiness, fatigue, insomnia, and anxiety/depression compared to males. CHAPTER 3 of this thesis reviews polygraphy data from patients with mild OSA. Male patients were found to have significantly more breathing disturbances than females, however many of these difference disappeared when updated scoring criteria were used. Some weak correlations were found between respiratory parameters and symptoms; however, no clear conclusions could be drawn. CHAPTER 4 outlines the development of a new AutoSet device designed for female- specific breathing patterns. The remaining chapters (CHAPTER 5, and CHAPTER 6) of this thesis describe the testing and validation activities undertaken on the AutoSet F, including a clinical trial to test efficacy; a bench test to compare performance against other commercially available devices; a controlled product launch to validate the features of the algorithm; and finally a clinical trial which demonstrated improvements in sleep efficacy and quality of life over a three-month usage period. In summary, this thesis has shown that at the mild end of the OSA spectrum females are more symptomatic than males, even though respiratory differences in the genders are less pronounced than those described in moderate-to-severe patients. An AutoSet designed specifically for female OSA patients was successful in demonstrating efficacy and clinical effectiveness

Snoring and sleep apnea in children

Snoring is a primary and major clinical symptom of upper airway obstruction during sleep. Sleep-disordered breathing ranges from primary snoring to significant partial upper airway obstruction, and obstructive sleep apnea. Adult snoring and obstructive sleep apnea have been extensively studied, whereas less is known about these disorders in children. Snoring and more severe obstructive sleep apnea have been shown to have a harmful effect on the neurobehavioral development of children, but the mechanisms of this effect remains unknown. Furthermore, the correlation of this effect to objective sleep study parameters remains poor. This study evaluated the prevalence of snoring in preschool-aged children in Finland. Host and environmental risk factors, and neurobehavioral and neurocognitive symptoms of children suffering from snoring or obstructive sleep apnea were also investigated. The feasibility of acoustic rhinometry in young children was assessed. The prevalence and risk factors of snoring (I) were evaluated by a questionnaire. The random sample included 2100 children aged 1-6 years living in Helsinki. All 3- to 6-year-old children whose parents reported their child to snore always, often, or sometimes were categorized as snorers, and invited to participate to the clinical study (II-IV). Non-snoring children whose parents were willing to participate in the clinical study were invited to serve as controls. Children underwent a clinical ear-nose-throat examination. Emotional, behavioral, and cognitive performances were evaluated by Child Behavioral Checklist (CBCL), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) and NEPSY-A Developmental Neuropsychological Assessment (NEPSY). Nasal volume was measured by acoustic rhinometry, and nasal resistance by rhinomanometry. Lateral and posteroanterior cephalometry were performed. A standard overnight ambulatory polysomnography was performed in the home environment. Twenty-six healthy children were tested in order to assess the feasibility of acoustic rhinometry in young children (V). Snoring was common in children; 6.3% of children snored always or often, whereas 81.3% snored never or occasionally. No differences were apparent between snorers and non-snorers regarding age, or gender. Pediatric snoring was associated with recurrent upper respiratory infections, otitis media, and allergic rhinitis. Exposure to parental tobacco smoke, especially maternal smoking, was more common among snorers. Rhinitis was more common among children who exposured to tobacco smoke. Overnight polysomnography (PSG) was performed on 87 children; 74% showed no signs of significant upper airway obstruction during sleep. Three children had obstructive apnea/hypopnea index (OAHI) greater than 5/h. Age, gender, or a previous adenoidectomy or tonsillectomy did not correlate with OAHI, whereas tonsillar size did correlate with OAHI. Relative body weight and obesity correlated with none of the PSG parameters. In cephalometry, no clear differences or correlations were found in PSG parameters or between snorers and non-snorers. No correlations were observed between acoustic rhinometry, rhinomanometry, and PSG parameters. Psychiatric symptoms were more frequent in the snoring group than in the nonsnoring group. In particular, anxious and depressed symptoms were more prevalent in the snoring group. Snoring children frequently scored lower in language functions. However, PSG parameters correlated poorly with neurocognitive test results in these children. This study and previous studies indicate that snoring without episodes of obstructive apnea or SpO2 desaturations may cause impairment in behavioral and neurocognitive functions. The mechanism of action remains unknown. Exposure to parental tobacco smoke is more common among snorers than non-snorers, emphasizing the importance of a smoke-free environment. Children tolerated acoustic rhinometry measurements well.Unenaikainen ylähengitystieahtauma käsittää jatkumon ajoittaisesta hiljaisesta kuorsaamisesta vaikea-asteiseen obstruktiiviseen uniapneaan, jossa koko uni on toistuvien tukoksellisten hengitystaukojen rikkoma. Vaikea-asteisen obstruktiivisen uniapnean tiedetään voivan vaikuttaa sekä lapsen henkiseen että fyysiseen kehitykseen, mutta yleisemmin on osoitettu kuorsaavien lasten pärjäävän verrokkeja huonommin koulussa. Selvitimme 1 - 6-vuotiaiden helsinkiläisten lasten kuorsauksen yleisyyttä kyselykaavakkeella. Aineiston valinta perustui satunnaistettuun otantaan väestörekisterikeskuksesta (n=2100). Vastanneista (n=1471, 71%) lapsista 92 (6,3%) kuorsasi aina tai lähes aina, ajoittain kuorsasi 183 lasta (12,4 %) ja 1196 (81,3%) lapsista ei kuorsannut koskaan tai kuorsasi satunnaisesti. Kutsuimme kaikki 3 - 6-vuotiaat aina tai lähes aina kuorsaavat lapset sekä halukkaat terveet verrokit, jatkotutkimuksiin. Jatkotutkimuksiin osallistui 45 kuorsaava lasta ja 52 ei-kuorsaavaa lasta. Tavoitteenamme oli selvittää kuorsauksen riskitekijöitä, minkä asteisista unenaikaisista hengityshäiriöstä lapsen kärsivät ja millaisia päiväoireita kuorsaus aiheuttaa lapselle. Lisäksi selvitimme terveillä vapaaehtoisilla lapsilla (n=26) jo aiemmin aikuisilla käytössä olevan mittausmenetelmän, akustisen rinometrian käyttökelpoisuutta lasten nenän tilavuuden arvioinnissa. Kyselytutkimuksen perusteella kuorsaavien ja ei-kuorsaavien lasten välillä ei ollut eroja sukupuolen, iän eikä painon osalta. Sen sijaan vanhempien ja erityisesti äidin tupakointi olivat riskitekijöitä lapsen kuorsaukselle (P < .01). Ero kuorsaajien ja eikuorsaajien välillä oli merkittävä, vaikka lapsi ei altistunut tupakansavulle sisätiloissa. Kuorsaavilla lapsilla oli ei-kuorsaavia lapsia useammin ylempien hengitysteiden infektioita, välikorvan tulehduksia ja allergista nuhaa (P < .001). Nenän tilavuutta ja ilmavirtausta arvioitiin akustisen rinometrian avulla. Menetelmä soveltui hyvin jo alle kouluikäisillä lapsilla. Nenämittauksissa ei todettu eroja kuorsaavien ja eikuorsaavien lasten välillä. Jatkotutkimukseen osallistuneille lapsille tehtiin koko yön kestävä unirekisteröinti(n=87). Kolmella kuorsaavalla lapsella unirekisteröinti oli selkeästi poikkeava (OAHI >5/h). Lapsen ikä, sukupuoli, paino tai nenämittaukset tulokset eivät korreloineet unirekisteröinnin tuloksiin. Nielurisojen koko sen sijaan korreloi obstruktiivisten hengitystukosten määrään (OAHI) ja voimistuneeseen hengitystyöhön (P < .01). Lapsen tunne-elämää, käytöshäiriöitä ja älykkyyttä mitattiin neuropsykologisilla testeillä (CBCL, WPPSI-R ja NEPSY-A). Psyykkiset oireet, erityisesti ahdistus ja masennus (P = . 04) olivat yleisempiä kuorsaavilla lapsilla verrattuna ei-kuorsaaviin lapsiin. Lisäksi kuorsaavilla lapsilla oli huonommat kielelliset valmiudet (P < .01). Kokonaisälykkyydessä ei ollut eroja ryhmien välillä. Unirekisteröinnin tulokset eivät korreloineet neuropsykologisten ja käyttäytymistä mittaavien testien kanssa. Kuorsaus on suhteellisen yleinen oire lapsella. Se aiheuttaa jo alle kouluikäisellä ahdistus- ja masennusoireita sekä vaikeuksia kielellisissä taidoissa. Tarkka mekanismi, miksi kuorsaus aiheuttaa lapselle päiväoireita, on epäselvä. Terveydenhuollossa on tärkeä tunnistaa lasten kuorsaus ja ohjata lapsi jatkotutkimuksiin ja -hoitoon. Lapsen altistuminen vanhempien tupakoinnille lisää lapsen riskiä kuorsaukselle, jonka vuoksi kuorsaavien lasten hoidossa tulisi kiinnittää huomiota myös vanhempien mahdolliseen tupakointiin

Endokrinní a metabolické aspekty vybraných spánkový ch poruch

Endokrinní a metabolické aspekty vybraných spánkových poruch MUDr. Zuzana Vimmerová Lattová Abstrakt: Výsledky epidemiologických a experimentálních studií naznačují negativní vliv krátké doby trvání spánku nebo přerušovaného spánku na glukózovou toleranci. Doposud však nebyly provedeny žádné srovnávací studie glukózového metabolismu u klinických spánkových poruch. Dysfunkce HPA osy může hrát stěžejní roli v patofysiologii některých spánkových poruch, u jiných poruch spánku může být sekundární k narušenému spánku. Dysfunkce HPA osy je také považována za možnou příčinu poruch glukózové tolerance spojených s poruchami spánku. Nicméně údaje o funkci HPA osy u spánkových poruch jsou skrovné a konfliktní. Vyšetřili jsme celkem 25 pacientů s obstrukční spánkovou apnoe (OSA), 18 pacientů se syndromem neklidných nohou (RLS), 21 pacientů s primární insomnií a porovnali je s 33 zdravými kontrolami. Provedli jsme orální glukózový toleranční test (OGTT) a hodnotili další parametry metabolismu sacharidů. Dynamická odezva HPA systému byla hodnocena DEX- CRH-testem, který spojuje supresi (dexametazon) a stimulaci (CRH) HPA osy. Zaznamenali jsme vyšší výskyt poruch glukózové tolerance u pacientů s OSA (OR: 4.9) a RLS (OR: 4.7) ve srovnání s kontrolní skupinou, nikoli však u primárních insomniaků. Kromě toho byly u těchto...Endocrine and Metabolic Aspects of Various Sleep Disorders MUDr. Zuzana Vimmerová Lattová Abstract: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. However, no comparative studies of glucose metabolism have been conducted in clinical sleep disorders. Dysfunction of the HPA axis may play a causative role in some sleep disorders and in other sleep disorders it may be secondary to the sleep disorder. Moreover, dysfunction of the HPA axis is regarded as a possible causative factor for the impaired glucose sensitivity associated with disturbed sleep. However, data on HPA system activity in sleep disorders are sparse and conflicting. We studied 25 obstructive sleep apnea (OSA) patients, 18 restless legs syndrome (RLS) patients, 21 patients with primary insomnia and compared them to 33 healthy controls. We performed oral glucose tolerance test and assessed additional parameters of glucose metabolism. The dynamic response of the HPA system was assessed by the DEX-CRH-test which combines suppression (dexamethasone) and stimulation (CRH) of the stress hormone system. Compared to controls, increased rates of impaired glucose tolerance were found in OSA (OR: 4.9) and RLS (OR: 4.7), but not in primary insomnia. In addition, HbA1c...Department of Psychiatry First Faculty of Medicine and General University Hospital in PraguePsychiatrická klinika 1. LF a VFN v PrazeFirst Faculty of Medicine1. lékařská fakult