Impact of arousal threshold and respiratory effort on the duration of breathing events across sleep stage and time of night

Wains, Soheeb A.; El‐Chami, Mohamad; Lin, Ho‐Sheng; Mateika, Jason H.

doi:10.1016/j.resp.2016.12.009

Cited by 10 publications

(6 citation statements)

References 19 publications

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“…In secondary analyses, we also examined respiratory event duration, which is shorter in AAs than EAs, and partially reflects respiratory arousability and chemoreflex sensitivity, which when abnormal can lead to sleep fragmentation (55)(56)(57). In the region of chromosome 16q12-21, we detected four variants on RP11-96H17.1 associated with event duration.…”

Section: Discussionmentioning

confidence: 99%

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans

Wang

Cade

Sofer

et al. 2018

Human Molecular Genetics

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Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO 2) and percentage time SaO 2 < 90%] and a secondary trait (respiratory event duration) in a Hispanic/Latino American population study of 11 575 individuals with significant variation in ancestral background. Linear mixed models were performed using previously inferred African, European and Amerindian local genetic ancestry markers. Global African ancestry was associated with a lower AHI, higher SaO 2 and shorter event duration. Admixture mapping analysis of the primary OSA traits identified local African ancestry at the chromosomal region 2q37 as genome-wide significantly associated with AHI (P < 5.7 × 10 −5), and European and Amerindian ancestries at 18q21 suggestively associated with both AHI and percentage time SaO 2 < 90% (P < 10 −3). Follow-up joint ancestry-SNP association analyses identified novel variants in ferrochelatase (FECH), significantly associated with AHI and percentage time SaO 2 < 90% after adjusting for multiple tests (P < 8 × 10 −6). These signals contributed to the admixture mapping associations and were replicated in independent cohorts. In this first admixture mapping study of OSA, novel associations with variants in the iron/heme metabolism pathway suggest a role for iron in inf luencing respiratory traits underlying OSA.

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Section: Discussionmentioning

confidence: 99%

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans

Wang

Cade

Sofer

et al. 2018

Human Molecular Genetics

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“…event termination, a concept also recently validated outside our laboratory. 17 Our method also accounts for individual variability in the ventilatory response to arousal 3,5,8,10 ; that is, simply measuring ventilation rather than estimating the ventilatory drive prior to arousal weakened the correlations observed (see Supplementary Material). Polysomnographic values were also related to known clinical correlates of the arousal threshold (event length, apneas versus hypopneas, desaturation): Respiratory events tend to become longer overnight as a manifestation of an increased arousal threshold.…”

Section: Consistency With Available Literaturementioning

confidence: 99%

“…15 Thus, a lower arousal threshold in lighter versus deeper sleep is believed to contribute to sleep apnea. 9,[15][16][17] A lower arousal threshold also probably interacts with increased chemosensitivity to promote respiratory instability. 18,19 Available evidence also suggests that increasing the arousal threshold with a hypnotic (eszopiclone) can improve OSA severity in patients with a low arousal threshold.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea

Sands

Terrill

Edwards

et al. 2017

Sleep

132

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“… 146 In addition, recent studies from the Mateika group indicate that several of the key contributors to OSA such as airway collapsibility, arousal threshold, and respiratory control are influenced by circadian phase. 166 – 168 Thus, novel strategies that target the circadian system may have therapeutic potential in OSA.…”

Section: Introductionmentioning

confidence: 99%

Obstructive sleep apnea: current perspectives

Osman

Carter

Carberry

2018

NSS

311

185

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Abstract:The prevalence of obstructive sleep apnea (OSA) continues to rise. So too do the health, safety, and economic consequences. On an individual level, the causes and consequences of OSA can vary substantially between patients. In recent years, four key contributors to OSA pathogenesis or "phenotypes" have been characterized. These include a narrow, crowded, or collapsible upper airway "anatomical compromise" and "non-anatomical" contributors such as ineffective pharyngeal dilator muscle function during sleep, a low threshold for arousal to airway narrowing during sleep, and unstable control of breathing (high loop gain). Each of these phenotypes is a target for therapy. This review summarizes the latest knowledge on the different contributors to OSA with a focus on measurement techniques including emerging clinical tools designed to facilitate translation of new cause-driven targeted approaches to treat OSA. The potential for some of the specific pathophysiological causes of OSA to drive some of the key symptoms and consequences of OSA is also highlighted.

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Impact of arousal threshold and respiratory effort on the duration of breathing events across sleep stage and time of night

Cited by 10 publications

References 19 publications

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans

Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea

Obstructive sleep apnea: current perspectives

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