Modeling Hypersomnolence in Sleep-disordered Breathing

Punjabi, Naresh M.; O’Hearn, Daniel; Neubauer, David N.; Nieto, F. Javier; Schwartz, Alan R.; Smith, P. L.; Bandeen‐Roche, Karen

doi:10.1164/ajrccm.159.6.9808095

Cited by 130 publications

(99 citation statements)

References 13 publications

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“…Standard criteria were employed to evaluate the breathing patterns during sleep. All respiratory events were defined as previously described (29,30). Apnea was defined as a drop in the peak thermal sensor excursion by at least 90% of baseline for at least 10 seconds.…”

Section: Study Protocolmentioning

confidence: 99%

Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity

Polotsky

Patil

Savransky

et al. 2009

Am J Respir Crit Care Med

190

139

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Rationale: Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity. Objectives: To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery. Methods: We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n 5 20) were obtained during bariatric surgery. Measurements and Main Results: Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 6 29 events/hour and the median oxygen desaturation during apneic events was 4.6 6 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology. Conclusions: Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.Keywords: hypoxemia; fatty liver disease; metabolic syndrome; sleepdisordered breathing; liver injury Obstructive sleep apnea (OSA) is a complex disorder consisting of upper airway obstruction, chronic intermittent hypoxia (CIH), and sleep fragmentation (1). Epidemiologic studies have demonstrated that OSA is associated with insulin resistance and glucose intolerance, independent of obesity (2-4). Clinical investigations have also shown that OSA results in low-grade systemic inflammation (5, 6). Both insulin resistance and systemic inflammation may contribute to the increased cardiovascular risk in patients with OSA (7-9). Insulin resistance, systemic inflammation, and OSA are particularly prevalent in patients with severe obesity defined as a body mass index (BMI) exceeding 40 kg/m 2 (2, 10-12). While obesity causes systemic inflammation, insulin resistance, and sleep apnea (12-15), sleep apnea may further exacerbate the inflammatory and metabolic disturbances (2, 3, 6). Nevertheless, it is not known whether concomitant OSA is implicated in metabolic dysregulation and systemic inflammation in severe obesity.One of the consequences of obesity and insulin resistance is nonalcoholic fatty liver disease (N...

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Section: Study Protocolmentioning

confidence: 99%

Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity

Polotsky

Patil

Savransky

et al. 2009

Am J Respir Crit Care Med

190

139

View full text Add to dashboard Cite

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“…The mean sleepiness score of UARS patients was 8.1 ¡ 3.6 (range 1-16), while the mean score of OSAS patients was 10.6 ¡ 5.2 (range [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. There were 16 OSAS and three UARS patients with an ESS score w10, which was defined as the upper point of normal range of sleepiness [33].…”

Section: Resultsmentioning

confidence: 99%

“…Different aspects of polysomnographical evaluations, such as changes in breathing (i.e. apnoea/hypopnoea [5][6][7][8] or hypoxaemia [7][8][9]), have been postulated as the main causes of EDS. In addition, reduction in the restorative nature of sleep by arousals [10][11][12], fragmentation of sleep [13,14], a lack of slow-wave sleep [15] and a reduction in total sleep time (TST) [16], have all been suggested as possible causes of EDS.…”

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confidence: 99%

“…However, some studies performed in patients with OSAS failed to show a strong association between sleep fragmentation and daytime somnolence [21,22]. Also in UARS, hypoxaemia, which was suggested to be an independent determinant of hypersomnolance in OSAS [7,8], is an excluding factor contributing to daytime somnolence. Therefore, there are some questions about daytime sleepiness in patients with OSAS and UARS that remain answered.…”

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confidence: 99%

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The role of mean inspiratory effort on daytime sleepiness

Pelin¹,

Karadeniz²,

Öztürk³

et al. 2003

Eur Respir J

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This study has investigated the role of average maximum inspiratory effort in excessive daytime sleepiness in patients with obstructive sleep apnoea syndrome (OSAS) and upper airway resistance syndrome (UARS).Fifteen patients diagnosed with UARS and 32 patients with OSAS, withw5.5 h total sleep time (TST) during 8 h of nocturnal polygraphic recordings, were included in the study. Demographical data, polysomnographical data and data about daytime sleepiness, including Epworth sleepiness scale (ESS) and multiple sleep latency test (MSLT), were evaluated. In order to compute the average maximum inspiratory effort from oesophageal pressure (Poes) measurements, maximum Poes was obtained from 20 representative obstructive respiratory events (obstructive apnoeas, hypopnoeas or flow limitations) for each sleep stage in both supine and side positions. From Poes measurements during sleep, the increase in Poes (DPoes) during respiratory events was also calculated.The average maximum Poes, DPoes, respiratory disturbance index (RDI) and arousal index were significantly correlated with ESS in OSAS patients. In patients with UARS, the only significant correlation was obtained between average maximum Poes and ESS. The MSLT score did not show any significant correlation with arousal index, number of stage variations, RDI, average Poes, DPoes, minimum oxygen saturation (Sa,O 2 ) and percentage of TST with an Sa,O 2 v90% in both UARS and OSAS patients. The results of multiple regression analysis showed that average maximum Poes correlates best with the variance in ESS for OSAS patients.In conclusion, the data from this study indicate the possible important role of average inspiratory effort in determining subjective sleepiness in both obstructive sleep apnoea syndrome and upper airway resistance syndrome patients.

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“…Airflow obstruction is thought to result from decreases in pharyngeal neuromuscular activity at sleep onset (2). These episodes lead to intermittent hypoxemia and recurrent arousals from sleep, accounting for the long-term neurocognitive (3,4), metabolic (5), and cardiovascular (6) sequelae of this disorder. Nasal continuous positive airway pressure remains the mainstay of treatment for moderate to severe obstructive sleep apnea (7).…”

mentioning

confidence: 99%

Acute Upper Airway Responses to Hypoglossal Nerve Stimulation during Sleep in Obstructive Sleep Apnea

Schwartz

Barnes

Hillman

et al. 2012

Am J Respir Crit Care Med

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Rationale: Hypoglossal nerve stimulation (HGNS) recruits lingual muscles, reduces pharyngeal collapsibility, and treats sleep apnea. Objectives: We hypothesized that graded increases in HGNS relieve pharyngeal obstruction progressively during sleep. Methods: Responses were examined in 30 patients with sleep apnea who were implanted with an HGNS system. Current (milliampere) was increased stepwise during non-REM sleep. Frequency and pulse width were fixed. At each current level, stimulation was applied on alternating breaths, and responses in maximal inspiratory airflow (V I max) and inspiratory airflow limitation (IFL) were assessed. Pharyngeal responses to HGNS were characterized by the current levels at which V I max first increased and peaked (flow capture and peak flow thresholds), and by the V I max increase from flow capture to peak (DV I max). Measurements and Main Results: HGNS produced linear increases in V I max from unstimulated levels at flow capture to peak flow thresholds (215 6 21 to 509 6 37 ml/s; mean 6 SE; P , 0.001) with increasing current from 1.05 6 0.09 to 1.46 6 0.11 mA. V I max increased in all patients and IFL was abolished in 57% of patients (non-IFL subgroup). In the non-IFL compared with IFL subgroup, the flow response slope was greater (1241 6 199 vs. 674 6 166 ml/s/mA; P , 0.05) and the stimulation amplitude at peak flow was lower (1.23 6 0.10 vs. 1.80 6 0.20 mA; P , 0.05) without differences in peak flow. Conclusions: HGNS produced marked dose-related increases in airflow without arousing patients from sleep. Increases in airflow were of sufficient magnitude to eliminate IFL in most patients and IFL and non-IFL subgroups achieved normal or near-normal levels of flow, suggesting potential HGNS efficacy across a broad range of sleep apnea severity.Keywords: obstructive sleep apnea; electrical hypoglossal nerve stimulation; pharynx; upper airway; titration Obstructive sleep apnea is characterized by recurrent episodes of upper airway obstruction during sleep (1). Airflow obstruction is thought to result from decreases in pharyngeal neuromuscular activity at sleep onset (2). These episodes lead to intermittent hypoxemia and recurrent arousals from sleep, accounting for the long-term neurocognitive (3, 4), metabolic (5), and cardiovascular (6) sequelae of this disorder. Nasal continuous positive airway pressure remains the mainstay of treatment for moderate to severe obstructive sleep apnea (7). Difficulties adhering to therapy can limit its effectiveness in the home setting (8, 9), and alternatives have been generally less effective in relieving upper airway obstruction during sleep (10-12).Hypoglossal nerve stimulation (HGNS) has been piloted as treatment for obstructive sleep apnea (13). Implantable HGNS systems have been developed to stimulate the hypoglossal nerve during inspiration, and recruit the lingual musculature, leading to decreases in pharyngeal collapsibility during sleep (14-17). Motor activity protrudes the tongue, and mitigates airflow obstruction during sleep (18,19)....

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Modeling Hypersomnolence in Sleep-disordered Breathing

Cited by 130 publications

References 13 publications

Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity

Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity

The role of mean inspiratory effort on daytime sleepiness

Acute Upper Airway Responses to Hypoglossal Nerve Stimulation during Sleep in Obstructive Sleep Apnea

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