(762.1) Obesity-Induced Breathing Variability During Sleep Is Independent of Apneas and Sleep Fragmentation

Poster Board Number: E528

Lenise Kim (The Johns Hopkins University School of Medicine), Chloe Alexandre (The Johns Hopkins University School of Medicine), Huy Pho (The Johns Hopkins University School of Medicine), Alban Latremoliere (The Johns Hopkins University School of Medicine, The Johns Hopkins University School of Medicine), Vsevolod Polotsky (The Johns Hopkins University School of Medicine), Luu Pham (The Johns Hopkins University School of Medicine)

Introduction: Obesity is a major cause of sleep-disordered breathing (SDB). Conventional metrics of SDB, such as the apnea-hypopnea index, can be confounded by the effects of obesity on oxygenation and lack of standard definitions. Thus, the impact of SBD on sleep is often difficult to quantify. Sleep fragmentation is frequently observed in obese individuals, but whether it occurs independently of SDB remains unknown. Quantitative analysis of ventilation may delineate the effects of obesity on breathing patterns and sleep fragmentation. We aimed to examine the effects of obesity on respiratory patterns during sleep and the relationship between obesity-related respiratory variability and sleep fragmentation.

Methods: Sleep recordings were performed in 15 male lean C57BL/6J mice and 17 male diet-induced obese (DIO) mice on the same genetic background. We applied Poincaré analysis of minute ventilation (VE) during sleep to estimate the breathing variability. Apneas were scored as ≥90% reductions in airflow for two breath cycles or ≥0.7s regardless the presence of arousals. Arousals were defined as single waking events lasting less than 16s. Arousals were classified as respiratory when associated with ≥30% drops in VE from baseline.

Results: Breathing variability was significantly higher in DIO mice during NREM sleep, but not during REM sleep. Obesity was associated with an increased apnea severity and 45% greater sleep fragmentation. However, obesity-induced breathing variability was not affected by apnea or arousal indexes. Respiratory arousals comprised 15% of the arousals in both strains.

Conclusions: Obesity increased respiratory variability during NREM sleep independently of apneas and macro-sleep architecture. Obesity caused sleep fragmentation that was not fully explained by SDB severity. Our quantitative analysis of VE identified differences in breathing variability in obesity that were not captured by traditional SDB metrics, which may be applicable for human SDB.

NHLBI R01 HL135483 and NHLBI 2R01 HL133100-05, American Academy of Sleep Medicine Foundation 238-BS-20, and American Thoracic Society Unrestricted Award (to L.V.P.), NIH R01 HL128970, R01 HL133100, and R01 HL13892 (V.Y.P.), NIH R01 NS112266 (to A.L.), Johns Hopkins Blaustein Pain Research Grant (to C.A. and A.L.), and American Heart Association Postdoctoral Fellowship Award 828142 (to L.J.K.).
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Obesity is associated with decreased ventilation and augmented breathing variability during NREM sleep. Normalized minute ventilation (VE) was significantly lower in diet-induced obese (DIO) compared to lean C57BL/6J mice. Individual Poincaré plots showed a larger dispersion of VE data points in DIO mice compared to lean mice. DIO mice showed an augmented short-term and long-term breathing variability during NREM sleep, indicated by higher SD1 and SD2 values, respectively. β: beta coefficient.; Obesity-related breathing variability during NREM sleep is independent of sleep apneas and sleep fragmentation. Minute ventilation (VE) points related to apneas and arousals were excluded from the analysis and SD1 and SD2 remained increased in diet-induced obese (DIO) mice. Sleep fragmentation in obesity is mainly attributed to non-respiratory arousals. The proportion of respiratory arousals was similar between strains (~15%). β: beta coefficient.