Christopher E. Kline

The Effect of Exercise Training on Obstructive Sleep Apnea and Sleep Quality: A Randomized Controlled Trial

STUDY OBJECTIVES To evaluate the efficacy of a 12-week exercise training program for reducing obstructive sleep apnea (OSA) severity and improving sleep quality, and to explore possible mechanisms by which exercise may reduce OSA severity. DESIGN Randomized controlled trial. SETTING Clinical exercise physiology center, sleep laboratory. PARTICIPANTS Forty-three sedentary and overweight/obese adults aged 18-55 years with at least moderate-severity untreated OSA (screening apnea-hypopnea index [AHI] ≥ 15). INTERVENTIONS Participants randomized to exercise training (n = 27) met 4 times/week for 12 weeks and performed 150 min/week of moderate-intensity aerobic activity, followed by resistance training twice/week. Participants randomized to a stretching control (n = 16) met twice weekly for 12 weeks to perform low-intensity exercises designed to increase whole-body flexibility. MEASUREMENTS AND RESULTS OSA severity was assessed with one night of laboratory polysomnography (PSG) before and following the 12-week intervention. Measures of sleep quality included PSG, actigraphy (7-10 days), and the Pittsburgh Sleep Quality Index. Compared with stretching, exercise resulted in a significant AHI reduction (exercise: 32.2 ± 5.6 to 24.6 ± 4.4, stretching: 24.4 ± 5.6 to 28.9 ± 6.4; P < 0.01) as well as significant changes in oxygen desaturation index (ODI; P = 0.03) and stage N3 sleep (P = 0.03). Reductions in AHI and ODI were achieved without a significant decrease in body weight. Improvements in actigraphic sleep and subjective sleep quality were also noted following exercise compared with stretching. CONCLUSIONS Exercise training had moderate treatment efficacy for the reduction of AHI in sedentary overweight/obese adults, which suggests that exercise may be beneficial for the management of OSA beyond simply facilitating weight loss. TRIAL REGISTRATION Clinicaltrials.gov identification number NCT00956423.

Dose-response effects of exercise training on the subjective sleep quality of postmenopausal women: exploratory analyses of a randomised controlled trial

Objective To investigate whether a dose–response relationship existed between exercise and subjective sleep quality in postmenopausal women. This objective represents a post hoc assessment that was not previously considered. Design Parallel-group randomised controlled trial. Setting Clinical exercise physiology laboratory in Dallas, Texas. Participants 437 sedentary overweight/obese postmenopausal women. Intervention Participants were randomised to one of four treatments, each of 6 months of duration: a non-exercise control treatment (n=92) or one of three dosages of moderate-intensity exercise (50% of VO2peak), designed to meet 50% (n=151), 100% (n=99) or 150% (n=95) of the National Institutes of Health Consensus Development Panel physical activity recommendations. Exercise dosages were structured to elicit energy expenditures of 4, 8 or 12 kilocalories per kilogram of body weight per week (KKW), respectively. Analyses were intent to treat. Primary outcome measures Continuous scores and odds of having significant sleep disturbance, as assessed by the Sleep Problems Index from the 6-item Medical Outcomes Study Sleep Scale. Outcome assessors were blinded to participant randomisation assignment. Results Change in the Medical Outcomes Study Sleep Problems Index score at 6 months significantly differed by treatment group (control: −2.09 (95% CI −4.58 to 0.40), 4 KKW: −3.93 (−5.87 to −1.99), 8 KKW: −4.06 (−6.45 to −1.67), 12 KKW: −6.22 (−8.68 to −3.77); p=0.04), with a significant dose–response trend observed (p=0.02). Exercise training participants had lower odds of having significant sleep disturbance at postintervention compared with control (4 KKW: OR 0.37 (95% CI 0.19 to 0.73), 8 KKW: 0.36 (0.17 to 0.77), 12 KKW: 0.34 (0.16 to 0.72)). The magnitude of weight loss did not differ between treatment conditions. Improvements in sleep quality were not related to changes in body weight, resting parasympathetic control or cardiorespiratory fitness. Conclusion Exercise training induced significant improvement in subjective sleep quality in postmenopausal women, with even a low dose of exercise resulting in greatly reduced odds of having significant sleep disturbance. Trial registration number clinicaltrials.gov identifier: NCT00011193.

No Effect of 8-Week Time-in-Bed Restriction on Glucose Tolerance in Older Long Sleepers

The aim of this study was to investigate the effects of 8 weeks of moderate restriction of time in bed (TIB) on glucose tolerance and insulin sensitivity in healthy older self‐reported long sleepers. Forty‐two older adults (ages 50–70 years) who reported average sleep durations of ≥8.5 h per night were assessed. Following a 2‐week baseline, participants were randomly assigned to two 8‐week treatments: either (i) TIB restriction (n = 22), which involved following a fixed sleep schedule in which time in bed was reduced by 90 min compared with baseline; (ii) a control (n = 18), which involved following a fixed sleep schedule but no imposed change of TIB. Sleep was monitored continuously via wrist actigraphy recordings, supplemented with a daily diary. Glucose tolerance and insulin sensitivity were assessed before and following the treatments. Compared with the control treatment, TIB restriction resulted in a significantly greater reduction of nocturnal TIB (1.39 ± 0.40 h versus 0.14 ± 0.26 h), nocturnal total sleep time (TST) (1.03 ± 0.53 h versus 0.40 ± 0.42 h), and 24‐h TST (1.03 ± 0.53 h versus 0.33 ± 0.43 h) from baseline values. However, no significant effect of TIB restriction was found for glucose tolerance or insulin sensitivity. These results suggest that healthy older long sleepers can tolerate 8 weeks of moderate TIB restriction without impairments in glucose tolerance or insulin sensitivity.

The Bidirectional Relationship Between Exercise and Sleep Implications for Exercise Adherence and Sleep Improvement

Exercise has long been associated with better sleep, and evidence is accumulating on the efficacy of exercise as a nonpharmacologic treatment option for disturbed sleep. Recent research, however, has noted that poor sleep may contribute to low physical activity levels, emphasizing a robust bidirectional relationship between exercise and sleep. This article will briefly review the evidence supporting the use of exercise as a nonpharmacologic treatment for sleep disturbance, outline future research that is needed to establish the viability of exercise as a behavioral sleep treatment, describe recent research that has emphasized the potential influence of poor sleep on daytime activity levels, and discuss whether improving sleep may facilitate adoption and/or better adherence to a physically active lifestyle. With poor sleep and physical inactivity each recognized as key public health priorities, additional research into the bidirectional relationship between exercise and sleep has significant implications for facilitating greater exercise adherence and improving sleep in society.

Exercise training improves selected aspects of daytime functioning in adults with obstructive sleep apnea.

STUDY OBJECTIVES To explore the utility of exercise training for improving daytime functioning in adults with obstructive sleep apnea (OSA). METHODS Forty-three sedentary and overweight/obese adults aged 18-55 years with at least moderate-severity untreated OSA (apnea-hypopnea index ≥ 15) were randomized to 12 weeks of moderate-intensity aerobic and resistance exercise training (n = 27) or low-intensity stretching control treatment (n = 16). As part of a trial investigating the efficacy of exercise training on OSA severity, daytime functioning was assessed before and following the intervention. Sleepiness, functional impairment due to sleepiness, depressive symptoms, mood, and quality of life (QOL) were evaluated with validated questionnaires, and cognitive function was assessed with a neurobehavioral performance battery. OSA severity was measured with one night of laboratory polysomnography before and following the intervention. RESULTS Compared with stretching control, exercise training resulted in significant improvements in depressive symptoms, fatigue and vigor, and aspects of QOL (p < 0.05). Sleepiness and functional impairment due to sleepiness also were improved following exercise versus control to a similar degree in terms of effect sizes (d > 0.5), though these changes were not statistically significant. No neurobehavioral performance improvements were found. Reduced fatigue following exercise training was mediated by a reduction in OSA severity, but changes in OSA severity did not significantly mediate improvement in any other measure of daytime functioning. CONCLUSIONS These data provide preliminary evidence that exercise training may be helpful for improving aspects of daytime functioning of adults with OSA. Larger trials are needed to further verify the observed improvements.

Persistence of Viral Reservoirs in Multiple Tissues after Antiretroviral Therapy Suppression in a Macaque RT-SHIV Model

Although antiretroviral therapy (ART) can suppress HIV-1 replication sufficiently to eliminate measurable plasma viremia, infected cells remain and ensure viral recrudescence after discontinuation of ART. We used a macaque model of HIV-1/AIDS to evaluate the location of infected cells during ART. Twelve macaques were infected with RT-SHIVmne, a SIV containing HIV-1 reverse transcriptase, conferring sensitivity to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten to fourteen weeks post-infection, 6 animals were treated with 3 or 4 antiretroviral drugs for 17-20 weeks; 6 control animals remained untreated. Viral DNA (vDNA) and RNA (vRNA) were measured in peripheral blood mononuclear cells (PBMC) and at necropsy in multiple tissues by quantitative PCR and RT-PCR. The majority of virally infected cells were located in lymphoid tissues with variable levels in the gastrointestinal tract of both treated and untreated animals. Tissue viral DNA levels correlated with week 1 plasma viremia, suggesting that tissues that harbor proviral DNA are established within the first week of infection. PBMC vDNA levels did not correlate with plasma viremia or tissue levels of vDNA. vRNA levels were high in lymphoid and gastrointestinal tissues of the untreated animals; animals on ART had little vRNA expressed in tissues and virus could not be cultured from lymph node resting CD4+ cells after 17-20 weeks on ART, indicating little or no ongoing viral replication. Strategies for eradication of HIV-1 will need to target residual virus in ART suppressed individuals, which may not be accurately reflected by frequencies of infected cells in blood.

CIRCADIAN RHYTHMS OF PSYCHOMOTOR VIGILANCE, MOOD, AND SLEEPINESS IN THE ULTRA-SHORT SLEEP/WAKE PROTOCOL

Despite its advantages as a chronobiological technique, the ultra-short sleep/wake protocol remains underutilized in circadian rhythm research. The purpose of this study was to examine circadian rhythms of psychomotor vigilance (PVT), mood, and sleepiness in a sample (n=25) of healthy young adults while they adhered to a 3 h ultra-short sleep/wake protocol. The protocol involved 1 h sleep intervals in darkness followed by 2 h wake intervals in dim light, repeated for 50–55 h. A 5 min PVT test was conducted every 9 h with the standard metrics of mean reaction time (RT; RTmean), median RT (RTmed), fastest 10% of responses (RT10fast), and reciprocal of the 10% slowest responses (1/RT10slow). Subjective measures of mood and sleepiness were assessed every 3 h. A cosine fit of intra-aural temperature, assessed three times per wake period, established the time of the body temperature minimum (Tmin). Mood, sleepiness, and PVT performances were expressed relative to individual means and compared across eight times of day and twelve 2 h intervals relative to Tmin. Significant time-of-day and circadian patterns were demonstrated for each of the PVT metrics, as well as for mood and sleepiness. Most mood subscales exhibited significant deterioration in day 2 of the protocol without alteration of circadian pattern. However, neither sleepiness nor performance was worse on the second day of observation compared to the first day. These data provide further support for the use of the ultra-short sleep/wake protocol for measurement of circadian rhythms. (Author correspondence: syoungstedt@sc.edu)

Blunted heart rate recovery is improved following exercise training in overweight adults with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) predisposes individuals to cardiovascular morbidity, and cardiopulmonary exercise test (CPET) markers prognostic for cardiovascular disease have been found to be abnormal in adults with OSA. Due to the persistence of OSA and its cardiovascular consequences, whether the cardiovascular adaptations normally conferred by exercise are blunted in adults not utilizing established OSA treatment is unknown. The aims of this study were to document whether OSA participants have abnormal CPET responses and determine whether exercise modifies these CPET markers in individuals with OSA. METHODS The CPET responses of 43 sedentary, overweight adults (body mass index [BMI]>25) with untreated OSA (apnea-hypopnea index [AHI]≥ 15) were compared against matched non-OSA controls (n=9). OSA participants were then randomized to a 12-week exercise training (n=27) or stretching control treatment (n=16), followed by a post-intervention CPET. Measures of resting, exercise, and post-exercise recovery heart rate (HRR), blood pressure, and ventilation, as well as peak oxygen consumption (VO(2peak)), were obtained. RESULTS OSA participants had blunted HRR compared to non-OSA controls at 1 (P=.03), 3 (P=.02), and 5-min post-exercise (P=.03). For OSA participants, exercise training improved VO2 peak (P=.04) and HRR at 1 (P=.03), 3 (P<.01), and 5-min post-exercise (P<.001) compared to control. AHI change was associated with change in HRR at 5-min post-exercise (r=-.30, P<.05), but no other CPET markers. CONCLUSIONS These results suggest that individuals with OSA have autonomic dysfunction, and that exercise training, by increasing HRR and VO2 peak, may attenuate autonomic imbalance and improve functional capacity independent of OSA severity reduction.

Cross-Sectional Associations between Multiple Lifestyle Behaviors and Health-Related Quality of Life in the 10,000 Steps Cohort

Background The independent and combined influence of smoking, alcohol consumption, physical activity, diet, sitting time, and sleep duration and quality on health status is not routinely examined. This study investigates the relationships between these lifestyle behaviors, independently and in combination, and health-related quality of life (HRQOL). Methods Adult members of the 10,000 Steps project (n = 159,699) were invited to participate in an online survey in November-December 2011. Participant socio-demographics, lifestyle behaviors, and HRQOL (poor self-rated health; frequent unhealthy days) were assessed by self-report. The combined influence of poor lifestyle behaviors were examined, independently and also as part of two lifestyle behavior indices, one excluding sleep quality (Index 1) and one including sleep quality (Index 2). Adjusted Cox proportional hazard models were used to examine relationships between lifestyle behaviors and HRQOL. Results A total of 10,478 participants provided complete data for the current study. For Index 1, the Prevalence Ratio (p value) of poor self-rated health was 1.54 (p = 0.001), 2.07 (p≤0.001), 3.00 (p≤0.001), 3.61 (p≤0.001) and 3.89 (p≤0.001) for people reporting two, three, four, five and six poor lifestyle behaviors, compared to people with 0–1 poor lifestyle behaviors. For Index 2, the Prevalence Ratio (p value) of poor self-rated health was 2.26 (p = 0.007), 3.29 (p≤0.001), 4.68 (p≤0.001), 6.48 (p≤0.001), 7.91 (p≤0.001) and 8.55 (p≤0.001) for people reporting two, three, four, five, six and seven poor lifestyle behaviors, compared to people with 0–1 poor lifestyle behaviors. Associations between the combined lifestyle behavior index and frequent unhealthy days were statistically significant and similar to those observed for poor self-rated health. Conclusions Engaging in a greater number of poor lifestyle behaviors was associated with a higher prevalence of poor HRQOL. This association was exacerbated when sleep quality was included in the index.

Sleep Hygiene Behaviors Among Midlife Women with Insomnia or Sleep-Disordered Breathing: The SWAN Sleep Study

BACKGROUND Insomnia and sleep-disordered breathing (SDB) are the most common sleep disorders among midlife women. Although promoting sleep hygiene behaviors may be a useful behavioral approach for the management of insomnia or SDB, the frequency with which women engage in these behaviors is unclear. METHODS Participants were from the Study of Womens Health Across the Nation (SWAN) Sleep Study (N=321; age range=48-58 years). Out of the full sample, 10.3% (n=33) met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnostic criteria for insomnia, 15.3% (n=49) had clinically significant SDB (apnea-hypopnea index ≥15), and 4.7% (n=15) met criteria for both insomnia and SDB, resulting in an overall prevalence of 15.0% (n=48) for insomnia and 19.9% (n=64) for SDB. Participants provided diary-based assessments of sleep hygiene behaviors for 14-35 days. Two positive behaviors (sufficient exercise, regular morning out-of-bed time) and four negative behaviors (taking long daytime naps, caffeine consumption near bedtime, alcohol consumption near bedtime, smoking) were examined. These behaviors were compared between women with and without insomnia or SDB following adjustment for sociodemographic factors and mental and physical health indices. RESULTS Women with insomnia engaged in significantly fewer negative sleep hygiene behaviors than women without insomnia (1.61±0.15 vs. 2.09±0.09 behaviors; p<0.01); specifically, women with insomnia were less likely to take long naps (odds ratio [OR]=0.30, 95% confidence interval [CI]: 0.12-0.74) or consume caffeine near bedtime (OR=0.44, 95% CI: 0.20-0.98). In contrast, women with SDB were less likely to be physically active than women without SDB (OR=0.52, 95% CI: 0.27-0.98), but no other differences in sleep hygiene behaviors were observed. CONCLUSIONS These data suggest that insomnia in midlife women is not associated with poor sleep hygiene. Increasing physical activity may be a valuable recommendation for midlife women with SDB.