Compensatory responses to increased mechanical abnormalities in COPD during sleep.

PURPOSE: To assess whether night-time increases in mechanical loading negatively impact respiratory muscle function in COPD and whether compensatory increases in inspiratory neural drive (IND) are adequate to stabilize ventilatory output and arterial oxygen saturation, especially during sleep when wakefulness drive is withdrawn. METHODS: 21 patients with moderate-to-severe COPD and 20 age-/sex-matched healthy controls (CTRL) participated in a prospective, cross-sectional, one-night study to assess the impact of COPD on serial awake, supine inspiratory capacity (IC) measurements and continuous dynamic respiratory muscle function (esophageal manometry) and IND (diaphragm electromyography, EMGdi) in supine sleep. RESULTS: Supine inspiratory effort and EMGdi were consistently twice as high in COPD versus CTRL (p < 0.05). Despite overnight increases in awake total airways resistance and dynamic lung hyperinflation in COPD (p < 0.05; not in CTRL), elevated awake EMGdi and respiratory effort were unaltered in COPD overnight. At sleep onset (non-rapid eye movement sleep, N2), EMGdi was decreased versus wakefulness in COPD (- 43 ± 36%; p < 0.05) while unaffected in CTRL (p = 0.11); however, respiratory effort and arterial oxygen saturation (SpO2) were unchanged. Similarly, in rapid eye movement (stage R), sleep EMGdi was decreased (- 38 ± 32%, p < 0.05) versus wakefulness in COPD, with preserved respiratory effort and minor (2%) reduction in SpO2. CONCLUSIONS: Despite progressive mechanical loading overnight and marked decreases in wakefulness drive, inspiratory effort and SpO2 were well maintained during sleep in COPD. Preserved high inspiratory effort during sleep, despite reduced EMGdi, suggests continued (or increased) efferent activation of extra-diaphragmatic muscles, even in stage R sleep. CLINICAL TRIAL INFORMATION: The COPD data reported herein were secondary data (Placebo arm only) obtained through the following Clinical Trial: "Effect of Aclidinium/Formoterol on Nighttime Lung Function and Morning Symptoms in Chronic Obstructive Pulmonary Disease" ( https://clinicaltrials.gov/ct2/show/NCT02429765 ; NCT02429765).

Deterioration of Nighttime Respiratory Mechanics in COPD: Impact of Bronchodilator Therapy.

BACKGROUND: COPD is associated with nighttime respiratory symptoms, poor sleep quality, and increased risk of nocturnal death. Overnight deterioration of inspiratory capacity (IC) and FEV1 have been documented previously. However, the precise nature of this deterioration and mechanisms by which evening bronchodilation may mitigate this occurrence have not been studied. RESEARCH QUESTION: What is the effect of evening dosing of dual, long-acting bronchodilation on detailed nocturnal respiratory mechanics and inspiratory neural drive (IND)? STUDY DESIGN AND METHODS: A double-blind, randomized, placebo-controlled crossover study assessed the effects of evening long-acting bronchodilation (aclidinium bromide/formoterol fumarate dihydrate: 400/12 µg) or placebo on morning trough IC (12 h after the dose; primary outcome) and serial overnight measurements of spirometry, dynamic respiratory mechanics, and IND (secondary outcomes). Twenty participants with COPD (moderate/severe airway obstruction and lung hyperinflation) underwent serial measurements of IC, spirometry, breathing pattern, esophageal and transdiaphragmatic pressures, and diaphragm electromyography (diaphragmatic electromyography as a percentage of maximum; IND) at 6 time points from 0 to 12 h after the dose and compared with sleeping IND. RESULTS: Compared with placebo, evening bronchodilation was not associated with increased morning trough IC 12 h after the dose (P = .48); however, nadir IC (lowest IC, independent of time), peak IC, area under the curve for 12 h after the dose, and IC for 10 h after the dose were improved (P < .05). During placebo, total airways resistance, lung hyperinflation, IND, and tidal esophageal and transdiaphragmatic pressure swings all increased significantly overnight compared with baseline evening values; however, each of these parameters improved with bronchodilator treatment (P < .05) with no change in ventilation or breathing pattern. INTERPRETATION: Respiratory mechanics significantly deteriorated at night during placebo. Although the morning trough IC was unchanged, evening bronchodilator treatment was associated consistently with sustained overnight improvements in dynamic respiratory mechanics and inspiratory neural drive compared with placebo CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02429765.

Comparing a combination of validated questionnaires and level III portable monitor with polysomnography to diagnose and exclude sleep apnea.

STUDY OBJECTIVES: Questionnaires have been validated as screening tools in adult populations at risk for obstructive sleep apnea (OSA). Portable monitors (PM) have gained acceptance for confirmation of OSA in some patients with a high pretest probability of the disorder. We evaluated the combined diagnostic utility of 3 validated questionnaires and a Level III PM in the diagnosis and exclusion of OSA, as compared with in-laboratory polysomnography (PSG) derived apnea hypopnea index (AHI). METHODS: Consecutive patients referred to the Sleep Disorders Clinic completed 3 testing components: (1) 3 questionnaires (Berlin, STOP-Bang, and Sleep Apnea Clinical Score [SACS]); (2) Level III at-home PM (MediByte) study; and (3) Level I in-laboratory PSG. The utility of individual questionnaires, the Level III device alone, and the combination of questionnaires and the Level III device were compared with the PSG. RESULTS: One hundred twenty-eight patients participated in the study (84M, 44F), mean ± SD age 50 ± 12.3years, BMI 31 ± 6.6 kg/m(2). At a PSG threshold AHI = 10, the PM derived respiratory disturbance index (RDI) had a sensitivity and specificity of 79% and 86%, respectively. The sensitivity and specificity for the other screening tools were: Berlin 88%, 25%; STOP-Bang 90%, 25%; SACS 33%, 75%. The sensitivity and specificity at a PSG AHI = 15 were: PM 77%, 95%; Berlin 91%, 28%; STOP-Bang 93%, 28%; SACS 35%, 78%. CONCLUSIONS: Questionnaires alone, possibly given a reliance on sleepiness as a symptom, cannot reliably rule out the presence of OSA. Objective physiological measurement is critical for the diagnosis and exclusion of OSA.

Position paper by Canadian dental sleep medicine professionals on the role of different health care professionals in managing obstructive sleep apnea and snoring with oral appliances.

The present Canadian position paper contains recommendations for the management by dentists of sleep-disordered breathing in adults with the use of oral appliances (OAs) as a treatment option for snoring and obstructive sleep apnea (OSA). The recommendations are based on literature reviews and expert panel consensus. OAs offer an effective, first-line treatment option for patients with mild to moderate OSA who prefer an OA to continuous positive airway pressure (CPAP) therapy, or for severe OSA patients who cannot tolerate CPAP, are inappropriate candidates for CPAP or who have failed CPAP treatment attempts. The purpose of the present position paper is to guide interdisciplinary teamwork (sleep physicians and sleep dentists) and to clarify the role of each professional in the management of OA therapy. The diagnosis of OSA should always be made by a physician, and OAs should be fitted by a qualified dentist who is trained and experienced in dental sleep medicine. Follow-up assessment by the referring physician and polysomnography or sleep studies are required to verify treatment efficacy. The present article emphasizes the need for a team approach to OA therapy and provides treatment guidelines for dentists trained in dental sleep medicine. Many of the dentists and sleep physicians who contributed to the preparation of the present article are members of the Canadian Sleep Society and the authors reached a consensus based on the current literature.

Validation of the MediByte® type 3 portable monitor compared with polysomnography for screening of obstructive sleep apnea.

BACKGROUND: Portable monitors are increasingly being used as a diagnostic screening tool for obstructive sleep apnea (OSA), and in-laboratory validation of these devices with polysomnography (PSG) is required. OBJECTIVE: To assess the reliability of the MediByte (Braebon Medical Corporation, Canada) type 3 screening device compared with overnight PSG. METHODS: To cover a range of OSA severity, a consecutive series of patients wore the screening device while simultaneously undergoing PSG. Data acquired from the screener and PSG were blinded and scored separately. The number of apneas and hypopneas per hour were calculated using recording time (respiratory disturbance index [RDI]) for the MediByte device, and sleep time (apnea-hypopnea index [AHI]) for PSG. RESULTS: Data from 73 patients with a mean age of 53 years and body mass index of 32.2 kg/m2 showed high measurement association between the RDI and AHI, with a Pearson correlation of 0.92, accounting for 85% of the variance. Based on Bland-Altman measurement agreement, the mean difference between the RDI and AHI (-5.9±11.2 events/h) indicated screener under-reporting. For an AHI of greater than 15 events/h, the sensitivity and specificity of the screener was 80% and 97%, respectively; for an AHI of greater than 30 events/h, the positive predictive value was 100%, while the negative predictive value was 88%. CONCLUSION: The MediByte device accurately identified patients without OSA and had a high sensitivity for moderate-to-severe OSA.

Use of Bioimpedance to Assess Changes in Hemodynamics During Acute Administration of CPAP.

BACKGROUND: Attempts to investigate the mechanisms by which continuous positive airway pressure (CPAP) therapy improves heart function in patients with obstructive sleep apnea (OSA) have been limited by the lack of non-invasive methods to assess cardiac performance. We used transthoracic electrical bioimpedance (TEB) to assess acute hemodynamic changes including heart rate (HR), stroke volume (SV), cardiac output (CO) and cardiac index (CI) during PAP titration in (1) post-operative cardiac surgery patients, (2) patients with severe OSA, and (3) normal healthy volunteers. METHODS: Post-operative cardiac surgery patients were studied via TEB and pulmonary artery catheter (PAC) during acute titration of positive end-expiratory pressure (PEEP) while mechanically ventilated. Patients with severe OSA were studied non-invasively by TEB during acute CPAP titration in supine stage 2 sleep, and normal subjects while awake and recumbent. RESULTS: In post-operative cardiac surgery patients (n = 3), increasing PEEP to 18 cmH2O significantly reduced SV and CI relative to baseline. There was no difference between TEB and PAC in terms of ability to assess variations in hemodynamic parameters. In patients with severe OSA (n = 3), CPAP titration to optimal pressure to alleviate obstructive apneas reduced HR, SV, CO and CI significantly compared to without CPAP. In three healthy subjects, maximal tolerated CPAP reduced SV and CO significantly compared to baseline. CONCLUSIONS: Acute administration of CPAP causes a decrease in CO and CI, apparently a consequence of a reduction in SV. TEB appears to be an accurate and reproducible non-invasive method of detecting changes in hemodynamics.

Canadian Sleep Society/Canadian Thoracic Society position paper on the use of portable monitoring for the diagnosis of obstructive sleep apnea/hypopnea in adults.

The present position paper on the use of portable monitoring (PM) as a diagnostic tool for obstructive sleep apnea/hypopnea (OSAH) in adults was based on consensus and expert opinion regarding best practice standards from stakeholders across Canada. These recommendations were prepared to guide appropriate clinical use of this new technology and to ensure that quality assurance standards are adhered to. Clinical guidelines for the use of PM for the diagnosis and management of OSAH as an alternative to in-laboratory polysomnography published by the American Academy of Sleep Medicine Portable Monitoring Task Force were used to tailor our recommendations to address the following: indications; methodology including physician involvement, physician and technical staff qualifications, and follow-up requirements; technical considerations; quality assurance; and conflict of interest guidelines. When used appropriately under the supervision of a physician with training in sleep medicine, and in conjunction with a comprehensive sleep evaluation, PM may expedite treatment when there is a high clinical suspicion of OSAH.

Evaluation and treatment of sleep complaints: patients' subjective responses.

BACKGROUND: This study set out to evaluate whether patients' expectations affected their responses to treatment of a sleep disorder. METHODS: Fifty consecutive patients attending a sleep clinic for the first time and who had different diagnoses of sleep disorders were included in this study. The patients completed a set of 6 questionnaires on 7 occasions as they progressed through the process of a sleep clinic referral, assessment and treatment. Self-report questionnaires were used to assess their sleepiness, fatigue and alertness. Predictor measures included mental health and individual items assessing expectation regarding the seriousness of the sleep problem. A battery of questions dealt with mental health issues, patients' expectation and their commitment to the sleep investigation and treatment process. Each patient's responses were examined over a period of 6 months. RESULTS: Immediately following their interview with the sleep consultant, the patients' concern regarding their sleep problem was higher than the first measures obtained at baseline. Compared to prior to their first consultation with a sleep specialist, while on treatment they directed more attention to their sleep problem when problems associated with fatigue were reduced. Although there was a lessening in fatigue with treatment, subjectively rated sleepiness (Epworth Sleepiness Scale) did not vary over the study. Contact with a sleep center and the diagnosis and treatment of individual sleep problems also resulted in improved satisfaction with life. CONCLUSIONS: Contact with and treatment at a sleep clinic was found to be beneficial. The fatigue levels were reduced and the patients had greater life satisfaction regardless of the diagnosis and treatment of their sleep disorder, although subjective sleepiness did not change. Patient expectations were not critical in determining the outcome of the sleep clinic assessment.

Nocturnal sleep, daytime sleepiness, and napping among women with significant emotional/behavioral premenstrual symptoms.

The objective of this study is to examine daytime sleepiness and alertness and nap characteristics among women with significant emotional/behavioral premenstrual symptoms, and to determine their relationship with nocturnal sleep. Participants spent one night during the follicular phase and two nights during the late-luteal phase, one of which occurred after a 40 min opportunity to nap, sleeping in the laboratory. Subjective measures of sleepiness and alertness were completed during the afternoon of each recording. Setting took place at the sleep laboratory at the University of Ottawa. A total number of participants were 10 women with significant and nine women with minimal emotional/behavioral premenstrual symptoms (mean age 26 years). The results were compared with the follicular phase, both groups of women had less slow wave sleep and more stage 2 sleep at night, as well as a higher daytime and nocturnal mean and maximum temperature during the late-luteal phase. Women with significant symptoms were sleepier and less alert during the late-luteal phase and had a higher overall mean nocturnal temperature compared with women with minimal symptoms. No significant differences were found between the two groups on nap characteristics and nocturnal sleep characteristics. Results show that women with more severe premenstrual symptoms are sleepier during the late-luteal phase than women with minimal symptoms. The increased daytime sleepiness seems to be unrelated to nocturnal sleep or nap characteristics.

Circadian rhythms, sleep, and the menstrual cycle.

Women with ovulatory menstrual cycles have a circadian rhythm superimposed on the menstrual-associated rhythm; in turn, menstrual events affect the circadian rhythm. In this paper, we review circadian rhythms in temperature, selected hormone profiles, and sleep-wake behavior in healthy women at different phases of the menstrual cycle. The effects on menstrual cycle rhythmicity of disrupted circadian rhythms, for example, with shiftwork and altered circadian rhythms in women with menstrual-related mood disturbances, are discussed. Compared to the follicular phase, in the post-ovulation luteal phase, body temperature is elevated, but the amplitude of the temperature rhythm is reduced. Evidence indicates that the amplitude of other rhythms, such as melatonin and cortisol, may also be blunted in the luteal phase. Subjective sleep quality is lowest around menses, but the timing and composition of sleep remains relatively stable across the menstrual cycle in healthy women, apart from an increase in spindle frequency activity and a minor decrease in rapid eye movement (REM) sleep during the luteal phase. Disruption of circadian rhythms is associated with disturbances in menstrual function. Female shiftworkers compared to non-shiftworkers are more likely to report menstrual irregularity and longer menstrual cycles. There also is accumulating evidence that circadian disruption increases the risk of breast cancer in women, possibly due to altered light exposure and reduced melatonin secretion. Further investigations into the biological consequences of circadian disruption in women will offer insight into some menstrual-associated disorders, including mood changes, as well as reproductive function and possible links with breast cancer.

The acute impact of continuous positive airway pressure on nasal resistance: a randomized controlled comparison.

Subjective nasal obstruction is common among users of continuous positive airway pressure (CPAP). The aim of this study was to measure the acute effect of CPAP on nasal resistance and nasal symptoms in awake normal subjects. Twenty-four healthy CPAP-naive adults [8 men, 16 women; mean age 30 yr (SD 14)] underwent a randomized controlled crossover study comparing nasal CPAP (8 cmH(2)O) for 6 h on one occasion and the control condition (nasal mask without CPAP) on the other. Nasal resistance measurements (posterior active rhinometry) before and after the test exposure were similar on both test days. Nasal resistance during CPAP exposure [2.04 cmH(2)O.l(-1).s (SD 0.72)] was significantly lower than that of the control [2.67 cmH(2)O.l(-1).s (SD 1.07)]: mean difference 0.66 cmH(2)O.l(-1).s, 95% confidence interval 0.19-1.13 cmH(2)O.l(-1).s. The gradient in pressure from CPAP mask to posterior naris during CPAP exposure varied from 1.6 to 2 cmH(2)O but was not significantly different between time points. Subjective nasal symptom scores and peak nasal inspiratory flow rates did not change significantly on either test day. We conclude that in awake CPAP-naive normal subjects, acute CPAP exposure is associated with a reduction in nasal resistance compared with the control condition, but it is not associated with an immediate post-CPAP change in subjective or objective nasal resistance.

The influence of the menstrual cycle on upper airway resistance and breathing during sleep.

STUDY OBJECTIVE: Female hormones, specifically progesterone, that peak in the luteal phase may play a significant role in protecting premenopausal women from sleep-disordered breathing. The influence of female hormones on upper airway resistance during sleep was investigated during the follicular and luteal phases of normal menstrual cycles. SETTING: Hospital-based sleep laboratory. DESIGN AND PARTICIPANTS: Healthy women with verified ovulatory cycles and without sleep complaints were recruited into the study. Sleep and upper airway resistance data (mean +/- SD) were collected on 2 nights from 11 women (21-49 years of age [28 +/- 9 years], body mass index of 22.8 +/- 3.6 kg/m2), once during the follicular phase (day 6-11) and once in the luteal phase (day 19-23) in random order. MEASUREMENTS AND RESULTS: Nasal resistance, standardized to a flow rate of 0.3 L/second, measured using posterior active rhinomanometry immediately prior to the sleep study, did not differ between the 2 phases. The respiratory disturbance index tended to be higher in the follicular phase than in the luteal phase and was above 5 per hour for 3 women in the follicular phase. Upper airway resistance, controlled for flow rate and body position, was calculated for 50 random breaths during wakefulness, stage 1, stage 2, slow-wave, and rapid eye movement sleep. During wake and stage 2 sleep, upper airway resistance was significantly higher in the follicular phase than in the luteal phase, as was the overall upper airway resistance combined for wake and across all sleep stages. Combining data from the 2 nights, compared to wake, upper airway resistance increased in stage 2, slow-wave, and rapid eye movement sleep. CONCLUSIONS: Within the menstrual cycle, upper airway resistance is lower in the luteal compared with the follicular phase.

Self-reported sleep across the menstrual cycle in young, healthy women.

OBJECTIVE: To establish the association between subjective sleep and phase of the menstrual cycle in healthy, young, ovulating women. METHODS: Twenty-six women (mean age: 21 years) who did not suffer from any menstrual-associated disorders, and in whom we had detected ovulation, completed daily questionnaires about their sleep over 1 month. RESULTS: The women reported a lower sleep quality over the 3 premenstrual days and 4 days during menstruation, compared to the mid-follicular and early/mid luteal phases. Total sleep time, sleep onset latency, number and duration of awakenings, and morning vigilance were not affected by the menstrual cycle. CONCLUSION: The normal, ovulatory cycle is associated with changes in the perception of sleep quality but not sleep continuity in healthy, young women. The temporal relationship of sleep complaints with menstrual phase should be considered in the evaluation of sleep disorders, particularly insomnia, in women.

Partitioning of inhaled ventilation between the nasal and oral routes during sleep in normal subjects.

The oral and nasal contributions to inhaled ventilation were simultaneously quantified during sleep in 10 healthy subjects (5 men, 5 women) aged 43 +/- 5 yr, with normal nasal resistance (mean 2.0 +/- 0.3 cmH(2)O. l(-1). s(-1)) by use of a divided oral and nasal mask. Minute ventilation awake (5.9 +/- 0.3 l/min) was higher than that during sleep (5.2 +/- 0.3 l/min; P < 0.0001), but there was no significant difference in minute ventilation between different sleep stages (P = 0.44): stage 2 5.3 +/- 0.3, slow-wave 5.2 +/- 0.2, and rapid-eye-movement sleep 5.2 +/- 0.2 l/min. The oral fraction of inhaled ventilation during wakefulness (7.6 +/- 4%) was not significantly different from that during sleep (4.3 +/- 2%; mean difference 3.3%, 95% confidence interval -2.1-8.8%, P = 0.19), and no significant difference (P = 0.14) in oral fraction was observed between different sleep stages: stage two 5.1 +/- 2.8, slow-wave 4.2 +/- 1.8, rapid-eye-movement 3.1 +/- 1.7%. Thus the inhaled oral fraction in normal subjects is small and does not change significantly with sleep stage.

Acetaminophen does not affect 24-h body temperature or sleep in the luteal phase of the menstrual cycle.

Body temperature and sleep change in association with increased progesterone in the luteal phase of the menstrual cycle in young women. The mechanism by which progesterone raises body temperature is not known but may involve prostaglandins, inducing a thermoregulatory adjustment similar to that of fever. Prostaglandins also are involved in sleep regulation and potentially could mediate changes in sleep during the menstrual cycle. We investigated the possible role of central prostaglandins in mediating menstrual-associated 24-h temperature and sleep changes by inhibiting prostaglandin synthesis with a therapeutic dose of the centrally acting cyclooxygenase inhibitor acetaminophen in the luteal and follicular phases of the menstrual cycle in young women. Body temperature was raised, and nocturnal amplitude was blunted, in the luteal phase compared with the follicular phase. Acetaminophen had no effect on the body temperature profile in either menstrual cycle phase. Prostaglandins, therefore, are unlikely to mediate the upward shift of body temperature in the luteal phase. Sleep changed during the menstrual cycle: on the placebo night in the luteal phase the women had less rapid eye movement sleep and more slow-wave sleep than in the follicular phase. Acetaminophen did not alter sleep architecture or subjective sleep quality. Prostaglandin inhibition with acetaminophen, therefore, had no effect on the increase in body temperature or on sleep in the midluteal phase of the menstrual cycle in young women, making it unlikely that central prostaglandin synthesis underlies these luteal events.

Exercise and sleep.

This paper reviews the literature on the association between exercise and sleep. The epidemiological and experimental evidence for whether or not acute and chronic exercise promote sleep is discussed, as well as moderating factors and agendas for future directions of study. The expectation that exercise will benefit sleep can partly be attributed to traditional hypotheses that sleep serves energy conservation, body restoration or thermoregulatory functions, all of which have guided much of the research in this field. Exercise is a complex activity that can be beneficial to general well-being but may also stress the body. Differences in the exercise protocols studied (e.g. aerobic or anaerobic, intensity, duration) and interactions between individual characteristics (e.g. fitness, age and gender) cloud the current experimental evidence supporting a sleep-enhancing effect of exercise. In addition, the tendency to study changes in small groups of good sleepers may also underestimate the efficacy of exercise for promoting sleep. Athough only moderate effect sizes have been noted, meta-analytical techniques have shown that exercise increased total sleep time and delayed REM sleep onset (10 min), increased slow-wave sleep (SWS) and reduced REM sleep (2-5 min). The sleep-promoting efficacy of exercise in normal and clinical populations has yet to be established empirically.