Summary Obstructive sleep apnoea is an increasingly common disorder of repeated upper airway collapse during sleep, leading to oxygen desaturation and disrupted sleep. Features include snoring, ...witnessed apnoeas, and sleepiness. Pathogenesis varies; predisposing factors include small upper airway lumen, unstable respiratory control, low arousal threshold, small lung volume, and dysfunctional upper airway dilator muscles. Risk factors include obesity, male sex, age, menopause, fluid retention, adenotonsillar hypertrophy, and smoking. Obstructive sleep apnoea causes sleepiness, road traffic accidents, and probably systemic hypertension. It has also been linked to myocardial infarction, congestive heart failure, stroke, and diabetes mellitus though not definitively. Continuous positive airway pressure is the treatment of choice, with adherence of 60–70%. Bi-level positive airway pressure or adaptive servo-ventilation can be used for patients who are intolerant to continuous positive airway pressure. Other treatments include dental devices, surgery, and weight loss.
The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized.
To define carefully the proportion of key anatomic and nonanatomic ...contributions in a relatively large cohort of patients with OSA and control subjects to identify pathophysiologic targets for future novel therapies for OSA.
Seventy-five men and women with and without OSA aged 20-65 years were studied on three separate nights. Initially, the apnea-hypopnea index was determined by polysomnography followed by determination of anatomic (passive critical closing pressure of the upper airway Pcrit) and nonanatomic (genioglossus muscle responsiveness, arousal threshold, and respiratory control stability; loop gain) contributions to OSA.
Pathophysiologic traits varied substantially among participants. A total of 36% of patients with OSA had minimal genioglossus muscle responsiveness during sleep, 37% had a low arousal threshold, and 36% had high loop gain. A total of 28% had multiple nonanatomic features. Although overall the upper airway was more collapsible in patients with OSA (Pcrit, 0.3 -1.5 to 1.9 vs. -6.2 -12.4 to -3.6 cm H2O; P <0.01), 19% had a relatively noncollapsible upper airway similar to many of the control subjects (Pcrit, -2 to -5 cm H2O). In these patients, loop gain was almost twice as high as patients with a Pcrit greater than -2 cm H2O (-5.9 -8.8 to -4.5 vs. -3.2 -4.8 to -2.4 dimensionless; P = 0.01). A three-point scale for weighting the relative contribution of the traits is proposed. It suggests that nonanatomic features play an important role in 56% of patients with OSA.
This study confirms that OSA is a heterogeneous disorder. Although Pcrit-anatomy is an important determinant, abnormalities in nonanatomic traits are also present in most patients with OSA.
Abstract
Study Objectives:
Arousals from sleep vary in duration and intensity. Accordingly, the physiological consequences of different types of arousals may also vary. Factors that influence arousal ...intensity are only partly understood. This study aimed to determine if arousal intensity is mediated by the strength of the preceding respiratory stimulus, and investigate other factors mediating arousal intensity and its role on post-arousal ventilatory and pharyngeal muscle responses.
Methods:
Data were acquired in 71 adults (17 controls, 54 obstructive sleep apnea patients) instrumented with polysomnography equipment plus genioglossus and tensor palatini electromyography (EMG), a nasal mask and pneumotachograph, and an epiglottic pressure sensor. Transient reductions in CPAP were delivered during sleep to induce respiratory-related arousals. Arousal intensity was measured using a validated 10-point scale.
Results:
Average arousal intensity was not related to the magnitude of the preceding respiratory stimuli but was positively associated with arousal duration, time to arousal, rate of change in epiglottic pressure and negatively with BMI (R2 > 0.10, P ≤ 0.006). High (> 5) intensity arousals caused greater ventilatory responses than low (≤ 5) intensity arousals (10.9 6.8–14.5 vs. 7.8 4.7–12.9 L/min; P = 0.036) and greater increases in tensor palatini EMG (10 3–17 vs. 6 2–11%max; P = 0.031), with less pronounced increases in genioglossus EMG.
Conclusions:
Average arousal intensity is independent of the preceding respiratory stimulus. This is consistent with arousal intensity being a distinct trait. Respiratory and pharyngeal muscle responses increase with arousal intensity. Thus, patients with higher arousal intensities may be more prone to respiratory control instability. These findings are important for sleep apnea pathogenesis.
Summary Acute sleep deprivation in experimental studies has been shown to induce pain hypersensitivity in females. However, the impact of natural sleep deficiency and fluctuations across the week on ...pain perception remains unclear. A sleep‐monitoring headband and self‐reports were utilized to assess objective and subjective sleep in longer (> 6 hr) and short sleepers (< 6 hr). Pain sensitivity measures including heat, cold, pressure pain thresholds, pain inhibition (conditioned pain modulation) and facilitation (tonic pain summation) were assessed on Mondays and Fridays. Forty‐one healthy young (23.9 ± 0.74 years) women participated. Short sleepers slept on average 2 hr less than longer sleepers (297.9 ± 8.2 min versus 418.5 ± 10.9 min) and experienced impaired pain inhibitory response (mean = −21.14 ± 7.9°C versus mean = 15.39 ± 9.5°C; p = 0.005). However, no effect was observed in pain thresholds and pain summation ( p > 0.05). Furthermore, pain modulatory responses differed between Mondays and Fridays. Chronic sleep deficiency (< 6 hr) compromises pain responses, notably on Mondays. Maintaining a consistent sleep pattern with sufficient sleep (> 6 hr) throughout the week may protect against pain sensitization and the development of chronic pain in females. Further research is needed, especially in patients with chronic pain.
Central sleep apnea (CSA) is characterized by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas exchange. These nighttime ...breathing disturbances can lead to important comorbidity and increased risk of adverse cardiovascular outcomes. There are several manifestations of CSA, including high altitude-induced periodic breathing, idiopathic CSA, narcotic-induced central apnea, obesity hypoventilation syndrome, and Cheyne-Stokes breathing. While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. This brief review summarizes the underlying physiology and modulating components influencing ventilatory control in CSA, describes the etiology of each of the various forms of CSA, and examines the key factors that may exacerbate apnea severity. The clinical implications of improved CSA pathophysiology knowledge and the potential for novel therapeutic treatment approaches are also discussed.
An anatomically narrow/highly collapsible upper airway is the main cause of obstructive sleep apnea (OSA). Upper airway muscle activity contributes to airway patency and, like apnea severity, can be ...sleep stage dependent. Conversely, existing data derived from a small number of participants suggest that upper airway collapsibility, measured by the passive pharyngeal critical closing pressure (Pcrit) technique, is not sleep stage dependent. This study aimed to determine the effect of sleep stage on Pcrit and upper airway muscle activity in a larger cohort than previously tested.
Pcrit and/or muscle data were obtained from 72 adults aged 20-64 y with and without OSA.Pcrit was determined via transient reductions in continuous positive airway pressure (CPAP) during N2, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Genioglossus and tensor palatini muscle activities were measured: (1) awake with and without CPAP, (2) during stable sleep on CPAP, and (3) in response to the CPAP reductions used to quantify Pcrit.
Pcrit was 4.9 ± 1.4 cmH2O higher (more collapsible) during REM versus SWS (P = 0.012), 2.3 ± 0.6 cmH2O higher during REM versus N2 (P < 0.001), and 1.6 ± 0.7 cmH2O higher in N2 versus SWS (P = 0.048). Muscle activity decreased from wakefulness to sleep and from SWS to N2 to REM sleep for genioglossus but not for tensor palatini. Pharyngeal muscle activity increased by ∼50% by breath 5 following CPAP reductions.
Upper airway collapsibility measured via the Pcrit technique and genioglossus muscle activity vary with sleep stage. These findings should be taken into account when performing and interpreting "passive" Pcrit measurements.
Females have increased pain sensitivity and are more vulnerable to chronic pain conditions. Sleep disturbances are comorbid with chronic pain and exacerbate pain symptoms. Different types of sleep ...disturbance affect pain perception distinctly, but it is not clear if these effects are equal in men and women. This systematic review investigated potential differences in how sleep disturbance affects pain in males and females. We searched EBSCO, MEDLINE, Psych INFO, Science Direct, and Web of Science from January 2001 to November 2022 and found 38 studies with 978 participants. Separate random-effects models were used to estimate the pooled effect sizes based on standardized mean differences (SMDs) of experimental sleep disturbance paradigms on various pain outcomes. Sex moderated the effect of sleep disturbance on pain facilitation (SMD = 0.13; 95%CI: 0.004 to 0.022; p=.009) and pain inhibition (SMD = 0.033; 95%CI: 0.011 to 0.054; p=.005), with increased facilitation and decreased inhibition in females, but the opposite effect in males. Further, age moderated the effects of total sleep deprivation (SMD = −0.194; 95%CI -0.328 to -0.060; p=.008) on pain sensitivity and fragmented sleep (SMD = −0.110; 95%CI: 0.148 to -0.072; p<.001) on pain threshold. While the moderating effect of sex and age on the sleep-pain relationship was small, these factors need to be considered in future sleep-pain research.
There is not a clinically available technique for measuring the physiological traits causing obstructive sleep apnea (OSA). Therefore, it is often difficult to determine why an individual has OSA or ...to what extent the various traits contribute to the development of OSA. In this study, we present a noninvasive method for measuring four important physiological traits causing OSA: 1) pharyngeal anatomy/collapsibility, 2) ventilatory control system gain (loop gain), 3) the ability of the upper airway to dilate/stiffen in response to an increase in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which continuous positive airway pressure (CPAP) is dropped from an optimum to various suboptimum pressures for 3- to 5-min intervals during sleep. Each individual's set of traits is entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual. Results from 14 subjects (10 with OSA) are described. Repeatability measurements from separate nights are also presented for four subjects. The measurements and model illustrate the multifactorial nature of OSA pathogenesis and how, in some individuals, small adjustments of one or another trait (which might be achievable with non-CPAP agents) could potentially treat OSA. This technique could conceivably be used clinically to define a patient's physiology and guide therapy based on the traits.
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