L Hess

A mechanism for upper airway stability during slow wave sleep.

STUDY OBJECTIVES The severity of obstructive sleep apnea is diminished (sometimes markedly) during slow wave sleep (SWS). We sought to understand why SWS stabilizes the upper airway. Increased single motor unit (SMU) activity of the major upper airway dilating muscle (genioglossus) should improve upper airway stability. Therefore, we hypothesized that genioglossus SMUs would increase their activity during SWS in comparison with Stage N2 sleep. DESIGN The activity of genioglossus SMUs was studied on both sides of the transition between Stage N2 sleep and SWS. SETTING Sleep laboratory. PARTICIPANTS Twenty-nine subjects (age 38 ± 13 yr, 17 males) were studied. INTERVENTION SWS. MEASUREMENT AND RESULTS Subjects slept overnight with fine-wire electrodes in their genioglossus muscles and with full polysomnographic and end tidal carbon dioxide monitors. Fifteen inspiratory phasic (IP) and 11 inspiratory tonic (IT) units were identified from seven subjects and these units exhibited significantly increased inspiratory discharge frequencies during SWS compared with Stage N2 sleep. The peak discharge frequency of the inspiratory units (IP and IT) was 22.7 ± 4.1 Hz in SWS versus 20.3 ± 4.5 Hz in Stage N2 (P < 0.001). The IP units also fired for a longer duration (expressed as a percentage of inspiratory time) during SWS (104.6 ± 39.5 %TI) versus Stage N2 sleep (82.6 ± 39.5 %TI, P < 0.001). The IT units fired faster during expiration in SWS (14.2 ± 1.8 Hz) versus Stage N2 sleep (12.6 ± 3.1 Hz, P = 0.035). There was minimal recruitment or derecruitment of units between SWS and Stage N2 sleep. CONCLUSION Increased genioglossus SMU activity likely makes the airway more stable and resistant to collapse throughout the respiratory cycle during SWS.

Physiological mechanisms of upper airway hypotonia during REM sleep.

STUDY OBJECTIVES Rapid eye movement (REM)-induced hypotonia of the major upper airway dilating muscle (genioglossus) potentially contributes to the worsening of obstructive sleep apnea that occurs during this stage. No prior human single motor unit (SMU) study of genioglossus has examined this possibility to our knowledge. We hypothesized that genioglossus SMUs would reduce their activity during stable breathing in both tonic and phasic REM compared to stage N2 sleep. Further, we hypothesized that hypopneas occurring in REM would be associated with coincident reductions in genioglossus SMU activity. DESIGN The activity of genioglossus SMUs was studied in (1) neighboring epochs of stage N2, and tonic and phasic REM; and (2) during hypopneas occurring in REM. SETTING Sleep laboratory. PARTICIPANTS 29 subjects (38 ± 13 y) (17 male). INTERVENTION Natural sleep, including REM sleep and REM hypopneas. MEASUREMENT AND RESULTS Subjects slept overnight with genioglossus fine-wire intramuscular electrodes and full polysomnography. Forty-two SMUs firing during one or more of stage N2, tonic REM, or phasic REM were sorted. Twenty inspiratory phasic (IP), 17 inspiratory tonic (IT), and five expiratory tonic (ET) SMUs were characterized. Fewer units were active during phasic REM (23) compared to tonic REM (30) and stage N2 (33). During phasic REM sleep, genioglossus IP and IT SMUs discharged at slower rates and for shorter durations than during stage N2. For example, the SMU peak frequency during phasic REM 5.7 ± 6.6 Hz (mean ± standard deviation) was less than both tonic REM 12.3 ± 9.7 Hz and stage N2 16.1 ± 10.0 Hz (P < 0.001). The peak firing frequencies of IP/IT SMUs decreased from the last breath before to the first breath of a REM hypopnea (11.8 ± 10.9 Hz versus 5.7 ± 9.4 Hz; P = 0.001). CONCLUSION Genioglossus single motor unit activity is significantly reduced in REM sleep, particularly phasic REM. Single motor unit activity decreases abruptly at the onset of REM hypopneas.

Sitting and supine esophageal pressures in overweight and obese subjects.

Esophageal pressure (PEs) can be used to approximate pleural pressure (Ppl) and might be clinically useful, particularly in the obese e.g., to guide mechanical ventilator settings in critical illness. However, mediastinal artifact (the difference between true Ppl and PEs) may limit acceptance of the measurement, and reproducibility of PEs measurements remains unknown. Therefore, we aimed to assess the effect of body posture on PEs in a cohort of obese, but healthy subjects, some of whom had multiple measurements, to address the clinical robustness of esophageal manometry. Twenty‐five overweight and obese subjects (BMI > 25 kg/m2) and 11 control lean subjects (BMI < 25 kg/m2) underwent esophageal manometry with pressures measured seated and supine. Twenty overweight and obese subjects had measurements repeated after ∼1 to 2 weeks. Anthropometric data and sitting and supine spirometry were recorded. The average end‐expiratory PEs sitting and supine were greater in the overweight and obese group than the lean group (sitting −0.1 ± 2.1 vs. −3.3 ± 1.2 cmH2O, supine 9.3 ± 3.3 vs. 6.9 ± 2.8 cmH2O, respectively). The mean differences between repeated measurements were small (−0.3 ± 1.7 cmH2O sitting and −0.1 ± 1.5 cmH2O supine). PEs correlated with a number of anthropometric and spirometric variables. In conclusion, PEs are slightly greater in overweight and obese subjects than lean subjects; but changes with position are similar in both groups. These data indicate that mediastinal weight and postural effects on PEs are within a clinically acceptable range, and suggest that esophageal manometry can be used to inform clinical decision making across wide range of body types.

Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea

Rationale: Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patients own phenotypic causes (“traits”) if a clinically applicable approach were available. Objectives: Here we aimed to provide a means to quantify two key contributors to OSA—pharyngeal collapsibility and compensatory muscle responsiveness—that is applicable to diagnostic polysomnography. Methods: Based on physiological definitions, pharyngeal collapsibility determines the ventilation at normal (eupneic) ventilatory drive during sleep, and pharyngeal compensation determines the rise in ventilation accompanying a rising ventilatory drive. Thus, measuring ventilation and ventilatory drive (e.g., during spontaneous cyclic events) should reveal a patients phenotypic traits without specialized intervention. We demonstrate this concept in patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using “gold standard” ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11). Measurements and Main Results: Polysomnography‐derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive airway pressure manipulation (R = 0.67, P < 0.0001; and R = 0.64, P < 0.001; respectively). Polysomnographic estimates effectively stratified patients into high versus low subgroups (accuracy, 69‐86% vs. ventilatory drive measures; P < 0.05). Traits were near‐identical using nasal pressure versus pneumotach (N = 11, R ≥ 0.98, both traits; P < 0.001). Conclusions: Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.

The effect of lung stretch during sleep on airway mechanics in overweight and obese asthma

Both obesity and sleep reduce lung volume and limit deep breaths, possibly contributing to asthma. We hypothesize that increasing lung volume dynamically during sleep would reduce airway resistance in asthma. Asthma (n=10) and control (n=10) subjects were studied during sleep at baseline and with increased lung volume via bi-level positive airway pressure (BPAP). Using forced oscillations, respiratory system resistance (R(rs)) and reactance (X(rs)) were measured during sleep and R(rs) was partitioned to upper and lower airway resistance (R(up), R(low)) using an epiglottic pressure catheter. R(rs) and R(up) increased with sleep (p<0.01) and X(rs) was decreased in REM (p=0.02) as compared to wake. R(rs), R(up), and R(low), were larger (p<0.01) and X(rs) was decreased (p<0.02) in asthma. On BPAP, R(rs) and R(up) were decreased (p<0.001) and X(rs) increased (p<0.01), but R(low) was unchanged. High R(up) was observed in asthma, which reduced with BPAP. We conclude that the upper airway is a major component of R(rs) and larger lung volume changes may be required to alter R(low).

Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy

A possible precision-medicine approach to treating obstructive sleep apnoea (OSA) involves targeting ventilatory instability (elevated loop gain) using supplemental inspired oxygen in selected patients. Here we test whether elevated loop gain and three key endophenotypic traits (collapsibility, compensation and arousability), quantified using clinical polysomnography, can predict the effect of supplemental oxygen on OSA severity. 36 patients (apnoea–hypopnoea index (AHI) >20 events·h−1) completed two overnight polysomnographic studies (single-blinded randomised-controlled crossover) on supplemental oxygen (40% inspired) versus sham (air). OSA traits were quantified from the air-night polysomnography. Responders were defined by a ≥50% reduction in AHI (supine non-rapid eye movement). Secondary outcomes included blood pressure and self-reported sleep quality. Nine of 36 patients (25%) responded to supplemental oxygen (ΔAHI=72±5%). Elevated loop gain was not a significant univariate predictor of responder/non-responder status (primary analysis). In post hoc analysis, a logistic regression model based on elevated loop gain and other traits (better collapsibility and compensation; cross-validated) had 83% accuracy (89% before cross-validation); predicted responders exhibited an improvement in OSA severity (ΔAHI 59±6% versus 12±7% in predicted non-responders, p=0.0001) plus lowered morning blood pressure and “better” self-reported sleep. Patients whose OSA responds to supplemental oxygen can be identified by measuring their endophenotypic traits using diagnostic polysomnography. A subgroup of patients with obstructive sleep apnoea who benefit from stabilising ventilatory control with supplemental oxygen therapy can be recognised by estimating pathophysiological mechanisms from a routine diagnostic sleep study http://ow.ly/yeVp30lewG4