Nocturnal bilevel positive airway pressure for the treatment of asthma.

Nocturnal worsening of asthma may be due to reduced lung volumes and fewer sigh breaths, which have been shown to increase airway resistance and bronchoreactivity. We hypothesized that mimicking deep inspiration using nocturnal mechanical support would improve symptoms in patients with asthma. Subjects with asthma underwent usual care and bilevel positive airway pressure (PAP) therapy for 4 weeks, separated by 4 weeks, and methacholine challenge (PC20) and subjective assessments. 13 patients with asthma alone and 8 with asthma + OSA completed the protocol. Change in bronchoreactivity (ratio of Post/Pre PC20) was not significantly different during usual care and bilevel PAP [0.86 (IQR 0.19, 1.82) vs 0.94 (IQR 0.56, 2.5), p = 0.88], nor was the change in Asthma Control Test different: 0.1 ±â€¯2.2 vs. -0.2 ±â€¯2.9, p = 0.79, respectively. Bilevel PAP therapy for four weeks did not improve subjective or objective measures of asthma severity in patients with asthma or those with asthma and OSA, although there was heterogeneity in response.

A pilot study investigating the effects of continuous positive airway pressure treatment and weight-loss surgery on autonomic activity in obese obstructive sleep apnea patients.

BACKGROUND: We have previously demonstrated that severity of obstructive sleep apnea (OSA) as measured by the apnea-hypopnea index (AHI) is a significant independent predictor of readily-computed time-domain metrics of short-term heart rate variability (HRV). METHODS: We aimed to assess time-domain HRV measured over 5-min while awake in a trial of obese subjects undergoing one of two OSA therapies: weight-loss surgery (n=12, 2 males, median and interquartile range (IQR) for BMI 43.7 [42.0, 51.4] kg/m2, and AHI 18.1 [16.3, 67.5] events/h) or continuous positive airway pressure (CPAP) (n=15, 11 males, median BMI 33.8 [31.3, 37.9] kg/m2, and AHI 36.5 [24.7, 77.3] events/h). Polysomnography was followed by electrocardiography during wakefulness; measurements were repeated at 6 and 12-18 months post-intervention. RESULTS: Despite similar measurements at baseline, subjects who underwent surgery exhibited greater improvement in short-term HRV than those who underwent CPAP (p=0.04). CONCLUSIONS: Our data suggest a possible divergence in autonomic function between the effects of weight loss resulting from bariatric surgery, and the amelioration of obstructive respiratory events resulting from CPAP treatment. Randomized studies are necessary before clinical recommendations can be made.

Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The magnitude of the post-apnea/hypopnea ventilatory overshoot following arousal may perpetuate subsequent respiratory events in obstructive sleep apnea (OSA) patients, potentially contributing to the disorder's severity. As acetazolamide can reduce apnea severity in some patients, we examined the effect of acetazolamide on the ventilatory response to spontaneous arousals in CPAP-treated OSA patients. DESIGN: We assessed the ventilatory response to arousal in OSA patients on therapeutic CPAP before and after administration of acetazolamide for 7 days. SETTING: Sleep research laboratory. PARTICIPANTS: 12 (7M/5F) CPAP-treated OSA patients. INTERVENTIONS: Sustained-release acetazolamide 500 mg by mouth twice daily for one week. MEASUREMENTS AND RESULTS: A blinded investigator identified spontaneous arousals (3-15 s) during NREM sleep. Breath-by-breath measurements of minute ventilation, end-tidal CO(2), tidal volume, expiratory/inspiratory-time, and total breath duration were determined (4-s intervals) 32 s prior and 60 s following each arousal. Acetazolamide significantly increased resting ventilation (7.3 ± 0.2 L/min versus 8.2 ± 0.4 L/min; P < 0.05) and attenuated the percent increase in ventilation following arousal by ~2.5 fold (122.0% ± 4.4% versus 108.7% ± 3.5% pre-arousal level; P < 0.05). There was a positive correlation between the mean increase in ventilatory response to arousal and mean AHI (r(2) = 0.44, P = 0.01). However, absolute peak levels of ventilation following arousal remained unchanged between conditions (8.8 ± 0.4 L/min versus 8.9 ± 0.1 L/min). CONCLUSIONS: Acetazolamide substantially attenuates the increase in ventilation following spontaneous arousal from sleep in OSA patients. This study suggests an additional mechanism by which acetazolamide may contribute to the improvement in ventilatory instability and OSA severity. The data also provide support for reinforcing the importance of ventilatory control in OSA pathogenesis.

Sitting and supine esophageal pressures in overweight and obese subjects.

Esophageal pressure (P(Es)) can be used to approximate pleural pressure (P(pl)) 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 P(pl) and P(Es)) may limit acceptance of the measurement, and reproducibility of P(Es) measurements remains unknown. Therefore, we aimed to assess the effect of body posture on P(Es) 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/m(2)) and 11 control lean subjects (BMI < 25 kg/m(2)) 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 P(Es) 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 cm H(2)O, supine 9.3 ± 3.3 vs. 6.9 ± 2.8 cm H(2)O, respectively). The mean differences between repeated measurements were small (-0.3 ± 1.7 cm H(2)O sitting and -0.1 ± 1.5 cm H(2)O supine). P(Es) correlated with a number of anthropometric and spirometric variables. In conclusion, P(Es) 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 P(Es) 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.

Measuring upper and lower airway resistance during sleep with the forced oscillation technique.

The forced oscillation technique (FOT) is a non-invasive technique to monitor airway obstruction in those with asthma. The aim of this study was to design and validate a system to use FOT during sleep, both with and without bi-level positive airway pressure (BPAP), and to separate upper airway resistance from lower. 8 Hz pressure oscillations were supplied, over which the subject breathed, pressure and flow measurements were then used to calculate impedance. A phase-shift induced by the pressure transducer tubing was characterized, and FOT resistance was compared to steady flow resistance both with and without BPAP. A Millar catheter was used to measure pressure at the epiglottis, allowing the separation of upper from lower airway resistance. A phase shift of -0.010 s was calculated for the pressure transducer tubing, and the average error between FOT and steady flow resistance was -0.2 ± 0.2 cmH2O/L/s without BPAP and 0.4 ± 0.2 cmH2O/L/s with BPAP. The system was tested on three subjects, one healthy, one with obstructive sleep apnea, and one with asthma. The FOT was well tolerated and resistance was separated into upper and lower airway components. This setup is suitable for monitoring both upper and lower airway obstruction during sleep in those with and without asthma.

Neurogenic changes in the upper airway of patients with obstructive sleep apnea.

RATIONALE: Controversy persists regarding the presence and importance of hypoglossal nerve dysfunction in obstructive sleep apnea (OSA). OBJECTIVES: We assessed quantitative parameters related to motor unit potential (MUP) morphology derived from electromyographic (EMG) signals in patients with OSA versus control subjects and hypothesized that signs of neurogenic remodeling would be present in the patients with OSA. METHODS: Participants underwent diagnostic sleep studies to obtain apnea-hypopnea indices. Muscle activity was detected with 50-mm concentric needle electrodes. The concentric needle was positioned at more than 10 independent sites per subject, after the local anatomy of the upper airway musculature was examined by ultrasonography. All activity was quantified with subjects awake, during supine eupneic breathing while wearing a nasal mask connected to a pneumotachograph. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which extracted motor unit potential trains (MUPTs) contributed by individual motor units from the composite EMG signals. Quantitative measurements of MUP templates, including duration, peak-to-peak amplitude, area, area-to-amplitude ratio, and size index, were compared between the untreated patients with OSA and healthy control subjects. MEASUREMENTS AND MAIN RESULTS: A total of 1,655 MUPTs from patients with OSA (n = 17; AHI, 55 ± 6/h) and control subjects (n = 14; AHI, 4 ± 1/h) were extracted from the genioglossus muscle EMG signals. MUP peak-to-peak amplitudes in the patients with OSA were not different compared with the control subjects (397.5 ± 9.0 vs. 382.5 ± 10.0 µV). However, the MUPs of the patients with OSA were longer in duration (11.5 ± 0.1 vs. 10.3 ± 0.1 ms; P < 0.001) and had a larger size index (4.09 ± 0.02 vs. 3.92 ± 0.02; P < 0.001) compared with control subjects. CONCLUSIONS: These results confirm and quantify the extent and existence of structural neural remodeling in OSA.

A possible method to predict response to non-pharmacological insomnia therapy.

STUDY OBJECTIVES: To determine if electrocardiographic parameters are predictive of response to non-pharmacological insomnia therapy. DESIGN: Secondary analysis of heart rate parameters from a double blind, randomized, sham-controlled trial at multiple study sites. SETTING: Six sites in the United States were used for the data collection. PARTICIPANTS: One hundred ninety-eight healthy subjects with no sleep disorders. INTERVENTIONS: Subjects were studied on 2 consecutive nights, a baseline night and a therapy night. On the therapy night, subjects were phase advanced 4 h and randomized to receive either sham or vestibular stimulation, an experimental therapy for insomnia. MEASUREMENTS AND RESULTS: ECG data were recorded and analyzed for the 5-min periods preceding and following sleep onset. Analyses were conducted on those who did and did not respond to therapy, as defined by latency from bedtime to persistent sleep (LPS). Responders to therapy were found to have higher low-frequency (LF) power at baseline during wakefulness than non-responders, and responders had higher high-frequency (HF) power during therapy than non-responders on therapy. Furthermore, responders > 35 y had elevated LF power at baseline than non-responders > 35 y (p < 0.05). No differences were seen in the sham group in identical analyses, ruling out a nonspecific effect of sleep onset. CONCLUSIONS: Heart rate variability analyses indicate that differences exist between those who respond to insomnia therapy and those that do not, particularly in an older subset of subjects. Further research into the use of ECG and other physiological parameters to stratify response to therapeutic interventions is warranted.