Bai-Ting He

Neural Respiratory Drive and Arousal in Patients with Obstructive Sleep Apnea Hypopnea

STUDY OBJECTIVES It has been hypothesized that arousals after apnea and hypopnea events in patients with obstructive sleep apnea are triggered when neural respiratory drive exceeds a certain level, but this hypothesis is based on esophageal pressure data, which are dependent on flow and lung volume. We aimed to determine whether a fixed threshold of respiratory drive is responsible for arousal at the termination of apnea and hypopnea using a flow independent technique (esophageal diaphragm electromyography, EMGdi) in patients with obstructive sleep apnea. SETTING Sleep center of state Key Laboratory of Respiratory Disease. PATIENTS Seventeen subjects (two women, mean age 53 ± 11 years) with obstructive sleep apnea/hypopnea syndrome were studied. METHODS We recorded esophageal pressure and EMGdi simultaneously during overnight full polysomnography in all the subjects. MEASUREMENTS AND RESULTS A total of 709 hypopnea events and 986 apnea events were analyzed. There was wide variation in both esophageal pressure and EMGdi at the end of both apnea and hypopnea events within a subject and stage 2 sleep. The EMGdi at the end of events that terminated with arousal was similar to those which terminated without arousal for both hypopnea events (27.6% ± 13.9%max vs 29.9% ± 15.9%max, P = ns) and apnea events (22.9% ± 11.5%max vs 22.1% ± 12.6%max, P = ns). The Pes at the end of respiratory events terminated with arousal was also similar to those terminated without arousal. There was a small but significant difference in EMGdi at the end of respiratory events between hypopnea and apnea (25.3% ± 14.2%max vs 21.7% ± 13.2%max, P < 0.05]. CONCLUSIONS Our data do not support the concept that there is threshold of neural respiratory drive that is responsible for arousal in patients with obstructive sleep apnea.

Coexistence of OSA may compensate for sleep related reduction in neural respiratory drive in patients with COPD

Background The mechanisms underlying sleep-related hypoventilation in patients with coexisting COPD and obstructive sleep apnoea (OSA), an overlap syndrome, are incompletely understood. We compared neural respiratory drive expressed as diaphragm electromyogram (EMGdi) and ventilation during stage 2 sleep in patients with COPD alone and patients with overlap syndrome. Methods EMGdi and airflow were recorded during full polysomnography in 14 healthy subjects, 14 patients with OSA and 39 consecutive patients with COPD. The ratio of tidal volume to EMGdi was measured to indirectly assess upper airway resistance. Results Thirty-five patients with COPD, 12 healthy subjects and 14 patients with OSA completed the study. Of 35 patients with COPD, 19 had COPD alone (FEV1 38.5%±16.3%) whereas 16 had an overlap syndrome (FEV1 47.5±16.2%, AHI 20.5±14.1 events/hour). Ventilation (VE) was lower during stage 2 sleep than wakefulness in both patients with COPD alone (8.6±2.0 to 6.5±1.5 L/min, p<0.001) and those with overlap syndrome (8.3±2.0 to 6.1±1.8 L/min). Neural respiratory drive from wakefulness to sleep decreased significantly for patients with COPD alone (29.5±13.3% to 23.0±8.9% of maximal, p<0.01) but it changed little in those with overlap syndrome. The ratio of tidal volume to EMGdi was unchanged from wakefulness to sleep in patients with COPD alone and healthy subjects but was significantly reduced in patients with OSA or overlap syndrome (p<0.05). Conclusions Stage 2 sleep-related hypoventilation in COPD alone is due to reduction of neural respiratory drive, but in overlap syndrome it is due to increased upper airway resistance.

Tai Chi and Pulmonary Rehabilitation Compared for Treatment-Naive Patients With COPD: A Randomized Controlled Trial

Background In COPD, functional status is improved by pulmonary rehabilitation (PR) but requires specific facilities. Tai Chi, which combines psychological treatment and physical exercise and requires no special equipment, is widely practiced in China and is becoming increasingly popular in the rest of the world. We hypothesized that Tai Chi is equivalent (ie, difference less than ±4 St. George’s Respiratory Questionnaire [SGRQ] points) to PR. Methods A total of 120 patients (mean FEV1, 1.11 ± 0.42 L; 43.6% predicted) bronchodilator‐naive patients were studied. Two weeks after starting indacaterol 150 &mgr;g once daily, they randomly received either standard PR thrice weekly or group Tai Chi five times weekly, for 12 weeks. The primary end point was change in SGRQ prior to and following the exercise intervention; measurements were also made 12 weeks after the end of the intervention. Results The between‐group difference for SGRQ at the end of the exercise interventions was –0.48 (95% CI PR vs Tai Chi, –3.6 to 2.6; P = .76), excluding a difference exceeding the minimal clinically important difference. Twelve weeks later, the between‐group difference for SGRQ was 4.5 (95% CI, 1.9 to 7.0; P < .001), favoring Tai Chi. Similar trends were observed for 6‐min walk distance; no change in FEV1 was observed. Conclusions Tai Chi is equivalent to PR for improving SGRQ in COPD. Twelve weeks after exercise cessation, a clinically significant difference in SGRQ emerged favoring Tai Chi. Tai Chi is an appropriate substitute for PR. Trial Registry ClinicalTrials.gov; No.: NCT02665130; URL: www.clinicaltrials.gov.

Physiological responses to Tai Chi in stable patients with COPD.

We compared the physiological work, judged by oxygen uptake, esophageal pressure swing and diaphragm electromyography, elicited by Tai Chi compared with that elicited by constant rate treadmill walking at 60% of maximal load in eleven patients with COPD (Mean FEV1 61% predicted, FEV1/FVC 47%). Dynamic hyperinflation was assessed by inspiratory capacity and twitch quadriceps tension (TwQ) elicited by supramaximal magnetic stimulation of the femoral nerve was also measured before and after both exercises. The EMGdi and esophageal pressure at the end of exercise were similar for both treadmill exercise and Tai Chi (0.109±0.047 mV vs 0.118±0.061 mV for EMGdi and 22.3±7.1 cmH2O vs 21.9±8.1 cmH2O for esophageal pressure). Moreover the mean values of oxygen uptake during Tai Chi and treadmill exercise did not differ significantly: 11.3 ml/kg/min (51.1% of maximal oxygen uptake derived from incremental exercise) and 13.4 ml/kg/min (52.5%) respectively, p>0.05. Respiratory rate during Tai Chi was significantly lower than that during treadmill exercise. Both Tai Chi and treadmill exercise elicited a fall in IC at end exercise, indicating dynamic hyperinflation, but this was statistically significant only after treadmill exercise. TwQ decreased significantly after Tai Chi but not after treadmill. We conclude that Tai Chi constitutes a physiologically similar stimulus to treadmill exercise and may therefore be an acceptable modality for pulmonary rehabilitation which may be culturally more acceptable in some parts of the world.

Neural respiratory drive and ventilation in patients with chronic obstructive pulmonary disease during sleep.

To the Editor: Patients with chronic obstructive pulmonary disease (COPD) experience sleep-related hypoventilation (1, 2). However, there is controversy as to whether this occurs due to an increase in upper airway resistance or a reduction in neural respiratory drive. Elevated neural respiratory drive in wakefulness is well documented in COPD (3). O’Donoghue and coworkers (4) reported in patients with COPD that a sleep-related hypoventilation was due to increased upper airway resistance, and Ballard and coworkers (5) reported an increase in upper airway resistance moving from wakefulness to sleep, although upper airway resistance was not consistently greater during sleep (see Figure 3 of their article [5]). Moreover, in healthy young adults, a poor correlation was observed between changes in ventilation and upper airway resistance (6). Morrell and coworkers (7) addressed the question directly in tracheotomized subjects, confirming hypoventilation during sleep, thus excluding an obligate contribution from upper airway resistance. To further address the question, we performed diaphragm electromyography (EMGdi) using a multipair esophageal electrode as an index of neural respiratory drive (8–11). Some of the data have been previously reported in abstract form (12). A total of 17 stable patients with moderate to very severe COPD and 14 age-matched normal subjects participated. All subjects were free from obstructive sleep apnea (OSA; apnea–hypopnea index < 5.0 events/h) and snoring confirmed by prior overnight polysomnography, and were free from clinically significant coexisting diseases, including neuromuscular disorders. The study was approved by the Ethics Committee of the Chinese State Key Laboratory of Respiratory Disease, and all patients gave their informed consent to participate. A multipair esophageal electrode catheter (Yinghui Medical Technology Co., Ltd, Guangzhou, China) was used as previously described (8) to record the EMGdi during overnight polysomnography (9–11). Airflow was recorded with a pneumotachograph connected to a full facemask. Maximal EMGdi was recorded from maximal voluntary inspiratory maneuvers. Polysomnography was manually analyzed based on standard criteria (13). The root mean square (RMS) of the EMGdi (RMSEMGdi) was calculated by computer with a time constant of 100 milliseconds. Efficacy of neural respiratory drive was defined as the ratio of minute ventilation to peak RMSEMGdi of each breath. Data were selected during stable breathing without respiratory events. Data collected for 10 minutes before sleep and for at least 15 minutes during non–rapid eye movement (NREM) and REM in the supine position were selected for analysis. Two-way ANOVA was used to test differences between wakefulness, NREM, and REM sleep; data are presented as means (±SD), and statistical significance was determined as a P value of less than 0.05. Some subjects could not tolerate the full facemask, and satisfactory measurements were therefore obtained in 10 male patients with COPD (age, 59.3 ± 11.5 yr; body mass index, 20.8 ± 3.1 kg/m2; FEV1, 34.2 ± 15.8% predicted; FEV1/FVC, 37.8 ± 11.6%; oxygen saturation <90%, 2.0 ± 4.0% of total sleep time) and 10 control subjects (nine males and one female, age, 58.1 ± 9.0 yr; body mass index, 22.8 ± 2.8 kg/m2; FEV1 97.8 ± 9.5% predicted). The maximal RMSEMGdi measured from patients with COPD was similar to control subjects (180.7 ± 92.0 μV vs. 161.7 ± 53.6 μV). RMSEMGdi, as a percent maximal, in patients with COPD was significantly higher than that in normal subjects during wakefulness, NREM, and REM (Table 1). Compared with wakefulness, the RMSEMGdi decreased by 31 (±12)% in NREM, and further decreased by 49 (±12)% in REM sleep in patients with COPD. Similarly, ventilation decreased by 30 (±14)% in NREM and 44 (±11)% in REM. As shown in Table 1, the reduction in ventilation was principally mediated by tidal volume. The reductions in the RMSEMGdi and ventilation were of smaller magnitude in normal subjects. The efficacy of neural respiratory drive in normal subjects was significantly higher than that in patients with COPD during both wakefulness and sleep. However, sleep did not change the efficacy of neural respiratory drive in either patients with COPD or normal subjects (Table 1 and Figure 1). Table 1. The Root Mean Square of the Diaphragm Electromyography and Ventilation during Wakefulness and Sleep and Their Change Compared with Wakefulness Figure 1. Polysomnography including five-channel diaphragm electromyography (EMGdi; 1–5) from a multipair esophageal electrode, airflow from pneumotachograph, end-tidal CO2, electroencephalogram (EEG; C3A2 and C4A1), and left and right electrooculograms ... This is the first study to simultaneously accurately record ventilation with a pneumotachograph connected to a full facemask and EMGdi, during wakefulness, NREM, and REM sleep, in patients with COPD without coexisting OSA. The efficacy of neural respiratory drive reflects upper airway resistance if lung mechanics and lower airway resistance remain the same. Because this is considered to be the case (4, 5), we speculate that the unchanged efficacy of neural respiratory drive between wakefulness and sleep argues against a substantial increase in upper airway resistance during sleep in either nonobese patients with COPD or normal subjects. This result is consistent with the work of Meurice and coworkers (14), who reported that upper airway resistance changed little in some patients with COPD during sleep. Although O’Donoghue and colleagues (4) concluded that sleep-related hypoventilation in patients with COPD was because of a threefold increase in upper airway resistance, the subjects they studied may have had mild OSA, because an apnea–hypopnea index up to 10 events/h was permitted. Our results are consistent with the results reported by Morrell and coworkers (7), who showed that the development of sleep-related hypoventilation is independent of upper airway resistance, because the reduction of ventilation from wakefulness to NREM sleep in subjects who were breathing through the upper airway was similar to that in laryngectomized subjects who were breathing through a tracheal stoma. Our conclusions are also consistent with other data supporting the case that reduction of neural respiratory drive is important in sleep-related hypoventilation. For example, when continuous positive airway pressure is applied in patients with COPD to eliminate upper airway resistance (1), or to normalize upper airway resistance to waking levels in normal subjects (15), sleep-related hypoventilation is still evident. Naturally, our study has some limitations. We had a relatively small sample size, and all patients were from one ethnic group and were not in respiratory failure, which could modify pharyngeal behavior (15). Our data are only representative of those who could sleep while instrumented. Thus, our findings should not be extended uncritically to all patients with COPD. However, in contrast to the previous hypothesis that hypoventilation is principally due to upper airway resistance, our study suggests that sleep-associated hypoventilation in patients with COPD is mainly related to reduction of neural respiratory drive. This observation suggests that noninvasive positive-pressure ventilation is a more logical approach than continuous positive airway pressure to the treatment of nocturnal hypoventilation in COPD.