Electrical stimulation as a therapeutic approach in obstructive sleep apnea - a meta-analysis.

PURPOSE: Electrical stimulation of the upper airway dilator muscles is an emerging treatment for obstructive sleep apnea (OSA). Invasive hypoglossal nerve stimulation (HNS) has been accepted as treatment alternative to continuous positive airway pressure (CPAP) for selected patients, while transcutaneous electrical stimulation (TES) of the upper airway is being investigated as non-invasive alternative. METHODS: A meta-analysis (CRD42017074674) on the effects of both HNS and TES on the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS) in OSA was conducted including published evidence up to May 2018. Random-effects models were used. Heterogeneity and between-study variance were assessed by I2 and τ2, respectively. RESULTS: Of 41 identified clinical trials, 20 interventional trials (n = 895) could be pooled in a meta-analysis (15 HNS [n = 808], 5 TES [n = 87]). Middle-aged (mean ± SD 56.9 ± 5.5 years) and overweight (body mass index 29.1 ± 1.5 kg/m2) patients with severe OSA (AHI 37.5 ± 7.0/h) were followed-up for 6.9 ± 4.0 months (HNS) and 0.2 ± 0.4 months (TES), respectively. The AHI improved by - 24.9 h-1 [95%CI - 28.5, - 21.2] in HNS (χ2 79%, I2 82%) and by - 16.5 h-1 [95%CI - 25.1, - 7.8] in TES (χ2 7%, I2 43%; both p < 0.001). The ESS was reduced by - 5.0 (95%CI - 5.9, - 4.1) (p < 0.001). CONCLUSION: Both invasive and transcutaneous electrical stimulation reduce OSA severity by a clinically relevant margin. HNS results in a clinically relevant improvement of symptoms. While HNS represents an invasive treatment for selected patients with moderate to severe OSA, TES should be further investigated as potential non-invasive approach for OSA.

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.

[Efficacies of continuous positive airway pressure on mixed sleep respiratory events in patients with sleep apnea].

OBJECTIVE: To explore the efficacies of continuous positive airway pressure (CPAP) for mixed sleep apnea (MSA) events in patients with sleep apnea. METHODS: A total of 21 patients with sleep apnea whose MSA events >10 events/h on overnight polysomnography (PSG) were studied. They were selected from the Sleep Center, Guangzhou Institute of Respiratory Disease. Ten of them were diagnosed only by conventional polysomnography (PSG group) while the diagnosis of another 11 patients was further confirmed by diaphragm electromyogram (EMG) (EMG group). All of them were treated by CPAP titrated manually on PSG. RESULTS: Manual CPAP titrating pressure in PSG group was (8.1 ± 2.2) cmH2O (1 cmH2O = 0.098 kPa) and it was similar to that in EMG group ((8.9 ± 1.5) cmH2O). Apnea-hypopnea index (AHI) decreased significantly after CPAP in both PSG group (6.9 (3.5, 10.2) vs 62.2 (54.7, 71.4) events/h) and EMG group (1.5 (0.5, 5.5) vs 71.3 (59.5, 79.5) events/h) (both P < 0.01). CPAP could eliminate MSA diagnosed either by conventional PSG (0.1 (0.0, 0.4) vs 29.6 (19.6, 32.4) events/h) or by diaphragm EMG (0.0 (0.0, 0.2) vs 18.1 (9.1, 19.3) events/h) (both P < 0.01). CONCLUSION: CPAP can effectively treat MSA events in patients with sleep apnea.

Exercise-induced bronchoconstriction assessed by a ratio of surface diaphragm EMG to tidal volume.

Exercise-induced bronchoconstriction (EIB) is usually assessed by changes in forced expiratory volume in 1 s (FEV1 ) which is effort dependent. The purpose of this study was to determine whether the diaphragm electromyogram (EMGdi ) recorded from chest wall surface electrodes could be used to reflect changes in airway resistance during an exercise challenge test and to distinguish patients with EIB from those without EIB. Ninety participants with or without asthma history were included in the study. FEV1 was recorded before and 5, 10, 15, and 20 min after exercise. EIB was defined as an FEV1 decline greater than 10% after exercise. A ratio of root mean square of EMGdi to tidal volume (EMGdi /VT ) was used to assess changes in airway resistance. Based on changes in FEV1 , 25 of 90 participants exhibited EIB; the remainder were defined as non-EIB participants. EMGdi /VT in EIB increased by 124% (19%-478%) which was significantly higher than that of 21% (-39% to 134%) in non-EIB participants (p < 0.001). At the optimal cutoff point (54% in EMGdi /VT ), the area under the ROC curve (AUC) for detection of a positive test was 0.92 (p < 0.001) with sensitivity 92% and specificity 88%. EMGdi /VT can be used to assess changes in airway resistance after exercise and could be used to distinguish participants with EIB from those without EIB.

Identifying bronchoconstriction from the ratio of diaphragm EMG to tidal volume.

BACKGROUND: A fall of ≥ 20 % in forced expiratory volume in the first second (FEV1) with a cumulative dose of histamine ≤ 7.8 µmol is considered to indicate bronchial hyperactivity, but no method exists for patients who cannot perform spirometry properly. Here we hypothesized that increases in respiratory central output measured by chest wall electromyography of the diaphragm (EMGdi-c) expressed as a function of tidal volume (EMGdi-c/VT) would have discriminative power to detect a 'positive' challenge test. METHODS: In a physiological study EMGdi was recorded from esophageal electrode (EMGdi-e) in 16 asthma patients and 16 healthy subjects during a histamine challenge test. In a second study, EMGdi from chest wall surface electrodes (EMGdi-c) was measured during a histamine challenge in 44 asthma patients and 51 healthy subjects. VT was recorded from a digital flowmeter during both studies. RESULTS: With histamine challenge test the change in EMGdi-e/VT in patients with asthma was significantly higher than that in healthy subjects (104.2 % ± 48.6 % vs 0.03 % ± 17.1 %, p < 0.001). Similarly there was a significant difference in the change of EMGdi-c/VT between patients with asthma and healthy subjects (90.5 % ± 75.5 % vs 2.4 % ± 21.7 %, p < 0.001). At the optimal cut-off point (29 % increase in EMGdi-c/VT), the area under the ROC curve (AUC) for detection of a positive test was 0.91 (p < 0.001) with sensitivity 86 % and specificity 92 %. CONCLUSIONS: We conclude that EMGdi-c/VT may be used as an alternative for the assessment of bronchial hypersensitivity and airway reversibility to differentiate patients with asthma from healthy subjects.

Apnoea-hypopnoea-index comparing the 2007 and 2012 American Academy of Sleep Medicine criteria in chronic obstructive pulmonary disease/obstructive sleep apnoea overlap syndrome.

BACKGROUND: In 2007 and 2012, the American Academy of Sleep Medicine (AASM) updated their scoring criteria for nocturnal respiratory events. We hypothesised that this could have led to changes in the apnoea-hypopnoea index (AHI) of patients with chronic obstructive pulmonary disease (COPD)/obstructive sleep apnoea (OSA) overlap syndrome. METHODS: In a retrospective study, polysomnographic (PSG) recordings of 34 patients with COPD/OSA overlap syndrome were independently analysed using the AASM criteria from 2007 (AASM2007) and 2012 (AASM2012). The primary outcome was the difference in AHI, the secondary outcomes were frequency of hypopnoeas, diagnosis of overlap syndrome and differences between the AASM 2007 recommended (AASM2007Rec) and altered (AASM2007Alt) classifications. Data are presented as mean (standard deviation) if normally distributed, and as median (interquartile range) if non-normally distributed. RESULTS: The PSGs of 34 elderly [aged 67 (7.0) years] and predominantly male (m:f, 31:3) patients with COPD [FEV1%pred 48.4% (19.6%)] were analysed. The AHI using AASM2007Rec criteria was 5.9 (2.0, 15.1) events/hour vs. 20.4 (11.5, 28.0) events/hour using the 2012 criteria (P<0.001); with the AASM2007Alt criteria, the AHI was 15.0 (9.3, 26.3) events/hour (P<0.001). Using the 2012 classification, the number of scored hypopnoeas increased by +48% compared to the AASM2007Rec criteria (P<0.001), 92% of these events were associated with arousal. Although statistically non-significant, using the AASM2007Alt classification, 12% of our cohort would not have been diagnosed with COPD/OSA overlap syndrome (P=0.114), this was also the case for 47% of the cohort when the AASM2007Rec classification was used (P<0.01). CONCLUSIONS: The use of the AASM2012 scoring rules results in a significantly higher AHI compared to the AASM2007 criteria in patients with COPD/OSA overlap syndrome, mostly due to an increased number of arousal-associated hypopnoeas. These observations are important for the definition of the COPD/OSA overlap syndrome.

Ultrasound assessment of upper airway dilator muscle contraction during transcutaneous electrical stimulation in patients with obstructive sleep apnoea.

BACKGROUND: Electrical current can be used to stimulate upper airway dilator muscles to treat obstructive sleep apnoea (OSA). Ultrasound devices are widely available and may be used to detect contraction of the upper airway dilator muscles assessing the functionality of electrical stimulation (ES) used for this treatment. METHODS: In a physiological sub-study of a randomised controlled trial, patients with OSA underwent ultrasound examination to assess contraction of the upper airway dilator muscles in response to transcutaneous ES. Ultrasound scans were scored according to the picture quality (poor = '0', acceptable = '1' and good = '2'). Tongue base thickness was assessed in mid-sagittal and coronal planes with (D2, A2) and without ES (D1, A1), while awake and seated. The primary outcome was to determine the increase in tongue thickness during ES in both views (D2 - D1 = ΔD), as well as any increase in the cross-sectional area (CSA) in the coronal view (A2 - A1 = ΔA). Data were presented as mean and standard deviation (SD). RESULTS: Fourteen patients [eight male, age 57.5 (9.8) years, body mass index (BMI) 29.5 (2.8) kg/m2] with OSA [Apnea-Hypopnea Index (AHI) 19.5 (10.6) × hour-1] were studied. Quality of the ultrasound scans was acceptable or good with 1.5 (0.5) points. In the mid-sagittal plane, ΔD was +0.17 (0.07) cm in midline and +0.21 (0.09) cm in the widest diameter, a percentual change of 12.2% (4%) and 12.8% (5.2%) (P<0.001, respectively). In the coronal plane, ΔD was +0.17 (0.04) cm, an increase of 12.3% (4.6%) (P<0.001, respectively), ΔA in the CSA increased by +18.9% (3.0%) with stimulation (P<0.001). There was a negative correlation between age and ΔA (r= -0.6, P=0.03), but no significant associations were found with gender, BMI, neck circumference, Epworth Sleepiness Scale (ESS), AHI, skin and subcutaneous tissue in the submental area. CONCLUSIONS: Ultrasound can visualise upper airway dilator muscle contraction during transcutaneous ES in awake patients with OSA. Contraction is best detected in the CSA of the tongue base in the coronal plane.

Absence of dynamic hyperinflation during exhaustive exercise in severe COPD reflects submaximal IC maneuvers rather than a nonhyperinflator phenotype.

Approximately 20% of chronic obstructive pulmonary disease (COPD) patients have been considered to have a "nonhyperinflator phenotype." However, this judgment depends on patients making a fully maximal inspiratory capacity (IC) maneuver at rest, since the IC during exercise is compared with this baseline measurement. We hypothesized that IC maneuvers at rest are sometimes submaximal and tested this hypothesis by measuring IC and associated neural respiratory drive at rest and during inhalation of CO2 and exercise in patients with COPD. Twenty-six COPD patients [age 66 ± 6 yr, mean forced expiratory volume in 1 s (FEV1) 40 ± 11% predicted] and 39 healthy subjects (age 39 ± 14 yr, FEV1 98 ± 12% predicted) were studied. IC and the diaphragm electromyogram (EMGdi) associated with it (EMGdi-IC) and forced inspiratory vital capacity (FIVC) and its corresponding EMGdi (EMGdi-FIVC) were measured during inhalation of 8% CO2 (8% CO2-92% O2) and room air. Incremental exhaustive cycle ergometer exercise was also performed in both patients with COPD and healthy subjects. IC, EMGdi-IC, FIVC, and EMGdi-FIVC during breathing 8% CO2 were significantly greater than those during breathing room air in both patients with COPD and healthy subjects (all P < 0.001). EMGdi-IC in patients with COPD constantly increased during exercise from 145 ± 40 µV at rest to 185 ± 52 µV at the end of exercise but change in IC was variable. Neural respiratory drive and its relevant IC increased during hypercapnia. Exercise-related hypercapnia in patients with COPD raises neural respiratory drives, which compensate for IC reduction, leading to underestimation of dynamic hyperinflation measured by IC at rest breathing room air.NEW & NOTEWORTHY Inspiratory capacity measured during hypercapnia is higher than that during eucapnia. Thus total lung capacity is not always be achieved by a standard inspiratory capacity maneuver, leading to risk of underestimation of dynamic hyperinflation in patients with severe chronic obstructive pulmonary disease after exhaustive exercise.

Domiciliary use of transcutaneous electrical stimulation for patients with obstructive sleep apnoea: a conceptual framework for the TESLA home programme.

Obstructive sleep apnoea (OSA) is a global health problem of increasing prevalence. Effective treatments are available with continuous positive airway pressure (CPAP) therapy and mandibular advancement devices (MAD). However, there is limited long-term adherence to therapy, as CPAP and MAD require permanent usage to avoid recurrence of the symptoms and adverse ill health. Alternative treatments would aid in the treatment cascade to manage OSA effectively whenever standard therapy has been trialled and failed. Hypoglossal nerve stimulation (HNS), an invasive approach to stimulate the pharyngeal dilator muscles of the upper airway during sleep, has been approved for the treatment of OSA by several healthcare systems in recent years. In parallel to the development of HNS, a non-invasive approach has been developed to deliver electrical stimulation. Transcutaneous electrical stimulation in obstructive sleep apnoea (TESLA) uses non-invasive electrical stimulation to increase neuromuscular tone of the upper airway dilator muscles of patients with OSA during sleep. Data from previous feasibility studies and randomised controlled trials have helped to identify a subgroup of patients who are "responders" to this treatment. However, further investigations are required to assess usability, functionality and task accomplishment of this novel treatment. Consideration of these factors in the study design of future clinical trials will strengthen research methodology and protocols, improve patient related outcome measures and assessments, to optimise this emerging therapeutical option. In this review, we will introduce a conceptual framework for the TESLA home programme highlighting qualitative aspects and outcomes.

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 µg 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 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.