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STUDY OBJECTIVES: Uncertainty exists over whether continuous positive airway pressure (CPAP) treatment improves moderate to vigorous physical activity levels in those with obstructive sleep apnea. We aimed to determine effects of CPAP on moderate to vigorous physical activity among participants with co-occurring cardiovascular disease and obstructive sleep apnea. METHODS: The Sleep Apnea cardioVascular Endpoints (SAVE) trial recruited participants with confirmed cardiovascular disease history and obstructive sleep apnea, 45–75 years old. The 2,687 participants (1,346 randomized to CPAP plus usual care and 1,341 to usual care alone) were followed up for a mean of 3.7 years. Self-reported physical activity was recorded at baseline, 6, 24, and 48 months using the Godin-Shepard Leisure Time Exercise Questionnaire (LTEQ). We also determined effects on any limitation of physical activity reported on the physical functioning subscale of the 36-item short form questionnaire (SF-36) and proportions of participants reaching guideline recommended physical activity levels. RESULTS: Among 2,601 participants with available data, those in the CPAP group reported significantly more physical activity compared to the usual care group, with approximately 20% higher reported moderate activities on the LTEQ during follow-up (adjusted mean 95% confidence interval) scores: 8.7, 7.5–9.9 vs 7.3, 6.1–8.5; P = .003). Those in the CPAP group also reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score 1.66, 95% confidence interval 0.87–2.45; P < 0.001), and more reported sufficient levels of physical activity to meet recommendations. CONCLUSIONS: CPAP has positive effects on improving physical activity levels, consistent with long-term health benefits. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease (SAVE); URL: https://clinicaltrials.gov/ct2/show/NCT00738179; Identifier: NCT00738179; and Registry: Australian New Zealand Clinical Trials Registry; Name: Sleep Apnea cardioVascular Endpoints study—An investigation of continuous positive airway pressure for the treatment of obstructive sleep apnea to prevent cardiovascular disease; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83062&isReview=true; Identifier: ACTRN12608000409370. CITATION: Stevens D, Loffler KA, Buman MP, et al. CPAP increases physical activity in obstructive sleep apnea with cardiovascular disease. J Clin Sleep Med. 2021;17(2):141–148.

Study objectives Sleep is associated with a reduction in ventilation and an increase in upper airway resistance (UAR) in patients with obstructive sleep apnea (OSA). However, there is no consensus on the standard for assessment of UAR and therefore it is important to develop a method to reliably assess UAR in patients with OSA. The purpose of the present study is to determine whether the ratio of neural respiratory drive (NRD) to flow can be used to assess changes in UAR in OSA during sleep. Methods A total of 24 patients (21 men) with OSA and 10 normal subjects (6 males) were studied. The UAR was assessed by the ratio of NRD to flow, which measured by esophageal pressure (Poes), diaphragm electromyography (EMGdi) and superficial diaphragm electromyography (SEMGdi) in various stages including wakefulness, N2 sleep, N2 sleep with snoring, hypopneas, the in the “preapnea” states in OSA versus wakefulness, sleeponset, N2 sleep, N3 sleep in normal subjects. All subjects underwent overnight full polysomnography using standard techniques. Results Our study indicate that UAR was progressively higher from wakefulness to N2 sleep, N2 sleep with snoring, hypopneas, and the in the “preapnea” states in patients with OSA and had obvious difference in statistical significance (p Conclusions It is feasible to use the ratio of neural respiratory drive to flow to assess UAR in patients with OSA during sleep.

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.

Background and aim Controversy exists regarding cardiovascular risk in relation to sleep duration. We determined sleep duration and major recurrent cardiovascular event associations in patients with obstructive sleep apnoea and established cardiovascular disease. Methods Secondary analyses of the international, multicenter, Sleep Apnea Cardiovascular Endpoints trial. Sleep duration was estimated from overnight home oximetry (ApneaLink monitor) used for obstructive sleep apnoea diagnosis. Cox proportional hazards models were used to determine associations of categorized sleep duration (8 h) and major cardiovascular outcomes: primary composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and any hospitalization for unstable angina, heart failure, or transient ischemic attack; secondary composite of cardiac and cerebral (stroke/transient ischemic attack) events. Results Oximetry-derived sleep duration estimates were available in 2687 participants (mean 61.2 years, 80.9% males) who experienced a total of 436 cardiovascular events over a mean follow-up of 3.7 years. Compared to the reference category, sleep duration was not associated with risk of the primary composite cardiovascular outcome (adjusted hazard ratio (HR) 1.00, 95% confidence interval 0.76–1.33, and HR 1.22, 95% confidence interval 0.98–1.52, for sleep duration 8 h, respectively). However, long sleep was associated with increased cerebral events (HR 1.67, 95% confidence interval 1.17–2.39; P = 0.005) and stroke alone (HR 1.79, 95% confidence interval 1.22–2.63; P = 0.003). Conclusions Long sleep duration is associated with an increased risk of stroke but not cardiac events in obstructive sleep apnoea patients with existing cardiovascular disease. Clinical trial registration The trial is registered at ClinicalTrials.gov (NCT00738179).

Background Inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are at increased risk for venous thromboembolism (VTE); however, the prophylaxis for VTE is largely underused in China. Identifying high-risk patients requiring thromboprophylaxis is critical to reduce the mortality and morbidity associated with VTE. This study aimed to evaluate and compare the validities of the Padua Prediction Score and Caprini risk assessment model (RAM) in predicting the risk of VTE in inpatients with AECOPD in China. Methods The inpatients with AECOPD were prospectively enrolled from seven medical centers of China between September 2017 and January 2020. Caprini and Padua scores were calculated on admission, and the incidence of 3-month VTE was investigated. Results Among the 3,277 eligible patients with AECOPD, 128 patients (3.9%) developed VTE within 3 months after admission. The distribution of the study population by the Caprini risk level was as follows: high, 53.6%; moderate, 43.0%; and low, 3.5%. The incidence of VTE increased by risk level as high, 6.1%; moderate, 1.5%; and low, 0%. According to the Padua RAM, only 10.9% of the study population was classified as high risk and 89.1% as low risk, with the corresponding incidence of VTE of 7.9 and 3.4%, respectively. The Caprini RAM had higher area under curve compared with the Padua RAM (0.713 ± 0.021 vs. 0.644 ± 0.023, p = 0.029). Conclusion The Caprini RAM was superior to the Padua RAM in predicting the risk of VTE in inpatients with AECOPD and might better guide thromboprophylaxis in these patients.

Background: Prone position ventilation (PPV) is an important strategy for patients with severe acute respiratory distress syndrome (ARDS). This prospective study investigated the use of electromyography of the diaphragm (EMGdi) for monitoring respiratory drive in patients with moderate to severe ARDS during long-term PPV Methods: An integrated nostril-gastric feeding tube containing an esophageal electrode and balloon was placed in 14 patients with severe ARDS prior to PPV. EMGdi and trans-pulmonary pressure (∆PL) data were collected before PPV (baseline), every 2 h during PPV, and 2 h after the restoration of supine position ventilation (post-2 h SPV). Results: In ARDS patients, the static compliance of the chest wall was significantly decreased after PPV. EMGdi levels were slightly lower in the early, middle, and late stages of PPV compared with baseline. Patients who received neuromuscular blocker experienced a greater drop in EMGdi from baseline than those who did not. Conclusions: For ARDS patients, EMGdi was slightly decreased after prolonged PPV. This is contrary to the change in diaphragm electromyography during normal body position changes. Monitoring EMGdi regularly during PPV in ARDS patients is feasible and can be used as a reference for lung protective ventilation strategies.

Background Whether continuous positive airway pressure (CPAP) treatment can improve depression or anxiety symptoms in obstructive sleep apnoea (OSA) patients remains uncertain. Methods Secondary analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, combined with a systematic review of randomised evidence. The SAVE secondary analyses involved 2410 patients with co-existing moderate–severe OSA and established cardiovascular disease randomly allocated to CPAP treatment plus usual care or usual care alone and followed up for 3·7 (SD 1·6) years. We evaluated the effect of CPAP treatment on depression and anxiety caseness (scores ≥ 8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A]) for OSA patients. Findings CPAP treatment was associated with reduced odds of depression caseness (adjusted odds ratio [OR] 0·80, 95% confidence interval [CI] 0·65–0·98, P = 0·031) compared to usual care in the SAVE trial and the treatment effect was greater in those with pre-existing depression symptoms. A systematic review of 20 randomised trials including 4255 participants confirmed a benefit of CPAP in reducing depression symptoms in OSA patients: the overall effect (standardised mean difference) was − 0·18 (95% CI − 0·24 to − 0·12). No effect of CPAP treatment on anxiety caseness was found both in patients of the SAVE study (adjusted OR 0·98, 95% CI 0·78–1·24, P = 0·89) and the systematic review. Interpretation CPAP reduces depression symptoms in patients with co-existing OSA and CVD independently of improvements in sleepiness., Highlights • Depression and anxiety are prevalent in patients with chronic conditions, such as obstructive sleep apnoea (OSA) and cardiovascular disease, and they adversely impact on prognosis and quality of life. Whether continuous positive airway pressure (CPAP) treatment can improve depression or anxiety symptoms in OSA patients still remains uncertain. We searched PubMed for studies in English language published before 1 Jan 2019 reporting of CPAP effect on depression and anxiety symptoms using the terms “continuous positive airway pressure”, “obstructive sleep apnoea”, “depression” and “anxiety”. A recent systematic review of randomised trials on the effect of CPAP on depression symptoms had found modest benefit of CPAP treatment for improving depression symptoms, however there was high heterogeneity. Existing findings are variable across studies due, in part, to different study designs, small patient numbers, short periods of follow-up, and from an emphasis on depression over anxiety patterns of abnormal mood. • Added value of this study: Analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) cohort of over 2400 patients with moderate to severe OSA and concomitant cardiovascular diseases who were followed up for an average of 3.7 years showed that the CPAP reduced depression symptoms within few months of treatment, independently of improvements in daytime sleepiness. The NNT (i.e. 15) for CPAP to prevent depression caseness (as defined by Hospital Anxiety and Depression Scale – Depression subscale score ≥ 8) is comparable to remission rates achieved for some established antidepressant drugs. However, analyses of the SAVE study showed no clear clinical benefit for anxiety symptoms. Systematic review of 20 included randomised controlled studies showed similar results as our SAVE secondary analyses. • Implications of all the available evidence: Our findings provide further support for the broader beneficial effects of CPAP in those with OSA, and especially those at high cardiovascular risk, where there is the potential for enhanced mood to improve long-term cardiovascular outcomes.

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.

Background Although recent evidence suggests that OSA treatment may cause weight gain, the long-term effects of CPAP on weight are not well established. Methods This study was a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) study, a multicenter, randomized trial of CPAP plus standard care vs standard care alone in adults with a history of cardiac or cerebrovascular events and moderate to severe OSA. Participants with weight, BMI, and neck and waist circumferences measured at baseline and during follow-up were included. Linear mixed models were used to examine sex-specific temporal differences, and a sensitivity analysis compared high CPAP adherers (≥ 4 h per night) with propensity-matched control participants. Results A total of 2,483 adults (1,248 in the CPAP group and 1,235 in the control group) were included (mean 6.1 ± 1.5 measures of weight available). After a mean follow-up of 3.78 years, there was no difference in weight change between the CPAP and control groups, for male subjects (mean [95% CI] between-group difference, 0.07 kg [–0.40 to 0.54]; P = .773) or female subjects (mean [95% CI] between-group difference, –0.14 kg [–0.37 to 0.09]; P = .233). Similarly, there were no significant differences in BMI or other anthropometric measures. Although male participants who used CPAP ≥ 4 h per night gained slightly more weight than matched male control subjects without CPAP (mean difference, 0.38 kg [95% CI, 0.04 to 0.73]; P = .031), there were no between-group differences in other anthropometric variables, nor were there any differences between female high CPAP adherers and matched control subjects. Conclusions Long-term CPAP use in patients with comorbid OSA and cardiovascular disease does not result in clinically significant weight change. Trial Registry ClinicalTrials.gov; No.: NCT00738179 ; URL: www.clinicaltrials.gov .

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

OBJECTIVE Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA. RESEARCH DESIGN AND METHODS Blood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea cardioVascular Endpoints (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A1c (HbA1c) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded. RESULTS Median follow-up was 4.3 years. In those with preexisting diabetes (n = 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA1c, or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n = 452) or new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable. CONCLUSIONS Among patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation.

Background: Obstructive sleep apnoea (OSA) is a common comorbidity in patients with cardiovascular (CV) disease. We aimed to identify specific OSA clinical phenotypes relating to risks of serious CV events and response to continuous positive airway pressure (CPAP) treatment. Methods: Post-hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) study in participants with moderate-to-severe OSA and coronary artery disease (CAD) and/or cerebrovascular disease (CeVD) randomised to CPAP plus usual care or usual care alone. Latent class analysis (LCA) was used to identify OSA clinical phenotypes among 2649 (out of 2687 total) patients with complete data on 19 patient-centered variables, supported by Bayesian information criteria and clinical interpretability. Cox regression models were used to evaluate risks of composite cardiac and stroke outcome events in phenotype groups. Preferential response to CPAP treatment was evaluated using interaction terms as well as the Chi-square test. Findings: LCA identified four OSA clinical phenotypes: CAD alone and with diabetes mellitus (CAD+DM), and CeVD alone and with DM (CeVD+DM), in 39%, 15%, 37% and 9% of participants, respectively. The rates of composite CV events were the highest in CAD+DM phenotype (HR 2.08, 95% CI 1.57–2.76) and for stroke were highest in CeVD+DM phenotype (HR 6.84, 95% CI 3.77–12.42). Adherence to CPAP treatment (nil or

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 FEV 1 , 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 1 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.

OBJECTIVES: Continuous positive airway pressure (CPAP) improves upper airway obstruction in patients with obstructive sleep apnoea (OSA), who often are overweight-obese. Although it is thought that CPAP improves long-term blood pressure control (BP), the impact of acute and short-term CPAP use on the cardiovascular system in obese patients has not been described in detail.METHODS: Obese patients (body mass index, BMI > 25 kg/m2) with OSA were studied awake, supine during incremental CPAP titration (4-20 cmH2O, +2 cmH2O/3 mins). BP was measured continuously with a beat-to-beat BP monitor (Ohmeda 2300, Finapres Medical Systems, Amsterdam/NL), BP variability (BPV) was calculated as the standard deviation of BP at each CPAP level, the 95% confidence interval (95%CI) was calculated and changes in BP and BPV were reported.RESULTS: 15 patients (12 male, 48 ± 10) years, BMI 38.9 ± 5.8 kg/m2) were studied; the baseline BP was 131.0 ± 10.2/85.1 ± 9.1 mmHg. BP and BPV increased linearly with CPAP titration (systolic BP r = 0.960, p CONCLUSION: Short-term incremental CPAP leads to significant increases in BP and BPV in obese patients with OSA while awake. Careful titration of pressures is required to minimise the risk of nocturnal awakenings while improving BP control.

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.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.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 %, p0.001). 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 %, p0.001). 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 (p0.001) with sensitivity 86 % and specificity 92 %.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.

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) and thus diagnosis of COPD associated obstructive sleep apnoea (OSA) overlap syndrome. Patients and methods In a retrospective study, polysomnographical recordings (PSG) of 11 patients with COPD/OSA overlap syndrome were independently analysed using the AASM criteria from 2007 and 2012. The primary outcome was the difference in AHI between the AASM 2012 and the AASM 2007 recommended and alternative scoring rules, secondary outcomes were the percentage of hypopnoeas and the diagnosis of overlap syndrome. Data are presented as mean (standard deviation) if normally distributed, and as median (interquartile range) for non-normally distributed data. Results The PSG of 11 obese, elderly and predominantly male patients with mild-moderate COPD were analysed (table). The AHI using AASM 2007 (recommended) criteria was 12.9 (5.8, 16.9) h-1 vs 18.7 (11.3, 24.7) h-1 using the 2012 criteria (p Conclusion The AHI significantly increases when the AASM 2012 instead of 2007 criteria are used in patients with COPD/OSA overlap syndrome, in parts due to a higher number of arousal-associated hypopnoeas. These observations will impact on the definition of the COPD/OSA overlap syndrome.

Ascending thoracic aortic aneurysms (ATAAs) are focal dilatations in the aorta that are prone to rupture or dissection. To accurately evaluate the rupture risk, one must know the local mechanical conditions at the rupture site and understand how rupture is triggered in a layered fibrous media. A challenge facing experimental studies of ATAA rupture is that the ATAA tissue is highly heterogeneous; experimental protocols that operate under the premise of tissue homogeneity will have difficulty delineating the location conditions. In this work, we employed a previously established pointwise identification method to characterize wall stress, strain, and property distributions to a sub-millimeter resolution. Based on the acquired field data, we obtained the local mechanical properties at the rupture site in nine ATAA tissue samples. The rupture stress, ultimate strain, energy density, and the toughness of the tested samples were also reported. Our results show that the direction of the rupture is aligned with the direction of maximum stiffness, indicating that higher stiffness is not always related to higher strength. It was also found that the rupture generally occurs at a location of highest stored energy. As a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the recruitment of collagen fibers in the deformation of the tissue is probably essential in ATAA rupture.A major challenge in the experimental study of aneurysm properties is that the tissues are heterogeneous. When the specimens are not reasonably homogeneous, traditional tests that work under the premise of tissue homogeneity cannot reliably delineate the local conditions at the rupture site. In this work, we investigated the local characteristics of rupture of human ascending aortic aneurysm tissue. We identified the stress, strain, and elastic properties to a submillimeter resolution. Based on the field values, we determined the local conditions - elastic properties, direction of maximum stiffness, stress, strain, energy consumption - at the rupture site. It was found that the tissues consistently cleave in the direction of the maximum stiffness, and generally occurs at the location of highest energy. Since a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the work suggests that the recruitment of collagen fibers in the deformation of the tissue is probably essential in aneurysm rupture.

The magnitude of tidal volume (VT) depends on neural respiratory drive overcoming respiratory resistance. We hypothesized that the ratio of EMGdi, an index of neural drive, to VT could detect histamine induced changes in lower airway resistance given the assumption that respiratory resistance (except for the lower airway resistance) is unaffected by histamine. Conventional histamine challenge tests were undertaken in 44 asthma patients (age 47±14 years; FEV1% 76±14) diagnosed by a history of repeated attack of asthma and positive bronchial challenge test and 51 healthy subjects (age 36 ± 13 years; FEV1% 96 ± 11). Diaphragm EMG was recorded from chest wall surface electrodes (EMGdi) under the fixed breathing frequency (18 times/min.) and an additional inspiratory load to improve a signal–noise ratio. Airflow was recorded with a digital output flowmeter. ΔFEV1 correlated with ΔEMGdi /VT (r=0.63). Corresponding to ≥20% fall in FEV1 during histamine challenge test, change in EMGdi/VT in patients with asthma was significantly higher than that in healthy subjects who received maximal dose (7.8 µmol) of histamine (90.5% ± 75.5% vs 2.4% ± 21.7%, p

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. Clinical trials registration number NCT00738179. Australia new zealand clinical trials registry number ACTRN12608000409370.

We tested the hypothesis that elastic binding of the abdomen (AB) would enhance neuromuscular efficiency of the human diaphragm during exercise. Twelve healthy non-obese men aged 24.8 ± 1.7 years (mean ± SE) completed a symptom-limited constant-load cycle endurance exercise test at 85% of their peak incremental power output with diaphragmatic electromyography (EMGdi) and respiratory pressure measurements under two randomly assigned conditions: unbound control (CTRL) and AB sufficient to increase end-expiratory gastric pressure (Pga,ee) by 5–8 cmH2O at rest. By design, AB increased Pga,ee by 6.6 ± 0.6 cmH2O at rest. Compared to CTRL, AB significantly increased the transdiaphragmatic pressure swing-to-EMGdi ratio by 85–95% during exercise, reflecting enhanced neuromuscular efficiency of the diaphragm. By contrast, AB had no effect on spirometric parameters at rest, exercise endurance time or an effect on cardiac, metabolic, ventilatory, breathing pattern, dynamic operating lung volume, and perceptual responses during exercise. In conclusion, AB was associated with isolated and acute improvements in neuromuscular efficiency of the diaphragm during exercise in healthy men. The implications of our results are that AB may be an effective means of enhancing neuromuscular efficiency of the diaphragm in clinical populations with diaphragmatic weakness/dysfunction.

Rationale Dynamic hyperinflation in patients with COPD is usually assessed by inspiratory capacity (IC) manoeuvres with the assumption that maximal activation of the respiratory muscles can be reliably achieved. Objectives We hypothesized that the neural output to the respiratory muscles during an IC manoeuvre will increase under the condition of exercise or hypercapnia, since these are known to increase neural output from the brainstem to the respiratory muscles. Methods Nineteen patients with COPD (mean FEV 1 =29.7±12.5%) and 31 normal subjects were studied. Diaphragm electromyogram (EMGdi) and IC were measured during exhaustive exercise and during inhalation of 8%CO 2 with or without hypoxia. Measurements and Main Results IC changed from 1.78 ± 0.50 L and 1.41 ± 0.40 L at rest to 2.18 ± 0.58 L and 1.29 ± 0.46 L at the end of exercise for normal subjects and COPD patients, respectively. The mean EMGdi during an IC manoeuver increased during exercise from 0.158 ± 0.036 mV and 0.172 ± 0.048mV at rest to 0.203 ± 0.041 mV and 0.220 ± 0.056mV at the end of exercise for normal subjects and patients with COPD, respectively. Both the IC and EMGdi observed during an IC manoeuver during inhalation of 8%CO 2 in normal subjects was significantly larger than those breathing room air (2.10±0.80L vs 1.87±0.60L for IC and 0.183±0.038 mV vs 0.154±0.040 mV for EMGdi, p Conclusions We conclude that the neural drive generated by an IC manoeuvre increases during exercise and hypercapnia, leading to potential underestimation of dynamic hyperinflation assessed by IC manoeuvres.

Background: Observational studies suggest continuous positive airway pressure (CPAP) treatment can reduce risks of serious cardiovascular (CV) events in people with OSA, but randomized data are lacking. We report results of the SAVE trial (ClinicalTrials.gov number NCT00738179) designed to close this evidence gap. Methods : SAVE was an investigator-initiated and conducted, international, multicentre, open-label, blinded endpoint, randomized controlled trial designed to test for superiority of CPAP plus usual care versus usual care alone on the primary efficacy composite endpoint of CV death, non-fatal myocardial infarction, non-fatal stroke, and any hospitalization for unstable angina, heart failure, or transient ischaemic attack. Eligibility criteria: age 45-75 years, prior cerebro- or coronary CV disease, OSA (≥4% oxygen desaturation index [ODI] ≥12/hr), Epworth sleepiness score (ESS) 3 hr/night over 1-2 week run-in phase. Results: 2717 patients were randomised between December 2008 and November 2013: 1359 to CPAP plus usual care and 1358 to usual care from 89 hospitals in 7 countries, with patient follow-up completed in January 2016. Groups were well balanced for baseline demographic/clinical characteristics (mean age 61 years, 81% male, 63% Asian) with BMI 28.6, ODI 28.2, snoring “almost every day” 83%, ESS 7.4. The main results will be presented at the conference. Conclusions: SAVE provides the first definitive randomised controlled trial evidence on the effectiveness of CPAP therapy on future CV events in patients with CV disease and co-occurring OSA.

Background: Respiratory muscle weakness is an important clinical problem. Tests of varying complexity and invasiveness are available to assess respiratory muscle strength. The relative precision of different tests in the detection of weakness is less clear, as is the value of multiple tests. Methods: The respiratory muscle function tests of clinical referrals who had multiple tests assessed in our laboratories over a 6-year period were analysed. Thresholds for weakness for each test were determined from published and in-house laboratory data. The patients were divided into three groups: those who had all relevant measurements of global inspiratory muscle strength (group A, n = 182), those with full assessment of diaphragm strength (group B, n = 264) and those for whom expiratory muscle strength was fully evaluated (group C, n = 60). The diagnostic outcome of each inspiratory, diaphragm and expiratory muscle test, both singly and in combination, was studied and the impact of using more than one test to detect weakness was calculated. Results: The clinical referrals were primarily for the evaluation of neuromuscular diseases and dyspnoea of unknown cause. A low maximal inspiratory mouth pressure (Pimax) was recorded in 40.1% of referrals in group A, while a low sniff nasal pressure (Sniff Pnasal) was recorded in 41.8% and a low sniff oesophageal pressure (Sniff Poes) in 37.9%. When assessing inspiratory strength with the combination of all three tests, 29.6% of patients had weakness. Using the two non-invasive tests (Pimax and Sniff Pnasal) in combination, a similar result was obtained (low in 32.4%). Combining Sniff Pdi (low in 68.2%) and Twitch Pdi (low in 67.4%) reduced the diagnoses of patients with diaphragm weakness to 55.3% in group B. 38.3% of the patients in group C had expiratory muscle weakness as measured by maximum expiratory pressure (Pemax) compared with 36.7% when weakness was diagnosed by cough gastric pressure (Pgas), and 28.3% when assessed by Twitch T10. Combining all three expiratory muscle tests reduced the number of patients diagnosed as having expiratory muscle weakness to 16.7%. Conclusion: The use of single tests such as Pimax, Pemax and other available individual tests of inspiratory, diaphragm and expiratory muscle strength tends to overdiagnose weakness. Combinations of tests increase diagnostic precision and, in the population studied, they reduced the diagnosis of inspiratory, specific diaphragm and expiratory muscle weakness by 19–56%. Measuring both Pimax and Sniff Pnasal resulted in a relative reduction of 19.2% of patients falsely diagnosed with inspiratory muscle weakness. The addition of Twitch Pdi to Sniff Pdi increased diagnostic precision by a smaller amount (18.9%). Having multiple tests of respiratory muscle function available both increases diagnostic precision and makes assessment possible in a range of clinical circumstances.

Background Exercise capacity in chronic obstructive pulmonary disease (COPD) is limited by both breathlessness and leg muscle fatigue. Neural respiratory drive, measured as diaphragm electromyogram (EMGdi) activity expressed as a proportion of maximum (EMGdi%max), quantifies the mechanical load on the respiratory muscles and relates closely to breathlessness. We tested the hypothesis that end-exercise EMGdi%max would be higher in patients stopping because of breathlessness than in those limited by leg fatigue. Methods EMGdi, ventilation, rate of oxygen consumption (VO 2 ), and ventilatory reserve (ventilation/maximum ventilatory volume ratio [VE/MVV]) were measured continuously in patients with COPD during exhaustive cycle ergometry. EMGdi was measured with a multipair oesophageal catheter passed per-nasally. Differences in physiological variables between groups of patients stopping because of breathlessness, leg fatigue, or both were assessed with one-way ANOVA. Findings 23 patients were included (median FEV 1 , 39% of predicted, IQR 30·0–56·8). End-exercise EMGdi%max was significantly higher in patients stopping exercise because of breathlessness (n=12, median EMGdi%max 75·7% [IQR 69·5–77·1]) than in those stopping because of leg fatigue (n=8, 44·1 [39·4–63·3]) or both (n=3, 74·1 [63·6–81·2]) (p=0·02). There were no significant differences between the groups in end-exercise ventilation (breathlessness 25·7 L/min [16·3–32·0] vs leg fatigue 31·5 [20·9–39·6] vs both 22·0 [17·7–35·7]), VO 2 , (13·4 mL/min per kg [11·6–14·2] vs 12·1 [10·4–14·8] vs 9·4 [9·1–12·4]), or VE/MVV (80·4% [72·6–88·3] vs 57·8 [52·1–92·6] vs 63·9 [34·5–88·9]). Interpretation These results suggest that patients limited by breathlessness due to ventilatory constraints can be identified as those reaching near-maximum levels of neural respiratory drive during exercise. Measurement of EMGdi%max during exercise could prove useful in identifying patients whose functional performance would be best optimised by improvment in pulmonary mechanics rather than interventions to train peripheral muscle groups. Funding None.

Background: Continuous positive airway pressure (CPAP) improves long-term blood pressure control (BP) in obese patients with obstructive sleep apnoea (OSA). However, the impact of short-term CPAP use on BP has not been established. We measured continuous BP during CPAP titration. Patients and Methods: Obese patients (BMI>30) were studied awake, supine during incremental CPAP titration (4-20cmH 2 O, +2cmH 2 O/3mins). Continuous BP was measured with a beat-to-beat BP monitor (Finapres). The electromyogram was recorded from inspiratory (parasternal intercostals, sEMG para ) and expiratory muscles (abdominal oblique, sEMG abdo ). BP variability was calculated as the standard deviation at each CPAP level. Results: 16 patients (13males, 47(10)years, BMI 38.5(5.8)kg/m 2 ) were studied. Baseline BP was 131.0(10.2)/85.1(9.1)mmHg. BP and BPV increased with incremental CPAP (systolic BP r=0.960,p abdo correlated with systolic (r=0.464,p=0.032) and diastolic BP (r=0.747,p=0.009) and CPAP level (r=0.782, p=0.004); there was no correlation between sEMG para and CPAP (r=-0.110,p=0.748). Conclusion: Short-term use of incremental CPAP leads to increases in BP and BPV. Expiratory muscle EMG was associated with observed changes in BP.

© Copyright 2013 Associated Professional Sleep Societies, Published by the American Academy of Sleep Medicine. Published version of the paper reproduced here with permission from the publisher., Study Objectives: To determine the clinical variables that best predict long- term continuous positive airway pressure (CPAP) adherence among patients with cardiovascular disease who have obstructive sleep apnea (OSA). Design: 12-mo prospective within-trial observational study. Setting: Centers in China, Australia, and New Zealand participating in the Sleep Apnea cardioVascular Endpoints (SAVE) study. Patients: There were 275 patients age 45-70 y with cardiovascular disease (i.e., previously documented transient ischemic attack, stroke, or coronary artery disease) and OSA (4% oxygen desaturation index (ODI) > 12) who were randomized into the CPAP arm of the SAVE trial prior to July 1, 2010. Methods: Age, sex, country of residence, type of cardiovascular disease, baseline ODI, severity of sleepiness, and Hospital Anxiety and Depression Scale (HADS) scores plus CPAP side effects and adherence at 1 mo were entered in univariate analyses in an attempt to identify factors predictive of CPAP adherence at 12 mo. Variables with P < 0.2 were then included in a multivariate analysis using a linear mixed model with sites as a random effect and 12-mo CPAP use as the dependent outcome variable. Measurements and Results: CPAP adherence at 1, 6, and 12 mo was (mean ± standard deviation) 4.4 ± 2.0, 3.8 ± 2.3, and 3.3 ± 2.4 h/night, respectively. CPAP use at 1 mo (effect estimate ± standard error, 0.65 ± 0.07 per h increase, P < 0.001) and side effects at 1 mo (-0.24 ± 0.092 per additional side effect, P = 0.009) were the only independent predictors of 12- mo CPAP adherence. Conclusion: Continuous positive airway pressure use in patients with coexisting cardiovascular disease and moderate to severe obstructive sleep apnea decreases significantly over 12 months. This decline can be predicted by early patient experiences with continuous positive airway pressure (i.e., adherence and side effects at 1 month), raising the possibility that intensive early interventions could improve long-term continuous positive airway pressure compliance in this patient population. Clinical Trials Register: Clinical Trials, http://www.clinicaltrials.gov, NCT00738179.

It is unknown whether respiratory motor output is constrained during exhaustive exercise in healthy adults. We hypothesised that neural inhibition did occur; to test this hypothesis we measured diaphragm EMG from a maximal inspiratory capacity maneuver (EMGdi-IC) at rest and during exercise. EMGdi-IC was measured before and after the amplitude of the diaphragm EMG entered a plateau phase in eleven healthy adults undertaking exercise at 60% and 80% of maximal workload achieved from incremental exercise. The mean EMGdi-IC at rest was 65 ± 16% of the maximum that could be obtained from a battery of inspiratory tasks. Before and after the plateau phase of diaphragm EMG, EMGdi-IC was 68 ± 13% and 72 ± 12% (p > 0.05) during 60% of the maximum workload, and was 70 ± 13% and 78 ± 13% (p > 0.05) during 80% of the maximum workload achieved on an incremental test. A further sub-study in which 5 participants exercised at 90% of the maximum workload also showed that EMGdi-IC was not diminished during exercise. Our data show that exercise condition does not reduce the magnitude of EMGdi-IC. This argues against neural inhibition as feature of submaximal exercise in healthy adults.

Background It is unknown whether efficiency of neural drive as expressed by a ratio of ventilation to the diaphragm electromyogram (EMGdi) in patients with COPD differs from that of healthy subjects during exercise and whether maximal neural drive is exhibited at the point of exercise termination. Methods We studied 12 male patients with COPD (mean ± SD age, 62.8 ± 10.3 years; FEV 1 , 28.1 ± 10.2% predicted) and 12 age- and sex-matched healthy subjects (age, 61.1 ± 7.2 years, FEV 1 , 101.5 ± 11.9% predicted). EMGdi was recorded from a multipair esophageal electrode during a constant work (80% of maximal oxygen consumption derived from a previous incremental exercise test) treadmill exercise. Minute ventilation and oxygen consumption were also measured. Results Root mean square (RMS) of the EMGdi increased initially and reached a plateau at submaximal drive during constant load exercise in both patients with COPD and healthy subjects. The ratio of ventilation to EMGdi remained stable during exercise in healthy subjects from beginning to the end (100% ± 70% at the beginning and 100% ± 39% at the end, P > .05), whereas the ratio decreased gradually during exercise in patients with COPD (from 85% ± 66% to 42% ± 13%, P Conclusions Efficiency of neural drive decreases in patients with COPD during treadmill exercise. Neural respiratory drive reached a submaximal plateau during constant load exercise in both healthy subjects and patients with COPD, indicating that it may not be the only factor determining exercise capacity.

Background Breathlessness is an important cause of exercise limitation and reduced quality of life for patients with chronic obstructive pulmonary disease (COPD). One of the challenges of breathlessness management in COPD is the lack of physiological markers that reliably correlate with patients' symptoms. The aim of this study was to test the hypothesis that neural respiratory drive (NRD), measured with diaphragm electromyogram (EMGdi) activity, is closely related to breathlessness in COPD. We also investigated whether neuroventilatory uncoupling, which is the dissociation of ventilation from NRD as a consequence of abnormal pulmonary mechanics, contributes to breathlessness intensity over an awareness of levels of NRD alone. Methods EMGdi and ventilation were measured continuously during exhaustive incremental cycle and treadmill exercise in 12 patients with COPD (mean FEV 1 38·7% predicted [SD 14·5]). EMGdi was expressed as a percentage of maximum (EMGdi%max), and relative to tidal volume expressed as a percentage of predicted vital capacity (EMGdi%max/VT%VCpred) to measure neuroventilatory uncoupling. Breathlessness (modified Borg scale) was recorded at baseline, at the end of each minute of exercise, and at completion of exercise. Linear regression analysis was used to determine the associations between breathlessness, EMGdi%max, neuroventilatory uncoupling, and ventilation. Findings EMGdi%max was closely related to breathlessness in both cycle ( r =0·98, p=0·0001) and treadmill exercise ( r =0·94, p=0·005), this association being at least as strong as that between neuroventilatory uncoupling and breathlessness (cycle r =0·94, p=0·005; treadmill r =0·91, p=0·01). The association between breathlessness and ventilation was poor when expansion of tidal volume became restricted, whereas the association between EMGdi%max and breathlessness remained close. Interpretation EMGdi%max is closely related to the intensity of exertional breathlessness in COPD. These data suggest that breathlessness in COPD can be largely explained by an awareness of levels of NRD, rather than the association between NRD and achieved ventilation. EMGdi%max could provide a useful physiological biomarker for breathlessness, with advantages over mechanical and ventilatory indices in COPD and the many other diseases in which neuroventilatory uncoupling occurs. Funding UK Medical Research Council, British Council.

Functional magnetic stimulation (FMS) of the thoracic nerve roots to simulate cough has been suggested as a treatment approach in patients unable to voluntarily activate the abdominal muscles. However, factors that could influence the efficacy of FMS in clinical use have not been evaluated. In the present investigation we studied train length, posture, and frequency to determine the optimal stimulation protocol. We also evaluated the use of a valve at the mouth to enhance glottic function and investigated whether lung volume at the time of stimulation would influence the tension generated by the abdominal muscles. Studies were performed using a Magstim rapid stimulator augmented by four booster packs in nine healthy subjects; we measured the change in gastric (DeltaPga(FMS)), esophageal (DeltaPes(FMS)), and mouth pressure and expiratory flow. With our apparatus pressure generation was maximized by having a train length of at least 300 ms and a frequency of 25 Hz. Posture and valve use were not important determinants of DeltaPga(FMS) or DeltaPes(FMS). Lung volume exerted only a minor influence on DeltaPga(FMS), but the ratio DeltaPes(FMS):DeltaPga(FMS) was increased at TLC compared with FRC. Expiratory flow was increased by adopting a seated posture and using an occlusion valve with an opening threshold close to the maximum DeltaPes(FMS) generated by the stimulus train; however, expiratory flow was susceptible to interference from glottic incoordination. Representative results (with train length 600 ms, 25 Hz, and 100% power, seated) were mean DeltaPga(FMS), 166 cm H(2)O; mean DeltaPes(FMS), 108 cm H(2)O; and mean expiratory flow, 311 L/min. We confirm that FMS of the abdominal muscles can generate a substantial positive intra-abdominal and intrathoracic pressure and, consequently, expiratory flow in normal subjects.