Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study.

INTRODUCTION: In people with obesity hypoventilation syndrome (OHS), breathing 100% oxygen increases carbon dioxide (PCO2), but its effect on pH is unknown. This study investigated the effects of moderate concentrations of supplemental oxygen on PCO2, pH, minute ventilation (VE) and physiological dead space to tidal volume ratio (VD/VT) among people with stable untreated OHS, with comparison to healthy controls. METHODS: In a double-blind randomised crossover study, participants breathed oxygen concentrations (FiO2) 0.28 and 0.50, each for 20 min, separated by a 45 min washout period. Arterialised-venous PCO2 (PavCO2) and pH, VE and VD/VT were measured at baseline, then every 5 min. Data were analysed using general linear model analysis. RESULTS: 28 participants were recruited (14 OHS, 14 controls). Among OHS participants (mean ± SD arterial PCO2 6.7 ± 0.5 kPa; arterial oxygen 8.9 ± 1.4 kPa) FiO2 0.28 and 0.50 maintained oxygen saturation 98-100%. After 20 min of FiO2 0.28, PavCO2 change (ΔPavCO2) was 0.3 ± 0.2 kPa (p = 0.013), with minimal change in VE and rises in VD/VT of 1 ± 5% (p = 0.012). FiO2 0.50 increased PavCO2 by 0.5 ± 0.4 kPa (p = 0.012), induced acidaemia and increased VD/VT by 3 ± 3% (p = 0.012). VE fell by 1.2 ± 2.1 L/min within 5 min then recovered individually to varying degrees. A negative correlation between ΔVE and ΔPavCO2 (r = -0.60, p = 0.024) suggested that ventilatory responses were the key determinant of PavCO2 rises. Among controls, FiO2 0.28 and 0.50 did not change PavCO2 or pH, but FiO2 0.50 significantly increased VE and VD/VT. CONCLUSION: Commonly used oxygen concentrations caused hypoventilation, PavCO2 rises and acidaemia among people with stable OHS. This highlights the potential dangers of this common intervention in this group.

Non-invasive ventilation during exercise training for people with chronic obstructive pulmonary disease.

BACKGROUND: Exercise training as a component of pulmonary rehabilitation improves health-related quality of life (HRQL) and exercise capacity in people with chronic obstructive pulmonary disease (COPD). However, some individuals may have difficulty performing exercise at an adequate intensity. Non-invasive ventilation (NIV) during exercise improves exercise capacity and dyspnoea during a single exercise session. Consequently, NIV during exercise training may allow individuals to exercise at a higher intensity, which could lead to greater improvement in exercise capacity, HRQL and physical activity. OBJECTIVES: To determine whether NIV during exercise training (as part of pulmonary rehabilitation) affects exercise capacity, HRQL and physical activity in people with COPD compared with exercise training alone or exercise training with sham NIV. SEARCH METHODS: We searched the following databases between January 1987 and November 2013 inclusive: The Cochrane Airways Group specialised register of trials, AMED, CENTRAL, CINAHL, EMBASE, LILACS, MEDLINE, PEDro, PsycINFO and PubMed.  SELECTION CRITERIA: Randomised controlled trials that compared NIV during exercise training versus exercise training alone or exercise training with sham NIV in people with COPD were considered for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review, extracted data and assessed risk of bias. Primary outcomes were exercise capacity, HRQL and physical activity; secondary outcomes were training intensity, physiological changes related to exercise training, dyspnoea, dropouts, adverse events and cost. MAIN RESULTS: Six studies involving 126 participants who completed the study protocols were included. Most studies recruited participants with severe to very severe COPD (mean forced expiratory volume in one second (FEV1) ranged from 26% to 48% predicted). There was an increase in percentage change peak and endurance exercise capacity with NIV during training (mean difference in peak exercise capacity 17%, 95% confidence interval (CI) 7% to 27%, 60 participants, low-quality evidence; mean difference in endurance exercise capacity 59%, 95% CI 4% to 114%, 48 participants, low-quality evidence). However, there was no clear evidence of a difference between interventions for all other measures of exercise capacity. The results for HRQL assessed using the St George's Respiratory Questionnaire do not rule out an effect of NIV (total score mean 2.5 points, 95% CI -2.3 to 7.2, 48 participants, moderate-quality evidence). Physical activity was not assessed in any study. There was an increase in training intensity with NIV during training of 13% (95% CI 1% to 27%, 67 participants, moderate-quality evidence), and isoload lactate was lower with NIV (mean difference -0.97 mmol/L, 95% CI -1.58mmol/L to -0.36 mmol/L, 37 participants, moderate-quality evidence). The effect of NIV on dyspnoea or the number of dropouts between interventions was uncertain, although again results were imprecise. No adverse events and no information regarding cost were reported. Only one study blinded participants, whereas three studies used blinded assessors. Adequate allocation concealment was reported in four studies. AUTHORS' CONCLUSIONS: The small number of included studies with small numbers of participants, as well as the high risk of bias within some of the included studies, limited our ability to draw strong evidence-based conclusions. Although NIV during lower limb exercise training may allow people with COPD to exercise at a higher training intensity and to achieve a greater physiological training effect compared with exercise training alone or exercise training with sham NIV, the effect on exercise capacity is unclear. Some evidence suggests that NIV during exercise training improves the percentage change in peak and endurance exercise capacity; however, these findings are not consistent across other measures of exercise capacity. There is no clear evidence that HRQL is better or worse with NIV during training. It is currently unknown whether the demonstrated benefits of NIV during exercise training are clinically worthwhile or cost-effective.

Online Education Improves Confidence in Mechanical Insufflation-Exsufflation.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is a cough augmentation technique used to support people with an ineffective cough. MI-E can be complex due to the number of different pressure, flow, and temporal setting adjustments needed to optimize cough efficacy. Many clinicians identify inadequate training, limited experience, and low confidence as barriers to MI-E use. The purpose of this study was to determine if an online education course could improve confidence and competence in the delivery of MI-E. METHODS: An e-mail invitation to participate was disseminated to physiotherapists with a caseload that involved airway clearance for adults. The exclusion criteria were self-reported confidence and clinical expertise in MI-E. The education was created by physiotherapists with extensive experience in the provision of MI-E. The education material reviewed theoretical and practical components and was designed to take 6 h to complete. Physiotherapists were randomized to either the intervention group, who had 3 weeks of access to the education or the control group who received no intervention. Respondents in both groups completed a baseline and a post-intervention questionnaire by using visual analog scales, 0 to 10, with the primary outcomes being confidence in the prescription and confidence in the application of MI-E. Ten multiple-choice questions that covered key components of MI-E fundamentals were also completed at baseline and post-intervention. RESULTS: The intervention group had a significant improvement in the visual analog scale after the education period with a between-group difference of mean 3.6 (95% CI 4.5 to 2.7) for prescription confidence and mean 2.9 (95% CI 3.9 to 1.9) for application confidence. There was also an improvement in the multiple-choice questions with a between-group difference of mean 3.2 (95% CI 4.3 to 2). CONCLUSIONS: Access to an evidence-based online education course improved confidence in the prescription and application of MI-E, and may be a valuable tool for training clinicians in the application of MI-E.

Perceptions of Noninvasive Ventilation During Exercise in Noninvasive Ventilation-Naïve Patients With COPD.

BACKGROUND: The perceptions of using noninvasive ventilation (NIV) during exercise in patients with COPD who are naïve to NIV is unknown. The present study aimed to examine the perceptions of using NIV during exercise in people with COPD and to determine the relationship between patient perceptions with both baseline patient characteristics and exercise outcomes. METHODS: During a trial examining the effect of NIV during exercise on dynamic hyperinflation in people with COPD who were naïve to NIV, participants completed a 5-point Likert scale questionnaire (scored strongly disagree -2 to strongly agree +2) before and after using NIV during exercise and a semi-structured interview after using NIV during exercise. RESULTS: Eighteen participants, mean age (SD) 69 (7) y, FEV1/FVC 0.44 (0.08), FEV1 39 (7)% predicted, completed the study. Prior to exercise with NIV, participants were neutral about NIV, (mean [SD]) (0.67[0.84]). After exercise with NIV, participants felt that NIV made breathing easier (1.00 [0.77]) and that it helped exercise (1.06 [0.64]). There were moderate correlations between feeling that NIV was comfortable or effective and a change in exercise endurance time (ρ = - 0.588, P = .02), isotime inspiratory capacity (ρ = 0.488, P = .03), and measures of resting hyperinflation (ρ = 0.603, \P = .02). Interviews revealed that despite feeling comfortable using NIV during exercise, NIV might be too complicated for patients to manage outside a supervised environment. CONCLUSIONS: Individuals with COPD, naïve to NIV, and using NIV during exercise for the first time reported a positive effect of NIV on breathlessness and exercise performance. Participants' perceived benefit of NIV correlated moderately with increased endurance time and resting hyperinflation and with a reduction in dynamic hyperinflation during exercise, suggesting that patient reports could also aid selection of those who will benefit from NIV during exercise.

Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity.

STUDY OBJECTIVES: The main cause of death in patients with obesity hypoventilation syndrome (OHS) is cardiac rather than respiratory failure. Here, we investigated autonomic-respiratory coupling and serum cardiac biomarkers in patients with OHS and obstructive sleep apnea (OSA) with comparable body mass index and apnea-hypopnea index. METHODS: Cardiopulmonary coupling (CPC) and cyclic variation of heart rate analysis was performed on the electrocardiogram signal from the overnight polysomnogram. Cardiac serum biomarkers were obtained in patients with OHS and OSA with a body mass index > 40 kg/m2. Samples were obtained at baseline and after 3 months of positive airway pressure (PAP) therapy in both groups. RESULTS: Patients with OHS (n = 15) and OSA (n = 36) were recruited. No group differences in CPC, cyclic variation of heart rate, and serum biomarkers were observed at baseline and after 3 months of PAP therapy. An improvement in several CPC metrics, including the sleep apnea index, unstable sleep (low-frequency coupling and elevated low-frequency coupling narrow band), and cyclic variation of heart rate were observed in both groups with PAP use. However, distinct differences in response characteristics were noted. Elevated low-frequency coupling narrow band coupling correlated with highly sensitive troponin-T (P < .05) in the combined cohort. Baseline highly sensitive troponin-T inversely correlated with awake oxygen saturation in the OHS group (P < .05). CONCLUSIONS: PAP therapy can significantly improve CPC stability in patients with obesity with OSA or OHS, with key differences. Elevated low-frequency coupling narrow band may function as a surrogate biomarker for early subclinical cardiac disease. Low awake oxygen saturation could also increase this biomarker in OHS. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Obesity Hypoventilation Syndrome and Neurocognitive Dysfunction; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367492; Identifier: ACTRN12615000122550. CITATION: Sivam S, Wang D, Wong KKH, et al. Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity. J Clin Sleep Med. 2022;18(4):1063-1071.

Bilevel Noninvasive Ventilation During Exercise Reduces Dynamic Hyperinflation and Improves Cycle Endurance Time in Severe to Very Severe COPD.

BACKGROUND: During exercise, dynamic hyperinflation (DH), measured by a reduction in inspiratory capacity (IC), increases exertional dyspnea and reduces functional capacity in many patients with severe COPD. Although noninvasive ventilation (NIV) during exercise can improve exercise duration, the effect on DH is unclear. RESEARCH QUESTIONS: In people with COPD, resting hyperinflation, and evidence of DH during exercise, does bilevel NIV during exercise reduce DH and increase endurance time compared with exercise with no NIV, and does NIV with an individually titrated expiratory positive airway pressure (T-EPAP) reduce DH and increase exercise endurance time more than NIV with standardized EPAP (S-EPAP) of 5 cm H2O? STUDY DESIGN AND METHODS: A randomized crossover trial in which investigators and participants were blinded between NIV interventions was performed. Participants (N = 19; FEV1 of 1.02 ± 0.24 L (39% ± 6% predicted) completed three constant work rate endurance cycle tests in random order-no NIV, NIV with S-EPAP, and NIV with T-EPAP-during exercise. Primary outcomes were isotime IC and exercise endurance time. Outcome measures from each intervention were compared at isotime and at end exercise by using a linear mixed-model analysis. RESULTS: Compared with no NIV, isotime IC and endurance time were greater with both NIV with S-EPAP (mean difference: 95% CI, 0.19 L [0.10-0.28]; 95% CI, 153 s [24-280], respectively) and T-EPAP (95% CI, 0.22 L [0.13-0.32]; 95% CI, 145 s [28-259], respectively). There was no difference between NIV with S-EPAP and NIV with T-EPAP. INTERPRETATION: In people with COPD and DH during exercise, NIV during exercise reduced DH and increased cycle endurance time. An S-EPAP of 5 cm H2O was adequate to obtain these benefits. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; No.: ACTRN12613000804785; URL: http://www.anzctr.org.au.

Non-invasive ventilation during arm exercise and ground walking in patients with chronic hypercapnic respiratory failure.

BACKGROUND AND OBJECTIVE: People with chronic hypercapnic respiratory failure (HRF) often have a ventilatory limitation to exercise with difficulty performing activities of daily living. Although non-invasive ventilation (NIV) appears to reduce the ventilatory limitation and improve exercise performance in people with severe COPD, the effect of NIV during functional activities such as unsupported arm exercise (UAE) and ground walking in people with chronic HRF is unclear. METHODS: Seventeen patients with chronic HRF (PaCO(2) 52.1 +/- 5.3 mm Hg) performed a series of UAE tests, and 15 patients (PaCO(2) 51.7 +/- 3.8 mm Hg) performed a series of endurance shuttle walk tests, with and without NIV in a randomized cross-over design. RESULTS: NIV during UAE increased endurance time by a mean of 91 s (95% confidence interval (CI): 10-172, P = 0.031) and reduced dyspnoea by a mean of 2.3 on the Borg scale (95% CI: 1.0-3.7, P = 0.002) compared with exercise without NIV. There was a non-significant increase in walking endurance time with NIV during exercise (119 s, 95% CI: -17 to 254, P = 0.081); however, isotime dyspnoea was unchanged compared with walking without NIV (-1.0, 95% CI: -3.0 to 1.0, P = 0.29). CONCLUSION: NIV during UAE increased endurance time and reduced dyspnoea compared with exercise without NIV in patients with chronic HRF. Investigation of the role of NIV as an adjunct to UAE training is warranted. In contrast, NIV during ground walking did not improve exercise capacity. However, the pressure support provided may have been inadequate as dyspnoea was not reduced.

Reliability of two goniometric methods of measuring active inversion and eversion range of motion at the ankle.

BACKGROUND: Active inversion and eversion ankle range of motion (ROM) is widely used to evaluate treatment effect, however the error associated with the available measurement protocols is unknown. This study aimed to establish the reliability of goniometry as used in clinical practice. METHODS: 30 subjects (60 ankles) with a wide variety of ankle conditions participated in this study. Three observers, with different skill levels, measured active inversion and eversion ankle ROM three times on each of two days. Measurements were performed with subjects positioned (a) sitting and (b) prone. Intra-class correlation coefficients (ICC[2,1]) were calculated to determine intra- and inter-observer reliability. RESULTS: Within session intra-observer reliability ranged from ICC[2,1] 0.82 to 0.96 and between session intra-observer reliability ranged from ICC[2,1] 0.42 to 0.80. Reliability was similar for the sitting and the prone positions, however, between sessions, inversion measurements were more reliable than eversion measurements. Within session inter-observer measurements in sitting were more reliable than in prone and inversion measurements were more reliable than eversion measurements. CONCLUSION: Our findings show that ankle inversion and eversion ROM can be measured with high to very high reliability by the same observer within sessions and with low to moderate reliability by different observers within a session. The reliability of measures made by the same observer between sessions varies depending on the direction, being low to moderate for eversion measurements and moderate to high for inversion measurements in both positions.

Validation of respiratory inductive plethysmography (LifeShirt) in obesity hypoventilation syndrome.

Validation of respiratory inductive plethysmography (LifeShirt system) (RIPLS) for tidal volume (VT), minute ventilation (V˙E), and respiratory frequency (fB) was performed among people with untreated obesity hypoventilation syndrome (OHS) and controls. Measures were obtained simultaneously from RIPLS and a spirometer during two tests, and compared using Bland Altman analysis. Among 13 OHS participants (162 paired measures), RIPLS-spirometer agreement was unacceptable for VT: mean difference (MD) 3 mL (1%); limits of agreement (LOA) -216 to 220 mL (±36%); V˙E MD 0.1 L min(-1) (2%); LOA -4.1 to 4.3 L min(-1) (±36%); and fB: MD 0.2 br min(-1) (2%); LOA -4.6 to 5.0 br min(-1) (±27%). Among 13 controls (197 paired measures), RIPLS-spirometer agreement was acceptable for fB: MD -0.1 br min(-1) (-1%); LOA -1.2 to 1.1 br min(-1) (±12%), but unacceptable for VT: MD 5 mL (1%); LOA -160 to 169 mL (±20%) and V˙E: MD 0.1 L min(-1) (1%); LOA -1.4 to 1.5 L min(-1) (±20%). RIPLS produces valid measures of fB among controls but not OHS patients, and is not valid for quantifying respiratory volumes among either group.

Validity of arterialised-venous P CO2, pH and bicarbonate in obesity hypoventilation syndrome.

This prospective study investigated the validity of arterialised-venous blood gases (AVBG) for estimating arterial carbon dioxide P CO2, pH and bicarbonate (HCO3(-)) in people with obesity hypoventilation syndrome (OHS). AVBGs were obtained from an upper limb vein, after heating the skin at 42-46°C. Arterial blood gas (ABG) and AVBG samples were taken simultaneously and compared using Bland Altman analysis. Between-group differences were assessed with independent t-tests or Mann-Whitney U tests. Forty-two viable paired samples were analysed, including 27 paired samples from 15 OHS participants, and 15 paired samples from 16 controls. AVBG-ABG agreement was not different between groups, or between dorsal hand, forearm and antecubital AVBG sampling sites, and was clinically acceptable for P Co2: mean difference (MD) 0.4 mmHg (0.9%), limits of agreement (LOA) -2.7-3.6 mmHg (± 6.6%); pH: MD -0.008 (-0.1%), LOA -0.023-0.008 (± 0.2%); and HCO3(-): MD -0.3 mmol L(-1) (-1.0%), LOA -1.8-1.2 mmol L(-1) (± 5.3%). AVBG provides valid measures of [Formula: see text] , pH, and HCO3(-) in OHS.

Bilevel ventilation during exercise in acute on chronic respiratory failure: a preliminary study.

To determine the immediate effects of bilevel non-invasive ventilation plus oxygen (NIV+O(2)) during exercise compared to exercise with O(2) alone in people recovering from acute on chronic hypercapnic respiratory failure (HRF), a randomised crossover study with repeated measures was performed. Eighteen participants performed six minute walk tests (6MWT) and 16 participants performed unsupported arm exercise (UAE) tests with NIV+O(2) and with O(2) alone in random order. Distance walked increased by a mean of 43.4m (95% CI 14.1 to 72.8, p=0.006) with NIV+O(2) compared to exercise with O(2) alone. In addition, isotime oxygen saturation increased by a mean of 5% (95% CI 2-7, p=0.001) and isotime dyspnoea was reduced [median 2 (interquartile range (IQR) 1-4) versus 4 (3-5), p=0.028] with NIV+O(2). A statistically significant increase was also observed in UAE endurance time with NIV+O(2) [median 201s (IQR 93-414) versus 157 (90-342), p=0.033], and isotime perceived exertion (arm muscle fatigue) was reduced by a mean of 1.0 on the Borg scale (95% CI -1.9 to -0.1, p=0.037) compared with O(2) alone. Non-invasive ventilation plus O(2) during walking resulted in an immediate improvement in distance walked and oxygen saturation, and a reduction in dyspnoea compared to exercise with O(2) alone in people recovering from acute on chronic HRF. The reduction of dyspnoea during walking and arm muscle fatigue during UAE observed with NIV+O(2) may allow patients to better tolerate exercise early in the recovery period.

Clinical commentary: obstetric and respiratory management of pregnancy with severe spinal muscular atrophy.

We present a combined obstetric and respiratory perspective on two pregnancies for a woman with severe Type 2 Spinal Muscular Atrophy (SMA). Our patient had the lowest prepregnancy weight (20 kg) and vital capacity of 0.34 L (VC 11% predicted) yet to be reported in the sparse literature on pregnancy with SMA. She delivered two live healthy infants via planned caesarean section without pregnancy or neonatal complication. We describe the respiratory and obstetric management techniques used for a pregnancy with this degree of respiratory compromise.