Cost-effectiveness of outpatient versus inpatient non-invasive ventilation setup in obesity hypoventilation syndrome: the OPIP trial.

BACKGROUND: Current guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective. METHODS: Patients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO2) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP). RESULTS: Between May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m2 and PaCO2 6.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO2 (difference -0.27 kPa, 95% CI -0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI -£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference -0.006, 95% CI -0.05 to 0.04). There were no differences in secondary outcomes. DISCUSSION: There was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference. TRIAL REGISTRATION NUMBERS: NCT02342899 and ISRCTN51420481.

Respiratory muscle metabolic activity on PET/CT correlates with obstructive ventilatory defect severity and prognosis in patients undergoing lung cancer surgery.

BACKGROUND AND OBJECTIVE: Respiratory muscle activity is increased in patients with chronic respiratory disease. 18 F-FDG-PET/CT can assess respiratory muscle activity. We hypothesized that respiratory muscles metabolism was correlated to lung function impairment and was associated to prognosis in patients undergoing lung cancer surgery based on the research question whether respiratory muscle metabolism quantitatively correlates with the severity of lung function impairment in patients? Does respiratory muscle hypermetabolism have prognostic value? METHODS: Patients undergoing 18 F-FDG-PET/CT and pulmonary function tests prior to lung cancer surgery were identified. Maximum Standardized Uptake Value (SUVm) were measured in each respiratory muscle group (sternocleidomastoid, scalene, intercostal, diaphragm), normalized against deltoid SUVm. Respiratory muscle hypermetabolism was defined as SUVm >90th centile in any respiratory muscle group. Clinical outcomes were collected from a prospective cohort. RESULTS: One hundred fifty-six patients were included, mostly male [110 (71%)], 53 (34%) with previous diagnosis of COPD. Respiratory muscle SUVm were: scalene: 1.84 [1.51-2.25], sternocleidomastoid 1.64 [1.34-1.95], intercostal 1.01 [0.84-1.16], diaphragm 1.79 [1.41-2.27]. Tracer uptake was inversely correlated to FEV1 for the scalene (r = -0.29, p < 0.001) and SCM (r = -0.17, p = 0.03) respiratory muscle groups and positively correlated to TLC for the scalene (r = 0.17, p = 0.04). Respiratory muscle hypermetabolism was found in 45 patients (28.8%), who had a lower VO2 max (15.4 [14.2-17.5] vs. 17.2 mL/kg/min [15.2-21.1], p = 0.07) and poorer overall survival when adjusting to FEV1% (p < 0.01). CONCLUSION: Our findings show respiratory muscle hypermetabolism is associated with lung function impairment and has prognostic significance. 18 F-FDG/PET-CT should be considered as a tool for assessing respiratory muscle activity and to identify high-risk patients.

Oxygen Uptake and Heart Rate On-Kinetics during Prehabilitation in Patients with Scheduled Non-Small Cell Lung Cancer Resection.

BACKGROUND: Oxygen uptake (V̇O2) and heart rate (HR) kinetics during a constant work-rate test (CWRT) are used to evaluate the response to exercise in healthy subjects as well as subjects with various pathologies. OBJECTIVES: This study aimed to explore the feasibility of these measures and their responsiveness to a prehabilitation program in patients with non-small cell lung cancer (NSCLC). METHOD: This study is preregistered (NCT04041297) ancillary analysis of a subgroup of individuals with NSCLC included in the Preo-Dens study (NCT03936764). Thirty individuals performed a moderate-CWRT before and after a 15-session prehabilitation program between July 2019 and April 2021. V̇O2 and HR on-kinetics were extracted from the first 240 s of breath-by-breath data using Box-Jenkins transfer functions. RESULTS: Pre/post V̇O2 on-kinetic feature values were reliable for 25/30 participants, and pre/post HR kinetic feature values were reliable for 19/30. V̇O2 time constant (τ) and mean response time reduced from pre-post prehabilitation (mean difference -7.8 s; 95% CI: -14.6 to -1.0, and -8.4 s; 95% CI: -14.7 to -2.0, respectively). For HR on-kinetics, τ did not change from pre-post prehabilitation (median difference -4.0 s; 95% CI: -36.0 to +11.0). V̇O2 and HR response amplitudes reduced significatively from pre-post prehabilitation (mean difference -38.6 mL/min; 95% CI: -73.3 to -3.9, and -3.1 beats/min; 95% CI: -6.4 to -0.2, respectively). CONCLUSION: V̇O2 on-kinetic analysis during moderate-CWRT is feasible in individuals with scheduled NSCLC resection, and results are responsive to prehabilitation. These results support a true speeding of the adaptation of aerobic metabolism after a 15-session prehabilitation program.

Effects of exercise training in people with non-small cell lung cancer before lung resection: a systematic review and meta-analysis.

INTRODUCTION: Exercise training before lung resection for non-small cell lung cancer is believed to decrease postoperative complications (POC) by improving cardiorespiratory fitness. However, this intervention lacks a strong evidence base. AIM: To assess the effectiveness of preoperative exercise training compared with usual care on POC and other secondary outcomes in patients with scheduled lung resection. METHODS: A systematic search of randomised trials was conducted by two authors. Meta-analysis was performed, and the effect of exercise training was estimated by risk ratios (RR) and mean differences, with their CIs. Clinical usefulness was estimated according to minimal important difference values (MID). RESULTS: Fourteen studies involving 791 participants were included. Compared with usual care, exercise training reduced overall POC (10 studies, 617 participants, RR 0.58, 95% CI 0.45 to 0.75) and clinically relevant POC (4 studies, 302 participants, Clavien-Dindo score ≥2 RR 0.42, 95% CI 0.25 to 0.69). The estimate of the effect of exercise training on mortality was very imprecise (6 studies, 456 participants, RR 0.66, 95% CI 0.20 to 2.22). The main risks of bias were a lack of participant blinding and selective reporting. Exercise training appeared to improve exercise capacity, pulmonary function and also quality of life and depression, although the clinical usefulness of the changes was unclear. The quality of the evidence was graded for each outcome. CONCLUSION: Preoperative exercise training leads to a worthwhile reduction in postoperative complications. These estimates were both accurate and large enough to make recommendations for clinical practice.

Defining successful non-invasive ventilation initiation: Data from a real-life cohort.

BACKGROUND AND OBJECTIVE: When home non-invasive ventilation (NIV) is initiated, five goals need to be achieved: a daily use >4 h/day, an improvement in gas exchange, health-related quality of life (HRQL) and sleep quality without side effects. Our aim was to assess how frequently these five goals were reached and the factors predictive of achievement. METHODS: We conducted a monocentric cohort study that included patients electively established on home NIV over 2 years. HRQL was assessed at baseline and follow-up by the Severe Respiratory Insufficiency questionnaire. Adequate initiation was defined as the achievement of at least three of five goals and successful initiation as the achievement of all. RESULTS: Two-hundred and fifty patients were included at baseline. NIV was initiated for: obesity hypoventilation syndrome (n = 95; 38%), neuromuscular disease (n = 70; 28%), chronic obstructive pulmonary disease (n = 66; 26%) and chest wall disease (n = 19; 8%). At follow-up, measures of all five goals were available in 141 (56%) patients. NIV initiation was adequate for 96 (68%) patients and successful for 12 (9%) patients. In multivariate analysis, a tidal volume ≥ 7.8 ml/kg of ideal body weight was associated with an increased likelihood of adequate NIV initiation (hazard ratio: 5.765 [95% CI:1.824-18.223], p = 0.006]. Improvement in daytime partial arterial carbon dioxide pressure (PaCO2 ) was not correlated to improvement in HRQL or sleep quality. Severe to very severe NIV-related side effects occurred in 114 (47%) patients and were associated with higher daytime PaCO2 (6.35 ± 1.08 vs. 5.92 ± 0.79 kPa, p < 0.001). CONCLUSION: Successful home NIV initiation is rarely achieved in real life. HRQL and NIV tolerance should be assessed to improve patient-centred outcomes.

Performance at stair-climbing test is associated with postoperative complications after lung resection: a systematic review and meta-analysis.

BACKGROUND: Thoracic surgery is the optimal treatment for early-stage lung cancer, but there is a high risk of postoperative morbidity. Therefore, it is necessary to evaluate patients' preoperative general condition and cardiorespiratory capacity to determine the risk of postoperative complications. The objective of this study was to assess whether the stair-climbing test could be used in the preoperative evaluation of lung resection patients to predict postoperative morbidity following thoracic surgery. METHODS: We performed a systematic review and a meta-analysis on the association between stair-climbing test result and morbidity/mortality after thoracic surgery. We analysed all articles published until May 2020 in the following databases: Pubmed/Medline, Pedro, The Cochrane library, Embase and CINAHL. The risk of bias was assessed using the Quality in Prognosis Studies tool. This meta-analysis is registered as PROSPERO CRD42019121348. RESULTS: 13 articles were included in the systematic review for a total of 2038 patients and 6 in the meta-analysis. There were multiple test evaluation criteria: rise time, height, desaturation and heart rate change. For the meta-analysis, we were able to pool data on the height of rise at a variable threshold: risk ratio 2.34 (95% CI 1.59 to 3.43) with I²=53% (p=0.06). The threshold for occurrence of complications was estimated at a 10 m climb. CONCLUSIONS: Our results indicate that the stair-climbing test could be used as a first-line functional screening test to predict postoperative morbidity following thoracic surgery and that patients with a poor test result (<10 m) should be referred to formal cardiopulmonary exercise testing.

Long-term survival following initiation of home non-invasive ventilation: a European study.

INTRODUCTION: Although home non-invasive ventilation (NIV) is increasingly used to manage patients with chronic ventilatory failure, there are limited data on the long-term outcome of these patients. Our aim was to report on home NIV populations and the long-term outcome from two European centres. METHODS: Cohort analysis including all patients established on home NIV from two European centres between 2008 and 2014. RESULTS: Home NIV was initiated in 1746 patients to treat chronic ventilatory failure caused by (1) obesity hypoventilation syndrome±obstructive sleep apnoea (OHS±OSA) (29.5%); (2) neuromuscular disease (NMD) (22.7%); and (3) obstructive airway diseases (OAD) (19.1%). Overall cohort median survival following NIV initiation was 6.6 years. Median survival varied by underlying aetiology of respiratory failure: rapidly progressive NMD 1.1 years, OAD 2.7 years, OHS±OSA >7 years and slowly progressive NMD >7 years. Multivariate analysis demonstrated higher mortality in patients with rapidly progressive NMD (HR 4.78, 95% CI 3.38 to 6.75), COPD (HR 2.25, 95% CI 1.64 to 3.10), age >60 years at initiation of home NIV (HR 2.41, 95% CI 1.92 to 3.02) and NIV initiation following an acute admission (HR 1.38, 95% CI 1.13 to 1.68). Factors associated with lower mortality were NIV adherence >4 hours per day (HR 0.64, 95% CI 0.51 to 0.79), OSA (HR 0.51, 95% CI 0.31 to 0.84) and female gender (HR 0.79, 95% CI 0.65 to 0.96). CONCLUSION: The mortality rate following initiation of home NIV is high but varies significantly according to underlying aetiology of respiratory failure. In patients with chronic respiratory failure, initiation of home NIV following an acute admission and low levels of NIV adherence are poor prognostic features and may be amenable to intervention.

AVAPS-AE versus ST mode: A randomized controlled trial in patients with obesity hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Average volume-assured pressure support-automated expiratory positive airway pressure (AVAPS-AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2-month AVAPS-AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health-related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV. METHODS: This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime Pa CO2 > 6 kPa, BMI ≥ 30 kg/m2 , clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months. RESULTS: Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow-up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS-AE group. At baseline, Pa CO2 was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS-AE group (P = 0.032). No significant between-group difference was observed for objective sleep quality indices. Improvement in Pa CO2 was similar between groups with a mean reduction of -0.87 kPa (95% CI: -1.12 to -0.46) in the ST group versus -0.87 kPa (95% CI: -1.14 to -0.50) in the AVAPS-AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS-AE group (P = 0.012). CONCLUSION: AVAPS-AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange.

Polysomnography versus limited respiratory monitoring and nurse-led titration to optimise non-invasive ventilation set-up: a pilot randomised clinical trial.

Polysomnography (PSG) is recommended for non-invasive ventilation (NIV) set-up in patients with chronic respiratory failure. In this pilot randomised clinical trial, we compared the physiological effectiveness of NIV set-up guided by PSG to limited respiratory monitoring (LRM) and nurse-led titration in patients with COPD-obstructive sleep apnoea (OSA) overlap. The principal outcome of interest was change in daytime arterial partial pressure of carbon dioxide (PaCO2) at 3 months. Fourteen patients with daytime PaCO2 >6 kPa and body mass index >30 kg/m2 were recruited. At 3 months, PaCO2 was reduced by -0.88 kPa (95% CI -1.52 to -0.24 kPa) in the LRM group and by -0.36 kPa (95% CI -0.96 to 0.24 kPa) in the PSG group. These pilot data provide support to undertake a clinical trial investigating the clinical effectiveness of attended limited respiratory monitoring and PSG to establish NIV in patients with COPD-OSA overlap. TRIAL NUMBER: Results, NCT02444806.

Nasal High Flow for Stable Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

There is a growing body of evidence supporting the use of nasal high flow (NHF) to treat acute respiratory failure, particularly in Chronic Obstructive Pulmonary Disease (COPD) patients. Conversely, there are sparse data evaluating its effects in stable COPD patients.We identified randomized controlled trial comparing the effects of delivering air or oxygen via NHF, compared with delivering the same gas without NHF, in stable COPD patients through a systematic search using MEDLINE, CENTRAL, Science Direct, and others sources until January 2019. Study selection, data extraction and assessment of the risk of bias (using the Cochrane Risk of Bias tool) was performed by two independent authors.We included 6 studies (339 participants). Our meta-analysis showed a significant reduction of arterial carbon dioxide pressure (PaCO2) at long (two studies, MD -3 mmHg, [95% Confidence interval (CI) -4 to -2]) and short-term (two studies, MD -3 mmHg [95% CI -4 to -2]). NHF significantly improved quality of life on the St George's Respiratory Questionnaire (two studies, MD -5 out of 100, [95% CI -8 to -2]). NHF significantly reduced the rate of acute exacerbation at 1 year (one study, rate ratio: 0.6, [95% CI 0.6 to 0.7]). NHF did not significantly improve exercise capacity, hospitalization rate or mortality, but improved breathing pattern.NHF reduced PaCO2, acute exacerbation and improved quality of life in stable COPD patients. Further long-term studies are needed to confirm the present results and provide more data on patient-centered outcome such as quality of life, exacerbation, hospitalization and mortality.

Home-based Neuromuscular Electrical Stimulation as an Add-on to Pulmonary Rehabilitation Does Not Provide Further Benefits in Patients With Chronic Obstructive Pulmonary Disease: A Multicenter Randomized Trial.

OBJECTIVE: To assess the additional effect of a home-based neuromuscular electrical stimulation (NMES) program as an add-on to pulmonary rehabilitation (PR), on functional capacity in subjects with chronic obstructive pulmonary disease (COPD). DESIGN: Single-blind, multicenter randomized trial. SETTING: Three PR centers. PARTICIPANTS: Subjects with severe to very severe COPD (N=73; median forced expiratory volume in 1 second, 1L (25th-75th percentile, 0.8-1.4L) referred for PR. Twenty-two subjects discontinued the study, but only 1 dropout was related to the intervention (leg discomfort). INTERVENTION: Subjects were randomly assigned to either PR plus quadricipital home-based NMES (35Hz, 30min, 5 time per week) or PR without NMES for 8 weeks. MAIN OUTCOME MEASURE: The 6-minute walk test (6MWT) was used to assess functional capacity. RESULTS: Eighty-two percent of the scheduled NMES sessions were performed. In the whole sample, there were significant increases in the distance walked during the 6MWT (P<.01), peak oxygen consumption (P=.02), maximal workload (P<.01), modified Medical Research Council dyspnea scale (P<.01), and Saint George's Respiratory Questionnaire total score (P=.01). There was no significant difference in the magnitude of change for any outcome between groups. CONCLUSIONS: Home-based NMES as an add-on to PR did not result in further improvements in subjects with severe to very severe COPD; moreover, it may have been a burden for some patients.

Six-minute Stepper Test to Set Pulmonary Rehabilitation Intensity in Patients with COPD - A Retrospective Study.

Pulmonary rehabilitation (PR) improves outcomes in patients with chronic obstructive pulmonary disease (COPD). Optimal assessment includes cardiopulmonary exercise testing (CPET), but consultations are limited. Field tests could be used to individualize PR instead of CPET. The six-minute stepper test (6MST) is easy to set up and its sensitivity and reproducibility have previously been reported in patients with COPD. The aim of this study was to develop a prediction equation to set intensity in patients attending PR, based on the 6MST. The following relationships were analyzed: mean heart rate (HR) during the first (HR1-3) and last (HR4-6) 3 minutes of the 6MST and HR at the ventilatory threshold (HRvt) from CPET; step count at the end of the 6MST and workload at the Ventilatory threshold (VT) (Wvt); and forced expiratory volume in 1 second and step count during the 6MST. This retrospective study included patients with COPD referred for PR who underwent CPET, pulmonary function evaluations and the 6MST. Twenty-four patients were included. Prediction equations were HRvt = 0.7887 × HR1-3 + 20.83 and HRvt = 0.6180 × HR4-6 + 30.77. There was a strong correlation between HR1-3 and HR4-6 and HRvt (r = 0.69, p < 0.001 and r = 0.57, p < 0.01 respectively). A significant correlation was also found between step count and LogWvt (r = 0.63, p < 0.01). The prediction equation was LogWvt = 0.001722 × step count + 1.248. The 6MST could be used to individualize aerobic training in patients with COPD. Further prospective studies are needed to confirm these results.

Domiciliary Non-invasive Ventilation in COPD: An International Survey of Indications and Practices.

Despite the fact that metanalyses and clinical guidelines do not recommend the routine use of domiciliary non-invasive ventilation (NIV) for patients diagnosed with severe stable Chronic Obstructive Pulmonary Disease (COPD) and with chronic respiratory failure, it is common practice in some countries. We conducted an international web-survey of physicians involved in provision of long-term NIV to examine patterns of domiciliary NIV use in patients diagnosed with COPD. The response rate was 41.6%. A reduction of hospital admissions, improvements in quality of life and dyspnea relief were considered as the main expected benefits for patients. Nocturnal oxygen saturation assessment was the principal procedure performed before NIV prescription. Recurrent exacerbations (>3) requiring NIV and failed weaning from in hospital NIV were the most important reasons for starting domiciliary NIV. Pressure support ventilation (PSV) was the most common mode, with "low" intensity settings (PSV-low) the most popular (44.4 ± 30.1%) compared with "high" intensity (PSV-high) strategies (26.9 ± 25.9%), with different geographical preferences. COPD is confirmed to be a common indication for domiciliary NIV. Recurrent exacerbations and failed weaning from in-hospital NIV were the main reasons for its prescription.

Health-related quality of life in patients with alpha-1 antitrypsin deficiency: the French experience.

The French registry of patients with alpha-1 antitrypsin deficiency (AATD)-associated emphysema was launched in 2006. Here, we aimed to report on the baseline characteristics of these patients, their health-related quality of life (HRQoL) and factors associated with HRQoL. Another goal was to survey the practices of French physicians regarding augmentation therapy. We included 273 patients with AATD, emphysema, obstructive-pattern [forced expiratory volume in 1 sec/forced volume capacity (FEV1/FVC) < 0.7], FEV1 ≤ 80% predicted. Mean (SD) age was 51.8 (11.1) years, 240 (87.9%) of patients were smokers or ex-smokers, mean (SD) FEV1 was 40.5% (15.7) predicted. Mean (SD) SGRQ score was 49.0 (20.0) and was higher for females than males (52.7 [20.7] vs 46.8 [18.2]; p = 0.01). Dyspnea showed the strongest association with SGRQ score (r = 0.65; p < 0.0001), followed by chronic bronchitis (r = 0.33; p < 0.0001) and wheezing (r = 0.32; p < 0.0001). Number of exacerbations in the year before inclusion was also significantly associated with SGRQ score (r = 0.36; p < 0.0001). The SGRQ score was associated with the 6-min walking distance (r = -0.53, p < 0.0001), FEV1 (% predicted, r = -0.53, p < 0.0001) and DLCO (% predicted, r = -0.52, p < 0.0001). It was also associated with the GOLD 2006 (r = 0.53; p < 0.0001) and GOLD 2011 (r = 0.63; p< 0.0001) classifications and with the BODE index (r = 0.37; p < 0.0001). Age, history of tobacco smoking or current smoking did not show any association with SGRQ total scores. On multivariate analysis, a model including age, chronic bronchitis, dyspnea (MRC scale), diffusing lung capacity and 6-min walking distance explained 57% of the variation in the score. The French registry provides important insights into the clinical characteristics of French patients with AATD-related emphysema.

Performance of the BODE index in patients with α1-antitrypsin deficiency-related COPD.

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD. We assessed the prognostic value of the BODE index in 191 patients followed from 2006 to 2012 in a French prospective cohort of patients with α1-antitrypsin deficiency. 20 patients died during follow-up and 22 underwent lung transplantation. Survival (95% CI) was 93.0% (91.7-94.3%) at 3 years and 76.0% (72.9-79.1%) at 5 years. The 3-year survival was 97.4% (96.6-98.2%), 98.0% (96.7-99.3%), 87.7% (84.5-90.9%) and 75.3% (66.0-84.6%) for patients with BODE index 0-2, 3-4, 5-6 and 7-10, respectively. Survival discrimination of the BODE index was better than with both forced expiratory volume in 1 s and Global Initiative for Chronic Obstructive Lung Disease classification. Regarding calibration, expected survival by BODE index was noticeably lower than observed survival. The BODE index showed very good survival discrimination in patients with α1-antitrypsin deficiency-related COPD. Larger studies are needed to support its use to drive patient referral for lung transplantation.