Gait differences between COPD and healthy controls: systematic review and meta-analysis.

BACKGROUND: Despite the importance of gait as a determinant of falls, disability and mortality in older people, understanding of gait impairment in COPD is limited. This study aimed to identify differences in gait characteristics during supervised walking tests between people with COPD and healthy controls. METHODS: We searched 11 electronic databases, supplemented by Google Scholar searches and manual collation of references, in November 2019 and updated the search in July 2021. Record screening and information extraction were performed independently by one reviewer and checked for accuracy by a second. Meta-analyses were performed in studies not considered at a high risk of bias. RESULTS: Searches yielded 21 085 unique records, of which 25 were included in the systematic review (including 1015 people with COPD and 2229 healthy controls). Gait speed was assessed in 17 studies (usual speed: 12; fast speed: three; both speeds: two), step length in nine, step duration in seven, cadence in six, and step width in five. Five studies were considered at a high risk of bias. Low-quality evidence indicated that people with COPD walk more slowly than healthy controls at their usual speed (mean difference (MD) -19 cm·s-1, 95% CI -28 to -11 cm·s-1) and at a fast speed (MD -30 cm·s-1, 95% CI -47 to -13 cm·s-1). Alterations in other gait characteristics were not statistically significant. CONCLUSION: Low-quality evidence shows that people with COPD walk more slowly than healthy controls, which could contribute to an increased falls risk. The evidence for alterations in spatial and temporal components of gait was inconclusive. Gait impairment appears to be an important but understudied area in COPD.

Small airways in asthma: From inflammation and pathophysiology to treatment response.

Small airways are characterized as those with an inner diameter less than 2 mm and constitute a major site of pathology and inflammation in asthma disease. It is estimated that small airways dysfunction may occur before the emergence of noticeable symptoms, spirometric abnormalities and imaging findings, thus characterizing them as "the quiet or silent zone" of the lungs. Despite their importance, measuring and quantifying small airways dysfunction presents a considerable challenge due to their inaccessibility in usual functional measurements, primarily due to their size and peripheral localization. Several pulmonary function tests have been proposed for the assessment of the small airways, including impulse oscillometry, nitrogen washout, body plethysmography, as well as imaging methods. Nevertheless, none of these methods has been established as the definitive "gold standard," thus, a combination of them should be used for an effective assessment of the small airways. Widely used asthma treatments seem to also affect several parameters of the small airways. Emerging biologic treatments show promising results in reducing small airways inflammation and remodelling, providing evidence for potential alterations in the disease's progression and outcomes. These novel therapies have implications not only in the clinical aspects of asthma but also in its inflammatory and functional aspects.

Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis.

BACKGROUND: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival. METHODS: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed. RESULTS: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75-0.88, p<0.001), gait speed (<0.80 m·s-1) (HR 3.55, 95% CI 1.72-7.36, p<0.001) and gait speed (per 1.0 m·s-1) (HR 7.55, 95% CI 1.11-51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s-1) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72-0.88, p<0.001; OR 3.36, 95% CI 1.42-7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis. CONCLUSION: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for.

Laboratory and free-living gait performance in adults with COPD and healthy controls.

Background: Gait characteristics are important risk factors for falls, hospitalisations and mortality in older adults, but the impact of COPD on gait performance remains unclear. We aimed to identify differences in gait characteristics between adults with COPD and healthy age-matched controls during 1) laboratory tests that included complex movements and obstacles, 2) simulated daily-life activities (supervised) and 3) free-living daily-life activities (unsupervised). Methods: This case-control study used a multi-sensor wearable system (INDIP) to obtain seven gait characteristics for each walking bout performed by adults with mild-to-severe COPD (n=17; forced expiratory volume in 1 s 57±19% predicted) and controls (n=20) during laboratory tests, and during simulated and free-living daily-life activities. Gait characteristics were compared between adults with COPD and healthy controls for all walking bouts combined, and for shorter (≤30 s) and longer (>30 s) walking bouts separately. Results: Slower walking speed (-11 cm·s-1, 95% CI: -20 to -3) and lower cadence (-6.6 steps·min-1, 95% CI: -12.3 to -0.9) were recorded in adults with COPD compared to healthy controls during longer (>30 s) free-living walking bouts, but not during shorter (≤30 s) walking bouts in either laboratory or free-living settings. Double support duration and gait variability measures were generally comparable between the two groups. Conclusion: Gait impairment of adults with mild-to-severe COPD mainly manifests during relatively long walking bouts (>30 s) in free-living conditions. Future research should determine the underlying mechanism(s) of this impairment to facilitate the development of interventions that can improve free-living gait performance in adults with COPD.

Effects of pharmacological and non-pharmacological interventions on physical activity outcomes in COPD: a systematic review and meta-analysis.

Rationale: The effect of pharmacological and non-pharmacological interventions on physical activity (PA) outcomes is not fully elucidated in patients with COPD. The objectives of the present study were to provide estimation of treatment effects of all available interventions on PA outcomes in patients with COPD and to provide recommendations regarding the future role of PA outcomes in pharmacological trials. Materials and methods: This review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported in line with PRISMA. Records were identified through searches of 12 scientific databases; the most updated search was performed in January 2023. Results: 74 studies published from 2000 to 2021 were included, with a total of 8140 COPD patients. Forced expiratory volume in 1 s % predicted ranged between 31% and 74%, with a mean of 55%. Steps/day constituted the most frequently assessed PA outcome in interventional studies. Compared to usual care, PA behavioural modification interventions resulted in improvements in the mean (95% CI) steps/day when implemented alone (by 1035 (576-1493); p<0.00001) or alongside exercise training (by 679 (93-1266); p=0.02). Moreover, bronchodilator therapy yielded a favourable difference of 396 (125-668; p=0.004) steps/day, compared to placebo. Conclusions: PA behavioural modification and pharmacological interventions lead to significant improvements in steps/day, compared to control and placebo groups, respectively. Compared to bronchodilator therapy, PA behavioural modification interventions were associated with a 2-fold greater improvement in steps/day. Large-scale pharmacological studies are needed to establish an intervention-specific minimal clinically important difference for PA outcomes as well as their convergent validity to accelerate qualification as potential biomarkers and efficacy end-points for regulatory approval.

The Role of Rehabilitation in Arterial Function Properties of Convalescent COVID-19 Patients.

Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement-the Mobilise-D study protocol.

BACKGROUND: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. METHODS/DESIGN: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson's Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. DISCUSSION: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. TRIAL REGISTRATION: ISRCTN12051706.

Technical validation of real-world monitoring of gait: a multicentric observational study.

INTRODUCTION: Existing mobility endpoints based on functional performance, physical assessments and patient self-reporting are often affected by lack of sensitivity, limiting their utility in clinical practice. Wearable devices including inertial measurement units (IMUs) can overcome these limitations by quantifying digital mobility outcomes (DMOs) both during supervised structured assessments and in real-world conditions. The validity of IMU-based methods in the real-world, however, is still limited in patient populations. Rigorous validation procedures should cover the device metrological verification, the validation of the algorithms for the DMOs computation specifically for the population of interest and in daily life situations, and the users' perspective on the device. METHODS AND ANALYSIS: This protocol was designed to establish the technical validity and patient acceptability of the approach used to quantify digital mobility in the real world by Mobilise-D, a consortium funded by the European Union (EU) as part of the Innovative Medicine Initiative, aiming at fostering regulatory approval and clinical adoption of DMOs.After defining the procedures for the metrological verification of an IMU-based device, the experimental procedures for the validation of algorithms used to calculate the DMOs are presented. These include laboratory and real-world assessment in 120 participants from five groups: healthy older adults; chronic obstructive pulmonary disease, Parkinson's disease, multiple sclerosis, proximal femoral fracture and congestive heart failure. DMOs extracted from the monitoring device will be compared with those from different reference systems, chosen according to the contexts of observation. Questionnaires and interviews will evaluate the users' perspective on the deployed technology and relevance of the mobility assessment. ETHICS AND DISSEMINATION: The study has been granted ethics approval by the centre's committees (London-Bloomsbury Research Ethics committee; Helsinki Committee, Tel Aviv Sourasky Medical Centre; Medical Faculties of The University of Tübingen and of the University of Kiel). Data and algorithms will be made publicly available. TRIAL REGISTRATION NUMBER: ISRCTN (12246987).

Walking on common ground: a cross-disciplinary scoping review on the clinical utility of digital mobility outcomes.

Physical mobility is essential to health, and patients often rate it as a high-priority clinical outcome. Digital mobility outcomes (DMOs), such as real-world gait speed or step count, show promise as clinical measures in many medical conditions. However, current research is nascent and fragmented by discipline. This scoping review maps existing evidence on the clinical utility of DMOs, identifying commonalities across traditional disciplinary divides. In November 2019, 11 databases were searched for records investigating the validity and responsiveness of 34 DMOs in four diverse medical conditions (Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture). Searches yielded 19,672 unique records. After screening, 855 records representing 775 studies were included and charted in systematic maps. Studies frequently investigated gait speed (70.4% of studies), step length (30.7%), cadence (21.4%), and daily step count (20.7%). They studied differences between healthy and pathological gait (36.4%), associations between DMOs and clinical measures (48.8%) or outcomes (4.3%), and responsiveness to interventions (26.8%). Gait speed, step length, cadence, step time and step count exhibited consistent evidence of validity and responsiveness in multiple conditions, although the evidence was inconsistent or lacking for other DMOs. If DMOs are to be adopted as mainstream tools, further work is needed to establish their predictive validity, responsiveness, and ecological validity. Cross-disciplinary efforts to align methodology and validate DMOs may facilitate their adoption into clinical practice.

Acute thoracoabdominal and hemodynamic responses to tapered flow resistive loading in healthy adults.

We investigated the acute physiological responses of tapered flow resistive loading (TFRL) at 30, 50 and 70 % maximal inspiratory pressure (PImax) in 12 healthy adults to determine an optimal resistive load. Increased end-inspiratory rib cage and decreased end-expiratory abdominal volumes equally contributed to the expansion of thoracoabdominal tidal volume (captured by optoelectronic plethysmography). A significant decrease in end-expiratory thoracoabdominal volume was observed from 30 to 50 % PImax, from 30 to 70 % PImax, and from 50 to 70 % PImax. Cardiac output (recorded by cardio-impedance) increased from rest by 30 % across the three loading trials. Borg dyspnoea increased from 2.36 ±â€¯0.20 at 30 % PImax, to 3.45 ±â€¯0.21 at 50 % PImax, and 4.91 ±â€¯0.25 at 70 % PImax. End-tidal CO2 decreased from rest during 30, 50 and 70 %PImax (26.23 ±â€¯0.59, 25.87 ±â€¯1.02 and 24.30 ±â€¯0.82 mmHg, respectively). Optimal intensity for TFRL is at 50 % PImax to maximise global respiratory muscle and cardiovascular loading whilst minimising hyperventilation and breathlessness.

Walking-related digital mobility outcomes as clinical trial endpoint measures: protocol for a scoping review.

INTRODUCTION: Advances in wearable sensor technology now enable frequent, objective monitoring of real-world walking. Walking-related digital mobility outcomes (DMOs), such as real-world walking speed, have the potential to be more sensitive to mobility changes than traditional clinical assessments. However, it is not yet clear which DMOs are most suitable for formal validation. In this review, we will explore the evidence on discriminant ability, construct validity, prognostic value and responsiveness of walking-related DMOs in four disease areas: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease and proximal femoral fracture. METHODS AND ANALYSIS: Arksey and O'Malley's methodological framework for scoping reviews will guide study conduct. We will search seven databases (Medline, CINAHL, Scopus, Web of Science, EMBASE, IEEE Digital Library and Cochrane Library) and grey literature for studies which (1) measure differences in DMOs between healthy and pathological walking, (2) assess relationships between DMOs and traditional clinical measures, (3) assess the prognostic value of DMOs and (4) use DMOs as endpoints in interventional clinical trials. Two reviewers will screen each abstract and full-text manuscript according to predefined eligibility criteria. We will then chart extracted data, map the literature, perform a narrative synthesis and identify gaps. ETHICS AND DISSEMINATION: As this review is limited to publicly available materials, it does not require ethical approval. This work is part of Mobilise-D, an Innovative Medicines Initiative Joint Undertaking which aims to deliver, validate and obtain regulatory approval for DMOs. Results will be shared with the scientific community and general public in cooperation with the Mobilise-D communication team. REGISTRATION: Study materials and updates will be made available through the Center for Open Science's OSFRegistry (https://osf.io/k7395).

Greater exercise tolerance in COPD during acute interval, compared to equivalent constant-load, cycle exercise: physiological mechanisms.

KEY POINTS: Exercise intolerance is common in chronic obstructive pulmonary disease (COPD) patients. In patients with COPD, we compared an interval exercise (IE) protocol (alternating 30 s at 100% peak work rate (WRpeak ) with 30 s at 50% WRpeak ) with moderate-intensity constant-load exercise (CLE) at 75% WRpeak , which yielded the same work rate. Exercise endurance time and total work output were almost twice as high for IE than CLE. At exercise isotime (when work completed was the same between IE and CLE), IE was associated with less dynamic hyperinflation, lower blood lactate concentration, and greater respiratory and locomotor muscle oxygenation, but there were no differences in ventilation or cardiac output. However, at the limit of tolerance for each modality, dynamic hyperinflation was not different between IE and CLE, while blood lactate remained lower and muscle oxygenation higher with IE. Taken together, these findings suggest that dynamic hyperinflation and not muscle-based factors dictate the limits of tolerance in these COPD patients. ABSTRACT: The relative importance of ventilatory, circulatory and peripheral muscle factors in determining tolerance to exercise in patients with chronic obstructive pulmonary disease (COPD) is not known. In 12 COPD patients (forced expiratory volume in one second: 58 ± 17%pred.) we measured ventilation, cardiac output, dynamic hyperinflation, local muscle oxygenation, blood lactate and time to exhaustion during (a) interval exercise (IE) consisting of 30 s at 100% peak work rate alternating with 30 s at 50%, and (b) constant-load exercise (CLE) at 75% peak work rate, designed to produce the same average work rate. Exercise time was substantially longer during IE than CLE (19.5 ± 4.8 versus 11.4 ± 2.1 min, p = 0.0001). Total work output was therefore greater during IE than CLE (81.3 ± 27.7 versus 48.9 ± 23.8 kJ, p = 0.0001). Dynamic hyperinflation (assessed by changes from baseline in inspiratory capacity, ΔIC) was less during IE than CLE at CLE exhaustion time (isotime, p = 0.009), but was similar at exhaustion (ΔICCLE : -0.38 ± 0.10 versus ΔICIE : -0.33 ± 0.12 l, p = 0.102). In contrast, at isotime, minute ventilation, cardiac output and systemic oxygen delivery did not differ between protocols (P > 0.05). At exhaustion in both protocols, the vastus lateralis and intercostal muscle oxygen saturation were higher in IE than CLE (p = 0.014 and p = 0.0002, respectively) and blood lactate concentrations were lower (4.9 ± 2.4 mmol l-1 versus 6.4 ± 2.2 mmol l-1 , p = 0.039). These results suggest that (1) exercise tolerance with COPD is limited by dynamic hyperinflation; and (2) cyclically lower (50%) effort intervals in IE help to preserve muscle oxygenation and reduce metabolic acidosis compared with CLE at the same average work rate; but these factors do not appear to determine time to exhaustion.

Effect of portable non-invasive ventilation on exercise tolerance in COPD: One size does not fit all.

In a cross-over RCT, portable NIV (pNIV) reduced dynamic hyperinflation (DH) compared to pursed lip breathing (PLB) during recovery from intermittent exercise in COPD, but not consistently in all subjects. In this post-hoc analysis, DH response was defined as a reduction ≥4.5 % of predicted resting inspiratory capacity with pNIV compared to PLB. At exercise iso-time (where work completed was consistent between pNIV and PLB), 8/24 patients were DH non-responders (DH: 240 ± 40 mL, p = 0.001 greater using pNIV). 16/24 were DH responders (DH: 220 ± 50 mL, p = 0.001 lower using pNIV). Compared to DH responders, DH non-responders exhibited greater resting DH (RV/TLC: 65 ± 4% versus 56 ± 2%; p = 0.028) and did not improve exercise tolerance (pNIV: 30.9 ± 3.4 versus PLB: 29.9 ± 3.3 min; p = 0.603). DH responders increased exercise tolerance (pNIV: 34.9 ± 2.4 versus PLB: 27.1 ± 2.3 min; p = 0.001). Resting RV/TLC% was negatively associated with the magnitude of DH when using pNIV compared to PLB (r=-0.42; p = 0.043). Patients with profound DH were less likely to improve exercise tolerance with pNIV. Further studies using auto-adjusted ventilators are warranted.

Use of pedometers as a tool to promote daily physical activity levels in patients with COPD: a systematic review and meta-analysis.

The aim of this study was to examine the use of pedometers as a tool to promote daily physical activity levels in patients with COPD.A systematic review meta-analysis of pedometer physical activity promotion in patients with COPD was conducted. Medline/PubMed, Cochrane Library, Web of Science and CINAHL were searched from inception to January 2019. The search strategy included the following keywords: physical activity promotion, pulmonary rehabilitation and daily physical activity. The eligibility criteria for selecting studies were randomised controlled trials reporting pedometer physical activity promotion in patients with COPD.Improvements in steps per day were found with pedometer physical activity promotion either standalone (n=12, mean 0.53 (95% CI 0.29-0.77); p=0.00001) or alongside pulmonary rehabilitation (n=7, 0.51 (0.13-0.88); p=0.006). A subgroup analysis reported significant differences in the promotion of physical activity based on baseline physical activity levels and the type of instrument used to assess levels of physical activity.Future trials should consider the way in which pedometers are used to promote physical activity to inform clinical practice in the setting of pulmonary rehabilitation.

Hemodynamic effects of portable non-invasive ventilation in healthy men.

VitaBreath is a portable, non-invasive ventilation device (pNIV) that relieves shortness of breath in COPD by delivering fixed inspiratory and expiratory positive airway pressures (IPAP/EPAP: 18/8 cmH2O). Fixed pressures may cause circulatory compromise. We investigated the circulatory effects of pNIV during normal breathing (NB) and after Eucapnic Voluntary Hyperpnoea trials (EVH) sustained at 80% MVV. In a balanced order sequence, 10 healthy men performed four trials on one visit: 1-min of pNIV (intervention) or 1-min quiet breathing (QB) during NB; and 1-min pNIV (intervention) or 1-min QB during recovery from 3-min EVH. Compared to QB, pNIV application was associated with greater cardiac output (CO: 1.6 ± 1.9 L.min-1; P = 0.03). One minute into recovery from EVH, pNIV caused greater CO (2.2 ± 1.6 L.min-1; P = 0.01) compared to QB. Mean blood pressure was not different with pNIV compared to control. pNIV increased thoracoabdominal volumes and breathing frequency during NB and recovery from EVH. pNIV application does not induce adverse hemodynamic effects in healthy men.

Cardiac output measurement during exercise in COPD: A comparison of dye dilution and impedance cardiography.

INTRODUCTION: Impedance cardiography (IC) derived from morphological analysis of the thoracic impedance signal is now commonly used for noninvasive assessment of cardiac output (CO) at rest and during exercise. However, in Chronic Obstructive Pulmonary Disease (COPD), conflicting findings put its accuracy into question. OBJECTIVES: We therefore compared concurrent CO measurements captured by IC (PhysioFlow: COIC ) and by the indocyanine green dye dilution method (CODD ) in patients with COPD. METHODS: Fifty paired CO measurements were concurrently obtained using the two methods from 10 patients (FEV1 : 50.5 ± 17.5% predicted) at rest and during cycling at 25%, 50%, 75% and 100% peak work rate. RESULTS: From rest to peak exercise COIC and CODD were strongly correlated (r = 0.986, P < 0.001). The mean absolute and percentage differences between COIC and CODD were 1.08 L/min (limits of agreement (LoA): 0.05-2.11 L/min) and 18 ± 2%, respectively, with IC yielding systematically higher values. Bland-Altman analysis indicated that during exercise only 7 of the 50 paired measurements differed by more than 20%. When data were expressed as changes from rest, correlations and agreement between the two methods remained strong over the entire exercise range (r = 0.974, P < 0.001, with no significant difference: 0.19 L/min; LoA: -0.76 to 1.15 L/min). Oxygen uptake (VO2 ) and CODD were linearly related: r = 0.893 (P < 0.001), CODD = 5.94 × VO2 + 2.27 L/min. Similar results were obtained for VO2 and COIC (r = 0.885, P < 0.001, COIC = 6.00 × VO2 + 3.30 L/min). CONCLUSIONS: These findings suggest that IC provides an acceptable CO measurement from rest to peak cycling exercise in patients with COPD.

Intermittent Use of Portable NIV Increases Exercise Tolerance in COPD: A Randomised, Cross-Over Trial.

During exercise, non-invasive ventilation (NIV) prolongs endurance in chronic obstructive pulmonary disease (COPD), but routine use is impractical. The VitaBreath device provides portable NIV (pNIV); however, it can only be used during recovery. We assessed the effect of pNIV compared to pursed lip breathing (PLB) on exercise tolerance. Twenty-four COPD patients were randomised to a high-intensity (HI: 2-min at 80% peak work rate (WRpeak) alternated with 2-min recovery; n = 13), or a moderate-intensity (MOD: 6-min at 60% WRpeak alternated with 2-min recovery; n = 11) protocol, and within these groups two tests were performed using pNIV and PLB during recovery in balanced order. Upon completion, patients were provided with pNIV; use over 12 weeks was assessed. Compared to PLB, pNIV increased exercise tolerance (HI: by 5.2 ± 6.0 min; MOD: by 5.8 ± 6.7 min) (p < 0.05). With pNIV, mean inspiratory capacity increased and breathlessness decreased by clinically meaningful margins during recovery compared to the end of exercise (HI: by 140 ± 110 mL and 1.2 ± 1.7; MOD: by 170 ± 80 mL and 1.0 ± 0.7). At 12 weeks, patients reported that pNIV reduced anxiety (median: 7.5/10 versus 4/10, p = 0.001) and recovery time from breathlessness (17/24 patients; p = 0.002); 23/24 used the device at least weekly. pNIV increased exercise tolerance by reducing dynamic hyperinflation and breathlessness in COPD patients.

Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits.

Pulmonary rehabilitation (PR) remains grossly underutilised by suitable patients worldwide. We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease (COPD) exacerbations, hospitalisations and emergency department (ED) visits.Following completion of an initial 2-month PR programme this prospective, randomised controlled trial (between December 2013 and July 2015) compared 12 months of home-based maintenance tele-rehabilitation (n=47) with 12 months of hospital-based, outpatient, maintenance rehabilitation (n=50) and also to 12 months of usual care treatment (n=50) without initial PR.In a multivariate analysis during the 12-month follow-up, both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1) acute COPD exacerbation (incidence rate ratio (IRR) 0.517, 95% CI 0.389-0.687, and IRR 0.635, 95% CI 0.473-0.853), respectively, and 2) hospitalisations for acute COPD exacerbation (IRR 0.189, 95% CI 0.100-0.358, and IRR 0.375, 95% CI 0.207-0.681), respectively. However, only home-based maintenance tele-rehabilitation and not hospital-based, outpatient, maintenance PR was an independent predictor of ED visits (IRR 0.116, 95% CI 0.072-0.185).Home-based maintenance tele-rehabilitation is equally effective as hospital-based, outpatient, maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations. In addition, it encounters a lower risk for ED visits, thereby constituting a potentially effective alternative strategy to hospital-based, outpatient, maintenance PR.