Differential Outcomes Following 4 Weeks of Aclidinium/Formoterol in Patients with COPD: A Reanalysis of the ACTIVATE Study.

Rationale: It is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD. Methods: In the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate (AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups. Results: A total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients. Conclusion: Individual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy. Clinical Trial Registration: The original ACTIVATE study was registered on ClinicalTrials.gov, registration number NCT02424344.

A pilot study on the feasibility and effectiveness of treadmill-based perturbations for assessing and improving walking stability in chronic obstructive pulmonary disease.

BACKGROUND: Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD. METHODS: 12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed. FINDINGS: Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants. INTERPRETATION: Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD.

An update on pulmonary rehabilitation techniques for patients with chronic obstructive pulmonary disease.

Introduction: Pulmonary rehabilitation (PR) is one of the core components in the management of patients with chronic obstructive pulmonary disease (COPD). In order to achieve the maximal level of independence, autonomy, and functioning of the patient, targeted therapies and interventions based on the identification of physical, emotional and social traits need to be provided by a dedicated, interdisciplinary PR team.Areas covered: The review discusses cardiopulmonary exercise testing in the selection of different modes of training modalities. Neuromuscular electrical stimulation as well as gait assessment and training are discussed as well as add-on therapies as oxygen, noninvasive ventilator support or endoscopic lung volume reduction in selected patients. The potentials of pulsed inhaled nitric oxide in patients with underlying pulmonary hypertension is explored as well as nutritional support. The impact of sleep quality on outcomes of PR is reviewed.Expert opinion: Individualized, comprehensive intervention based on thorough assessment of physical, emotional, and social traits in COPD patients forms a continuous challenge for health-care professionals and PR organizations in order to dynamically implement and adapt these strategies based on dynamic, more optimal understanding of underlying pathophysiological mechanisms.

Effects of Non-Invasive Ventilation Combined with Oxygen Supplementation on Exercise Performance in COPD Patients with Static Lung Hyperinflation and Exercise-Induced Oxygen Desaturation: A Single Blind, Randomized Cross-Over Trial.

The effects of non-invasive ventilation (NIV) in addition to supplemental oxygen on exercise performance in patients with chronic obstructive pulmonary disease (COPD) with hyperinflation and exercise-induced desaturation (EID) remain unclear. We hypothesized that these patients would benefit from NIV and that this effect would be an add-on to oxygen therapy. Thirteen COPD patients with a residual volume >150% of predicted, normal resting arterial oxygen pressure (PaO2) and carbon-dioxide pressure (PaCO2) and EID during a six-minute walk test were included. Patients performed four constant work-rate treadmill tests, each consisting of two exercise bouts with a recovery period in between, wearing an oronasal mask connected to a ventilator and oxygen supply. The ventilator was set to the following settings in fixed order with clockwise rotation: Sham (continuous positive airway pressure (CPAP) 2 cm H2O, FiO2 21%), oxygen (CPAP 2 cm H2O, FiO2 35%), NIV and oxygen (inspiratory positive airway pressure (IPAP) 14 cm H2O/expiratory positive airway pressure (EPAP) 6 cm H2O, inspired oxygen fraction (FiO2) 35%), intermittent (walking: Sham setting, recovery: NIV and oxygen setting). During the first exercise, bout patients walked further with the oxygen setting compared to the sham setting (225 ± 107 vs 120 ± 50 meters, p < 0.05), but even further with the oxygen/NIV setting (283 ± 128 meters; p < 0.05). Recovery time between two exercise bouts was shortest with NIV and oxygen. COPD patients with severe static hyperinflation and EID benefit significantly from NIV in addition to oxygen during exercise and recovery.

Wearable Finger Pulse Oximetry for Continuous Oxygen Saturation Measurements During Daily Home Routines of Patients With Chronic Obstructive Pulmonary Disease (COPD) Over One Week: Observational Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients can suffer from low blood oxygen concentrations. Peripheral blood oxygen saturation (SpO2), as assessed by pulse oximetry, is commonly measured during the day using a spot check, or continuously during one or two nights to estimate nocturnal desaturation. Sampling at this frequency may overlook natural fluctuations in SpO2. OBJECTIVE: This study used wearable finger pulse oximeters to continuously measure SpO2 during daily home routines of COPD patients and assess natural SpO2 fluctuations. METHODS: A total of 20 COPD patients wore a WristOx2 pulse oximeter for 1 week to collect continuous SpO2 measurements. A SenseWear Armband simultaneously collected actigraphy measurements to provide contextual information. SpO2 time series were preprocessed and data quality was assessed afterward. Mean SpO2, SpO2 SD, and cumulative time spent with SpO2 below 90% (CT90) were calculated for every (1) day, (2) day in rest, and (3) night to assess SpO2 fluctuations. RESULTS: A high percentage of valid SpO2 data (daytime: 93.27%; nocturnal: 99.31%) could be obtained during a 7-day monitoring period, except during moderate-to-vigorous physical activity (MVPA) (67.86%). Mean nocturnal SpO2 (89.9%, SD 3.4) was lower than mean daytime SpO2 in rest (92.1%, SD 2.9; P<.001). On average, SpO2 in rest ranged over 10.8% (SD 4.4) within one day. Highly varying CT90 values between different nights led to 50% (10/20) of the included patients changing categories between desaturator and nondesaturator over the course of 1 week. CONCLUSIONS: Continuous SpO2 measurements with wearable finger pulse oximeters identified significant SpO2 fluctuations between and within multiple days and nights of patients with COPD. Continuous SpO2 measurements during daily home routines of patients with COPD generally had high amounts of valid data, except for motion artifacts during MVPA. The identified fluctuations can have implications for telemonitoring applications that are based on daily SpO2 spot checks. CT90 values can vary greatly from night to night in patients with a nocturnal mean SpO2 around 90%, indicating that these patients cannot be consistently categorized as desaturators or nondesaturators. We recommend using wearable sensors for continuous SpO2 measurements over longer time periods to determine the clinical relevance of the identified SpO2 fluctuations.

Effectiveness of Pulmonary Rehabilitation in Patients With Chronic Obstructive Pulmonary Disease With Different Degrees of Static Lung Hyperinflation.

OBJECTIVE: To evaluate the effect of pulmonary rehabilitation (PR) on exercise performance and quality of life in patients with chronic obstructive pulmonary disease (COPD) with different degrees of static lung hyperinflation (LH). DESIGN: Retrospective cohort study. SETTING: PR network. PARTICIPANTS: A cohort of 1981 patients with COPD (55% men; age: 66.8±9.3y; forced expiratory volume in the first second%: 50.7±19.5; residual volume [RV]%: 163.0±49.7). INTERVENTION: An interdisciplinary PR program for patients with COPD consisting of 40 sessions. MAIN OUTCOME MEASURES: Participants were stratified into 5 quintiles according to baseline RV and were evaluated on the basis of pre- and post-PR 6-minute walk distance (6MWD), constant work rate test (CWRT), and Saint George's Respiratory Questionnaire (SGRQ), among other clinical parameters. RESULTS: With increasing RV quintile, patients were younger, more frequently women, had lower forced expiratory volume in the first second%, lower body mass index and fat-free mass index, shorter 6MWD, shorter CWRT, and worse SGRQ scores (P<.01). All RV strata improved after PR in all 3 outcomes (P<.001). Nevertheless, higher, compared to lower RV categories, had lower ΔCWRT (P<.01) but similar Δ6MWD (P=.948) and ΔSGRQ (P=.086) after PR. CONCLUSIONS: LH in COPD is related to younger age, female sex, lower body weight, worse exercise capacity and health status, but did not prevent patients from benefitting from PR. LH, however, influences walking and cycling response after PR differently.

Increased exercise tolerance using daytime mouthpiece ventilation for patients with diaphragm paralysis.

Mouthpiece ventilation can improve exercise tolerance in patients with unilateral or bilateral diaphragm paralysis http://ow.ly/X2Pd30dCT7n.