Comparison of a Supervised Home-Based Tele-Rehabilitation with Center-Based Pulmonary Rehabilitation: Protocol for a Randomized Non-Inferiority Multicenter Study in Ningxia.

Pulmonary rehabilitation (PR) is an effective intervention for people with chronic obstructive pulmonary disease (COPD). However, fewer than 5% of eligible individuals receive pulmonary rehabilitation, largely due to limited by the accessibility of rehabilitation and difficulties associated with travel and transport. Supervised home-based tele-rehabilitation (SHTR) is an alternative model to center-based pulmonary rehabilitation. We will determine whether supervised home-based tele-rehabilitation is non-inferior to center-based pulmonary rehabilitation. The participants will undergo an 8-week rehabilitation program. Pulmonary rehabilitation comprises four main modules: exercise training, education, nutritional support, and psychological and behavioral interventions. We mainly focus on the module of exercise training and education. The education module includes information on exercise training, nutrition, and psychology, which are presented in an educational booklet provided to each participant. Blinded assessors will evaluate the outcomes at baseline, post-intervention, and 6 months after the intervention. The primary outcome is the change in the 6-minute walking distance. Secondary outcomes will assess changes in the patients' 1-minute sit-to-stand test, maximal inspiratory pressure (MIP), scales (CAT, mMRC, HAD), diaphragm ultrasound (TD, DE, DIF), changes in extrathoracic muscle volume and mass, completion rate of patient exercise prescriptions, occurrence of adverse events, as well as disease exacerbation and rehospitalization rates after rehabilitation and during the 6-month follow-up. In order to improve the accessibility of pulmonary rehabilitation and patient-related outcomes, it is necessary to propose an alternative model of pulmonary rehabilitation. This trial will establish whether a supervised home-based tele-rehabilitation is not inferior to traditional center-based pulmonary rehabilitation. Chinese Clinical Trial Registry ChiCTR2300076969. Registered on October 25, 2023.

Xin H ，Wei S ，Zheng H ，Qi Y ，Xu S ，Wang B ，Jiang W ，Deng N ，Chen J ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Supervised pulmonary tele-rehabilitation and individualized home-based pulmonary rehabilitation for patients with COPD, unable to participate in center-based programs. The protocol for a multicenter randomized controlled trial - the REPORT study.

Chronic obstructive pulmonary disease (COPD) costs EURO 1.4 billion annually in healthcare costs. Pulmonary rehabilitation (PR) is a vital aspect of care for patients with COPD, but despite the compelling evidence, it is delivered to less than 30%. Frequent transport to the center-based program is regularly reported as reasons for non-attendance. The effectiveness and feasibility of pulmonary tele-rehabilitation (PTR) and home-based pulmonary rehabilitation (HPR) have never been investigated in patients with COPD who are unable to attend conventional outpatient PR. This study is a multicenter randomized controlled trial consisting of three parallel groups; PTR, HPR and a control group. 180 patients with moderate to very severe COPD, who are unable to attend in center-based PR programs will be included. The PTR group receives group-based resistance- and endurance training and patient education 60 min. twice a week for 10-weeks. HPR comprises an individual self-initiated home-based PR program with online motivational and professional counseling. The goal is to achieve at least 20 min. of muscle-endurance based exercises three days weekly for 10-weeks. The PTR and HPR group use a tablet with a conference system. The control group receives usual care (no PR). After completion of the intervention, the PTR and HPR groups are offered 65-weeks groupbased maintance program supervised once a week online via tablet. The primary outcome is change in respiratory symptoms measured with the COPD Assessment Test after 10-weeks (primary endpoint). The study aims to test a possible equivalence between PTR and HPR and their superiority to controls on respiratory symptoms. The study will provide valuable insights into the effectiveness of new rehabilitation models and maintenance programs for patients with COPD. If the two new delivery models can reduce respiratory symptoms, patients with moderate to very severe COPD can participate in both home- or centerbased PR. The trial is registrered and approved by the Ethics Committee of The Capital Region of Denmark (H-22015777; 29.08.2022) and the Danish Data Protection Agency (P-2022-245-13101, 25.05.2022). The trial is registrered at ClinicalTrials.gov, identifier: NCT05664945 (23.12.2022).

Nielsen C ，Godtfredsen N ，Molsted S ，Ulrik C ，Kallemose T ，Hansen H ... -  《PLoS One》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Inspiratory muscle training, with or without concomitant pulmonary rehabilitation, for chronic obstructive pulmonary disease (COPD).

Inspiratory muscle training (IMT) aims to improve respiratory muscle strength and endurance. Clinical trials used various training protocols, devices and respiratory measurements to check the effectiveness of this intervention. The current guidelines reported a possible advantage of IMT, particularly in people with respiratory muscle weakness. However, it remains unclear to what extent IMT is clinically beneficial, especially when associated with pulmonary rehabilitation (PR).   OBJECTIVES: To assess the effect of inspiratory muscle training (IMT) on chronic obstructive pulmonary disease (COPD), as a stand-alone intervention and when combined with pulmonary rehabilitation (PR). We searched the Cochrane Airways trials register, CENTRAL, MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Physiotherapy Evidence Database (PEDro) ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 20 October 2021. We also checked reference lists of all primary studies and review articles. We included randomized controlled trials (RCTs) that compared IMT in combination with PR versus PR alone and IMT versus control/sham. We included different types of IMT irrespective of the mode of delivery. We excluded trials that used resistive devices without controlling the breathing pattern or a training load of less than 30% of maximal inspiratory pressure (PImax), or both. We used standard methods recommended by Cochrane including assessment of risk of bias with RoB 2. Our primary outcomes were dyspnea, functional exercise capacity and health-related quality of life.  MAIN RESULTS: We included 55 RCTs in this review. Both IMT and PR protocols varied significantly across the trials, especially in training duration, loads, devices, number/ frequency of sessions and the PR programs. Only eight trials were at low risk of bias. PR+IMT versus PR We included 22 trials (1446 participants) in this comparison. Based on a minimal clinically important difference (MCID) of -1 unit, we did not find an improvement in dyspnea assessed with the Borg scale at submaximal exercise capacity (mean difference (MD) 0.19, 95% confidence interval (CI) -0.42 to 0.79; 2 RCTs, 202 participants; moderate-certainty evidence).   We also found no improvement in dyspnea assessed with themodified Medical Research Council dyspnea scale (mMRC) according to an MCID between -0.5 and -1 unit (MD -0.12, 95% CI -0.39 to 0.14; 2 RCTs, 204 participants; very low-certainty evidence).  Pooling evidence for the 6-minute walk distance (6MWD) showed an increase of 5.95 meters (95% CI -5.73 to 17.63; 12 RCTs, 1199 participants; very low-certainty evidence) and failed to reach the MCID of 26 meters. In subgroup analysis, we divided the RCTs according to the training duration and mean baseline PImax. The test for subgroup differences was not significant. Trials at low risk of bias (n = 3) demonstrated a larger effect estimate than the overall. The summary effect of the St George's Respiratory Questionnaire (SGRQ) revealed an overall total score below the MCID of 4 units (MD 0.13, 95% CI -0.93 to 1.20; 7 RCTs, 908 participants; low-certainty evidence).  The summary effect of COPD Assessment Test (CAT) did not show an improvement in the HRQoL (MD 0.13, 95% CI -0.80 to 1.06; 2 RCTs, 657 participants; very low-certainty evidence), according to an MCID of -1.6 units.  Pooling the RCTs that reported PImax showed an increase of 11.46 cmH2O (95% CI 7.42 to 15.50; 17 RCTs, 1329 participants; moderate-certainty evidence) but failed to reach the MCID of 17.2 cmH2O.  In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.  One abstract reported some adverse effects that were considered "minor and self-limited". IMT versus control/sham Thirty-seven RCTs with 1021 participants contributed to our second comparison. There was a trend towards an improvement when Borg was calculated at submaximal exercise capacity (MD -0.94, 95% CI -1.36 to -0.51; 6 RCTs, 144 participants; very low-certainty evidence). Only one trial was at a low risk of bias. Eight studies (nine arms) used the Baseline Dyspnea Index - Transition Dyspnea Index (BDI-TDI). Based on an MCID of +1 unit, they showed an improvement only with the 'total score' of the TDI (MD 2.98, 95% CI 2.07 to 3.89; 8 RCTs, 238 participants; very low-certainty evidence). We did not find a difference between studies classified as with and without respiratory muscle weakness. Only one trial was at low risk of bias. Four studies reported the mMRC, revealing a possible improvement in dyspnea in the IMT group (MD -0.59, 95% CI -0.76 to -0.43; 4 RCTs, 150 participants; low-certainty evidence). Two trials were at low risk of bias. Compared to control/sham, the MD in the 6MWD following IMT was 35.71 (95% CI 25.68 to 45.74; 16 RCTs, 501 participants; moderate-certainty evidence). Two studies were at low risk of bias. In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.  Six studies reported theSGRQ total score, showing a larger effect in the IMT group (MD -3.85, 95% CI -8.18 to 0.48; 6 RCTs, 182 participants; very low-certainty evidence). The lower limit of the 95% CI exceeded the MCID of -4 units. Only one study was at low risk of bias. There was an improvement in life quality with CAT (MD -2.97, 95% CI -3.85 to -2.10; 2 RCTs, 86 participants; moderate-certainty evidence). One trial was at low risk of bias. Thirty-two RCTs reported PImax, showing an improvement without reaching the MCID (MD 14.57 cmH2O, 95% CI 9.85 to 19.29; 32 RCTs, 916 participants; low-certainty evidence). In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.   None of the included RCTs reported adverse events. IMT may not improve dyspnea, functional exercise capacity and life quality when associated with PR. However, IMT is likely to improve these outcomes when provided alone. For both interventions, a larger effect in participants with respiratory muscle weakness and with longer training durations is still to be confirmed.

Ammous O ，Feki W ，Lotfi T ，Khamis AM ，Gosselink R ，Rebai A ，Kammoun S ... -  《Cochrane Database of Systematic Reviews》

Effects and mechanisms of supramaximal high-intensity interval training on extrapulmonary manifestations in people with and without chronic obstructive pulmonary disease (COPD-HIIT): study protocol for a multi-centre, randomized controlled trial.

Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls. COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated. The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease. Clinicaltrials.gov: NCT06068322. Prospectively registered on 2023-09-28.

Jakobsson J ，Burtin C ，Hedlund M ，Boraxbekk CJ ，Westman J ，Karalija N ，Stål P ，Sandström T ，Ruttens D ，Gosker HR ，De Brandt J ，Nyberg A ... -  《Trials》