Efficacy of community-based respiratory neuromuscular electrical stimulation on exercise capacity and quality of life in stable COPD: a randomized multicenter parallel-controlled trial protocol

Abstract

Background:

Chronic Obstructive Pulmonary Disease (COPD) is a common and prevalent condition that poses a significant threat to human health. Respiratory muscle fatigue is one of the common clinical manifestations of COPD. Currently, no effective treatment has been proposed to alleviate COPD symptoms. Respiratory neuromuscular electrical stimulation (RNES) enhances diaphragmatic contraction, lung volume, and ventilation through selective activation of type II muscle fibers, as evidenced in neurological and respiratory critical care settings. Although many COPD patients are managed through community care interventions, the efficacy of RNES in treating COPD patients has not been sufficiently studied. Here, we aim to investigate whether RNES can improve exercise capacity in COPD patients, as measured by 6-minute walk distance (6MWT).

Objectives:

To determine the efficacy of a community-based pulmonary rehabilitation (PR) program incorporating RNES on exercise capacity and symptoms in COPD patients. To evaluate its feasibility as a novel, affordable and accessible community PR model for COPD management.

Design:

This is a prospective, multicenter, randomized, parallel-controlled clinical trial, enrolling 60 patients with COPD.

Methods:

Sixty patients with stable COPD receiving inhalation therapy in 11 community health service centers in Beijing will be enrolled in the study. The potential of RNES to improve exercise capacity within this population will be explored in the study cohort. The enrolled patients will be randomized into two groups in a 1:1 ratio: control group (to receive conventional treatment) and experimental group (to receive conventional treatment plus RNES). During the treatment, the control group will receive conventional treatment without RNES, and those in the experimental group will receive 20/40 treatments over 6/12 weeks (1 session per day for 30 min) of RNES rehabilitation-assisted therapy plus conventional treatment. The primary outcome is exercise capacity based on changes in 6MWT at 12 weeks. The secondary outcome measures include changes from baseline in several indicators: dyspnea questionnaire, impact on daily living, anxiety and depression, pulmonary function, diaphragm function, respiratory muscle strength and body composition.

Discussion:

This clinical trial is designed to investigate whether rehabilitation assistance therapy with RNES will improve diaphragm mobility, respiratory muscle strength and endurance, enhance pulmonary ventilation, tidal volume, and promote alveolar carbon dioxide excretion in patients with stable COPD, which will improve the activity and exercise capacity. This study investigates the feasibility of RNES as a scalable rehabilitation intervention for COPD management in community healthcare settings.

Conclusion:

RNES will improve exercise capacity, quality of life in patients with COPD.

Trial registration:

The protocol has been registered at the Chinese Clinical Trial Registry (ChiCTR2200061675).

Keywords

COPD pulmonary rehabilitation randomized controlled trial respiratory neuromuscular electrical stimulation

Introduction

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and the third highest disability-adjusted life-year burden in China.^1,2 Respiratory muscle fatigue—characterized by diminished force-generating capacity and reduced contraction velocity of ventilatory muscles—represents a key pathophysiological mechanism underlying dyspnea and respiratory failure in COPD. To our knowledge, respiratory muscle fatigue may decrease exercise capacity, weight loss, malnutrition, sleep disorders, depression and anxiety, which severely affect the quality of life in COPD patients. Exercise is an important component of traditional pulmonary rehabilitation (PR), but its implementation in severe COPD patients is highly limited. Therefore, it is imperative to explore new PR models in COPD patients.

Currently, diaphragm pacing systems are categorized into two primary types: internal diaphragm pacing (IDP) and external diaphragm pacing (EDP). IDP is primarily employed for long-term ventilatory support, while EDP is predominantly used for short-term adjunctive therapy. Currently, EDP is primarily applied in pulmonary rehabilitation. The abdominal musculature functions as the principal expiratory muscle group. Through transcutaneous electrical stimulation such as EDP, synchronized activation of both the rectus abdominis and external/internal oblique muscles is achieved, eliciting coordinated contraction of these key expiratory muscles. This can increase intra-abdominal pressure, facilitating the upward movement of the diaphragm, increasing intrathoracic pressure, decreasing lung volume, and improving both ventilatory and mucus clearance functions.^3–5 Electrical stimulation of the abdominal muscles has been increasingly applied in clinics as a supplement to inspiratory muscle training.^6–9 However, few studies have investigated the role of EDP in COPD.

In this prospective, multicenter, randomized, parallel-controlled clinical trial, the efficacy of simultaneous application of respiratory neuromuscular electrical stimulation (RNES) with feedback stimulation to the diaphragm and abdominal muscles in stable patients with COPD will be investigated. In this technique, the diaphragm and abdominal muscles contract following stimulation of alternately outputting electrical currents using acoustic and visual signals, controlling inhalation and exhalation processes. The equipment is easy to operate in community settings, and can be mastered following a simple training. Evidence indicates that a minimum 8-week PR program is required to achieve clinically meaningful outcomes in COPD management.¹⁰ In this prospective cohort study, RNES will be applied for 6- or 12 weeks, with follow-up conducted at 12-, 24-, and 52-week post-intervention. The primary aim of the study is to determine the time-dependent efficacy and therapeutic durability of RNES across these clinically significant timepoints in 60 patients with stable COPD in community settings. The findings of the study are expected to improve functional capacity, mitigate respiratory symptoms, decrease hospitalization frequency, enhance rehabilitation adherence, and improve quality of life in stable COPD patients.

Methods

The reporting of this study conforms to the SPIRIT statement (see Additional File 1, Supplemental Material).^11,12

Study design and setting

The multicenter study will be conducted at China-Japan Friendship Hospital in Beijing. Patients will be admitted from 11 community health service centers, including Anzhen Community Health Service Center, Shichahai Community Health Service Center, Liulitun Community Health Service Center, Asian Games Village Community Health Service Center, Yuetan Community Health Service Center, Gaobeidian Community Health Service Center, Jinzhan Second Community Health Service Center, Hepingli Community Health Service Center, Sun Palace Community Health Service Center, Baliizhuang Second Community Health Service Center, and Cuigezhuang Community Health Service Center. Therefore, the study will be conducted in 11 different community health service centers.

This prospective, multicenter, randomized, parallel-controlled clinical trial seeks to evaluate the safety and efficacy of RNES stimulators for respiratory assistance in patients with stable COPD. The total study duration will be 3 years, which will be implemented in two phases, including a screening phase of 7 days and a treatment phase of 12 weeks. During the screening phase, the patients’ general health will be documented by a physician according to the inclusion and exclusion criteria. All female participants of childbearing potential will be required to complete a urine human chorionic gonadotropin test to confirm non-pregnancy status. Following initial screening to assess trial eligibility, qualified participants will undergo comprehensive baseline evaluations. The intervention protocol consists of 20 supervised treatment sessions administered over a 6-week period. At the end of each treatment session, a physician will conduct an interview to record device parameters and patient oxygen saturation levels. At the end of the 20 treatment sessions per week 6 of the trial, routine examinations will be performed following the trial procedure to observe the subjects’ response to treatment and the occurrence of adverse effects. After the checkup, patients will be informed about the option to continue with the 6-week, 20-treatment regimen. Patients who choose not to continue will be excluded from the study. Those who opt to continue will receive the full course of treatment. The primary and secondary outcomes will be observed at 6 weeks, 12 weeks, 24 weeks, and 52 weeks. The flow chart of the study is shown in Figure 1.

Figure 1.

Study participant flowchart.

Participants

The study will enroll patients diagnosed with stable COPD confirmed by post-bronchodilator forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) <0.70. For acute exacerbations, patients will be enrolled in the trial after 8 weeks of hospital discharge. Table 1 presents the inclusion and exclusion criteria.

Table 1.

Summary of trial inclusion and exclusion criteria.

Inclusion criteria
(1) Age 40–80 years old (Note: including 40 years old and 80 years old), gender is not limited. (2) Diagnosis of stable COPD is based on a history of smoking and other high-risk factors, clinical symptoms and signs, and pulmonary function tests. Requirements for the diagnosis of COPD are FEV₁/FVC <0.70 after inhalation of bronchodilators when performing pulmonary function tests.
Exclusion criteria
Subjects meeting any of the following criteria will be excluded from this study. (1) Subjects with a severe disease other than COPD that, in the judgment of the investigator, could result in any of the following: (i) the subject being at risk as a result of participation in this experiment; (ii) compromising the results of the experiment; and (iii) the subject being unable to complete the experiment. (2) Subjects with the following contraindications to respiratory neuromuscular stimulation: (i) bleeding tendency; (ii) coagulation disorders; (iii) spastic paralysis; (iv) presence of the following in the lower third of the sternocleidomastoid muscle, pectoralis major muscle, or abdomen: localization of acute purulent inflammation, site of skin breakdown, localization of malignant neoplasm, localization of cardiac pacemaker, localization of metal built-in objects; (v) cardiac region; (vi) carotid sinus site; (vii) severe heart, liver, and kidney failure, tested as follows: (a) subjects with cardiac function classes III (marked restriction of physical activity) and IV (unable to perform any physical activity) according to the cardiac function classification of the New York Heart Association (NYHA) of the United States; (b) unstable angina pectoris or myocardial infarction within 30 days before the screening period; (c) renal function: according to the Chronic Kidney Disease Epidemiology Institute (CKD-EPI) formula, at the time of the screening period examination, creatinine clearance calculated value ⩽30 ml/min; and (d) liver function: subjects with relevant test results within 3 months, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin measurements ⩾1.5 times the upper limit of normal values; (viii) patients with spasticity after cerebrovascular accidents; (ix) patients with severe cognitive deficits; (x) unconsciousness and limb osteoarthritis contractural deformities; (xi) those with neurologic stress; (xii) pregnant (positive pregnancy test) or lactating women; (xiii) thoracic and abdominal surgery after the wound has not yet healed locally; and (xiv) body surface electrode allergy. (3) History of acute exacerbation of COPD within 30 days before the screening period. (4) Suffering from other active lung diseases, for example, active tuberculosis (5) Subjects proposed to be treated with a combination of respiratory stimulant medications (e.g., dimethoate folinium hydrochloride, niclosamide, doxapram hydrochloride, and lorberal hydrochloride). (6) Subjects on invasive or noninvasive mechanical ventilation. (7) Participating in another interventional clinical trial within 30 days before the screening period. (8) Noncompliance with study guidelines or inability to cooperate with the investigator. (9) Other conditions that, in the judgment of the investigator, are not suitable for enrollment (e.g., psychiatric disorders and cognitive impairment).

The clinician or researcher will explain the results of the examination to the participant. All participants provided a written informed consent form. Participation in the trial will not interfere with the routine COPD management procedures.

Outcomes

The primary endpoint indicator of effectiveness is 6MWT, which is mainly used to evaluate exercise capacity.¹³ This study compares the improvement in 6-minute walk test distance (6MWD) between the experimental group and the control group. In patients with moderate-to-severe COPD, rehabilitation demonstrates clinically meaningful effects only when achieving the MCID of 35 m in the 6MWT.¹⁴ This threshold improvement correlates with significant impacts on key outcomes, including: (1) survival probability, (2) health-related quality of life, (3) exacerbation-related hospitalization frequency, and (4) healthcare resource utilization.

Secondary outcome indicators of validity are as follows:

(1) Symptom assessment: the modified Medical Research Council (mMRC) Dyspnea Scale scores will be applied to assess the patient’s self-perceived level of dyspnea on a scale of 0–4, with an mMRC score of ⩾2 indicating severe dyspnea symptoms.¹⁵ The COPD Assessment Test (CAT) scores reflect the health status and treatment outcome of patients with COPD. The CAT scores range from 0 to 40, with 0–10 representing mild clinical impact, 11–20 representing moderate clinical impact, 21–30 representing severe clinical impact, and 31–40 representing very severe clinical impact.¹⁶

(2) Activities of daily living (ADL) scores: ADL is an important predictor of mortality in patients with COPD, which can be used to assess the progress of the disease and the efficacy of rehabilitation.¹⁷

(3) The Hospital Anxiety and Depression Scale (HADS) scores: the HADS, with each of the anxiety and depression subscales consisting of seven items, will be administered to patients with COPD.¹⁸

(4) The Chinese version of the International Physical Activity Questionnaire (IPAQ) Short Form (IPAQ-C) scores: IPAQ-C, an adequately valid and reliable instrument, will be applied to assess the physical activity of COPD patients.¹⁹

(5) The St. George’s Respiratory Questionnaire (SGRQ) scores: SGRQ is an important tool for quantifying symptoms, mobility, and impact on daily life in patients with COPD and predicting patient survival.²⁰

(6) Pulmonary function indicators, including improvement in FEV₁, percentage of predicted FEV₁ value (FEV_1%pred), FVC, FEV₁ as a percentage of FVC (FEV₁/FVC), maximal ventilation per minute (MVV), and peak expiratory flow rate.

(7) Diaphragmatic function indicators: diaphragmatic ultrasound is an important assessment instrument in the progression of obstructive pulmonary disease and changes in lung function, dyspnea, and exercise capacity. Measurements include right diaphragm mobility (maximal inspiration), right diaphragm mobility (calming respiration), and diaphragm thickness rate of change.²¹

(8) Respiratory muscle function: maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) assessed using a Gio digital manometer.²²

(9) Body composition: Basal metabolic rate (BMR), phase angle (PhA), skeletal muscle mass index, visceral fat index, fat-free mass index (FFMI), and body fat percentage will be measured using bioelectrical impedance analysis (BIA), a simple, noninvasive assessment instrument, to reflect the skeletal muscle mass, cell membrane stability, and metabolic status of patients with COPD.²³

(10) Completion rate: The percentage of completed tests will be recorded. The missing value will be processed based on the missing value types.

Interventions

All patients with stable COPD will continue to inhale conventional medications, such as bronchodilators, based on their symptoms. All patients will be monitored by a multidisciplinary team of respiratory physicians, rehabilitation medicine physicians, physical therapists, nurses, and research assistants.

Patients in the experimental group will use an RNES device for 30 min. The respiratory rate will be regulated at 12 breaths/min, the stimulation frequency at 75 Hz, the diaphragm stimulation time at 1.1 s, the abdominal muscle stimulation time at 1.6 s, and the stimulation intensity range of 0–30 mA, and the intensity of treatment will be adjusted based on the patient’s tolerance and comfort level. The treatment will be applied on a once-daily schedule of 20 sessions for 6 weeks. The treatment will be applied for 40 sessions across 12 weeks, depending on the patient’s willingness after completing the mid-term assessment. However, if the patient is unwilling, the assessment will be removed from the group. The patients will be followed and evaluated for three core parameters: (1) therapeutic details of the intervention (session frequency × duration × intensity), (2) saturation of peripheral oxygen (SpO₂) measured via pulse oximetry, and (3) post-intervention dyspnea severity assessed using the mMRC.

For the control group, the participants will be prospectively assessed to monitor daily SpO₂ and post-intervention dyspnea severity using the mMRC. The researchers will perform a protocol-defined weekly surveillance via telemonitoring (phone/video consultations and SMS) to confirm the diary completeness and clinical status.

Data collection and management

The study protocol requirements: Experimental group: The participants will complete 20 intervention sessions within 6 weeks to ensure treatment integrity. Control group: The daily SpO₂ and dyspnea symptoms will be monitored, with standardized patient diary documentation. Investigator responsibilities: The researchers will perform weekly follow-ups to verify diary completion, record treatment compliance, and reinforce monitoring requirements.

Data collection will take place before the intervention (V0-V1), at the end of the 6-week intervention (V1), and at the end of the 12-week intervention (V2).

In this trial, operational data generated during study management will be automatically captured and archived in the study database. To ensure data integrity, all assessment measures will be independently entered by two investigators, followed by systematic cross-validation. Investigators will complete Case Report Forms (CRFs) for all enrolled participants. Following monitor verification, original CRFs are transferred to the data management team for processing. After transfer, no additional modifications are allowed. The data management system implements automated validation checks, with any identified inconsistencies generating electronic queries to the investigating sites for resolution. Discrepancies will be resolved based on the investigators’ written responses. The database will be locked after the resolution of all discrepancies.

Randomization

A table of random numbers generated using the SPSS statistical package will be employed. Sixty patients who meet the inclusion criteria will be enrolled and randomly assigned to the experimental group to receive RNES and the control group in a ratio of 1:1 based on the random number table (using blocking randomization within each center). This study will adopt an intention-to-treat analysis, preserving the benefits of randomization, reducing bias, and reflecting real-world effects. Allocations will be made by those not involved in the study. An independent biostatistics unit generated, prepared, and secured the envelopes to preserve allocation concealment integrity, thus minimizing selection bias. Following informed consent procedures and completion of baseline assessments, the study coordinator will open the randomization envelope to reveal participant allocation. In this open-label trial design, both investigators and participants will be immediately informed of group assignment, with subsequent implementation of the allocated intervention according to the study protocol. The researchers and participants will be informed of the study groups to which they were assigned. The experimental group will receive 20 sessions over 6 weeks and 40 sessions over 12 weeks, and outcomes will be measured at baseline (V0-V1), 20 sessions over 6 weeks (V1–V2), and 40 sessions over 12 weeks (V2). The study will be reported following the recommendations of the Integrated Reporting Pilot Standard. Baseline and follow-up information are presented in Table 2.

Table 2.

Summary of assessments.

Visiting arrangements	Visiting places	Screening period	Treatment follow-up period
Visiting arrangements	Visiting places	–7 Day~–1Day	Visits 1 Day–19 Day V0–V1	Visits 20 Day V1	Visits 21 Day–39 DayV1–V2	Visits 40 Day V2
Eligibility screening
Informed consent	Community	√
Entry standard	Community	√
Randomized grouping	Community	√
Demographic information	Community	√
Clinical examination	Community	√
Past medical history, allergy history, surgical history	Community	√
History of present illness	Community	√
Urinary pregnancy	China-Japan Friendship Hospital	√
Vital signs	community	√
Electrocardiography	China-Japan Friendship Hospital	√
Routine blood and blood biochemistry	China-Japan Friendship Hospital	√
Blood oxygen saturation	Community	√	√	√	√	√
Interventions
RNES
Assessments
Primary:6-minute walk test	Community	√		√		√
mMRC score	Community	√		√		√
CAT score	Community	√		√		√
ADL score	Community	√		√		√
HADS	Community	√		√		√
IPAQ-C	Community	√		√		√
SGRQ	Community	√		√		√
Pulmonary function assessment	China-Japan Friendship Hospital	√		√		√
Evaluation of diaphragm function	China-Japan Friendship Hospital	√		√		√
MIP, MEP	China-Japan Friendship Hospital	√		√		√
Body composition	China-Japan Friendship Hospital	√		√		√
Evaluation of instrument operational performance	Community			√		√
Combination of drugs	Community	√				√
Adverse event	Community		√	√	√	√

6MWT, 6-Minute walking test; ADL score, activities of daily living scores; CAT score, COPD Assessment Test; HADS, the Hospital Anxiety and Depression Scale scores; IPAQ-C, the Chinese version of the International Physical Activity Questionnaire (IPAQ) Short Form scores; MEP, maximum expiratory pressure; MIP, Maximum inspiratory pressure; mMRC score, modified Medical Research Council; SGRQ, the St. George’s Respiratory Questionnaire scores.

Sample size calculation

To estimate the required sample size, a parallel-group which does not receive the intervention is included as the control group. The 6MWT (the primary outcome) is used to calculate the sample size, since exercise capacity is one of the most sensitive outcome measures for detecting the benefit of rehabilitation.

Based on previous studies,¹⁴ a mean difference of 35 m in the 6MWT between the treatment and control groups, with a common standard deviation of 35 m, will be assumed. A 1:1 allocation ratio between the two groups will be used for the sample size calculation.

According to the study design, the test of superiority will be used, and the hypotheses will be tested as follows:

\begin{matrix} H_{0} : μ_{T} - μ_{C} \geq 0 \\ H_{1} : μ_{T} - μ_{C} < 0 \end{matrix}

$μ_{T}$ and $μ_{C}$ are indicators of data stability for the test and control groups, respectively. As this is a non-inferiority trial, the sample size is calculated using a one-sided test, with the type I error rate (α) set at 0.025 and type II error rate (β) at 0.2 (power = 80%).

Based on the available literature reports concerning similar products of the sponsor, the sample calculation parameters are set $μ_{T}$ - $μ_{C}$ to take 35 m, the standard deviation is taken as 35.0, and the calculation process will be completed using PASS 2008 software to determine which of the two groups is needed to complete the effective cases of 48 cases. To account for potential dropouts, a total of 60 participants will be planned for enrollment. The target sample size for each group (experimental and control) is 30, resulting in a total of 60 qualified subjects who will be randomly assigned to the two groups.

Statistical analysis plan

All statistical analyses will be performed using full intention-to-treat analyses, with scores on the dependent variables for dropouts carried over using the multiple imputation method. All statistical analyses will be performed using SPSS 26.0. Measurement data will be tested for superiority using the equivalent interval method, count data will be compared using the chi-square test (or Fisher’s exact test), and rank data will be analyzed using the Mann-Whitney (or Wilcoxon) rank sum test. Analysis of variance (ANOVA) or Kruskal-Wallis tests will be utilized for comparisons across multiple groups. Between-group comparisons will be conducted using the Cochran-Mantel-Haenszel (CMH) chi-square test, which accounts for the center factor, and, if necessary, a logistic regression model for between-group comparisons will be considered to correct for the influence of the center and other factors. The Bonferroni test will be applied for multiple comparisons of pre- and post-intervention changes between experimental and control groups, with particular emphasis on secondary outcome measures. All hypothesis testing will be two-sided, with an alpha (α) level of 0.05. Applicable descriptors and hypothesis tests will be selected as follows.

(1) Normal variables: mean and standard deviation, median, and minimum and maximum values will be used for statistical description and t-test and ANOVA will be used for hypothesis testing.

(2) Skewed variables: the median will be used to indicate the average level, with the interquartile (quartile) spacing indicating the degree of dispersion, for the rank sum test.

(3) Rank indicators: various scoring values listed in the frequency table and statistical description with the median and quartile spacing for rank sum test or Ridit analysis.

(4) Counting indicators: frequency table with percentage description for chi-square or exact probability method test.

Monitoring

The group of contract Research Organization (CRO) will be responsible for appointing clinical monitors and developing the monitoring plan. In accordance with Standard Operating Procedures and the monitoring plan, site monitoring visits will be conducted at study initiation, during active study phases (monthly), and at study closure. Monitoring activities will include the use of verification protocol compliance (including informed consent procedures), adherence to applicable regulatory requirements, data accuracy, subject safety and welfare, completeness of informed consent documentation, and proper maintenance of source records. Trial data will undergo 100% source data verification (SDV), with the SDV scope predefined in the monitoring plan. Site personnel will complete CRFs within 24–48 h after each subject visit. Monitors will conduct source document verification by cross-referencing CRF entries against medical records and other original source data, utilizing a risk-based methodology as outlined in the monitoring plan. A formal site close-out visit will be conducted at the end of study completion, following the monitoring plan guidelines.

The participants will be allowed to withdraw from this study at any time without any reason. Treatment discontinuation or study withdrawal is permitted under circumstances including but not limited to: (1) Post-enrollment discovery of ineligibility per inclusion/exclusion criteria; (2) Investigator-determined medical/safety concerns; (3) Subject unwillingness to continue participation; (4) Major protocol violation (Principal Investigator-confirmed); (5) Adverse event profile suggesting potential device-related health risks; (6) Acute exacerbation of chronic obstructive pulmonary disease (AECOPD). For all prematurely terminated subjects, investigators must document withdrawal reasons (e.g., adverse events, investigator decision) in the CRF. Participants who withdraw prematurely must complete all study termination procedures according to the predefined visit schedule.

All adverse events (AEs) occurring during the study will be accurately recorded in AE CRFs. These researchers will provide condition-specific management and conduct follow-up until symptom resolution or stabilization. A preliminary assessment classifying AEs as procedure-related events must be performed by investigators.

An independent study monitor will check the eligibility of participants, informed consent, protocol compliance, and overall integrity of gathered data.

Discussion

Generally, PR comprises exercise training, education, and self-management strategies aimed at alleviating symptoms such as dyspnea, improving psychological well-being, promoting long-term adherence to healthy behaviors, and enhancing quality of life in patients with COPD, in line with the Global Initiative for Chronic Obstructive Lung Disease (GOLD). However, it is very difficult for tertiary hospitals to provide long-term rehabilitation for patients with COPD, due to several factors including social resources, time constraints, physical distance, and self-efficacy. Moreover, geographic distance may hinder the outpatients’ adherence to long-term rehabilitation programs. Remote home-based rehabilitation programs are also faced with numerous hurdles, as it is difficult to monitor and adjust the intensity of exercise and other aspects of pulmonary rehabilitation. Thus, this study will investigate the therapeutic effect of applying RNES to patients with stable COPD in a community health service center, providing important information about PR intervention in COPD patients and exploring the factors leading to patients refusing PR, such as fear of exercise-induced shortness of breath, fatigue, and other uncomfortable manifestations. In addition, the study aims to address the limitations associated with time and physical distance constraints and improve the implementation of PR under the guidance of medical staff, thereby enhancing the management of stable COPD patients in community health service center through PR, ensuring quality of life.

Second, this study will explore new PR treatments for patients with stable COPD in a community health service center. Compared with the traditional rehabilitation technique, this method alternately outputs current stimulation through the phrenic nerve and abdominal muscle channels, accompanied by acoustic and optical signals, guiding the patients to independently cooperate with abdominal breathing training. This study seeks to apply RNES to assess the changes in stable COPD patients before and after treatment, aiming to alleviate dyspnea symptoms, reduce symptom burden, improve cardiorespiratory endurance, and facilitate the patient’s return to family and reintegration into society. Meanwhile, we will also assess the efficacy and safety of RNES to provide more evidence-based medical evidence for the use of PR in COPD patients. The RNES therapeutic device is user-friendly and can be operated by community doctors, physiotherapists, or nurses after appropriate training.

Finally, the technological approach adopted in this study will improve the respiratory symptoms, such as dyspnea, in patients with stable COPD from a multidimensional perspective.

Extracorporeal diaphragmatic pacing has been previously used to stimulate the phrenic nerve, which excites the motor nerve to transmit downward to the nerve endings or excites the sensory nerve to transmit upward to the spinal cord, thereby producing centripetal phrenic nerve excitation.²⁴ However, these studies primarily improve inspiratory function and do not address expiratory function. In this study, we will apply the RNES therapeutic instrument to stimulate the diaphragm and abdominal muscles alternately for 30 min to improve the patients’ ventilation function of the full respiratory cycle. In addition, the study incorporates breathing techniques such as pursed-lip breathing and abdominal breathing, helping patients adjust their breathing strategies. By overcoming the fear of dyspnea and fatigue related to exercise, the intervention also may improve patients’ psychological well-being and boost their acceptance of PR.

RNES maintains regular contraction of the body diaphragm, thereby increasing diaphragm blood flow, reducing diaphragm injury, decreasing airway resistance, increasing diaphragm thickness and mobility and rate of change, ultimately improving lung function and dyspnea symptoms, reducing the symptom burden of patients, and improving cardiorespiratory endurance and social reintegration of patients with stable COPD.

Compared with traditional rehabilitation, patients with moderate-to-severe COPD are unable to tolerate exercise training and refuse to perform whole-body exercise due to shortness of breath or lack of subjective motivation. This study aims to address these challenges by using the RNES device for passive training. The goal is to improve the 6MWT, optimize body composition, enhance endurance and muscle strength, and alleviate symptoms of anxiety and depression in COPD patients. This approach may enable patients to improve their physical function and mental well-being despite their limitations.

In summary, the results of this study will contribute to the development and evaluation of a community-based PR model based on community-applied respiratory neuroelectric stimulation to improve outcomes in stable COPD patients. Through patient education, respiratory training, and psychosocial support visits, this model will improve lung function, enhance the quality of life, reduce the risk of acute exacerbations, and reduce the consumption of healthcare resources in patients with stable COPD.²⁵ This program is intended to serve as a flexible supplement or alternative to traditional center-based PR for patients with stable COPD, helping to bridge the gap between tertiary care rehabilitation and telerehabilitation.

Conclusion

This study will enhance COPD rehabilitation by performing a community-based program with respiratory neuromuscular electrical stimulation. By addressing existing research gaps, it aims to provide robust empirical evidence for the use of a novel cost-effective approach that will improve adherence to intervention strategies among COPD patients. These findings demonstrate the potential for community-based therapeutic approaches to enhance chronic disease management paradigms, particularly through scalable COPD rehabilitation frameworks that improve both care delivery and patient outcomes.

Supplemental Material

sj-doc-1-tar-10.1177_17534666251385677 – Supplemental material for Efficacy of community-based respiratory neuromuscular electrical stimulation on exercise capacity and quality of life in stable COPD: a randomized multicenter parallel-controlled trial protocol

Supplemental material, sj-doc-1-tar-10.1177_17534666251385677 for Efficacy of community-based respiratory neuromuscular electrical stimulation on exercise capacity and quality of life in stable COPD: a randomized multicenter parallel-controlled trial protocol by Tianyi Yang, Shiwei Qumu, Lulu Yang, Jiaze He, Jieping Lei, Shan Jiang, Xiaoxia Ren and Ting Yang in Therapeutic Advances in Respiratory Disease

Footnotes

Acknowledgements

The authors will sincerely appreciate the medical staff of all participating hospitals, the multidisciplinary experts who will work on the project and data management, and all participants.

Declarations

ORCID iDs

Tianyi Yang

Jiaze He

Jieping Lei

Supplemental material

Supplemental material for this article is available online.

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