The Effects of Digital Health Interventions for Pulmonary Rehabilitation in People with COPD: A Systematic Review of Randomized Controlled Trials

Background and Objectives: Chronic Obstructive Pulmonary Disease (COPD) is the third most common cause of death globally. Pulmonary rehabilitation (PR) programmes are important to reduce COPD symptoms and improve the quality of life of people with COPD. Digital health interventions have recently been adopted in PR programmes, which allow people with COPD to participate in such programmes with low barriers. The aim of this study is to review and discuss the reported effects of digital health interventions on PR outcomes in people with COPD. Materials and Methods: To achieve the study goals, a systematic literature search was conducted using PubMed (MEDLINE), CINAHL, AMED, SPORTDiscus and the Physiotherapy Evidence Database. Randomised clinical trials (RCTs) were included if they met specified criteria. Two reviewers independently checked titles, abstracts, and performed full-text screening and data extraction. The quality assessment and risk of bias were performed in accordance with the PEDRO scale and Cochrane Risk of Bias tool 2, respectively. Results: Thirteen RCTs were included in this systematic review with 1525 participants with COPD. This systematic review showed the potential positive effect of digital health PR on the exercise capacity—measured by 6- and 12-min walking tests, pulmonary function, dyspnoea and health-related quality of life. There was no evidence for advantages of digital health PR in the improvement of anxiety, depression, and self-efficacy. Conclusions: Digital health PR is more effective than traditional PR in improving the pulmonary and physical outcomes for people with COPD, but there was no difference between the two PR programmes in improving the psychosocial outcomes. The certainty of the findings of this review is affected by the small number of included studies.


Introduction
Pulmonary rehabilitation (PR) is defined, according to the official American Thoracic Society/European Respiratory Society statement, as a "comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but Medicina 2024, 60, 963.https://doi.org/10.3390/medicina60060963https://www.mdpi.com/journal/medicinaare not limited to exercise training, education, and behaviour change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote long-term adherence to health-enhancing behaviours" [1].Chronic respiratory diseases include, but are not limited to, chronic obstructive pulmonary disease (COPD), which is a progressive lung condition characterized by airway inflammation, obstructed airflow, and a reduction in lung function leading, ultimately, to breathing difficulty [2].COPD was the third most common cause of death worldwide in 2019 [3].COPD may cause anxiety, depression, peripheral muscle fatigue, dyspnoea, reduction in the activities of daily living, and an increased incidence of hospitalisation.This has a negative effect on the quality of life of an individual and imposes a burden on healthcare systems worldwide [4,5].PR is the gate to reduce COPD symptoms, and to improve exercise capacity and overall quality of life [6].However, COPD patients face difficulties in accessing traditional PR services, whether due to high costs, limited infrastructure, lack of interest, and, even if they start PR, there is generally a poor adherence rate to PR programmes [6][7][8].A recent prospective multicentre cohort study found that only 1% of patients hospitalised with COPD exacerbation utilised PR after discharge, with no in-hospital interventions associated with increased PR use [9].This highlights the significant underutilisation of PR among COPD patients and the urgent need for effective interventions to increase PR uptake.There is thus a significant need to overcome these barriers, and with the technological revolution in recent years, the innovation of digital health interventions has triggered considerable interest in developing healthcare delivery, including PR for COPD patients.Digital technology is considered safe and feasible, and encompasses a wide range of technologies.Digital health is defined as technology employed to deliver remote care beyond the use of a telephone (e.g., the delivery of care using the internet, virtual reality systems, wearable devices and mobile apps) [10,11], which may provide a platform to increase the accessibility, flexibility, and effectiveness of PR programmes.It should be mentioned that digital health encompasses terms such as telehealth, telemedicine, eHealth, etc.
Despite the growing interest in digital health interventions to assist PR programmes, no systematic reviews have been conducted to explore the effectiveness of such interventions on people with COPD.Therefore, in this review, we will explore the effectiveness of using digital health interventions as PR interventions for people with COPD, highlighting the potential benefits and implications for clinical practice.

Objective
The aim of this study was to review and discuss the reported effects of digital health interventions on respiratory rehabilitation outcomes in people with COPD.

Design
A systematic review with narrative synthesis and quality assessment of published literature was conducted.In this systematic review, we considered the definition of "digital health" as a technology employed to deliver remote care beyond the use of a telephone (e.g., the delivery of care using the internet, virtual reality systems, wearable devices and mobile apps) [10,11].

Study Protocol
The protocol of the systematic review is registered in the international prospective register of systematic reviews database (PROSPERO) (PROSPERO 2023, CRD42023475514).
To not limit the search, outcome measures were not limited to any keywords.

Search Strategy
The search was conducted through EBSCO using the following databases: PubMed (MEDLINE), CINAHL, AMED, SPORTDiscus and Physiotherapy Evidence Database (PE-Dro).These databases were selected because of their comprehensive coverage of articles related to digital health, pulmonary rehabilitation in COPD, physiotherapy and exerciserelated research.The search was conducted for papers published between 1 January 1970 and 31 December 2023.All search records were managed using Endnote 21 (Clarivate Analytics, Philadelphia, PA, USA).To assure the reproducibility and accuracy of the search, the Medical Subject Headings (MeSH) were used.
To facilitate replication of findings, customized inquiries were performed for each database in accordance with the PRISMA guidelines.To gain a more comprehensive understanding of current research, grey literature was surveyed via the World Health Organization (WHO) International Clinical Trials Registry platform.
A summary of the keywords and search strategy is presented in Table 1.The rationale for selecting these specific databases and search terms was to capture a broad spectrum of relevant studies and ensure comprehensive coverage of the topic.

Inclusion and Exclusion Criteria
The inclusion and exclusion criteria were determined using the PICOS framework, which encompasses population, intervention, comparison, outcome measures, and study design.Articles were included if they were randomised controlled trials (RCTs) investigating the effects of digital health for pulmonary rehabilitation in adult men and women, aged >18 years old and diagnosed with COPD.Articles were excluded if they were not RCTs; did not use digital health for pulmonary rehabilitation; were not published in English; or were conference abstracts and any study that included participants with any other neurological, musculoskeletal, or cognitive disorders.

Study Selection
After conducting the search and eliminating duplicate entries, two reviewers (RB and AS) independently assessed the relevance of titles and abstracts.Subsequently, the same reviewers independently evaluated the full texts of relevant trials to determine their eligibility based on the inclusion and exclusion criteria.

Data Extraction and Synthesis
A meta-analysis was not performed due to the heterogeneity of the included trials.Despite the similar designs of the trials, variations in intervention types and outcome measures prevented a meaningful statistical aggregation of results.Therefore, a narrative synthesis approach was employed to qualitatively analyse and interpret the findings.
Information extracted from the included trials was tabulated and included the following: names of the authors, study designs, sample sizes, demographics such as sex and age, digital health services offered (including utilized technology), prescribed exercises, reported outcome measures, and principal findings.Additionally, details regarding the frequency, duration, intensity, and nature of exercises were documented when accessible.

Quality Assessment and Risk of Bias of the Included Trials
The evaluation of the included trials' quality was conducted using the PEDro scale, a recognized and dependable tool specifically designed for assessing the quality of interventional studies within the field of physiotherapy [12,13].PEDro scores were not employed as inclusion or exclusion criteria; rather, they served as a foundation for synthesizing the best evidence and identifying the strengths and weaknesses of each study.Scores on the PEDro scale range from 0 to 10, with scores of 9-10 denoting excellent quality, 6-8 indicating good quality, 4-5 reflecting low quality, and scores below 4 suggesting poor quality [14].
The risk of bias in the included trials was evaluated using the Cochrane Risk of Bias tool 2 (CROB 2).Two reviewers (RB and AS) independently assessed the risk of bias.The CROB 2 assessment encompassed the following: (1) bias stemming from randomization criteria; (2) bias due to deviations from intended interventions; (3) bias arising from missing outcome data; (4) bias in the measurement of outcomes; and (5) bias in the selection of reported results.

Study Selection
The initial search identified 79 titles, leaving 69 after the removal of duplicates.After screening the titles and abstracts, 24 trials were excluded: 4 were conference abstracts, 20 were not RCTs.After full text screening, it appeared 3 trials included participants who were not diagnosed with COPD, 7 used virtual reality games only and 22 trials were not RCTs.No relevant trials were found in the grey literature.Consequently, 13 trials were included in the review: 12 were RCTs, and 1 was a parallel group noninferiority trial.The included trials recruited 1525 participants with COPD.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart indicating the included and excluded trials is represented in Figure 1.The data extracted related to the respiratory function/symptoms of the studies included in this review are presented in Table 2. Other non-respiratory outcome measures are presented in Table S1 as supplementary material.A meta-analysis was not feasible because of the heterogeneity of the included trials.
-6MWT improved more with TG but not significant difference between both groups (p = 0.16).
-ISWT improved more with TG but not significant difference between both groups (p = 0.66).

Quality Assessment and Risk of Bias
The quality assessment and risk of bias of the trials were independently assessed by two assessors (RB and AS) using PEDro scores and the CROB2 tool.The PEDro scores of the included trials ranged from 6 to 9, indicating good to excellent quality trials (Table 3).One trial scored 6 because of the bias in blinding of all subjects and random allocation to groups [17], eight trials scored 7 because of bias in blinding of all subjects and allocation concealed [15,16,19,[21][22][23]25,26], three trials scored 8 because of bias in blinding of all subjects [18,24,27], and one trial scored 9 because of bias in blinding of therapists and assessors [20].The risk of bias using the CROB2 tool showed that 11 trials were at a low risk of bias (across all domains) [15,[18][19][20][21][22][23][24][25][26][27] and two trials were at "some concern" of risk of bias (some concerns in two domains) [16,17].A summary of the CROB2 results is shown in Figure 2.

Outcomes Assessed by Digital Health Intervention Trials
The included trials assessed different health outcomes that were categorised into pulmonary rehabilitation outcomes, quality of life, COPD symptoms, lung function, acute exacerbations and hospitalisations, and emergency department visits.

Exercise Capacity
Thirteen trials used different exercise capacity tests as a primary outcome measure including a 6-min walk test (6MWT), a 12-min walk test (12MWT), an endurance shuttle walking test (ESWT), number of steps per day (PAL), timed up-and-go (TUG), and a 1min sit-to-stand (1-min STS) (Table 2).
One trial used the 12MWT as an outcome measure for exercise capacity [17] and reported significant improvement in the 12MWT in both the intervention and control groups (tele-PR vs. regular PR).One trial used the ESWT [18] and reported a higher improvement in the intervention group compared with the control group (tele-PR vs. usual care).One trial used the PAL [23] and showed that both groups improved in PAL but no significant differences were found between them (tele-PR vs. usual care).One trial used STS [27]; the

Outcomes Assessed by Digital Health Intervention Trials
The included trials assessed different health outcomes that were categorised into pulmonary rehabilitation outcomes, quality of life, COPD symptoms, lung function, acute exacerbations and hospitalisations, and emergency department visits.

Exercise Capacity
Thirteen trials used different exercise capacity tests as a primary outcome measure including a 6-min walk test (6MWT), a 12-min walk test (12MWT), an endurance shuttle walking test (ESWT), number of steps per day (PAL), timed up-and-go (TUG), and a 1-min sit-to-stand (1-min STS) (Table 2).
One trial used the 12MWT as an outcome measure for exercise capacity [17] and reported significant improvement in the 12MWT in both the intervention and control groups (tele-PR vs. regular PR).One trial used the ESWT [18] and reported a higher improvement in the intervention group compared with the control group (tele-PR vs. usual care).One trial used the PAL [23] and showed that both groups improved in PAL but no significant differences were found between them (tele-PR vs. usual care).One trial used STS [27]; the test showed that both groups improved but without significant differences between them (tele-PR vs. usual care).One trial used the incremental shuttle walk test (ISWT) [18], where no significant differences in improvement were seen between the two groups (tele-PR vs. usual care) (Table 2) [18].
Functional Performance Inventory-Short Form (FBI-SF) One trial used FBI-SF to assess physical performance in six domains, including body care, household activities, physical exercise, recreation, spiritual activities and social interactions.No significant differences were observed in either group (tele-PR vs. usual care) after the follow-up [18] (Table S1: Supplementary Material).

Quality of Life Chronic Respiratory Disease Questionnaire (CRQ)
Four trials used the CRQ [15,18,25,27].Nguyen et al. reported an improvement in the activity of daily living (ADLs) in both groups (tele-PR vs. regular PR) at follow-up [15].Spielmanns et al. presented a significant improvement in both groups (tele-PR and usual care) for dyspnoea and fatigue but not the emotional aspect [27].However, Galdiz et al. reported no significant differences in either group (tele-PR and usual care) [25] but the emotional aspect only improved in the intervention group.Tsai et al. reported a significant improvement in CRQ total score following training in the intervention group but not in the control group (usual care) (Table S1: Supplementary Material [18]. Health-Related Quality of Life (HRQoL) Two trials used the HRQoL [15,25].Nguyen et al. reported a significant improvement in both groups (tele-PR and regular PR) after the intervention [15].Galdiz et al., however, reported a significant improvement in the intervention group (tele-PR vs. usual care) only at follow-up (Table S1: Supplementary Material) [25].
The 36-Item Short Form Health Survey (SF-36) Two trials used the SF-36 [15,25].Both trials showed a significantly larger improvement in health status in the intervention group compared to the control group (regular PR or usual care) (Table S1: Supplementary Material).St George's Respiratory Questionnaire (SGRQ) Four trials used the SGRQ [16,17,19,24].Two trials reported a significant improvement in both groups (tele-PR and regular PR) [17,19], and one trial reported a significant improvement in the intervention group, but not in the control group (usual care) [16].The fourth trial did not report significant improvements in SGRQ scores in either group (tele-PR or regular PR) (Table 2) [24].
Pulmonary Rehabilitation Adapted Index of Self Efficacy (PRAISE) Tsai et al. reported no significant differences in improvement in the PRAISE scores between both groups (tele-PR vs. usual care) at follow-up [18].

COPD Symptoms Medical Research Council Dyspnoea Scale (MRC)
Three trials used the MRC [16,19,21].Wang et al. reported a significant improvement in both the intervention and control groups (tele-PR and usual care) [16].Two trials [19,21] reported an improvement in the intervention group only (tele-PR vs. regular PR).

Lung Function
Only one trial assessed lung function using spirometry [16].The trial reported improvement in the intervention group, but no improvement in the control group (usual care) in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow.The maximum mid-expiratory flow significantly improved in both the intervention group and the control group (Table 2) [16].

Acute Exacerbation and Hospitalisations
One trial showed a significantly larger reduction in the incidence of acute exacerbations and hospitalisations in the intervention than the control group (usual care) [21].Vasilopoulou et al. (2017) reported a significantly lower rate in both the intervention and control groups (tele-PR and regular PR) [19].

Emergency Department Visits (ED)
One trial reported a significantly lower rate in both the intervention and the control group (tele-PR and regular PR) [19], However, ED had less significance with the intervention group only in another study (tele-PR vs. usual care) (Table S1: Supplementary Material) [21].

Discussion
To our knowledge, this is the first study that reviewed the reported effects of digital health interventions on pulmonary rehabilitation outcomes in people with COPD.A total of 13 RCTs were included in the systematic review with good to excellent quality; this makes the results trustworthy.The findings of this systematic review showed that the digital health interventions had a positive effect on dyspnoea, lung function, HRQoL and the incidence of hospitalizations and ED visits.This supports the use of digital health interventions for pulmonary rehabilitation outcomes.
The results of this review showed a potentially positive effect of integrating the digital health interventions with pulmonary rehabilitation on exercise capacity.The exercise capacity measures cover a range of tests, including the walking, timed up-and-go, and sit-to-stand tests.An improvement was shown in the walking tests (ESWT, 6 and 12MWT) [15][16][17][18][19].These trials used educational materials and an interaction between the patient and healthcare provider during the tele-rehabilitation programme that in themselves may improve the exercise capacity performance compared with the traditional interventions, as indicated in a meta-analysis among individuals with chronic illness [28].
The findings of this systematic review also suggest that digital health interventions improve dyspnoea symptoms and lung function [16,19,21].These three trials applied comprehensive rehabilitation programmes, including self-management, to improve dyspnoea and lung function.The literature supports the effectiveness of self-management on dyspnoea [29,30] and lung function [31] among individuals with COPD, and those trials suggest that such improvements can be further enhanced by incorporating digital health interventions in the rehabilitation programme.
The included trials measured HRQoL with different measures, including generic and disease-specific measures.The findings support the positive effect of digital health interventions, and that using digital health results in significant improvements [16,19,21].This improvement could be achieved by performing exercises [32,33], receiving educational material about COPD and PR [34] and/or applying a self-management approach [30,31].
Seven studies included in this systematic review compared the benefits of tele-PR and regular PR.While two studies showed that the tele-PR improved exercise capacity more than regular PR [15,19], four studies did not find a significant difference in improvement between the two groups [17,20,22,24].In terms of QOL, two studies showed an enhanced improvement in tele-PR compared to regular PR [19,26], while one study showed no differences [17].Furthermore, two studies revealed enhanced improvements in COPD signs and symptoms [19,20], and another two studies showed that the difference in improvement was not significant [15,24].Hansen et al., 2020 [20] showed a significantly larger reduction in depression and anxiety with tele-PR, while Bourne et al., 2017 indicated no differences with regular PR [24].Lastly, one study compared regular and tele-PR regarding self-efficacy, and it was significantly improved with tele-PR, but not with regular PR [15].Overall, these observations indicate that tele-PR does result in similar or even better-but never worseimprovements than regular PR and hence support the use of tele-PR as an alternative to regular PR, as it reduces the cost to patients and the healthcare system.
Lastly, the findings did not support the advantages of digital health interventions in the improvement of anxiety, depression and self-efficacy.Typically, pulmonary rehabilitation programmes focus on physical and breathing exercises [35,36] and the effectiveness of such programmes on psychosocial outcomes is apparently not further improved by the incorporation of digital health interventions.

Clinical Implications
The use of digital health interventions to support pulmonary rehabilitation among individuals with COPD improves pulmonary and physical outcomes.It may also reduce the cost of COPD-related sequalae by lowering the rate of exacerbations, hospitalizations, and ED visits.Therefore, this systematic review suggests that these interventions should be integrated with the usual care of people with COPD to maximize the health outcomes of these people.
Although there is a lack of evidence to show that digital PR is better than face-toface PR, it never led to a worse outcome.Therefore, a personalized approach should be used, with digital PR serving as an adjunct to regular PR [35,36] and perhaps even as an alternative to regular PR as it reduces the cost to patients and the healthcare system.
Digital health PR can take different forms: web-based, smartphone applications and video conferences.The results of this review showed that the effectiveness of digital health PR does not depend on its form; it relies more on the components of the intervention.Digital health PR should include a self-management programme, home monitoring, and an E-health telephone or platform [37].To optimize the effect of digital health PR, selfmanagement should include interventions to address physical and psychosocial issues.

Future Research
This systematic review highlights that there is a need to conduct more studies on the use of digital health interventions in pulmonary rehabilitation to strengthen the conclusion about the effectiveness of such interventions and to ensure its inclusion in pulmonary rehabilitation guidelines.

Limitations
This study is not without limitations.For example, the included trials were heterogeneous, and therefore a meta-analysis was not conducted.This limits the estimation of the magnitude of the effectiveness of digital health PR.Other limitations include potential publication bias, the varying quality of the included trials, and the exclusion of non-English-language trials.

Conclusions
This review supports that digital health PR for people with COPD is effective in improving pulmonary and physical outcomes and has no negative impact on psychosocial outcomes.The small number of included trials that used different forms of digital health PR limits the certainty of the findings of this review.

Supplementary Materials:
The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/medicina60060963/s1,Table S1 is reporting the results of the included studies about non-respiratory-related outcome measures (for example: anxiety and depression).

Figure 1 .
Figure 1.The PRISMA flowchart for the search records and the included trials.

Figure 1 .
Figure 1.The PRISMA flowchart for the search records and the included trials.

Figure 2 .
Figure 2. Results of the Cochrane Risk of Bias (CROB2) for the included trials.References cited in the figure are the following: [15-27].

Figure 2 .
Figure 2. Results of the Cochrane Risk of Bias (CROB2) for the included trials.References cited in the figure are the following: [15-27].

Author
Contributions: M.Z.D. and A.A. were responsible for the study conception and design.R.B. and A.M.S. extracted the data.M.Z.D., A.A., O.E. and H.D. were responsible for data interpretation.All authors have participated in writing-original draft preparation.All authors have participated in editing and completion of the manuscript.All authors have read and agreed to the published version of the manuscript.Funding: This research received no external funding.

Table 1 .
Summary of keywords used and search strategy.

Table 2 .
Summary of included trials that investigated the Effects of Digital Health Interventions for Pulmonary Rehabilitation in People with COPD: A Systematic Review of Randomized Controlled Trials (n = 13).
F: 2x/week for 8 weeks.I: Intensity personalised based on patient symptoms and capacity.T: 2 h/session.Education session for 1 h/session.T: aerobic, resistance, flexibility, breathing exercise.

Table 3 .
Results of the PEDro scale for quality assessment for the included randomised controlled trials.