Mapping the global research landscape and hotspot of exercise therapy and chronic obstructive pulmonary disease: A bibliometric study based on the web of science database from 2011 to 2020

Background: The application of exercise therapy (ET) in chronic obstructive pulmonary disease (COPD) is generating increasing clinical efficacy and social-economic value. In this study, research trends, evolutionary processes and hot topics in this field are detailed, as well as predictions of future development directions.

Methods: Search for literature in the field of COPD and ET and analyze data to generate knowledge graphs using VOSiewer and CiteSpace software. The time frame for the search was from 2011 to January 2021. Then we extracted full-text key information (such as title, journal category, publication date, author, country and institution, abstract, and keyword) and obtained the co-citation analysis. Use hierarchal clustering analysis software developed by VOSviewer to map common citations, and use Citespace software to plot trend networks.

Results: The United States topped the list with 27.91% of the number of articles posted, followed by the UK at 25.44%. Imperial College London was the highest number of article publications in institutions, followed by Maastricht University and the University of Toronto. The Royal Brompton Harefield NHS Foundation Trust was one of many research institutions and currently holds the highest average citations per item (ACI) value, followed by Imperial College London and the University of Leuven. Judging from the number of publications related to ET and COPD, it is mainly published in cell biology, respiratory pulmonary diseases, and rehabilitation experiments study medicine. The European Respiration Journal is the most widely published in this field, followed by the International Journal of Chronic Obstructive Pulmonary Disease and Respiratory Medicine.

Conclusion: COPD combined with ET is widely used in clinical practice and is on the rise. A distinctive feature of the field is multidisciplinary integration. Rehabilitation research for COPD involves multidisciplinary collaboration, tissue engineering, and molecular biology mechanism studies to help patients remodel healthy breathing. Multidisciplinary rehabilitation measures provide a solid foundation for advancing clinical efficacy in the field of COPD.

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT Exercise therapy in COPD: an emerging topic.

Introduction

Chronic obstructive pulmonary disease (COPD) is currently defined as “a preventable and treatable disease with some significant intrapulmonary and extrapulmonary inflammatory effects” (Neumeier and Keith, 2020) that may lead to serious consequences such as dyspnea in patients. Pathological manifestations of the lungs are characterized by limited airflow but are not completely reversible (Buist et al., 2007). Airflow restriction usually occurs on an ongoing basis and is associated with an abnormal inflammatory response to lung irritation from toxic particles or harmful gases (Lozano et al., 2012). The common perception of the disease is that it will be one of the major health challenges in the coming decades (GBD 2015 Chronic Respiratory Disease Collaborators, 2017). Prevalence surveys suggested that as many as nearly one in four adults aged 40 years and older worldwide had mild airflow obstruction (Mannino and Buist, 2007)).

Exercise therapy (ET) is a therapeutic form of training that improves the body’s exercise endurance and improves cardiopulmonary function. Many studies have proved that aerobic exercise is an effective way to improve systemic inflammation (Accordini et al., 2020), in particular, has a good effect on improving lung function and exercise ability, and reducing systemic inflammation in COPD patients (Wen et al., 2019). Braz Júnior et al. (2015) found that whole-body vibration (WBV) was effective in improving the 6-min walk distance (6MWD) ability of COPD patients with a good positive modulating effect on the quality of life assessed by the St. George’s Respiratory Questionnaire (SGRQ). Dong J. et al. (2021) study demonstrated that both qigong ET and cycle dynamometer training in COPD patients could improve cardiorespiratory endurance and quality of life, and that cycle dynamometer training played a more effective role in improving the severity of COPD clinical symptoms. Current studies have shown that patients with COPD could improve their exercise ability through short- and medium-to long-term tai chi exercises, and have the potential to improve dyspnea, enhance cardiopulmonary function, and improve the quality of life of COPD patients (Guo et al., 2016; Liu et al., 2021a).

According to the latest studies, ET has achieved a lot of signature progress in the treatment of COPD. As an important means of COPD pulmonary rehabilitation, long-term regular rehabilitation exercises have a good rehabilitation effect in alleviating patients’ breathing difficulties, delaying skeletal muscle atrophy, improving quality of life, and can effectively reduce the level of COPD systemic inflammation. Liu et al. (2021b) found that the oral administration of N-acetylcysteine (NAC) relieves inflammation in COPD patients and could regulate the imbalanced state of T helper 17 cells and regulatory T cells (Th17/Treg). From the perspective of the immunological concept, this result provides new diagnostic and therapeutic means for elderly patients with COPD. Similarly, 6 months of home-based aerobic exercise significantly reduced C-Reactive Protein in serum (CRP serum) and interleukin-8 (IL-8) levels in patients with COPD, and increased skeletal muscle strength and improved exercise capacity; compared with the control group, aerobic exercise groups-maintained serum Tumor Necrosis Factor Alpha (TNF-α) and interleukin-6 (IL-6) levels, suggesting that aerobic exercise could maintain or reduce inflammation levels and slow disease progression (Wang et al., 2014). Bernardi et al. (2015) found that respiratory muscle training improved ventilation patterns and uncoordinated movements of the thoracic cage in patients with COPD, increasing oxygen saturation during endurance training. Abd El-Kader et al. (2016) compared the anti-inflammatory effects of aerobic exercise and resistance training on COPD systemic inflammation. The result showed that both aerobic and resistive exercise could reduce serum TNF-α, interleukin-2 (IL-2), interleukin-4 (IL-4), IL-6, and CRP levels, and the effect of aerobic exercise on the reduction of the above inflammatory factors was significantly better than that of resistive exercise (Abd El-Kader et al., 2016). Based on the brain plasticity developed by the human body’s motor ability, ET has practical clinical significance and cost-effective economic value prospects.

Bibliometrics had the characteristics of bibliology and bibliometrics for quantitatively and qualitatively analysis (Chen, 2006). All included literature was allowed to quantitatively measure the contour distributions as well as study connections and clusters (Chen et al., 2014). Trends in this field of study were described and predicted by summarizing various literature data, including comparing contributions from different countries, institutions, journals, and authors (Chen, 2004). These data analysis techniques have been increasingly used in the development of guidelines and the evaluation of research trends (van Eck and Waltman, 2010). Many researchers in the medical field have adopted this method of literature analysis, such as respiratory medicine research (Waqas et al., 2020), biological signalling molecule research (Liang et al., 2021), genetics research (Alvarez-Peregrina et al., 2021), health information research (Dang et al., 2021), and endocrine disease research (Dong X. et al., 2021).

This study is based on literature data from Exercise Therapy and Chronic obstructive pulmonary disease on the Web of Science website, and the maps of the knowledge graph were done by VOSviewer and CiteSpace. The study presents the latest advance in the field of basic or clinical research in COPD, the evolution of hotspot research, and the prediction of future trends.

Methods

Data sources and search strategy

We identified the target databases for source literature searches as Science Citation Index Expanded (SCI-EXPANDED) and Social Science Citation Index (SSCI) of the Web of Science Core Database. The search formula was set to TS= (exercise* OR training* OR physical exercise* OR aerobic movement* OR exercise therapy* OR movement therapy* OR kinesiotherapy* OR rehabilitation exercises*) AND TS= (chronic obstructive pulmonary disease* OR COPD* OR chronic airflow obstruction* OR chronic obstructive lung disease*) and the search dates are from 1 January 2011, to 31 December 2020, with a total of 2,870 records searched (Figure 1).

FIGURE 1

FIGURE 1. Flowchart of study selection (Preferred Reporting Items for Exercise (ET) therapy and chronic obstructive pulmonary disease (COPD).

Inclusion and exclusion criteria

Original articles or commentaries published in peer review on the molecular mechanisms of exercise for COPD were incorporated. The exclusion criteria are 1) meeting summary or errata document; 2) Unpublished articles; 3) Duplicate publications; 4) Irrelevant articles.

Bibliometrics and visual analysis

2,798 articles were retrieved and imported into VOSviewer and CiteSpace for analysis. Firstly, calculating similarity matrices based on the co-occurrence matrices, CiteSpace is used to focus on discovering and analyzing the evolution of research trends and the relationships between cutting-edge hotspots and their associated knowledge bases (Chen, 2004). CiteSpace was also used to look for the intrinsic connections between different hotspots to obtain keywords related to strong co-occurrence bursts that serve as predictors of research trends to analyze the latest direction. Then, the similarity matrix technique for constructing the map was done by VOSviewer software. The term co-occurrence diagram in VOSviewer included only articles mentioned at least 50 times in the title and abstract and was analysed by binary algorithm counts. VOSviewer constructs maps based on co-occurrence matrices to complete the translation, multidimensional rotation, and panoramic mapping in map construction (van Eck and Waltman, 2010).

Results

Distribution of articles by year of publication

The search date was from 1 January 2011, to 31 December 2020, and a total of 2,798 articles were obtained after deleting 72 non-conforming records. From 2011 to 2020, the number of research papers published in this field showed an overall rapid upward trend (Figure 2), from 5,000 1-year articles to about 10,000 articles a year. During these 10 years, the number of articles peaked in 2018, reaching nearly 10,000 publications a year, and then declined in 2019 and 2020. In terms of citations, the number of citations published between 2011 and 2021 also increased year by year, and in 2020, the number of citations peaked, indicating that more and more researchers are beginning to pay attention to this field.

FIGURE 2

FIGURE 2. Trends in the growth of publications and the number of cited articles worldwide from 2011 to 2020.

Country/region distribution

Table 1 was shown the top two countries in terms of the number of articles published, ranking the United States at 15.26% and the United Kingdom at 13.33%. The total number of articles published by the two countries accounts for one-third of the total, and other countries such as Australia, Canada, and Brazil also accounted for about 10%, which showed that all countries had a strong willingness to study and innovate in this regard. The average citation rate of papers was expressed in average citations per item (ACI). Total link Strength was the total number of co-occurrences of keywords and other keywords in the VOSviewer software (including the number of repeated co-occurrences), the number of nodes indicated the number of connections with the node, the more the total number of connections, the larger the circle. China (42.32), the United States (34.9), and Netherlands (34.07) are the top three countries in ACI value, indicating that their research systems were established earlier and the results of the research were more mature.

TABLE 1

TABLE 1. Top 10 productive countries.

We selected publications published from 2011 to 2021 with a time slice of 1 year and selected the 30 most cited or appeared items from each slice. Selected tree ring history, for example, tree circle size, in node display mode, the size of which represented the number of papers published by a country, author, or institution. The lines between nodes represented cooperation, and the colour of the lines represented clustering. Rings of different sizes in the Atlas indicated frequency, different colours indicated different years, and the outermost purple circle indicated centrality. Nodes with a Fuchsia colour indicated important nodes with strong centrality, while other yellows were highlighted as key nodes affecting the field.

The colour of the circle represents the year of publication, and countries with close cooperation were shown with strong centrality key points of the purple circle. We found that the United States was the country that publishes the most papers and had close exchanges with Spain and Canada. European countries, mainly the United Kingdom, had also published a large number of papers in this field and had close exchanges with each other (Figure 3A). Many countries tended to work with a relatively stable country, generating three major national clusters in the graph, each often containing one or more national core research teams. Many authors tended to work with a relatively stable team of collaborators, so 4 major author clusters were generated in the graph, each of which typically contained two or more core authors (Figure 3B). The chart in Figure 3C was shown the cooperative institutions in this field, many of which had a considerable amount of publications, and maintained a certain degree of cooperation.

FIGURE 3

FIGURE 3. Cooperation map (A). Co-countries (B). Co-authors (C). Co-institutions in the studies of the COPD and Exercise Therapy. Figures 3A–C are used by CiteSpace.

Distribution of authors and research institutions

Table 2 expounded that Spruit, M. A. of Maastricht University in Netherlands published the most articles, followed by Wouters, E. F. of Maastricht University. Three of the top ten writers are from Netherlands.

TABLE 2

TABLE 2. Top 10 authors in the studies of COPD and exercise therapy.

Table 3 was shown that the institution with the most publications in the field of research was the College London with 108 copies, followed by Maastricht University in Netherlands with 95 copies and the University of Toronto in Canada with 87 copies. The contribution of a research institution was expressed in ACI value, and the highest ACI value in 10 years was Royal Brompton Harefield NHS Foundation Trust, with an ACI of 42.38, the second was Imperial College London, with an ACI of 36.25, and the third was Catholic University Leuven of Belgium, with an ACI of 35.28.

TABLE 3

TABLE 3. Top 10 institutions in the studies of COPD and exercise therapy.

Distribution of research disciplines

Table 4 outlined indicators based on the number of papers published to identify the top three disciplines, including Liberatory (56.62%), Medicine general internal (9.87%), and Cardiac cardiovascular systems (8.54%). Other disciplines represented in the literature include Health care sciences services (2.63%), Physiology (2.63%) and other disciplines, the above research was shown that the research carried out in this field was extensive and diverse, mainly around skeletal muscle protein degradation (Balnis et al., 2020), genotype (Silverman, 2020), inflammatory (Baldi et al., 2014; Abd El-Kader et al., 2016), and other related studies have been carried out in multiple disciplines.

TABLE 4

TABLE 4. The top 20 subject categories in the studies of the COPD and exercise therapy.

Table 5 was shown the ranking of journals with the largest number of articles published, the European respiration journal had the largest number of articles with 235 articles, the second most published was the international journal of chronic obstructive pulmonary disease with 189 articles, and Respiratory Medicine ranked third with 91 articles. The COPD: journal of chronic obstructive pulmonary disease, Respiratory care, and Respirology followed by 88, 82, and 82 articles. The contribution of a journal was expressed in ACI value, and the highest ACI value in 10 years was The American Journal of respiratory and critical care medicine (86.31) and BMJ open (86.31), followed by the Cochrane database of systematic reviews (71.49), Thorax (34.11), and BMJ open (86.31). Thorax (Chest).

TABLE 5

TABLE 5. Top 15 journals in the studies of COPD and exercise therapy.

Highly cited literature analysis

Table 6 outlined the article “An Official American Thoracic Society/European Respiratory Society Statement: Key Concepts and Advances in Pulmonary Rehabilitation” (Spruit et al., 2013) was the most cited. Spruit et al. (2013) published an official statement on advanced concepts and progressions in the functional recovery of pulmonary rehabilitation through the American Thoracic Society (ATS)/European Respiratory Society (ERS). The important role of respiratory rehabilitation in the precise management of chronic diseases was highlighted in this statement, and the role of healthy motor behaviour changes in optimizing and maintaining patient outcomes was further discussed. According to this Practice Guideline, pulmonary rehabilitation plays an important role in promoting self-efficacy and optimizing healthy behaviour change. To ensure that exercise training is effective, cardiorespiratory endurance, strength, and/or flexibility are improved by maximizing aerobic capacity and muscle strength through endurance training, interval training, resistance training, respiratory muscle training, and different training modes based on the individual needs of COPD patients.

TABLE 6

TABLE 6. Top 15 co-cited articles, cited authors and cited references.

The second most cited article was “Exercise as medicine—evidence for prescribing exercise as therapy in 26 different chronic diseases” (Pedersen and Saltin, 2015). Pedersen and Saltin (2015) collected the latest evidence-based medical evidence on exercise as a treatment for 26 different chronic lung diseases (such as chronic obstructive pulmonary disease, asthma, cystic fibrosis, and so on). This article proposed different chronic diseases and the effects of ET on the symptoms associated with related diseases, discussed possible mechanisms of action and updated with the best recommendations for the optimal type and dosage of exercise prescriptions. By summarizing the results of evidence-based physical exercise, this Statement found modest evidence of a significant increase in leg muscle strength suggesting that a combination of resistance and endurance training may not improve lung function in patients with COPD. But helped counteract protein degradation in COPD patients (Petersen et al., 2008), increasing cardiopulmonary fitness through effects on muscles and the heart. Optimal exercise prescribing was the ability to achieve gait, balance and breathing function through personalized supervision.

A third frequently cited article was “Pulmonary rehabilitation for chronic obstructive pulmonary disease” (McCarthy et al., 2015). McCarthy et al. (2015) explained that pulmonary rehabilitation, also known as respiratory rehabilitation, can relieve difficulty breathing and physical fatigue, regulating the emotional stress of patients with repeated illnesses. Existing findings strongly supported the need for pulmonary rehabilitation for severe COPD, including at least 4 weeks of exercise training, and in addition to a 6MWD test (a measure of functional exercise) (Puhan et al., 2011), there have been clinical and statistically significant improvements in health-related quality of life assessments such as dyspnea, fatigue, and emotional function (Bolton et al., 2013). These measurements were moderate and can help patients reestablish healthy breathing. The rehabilitation criteria recommended by the Cochrane Collaboration were the evaluation system for routine pulmonary function recovery. It was used to maximize the respiratory quality and life engagement and social value for COPD patients and was an important part of COPD management. This Cochrane Review/meta-analysis review clarified that lung function rehabilitation can improve the health-related quality of life in people with COPD, and future studies should further clarify the ideal cycle of rehabilitation programs, the intensity of training required, and the duration of rehabilitation outcomes. The above articles reflected the economic value and clinical efficacy feasibility of exercise therapy.

Depending on the type of literature, the most frequently cited literature was involved in six reviews and nine monographs. Judging from the publication dates of highly cited documents, 2013–2015 was the most cited, followed by 2011–2012. These time nodes can be seen as two important phases in the development of the study area. According to the number of co-institutions and countries/regions, ten articles dealt with more than three co-institutions and nine articles were related to the participation and cooperation of at least two countries.

The network of keywords co-citation

Keywords highlight the article’s fundamental content, and you can uncover research frontiers that were continually updating and changing in relevant knowledge fields by skimming through them quickly. In contrast, chronic obstructive pulmonary disease and exercise, the first 20 keywords with high frequency and centrality were listed in Table 7. The keywords cited with high frequency were rehabilitation (745), quality of life (555), lung function (506), dyspnea (338), and motor capacity (331). ET had significant clinical significance in relieving dyspnea (Laughlin and Roseguini, 2008) and fatiguing (Beaumont et al., 2018) in pulmonary rehabilitation, further improving emotional function (Lindenthaler et al., 2018) and enhancing individual confidence and control over their condition. Exercise therapy for prolonged (>6 months), which included aerobic exercise (Reis et al., 2013), endurance exercise (Iepsen et al., 2015), and inspiratory muscle training (Pleguezuelos et al., 2016), had been shown to help improve dyspnea, autonomous impedance capability, and life pleasure and reduced risk factors during acute exacerbations in COPD patients.

TABLE 7

TABLE 7. The top 20 keywords in the studies of the COPD and exercise therapy.

Keyword co-citation and clustering keywords are high-level roundups. High-frequency, highly centralized keywords often reflect research hotspots in the field. We analyzed publications within 1 year, as well as the top 30 levels of publications with the most citations or the most occurrences in each period. The 132 nodes and 987 links consisted of a combined co-occurrence keyword network (Figure 4A). Figure 4B was shown the use of VOSviewer software and presents a keyword co-occurrence network diagram. The more closely connected nodes, the more highly appeared frequency of the two keywords together. The four main research directions were represented by the four clusters of keywords in this field. Red had the largest area, green second, then blue third, and yellow can almost be negligible.

FIGURE 4

FIGURE 4. Map of keywords (A). Co-occurring keyword (B). Keyword clustering in the studies of the COPD and Exercise Therapy. Figure 4A is used by Citespace. Figure 4B is used by VOSviewer.

The red clusters consisted mainly of studies related to chronic obstructive pulmonary disease. On the one hand, it included conditions such as dyspnea, Bode index, and 6MWD, which were directly related to the disease. On the other hand, the exploitation of the potential mechanisms of cell transplantation, differentiation, proliferation, mitochondrial dysfunction, inflammation, and apoptosis helped to clarify the practical significance of COPD patients, tests, and subjects. To improve the efficacy of muscle cell transplantation, differentiation and proliferation, regulators of the first three sections (Agustí et al., 2012; Chaillou and Lanner, 2016; Britto et al., 2020; van Doorslaer de Ten Ryen et al., 2021) by drugs (Doucet et al., 2007; van Helvoort et al., 2007; Fiorentino et al., 2020), and tracking tools (Iepsen et al., 2016; Catteau et al., 2021) implemented. The mechanism of the movement was illustrated by the antioxidant, anti-inflammatory, and anti-apoptosis of the latter parts. Mechanisms included exercise-induced production and absorption of glucose in patients with COPD (Franssen et al., 2011), and the action of drugs such as β receptor agonists bronchodilators (Haarmann et al., 2015), metformin (Wu et al., 2021), trypsin-like serine protease inhibitors (Liang and Bowen, 2016), and so on.

The green clusters were mainly composed of research related to sports rehabilitation. On the one hand, several commonly used research methods are described, such as SMD, placebo, and RCTs, which were often used in medical control research. On the other hand, it described the rehabilitation-related situations of training, exercise training, management, and so on. Supplementation with high-intensity interval training (HIIT) in COPD patients compared with placebo groups corrected muscle disorders and improved moderate airflow obstruction and athletic performance (van de Bool et al., 2017). Paneroni et al. (2017) systematically evaluated the effectiveness of ET in patients with very severe COPD, and the meta-analysis results showed that ET could effectively improve exercise endurance, and more randomized controlled trials (RCTs) were needed to further clarify the basis for the scientific formulation of exercise prescriptions. Kerti et al. (2018) studied the degree of contribution of lung exercise training and its evaluation criteria in patients with COPD, and the results showed that the level of exercise tolerance for pulmonary rehabilitation depends on the combined effects of exercise capacity, improvement of inspiratory lung capacity, metabolism and respiratory muscle function. The use of metronomes to set the equation of exercise training intensity improved the respiratory patterns and short-term resistance training of COPD patients during exercise and helped provide supervised exercise parameters for family lung rehabilitation (Robles et al., 2017; Bernardi et al., 2018). COPD self-management improves patient engagement and the sustainability of athletic training through supervised collaboration with physicians and other medical rehabilitation personnel (Bourbeau et al., 2015).

The blue clusters were concentrated in other special cases. Words such as intervention, exacerbation, anxiety, and so forth were being studied for the possible negative effects of COPD on sports disorders. Skeletal muscle dysfunction in patients with COPD occurred not only in peripheral skeletal muscles but also affected the major respiratory diaphragm (Gea et al., 2013). The cause of skeletal muscle dysfunction was related to systemic inflammation, which can lead to changes in skeletal muscle tissue structure and decreased contractility by influencing skeletal muscle protein synthesis and catabolism (Barreiro and Gea, 2016) and apoptosis of skeletal muscle cells (Barreiro et al., 2015). Aerobic exercise can improve the inflammatory response in the body, thereby effectively improving body function (Van Helvoort et al., 2006). Moderate- and high-intensity aerobic exercise can significantly improve the structure and function of skeletal muscles in patients with COPD (Silva et al., 2018). However, there have been relatively few studies on the mechanism of systemic inflammation of skeletal muscle dysfunction in patients with exercise intervention COPD.

Joint evolutionary path

In Figure 5, the year corresponding to the dataset analysis indicated that the keyword appeared in the first year. The contact path between COPD and exercise rehabilitation was presented through the transition nodes. From 2011 to 2013, research in the field began focusing on dyspnea, obstructive, mortality, and physiological activity. In 2013–2015, reliability, guidelines, interventions, depression, and breathlessness received increasing attention in the field. The scientific effectiveness of medical research and the prevention and control of safety risks had been a high degree of emphasis from 2016 to 2017, with a new focus from 2018 to 2020 on benefits, safe walking tests and exercise tolerance.

FIGURE 5

FIGURE 5. Evolutionary path in the studies of the COPD and Exercise Therapy. Figure 5 is used by Citespace.

Research hotspots and cutting-edge analysis

In Table 8, the blue lines presented the timeline, and the red bands represented burst detection, which indicated the start year and duration of the different burst words. In addition, the research-meaningful keywords we were interested in reflect the evolutionary trends in the field. Validity was shown as the strongest explosive intensity, followed by Airflow obstructive, Care, and Hyperinflation. Terms such as Airflow obstructive, Hyperinflation, and Salmeterol began to emerge in 2011, but lasted shorter, ending around 2013. Chronic heart failure, Limitation, and Survival terms were popular between 2014 and 2016. Validation was currently at the forefront of this field of research and is in an explosive stage.

TABLE 8

TABLE 8. Top 15 keywords with the strongest citation bursts.

Discussion

Summary of findings

This study compiled relevant exercise therapy literature in the field of COPD from 2011 to 2020 and conducted a bibliometric analysis using Citespace and VOSviewer software. The study mainly evaluated the region and publication time of the article, the current research hotspots of COPD combined exercise therapy, and the author’s contribution. Keyword co-occurrence analysis is the hotspot we used to assess and determine researchers’ concerns during each period to uncover core topics in the context of clinical research. Multidisciplinary integration such as alveolar remodelling and rehabilitation engineering is a new trend in our identified research in the field of COPD.

Rehabilitation of COPD

The affordability of exercise therapy will be well demonstrated in future COPD application treatment; in addition, there are certain risks and limitations, as well as the exercise mode used, exercise capacity, exercise status, exercise pathway, exercise site and intensity, etc., and the treatment effect also varies from person to person. Indications for exercise therapy and patient acceptance of the possible risks that may occur have led to research controversial (Østergaard et al., 2018). For instance, Su et al. (2018) proposed that COPD patients weakened lung ventilation function and decreased oxygen uptake, which led to hypoxemia in organs such as skeletal muscle, which reduced the patient’s ability to exercise and developed waste muscle atrophy. Given the exercise risks and limitations of exercise intensity in the study, the researchers were cautious when conducting their research work. According to a meta-analysis of RCTs of physical exercise intensity, it was confirmed that HIIT and continuous ET had a similar effect on functional capacity and cardiovascular variables in patients with COPD, indicating the clinical effectiveness of ET for pulmonary rehabilitation (Adolfo et al., 2019). Liao et al. (2015) systematically evaluated the safety of resistance training in 750 patients with advanced COPD, and there was evidence that resistance training combined with endurance training significantly improved skeletal muscle strength, improved the total score of the SGRQ, and did not have adverse events under the intervention of scientific resistance training exercise. Inspiratory muscle training (IMT) in patients with COPD relieved excessive activation of the diaphragm and reduced dyspnea during exercise (Langer et al., 2018). A systematic review also found that expiratory muscle training (EMT) combined with IMT in patients with severe to very severe COPD showed that both were effective in improving respiratory muscle strength, but there was no significant difference between the 6WMD and dyspnea (Neves et al., 2014; Xu et al., 2018).

Exercise physiology and molecular mechanisms

First of all, over the past decade, in Europe and the United States, East Asian countries developed more interest in studying molecular mechanisms in this field. European and American countries have explored the initial research plan and gradually improved their research ideas to achieve clinical utility. In particular, both Imperial College London and the University of Toronto started early and have obtained some high-quality scientific clinical outcomes, including breathlessness rehabilitation (Man et al., 2016) and outcome measures combined ET (Jones et al., 2019), and the effects of post-rehabilitation exercise based on community (Butler et al., 2020). The researchers also explored the pulmonary protection mechanisms of COPD-related quadriceps muscle dysfunction, including sex differences (Sharanya et al., 2019), utilization of non-invasive imaging tools (Rozenberg et al., 2017), handgrip strength reflection (Fonseca et al., 2021), the clustering physiological responses to arm activity (Lima et al., 2016), and the physical activity during moderate (out-patient managed) (Alahmari et al., 2016). Monash University and the University of Bern studied the effects of peripheral muscle training (Bisca et al., 2017), the WBV intervention (Furness et al., 2012), and physical activity significantly correlated with quadriceps strength (Osthoff et al., 2013) on skeletal muscle dysfunction, exercise tolerance and functional performance. Italy’s studies found that respiratory rehabilitation interventions in COPD patients could reduce the inflammatory cytokine IL-6, and improve lung capacity and 6MWD ability (Baldi et al., 2014). In addition, Belgium research found that motor muscle work during HIIT could impair blood flow perfusion of the diaphragm and increase the feeling of dyspnea (Louvaris et al., 2021). Therefore, the United Kingdom’s cooperation with the United States research showed COPD patients needed to be able to achieve noninvasive monitoring of blood flow in the respiratory tract and motor muscles during exercise (Vogiatzis et al., 2020), and both German and Belgian studies have been validated to show that the near-infrared spectrum could be used to assess the respiratory and muscle blood flow index and prevent hyperpnea and muscle perfusion during exercise (Habazettl et al., 2010; Louvaris et al., 2018).

East Asian countries have focused on the dialectical treatment of the holistic view of COPD through the qigong and tai chi of traditional Chinese exercise therapy (TCET) for nearly 10 years (Guo et al., 2016; Dong J. et al., 2021). Among the many scientific research institutions that have made more leading achievements are Guangzhou Medical University, the Royal Brompton and Harefield and other cooperation institutions, such as NHS Foundation Trust and Imperial College. The study explored the physiological response of stable COPD to tai chi was similar to treadmill training, which could improve respiratory rate and diaphragm dynamic hyperinflation (Qiu et al., 2016). Scholars have also explored improvements in lung function and diaphragm thickness through respiratory muscle training (RMT) (Xu et al., 2018; Cheng et al., 2022). RMT devices combined with respiratory techniques could improve respiratory muscle strength, reduce TNF-α and IL-6, and have a significantly improved effect on the plasma level of oxidative stress marker-total antioxidant capacity (TAC) (Leelarungrayub et al., 2018).

Exercise therapy combined with rehabilitation engineering

Under the premise of multidisciplinary cross-intersection, the development of ET combined with rehabilitation engineering has received great impetus and technical support. The dynamic rehabilitation process of COPD is mainly studied through the literature in the field of computer informatics (McCabe et al., 2017) to further elaborate the mechanism of the intervention effect of exercise therapy. Chronic obstructive pulmonary disease systematically studies the related pulmonary disease of clinical rehabilitation technique and basic laboratory machines, involving clinical rehabilitation engineering, intelligent medical engineering, sport sciences and other disciplines, reflecting that one of the characteristics of the combination of exercise therapy and rehabilitation engineering is the integration and development of disciplines.

Rehabilitation engineering for noninvasive monitoring and widespread applications of wearable materials have increasingly become hot topics of concern for COPD researchers. For example, taking the initiative to participate in video games (Simmich et al., 2019), the active use of resistance breath muscle training devices (Włodarczyk and Barinow-Wojewódzki, 2015; Schaper-Magalhães et al., 2017; Daynes et al., 2018), wearable smart vests (Naranjo-Hernández et al., 2018) and a smartphone oximeter with a fingertip probe (Chan et al., 2019) could effectively monitor the respiratory rate of COPD patients. In addition, using interdisciplinary digital mobility results enabled scientific assessment of the clinical utility of physical activity (Polhemus et al., 2021) and remote rehabilitation systems combined with wearable equipment could help COPD patients to achieve better sports performance and healthy quality of life (Tey et al., 2017). The cross-development of disciplines in different fields will help to break through the technical difficulties that limit the development of a certain field.

Exosome and alveolar remodelling

Exosome and alveolar remodelling research, and tissue engineering research are hot and clinical efficacy areas in this field that need to be verified. Among the bibliometric results, we found that COPD was associated with exosome and alveolar remodelling in the research hotspots, and exosomes played an important role in the pathogenesis of COPD by regulating chronic inflammation (Tan et al., 2017; Sundar et al., 2019a), mitochondrial dysfunction (Lerner et al., 2016), emphysema (Klooster et al., 2015) and cystic fibrosis (Pedersen et al., 2015), and oxidative stress (Sundar et al., 2013). Exosomes are small lipid-binding vesicles found in lung tissue and bronchoalveolar lavage fluid (BALF) (Kaur et al., 2021). Exosomes act as potential biomarkers to promote cell-to-cell communication under normal and diseased conditions (Sundar et al., 2019b). Patients with COPD with small airway obstruction led to pulmonary ventilation dysfunction due to complex and dynamic hyperinflation alveolar pathological remodelling process. The expansion of the alveoli and worsening of contractile and diastolic function are associated with adaptive changes that occur at different levels, respectively by genetic selection, molecular biology, and cellular interstitial levels.

Limitations

Our comprehensive bibliometric research has some limitations, and for high-quality bibliometric analysis, the Web of Science database is searched by default, thus excluding non-SCI journals such as BMJ Open Respiratory Research, which may have many publications related to a variety of chronic pulmonary diseases. Furthermore, our group have not yet collected a more detailed analysis of study subjects suffering from multiple diseases in exercise therapy, such as the prevalence of exercise therapy and the burden of non-pharmacological treatment of multiple diseases in each region or centre where the sample had studied. To be inspired by the research program, our team recommended a systematic review of home exercise therapy and COPD topics, covering more databases of home exercise therapy and online therapists guiding lung rehabilitation. Secondary databases require global multi-scope research analysis and preliminary longitudinal cohort scheme design. Under the impact of the COVID-19 pandemic, COPD patients could choose between hospital outpatient sports training or home sports training. A meta-analysis conducted by Wuytack et al. (2018) yielded results that exercise training programs could help COPD patients improve lung respiratory symptoms, health-related quality of life, and exercise capacity, with low and moderate evidence that exercise training was equally effective whether in hospitals or at home.

Conclusion and future perspective

This research analyzed the research hotspots and frontiers of exercise therapy on COPD through VOSviewer and CiteSpace. The results showed that exercise improves the efficacy of skeletal muscle cell transplantation, differentiation and proliferation of COPD, and exercise antioxidant, anti-inflammatory, and anti-apoptotic is a hot research mechanism of exercise for COPD. Emerging mechanism research focuses typically on exosome and alveolar remodelling studies, and tissue engineering studies. In addition, future studies could delve into the interactions between different mechanisms and attempt to elucidate the recommended motility and intensity of exercise for COPD, particularly in emphysema, idiopathic pulmonary fibrosis, and interstitial lung disease.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

No identifiable images data statement are presented in the manuscript.

Author contributions

YZ was responsible for data collection and analysis and completed the first draft. WW and XL checked the consistency of the analysis results for omissions and reviewed the manuscript drafts. Contributions to the article were provided by the three authors after revision, and the final version was submitted after approval by all authors.

Funding

This research was funded by the National Natural Science Foundation of China (Grant Numbers 81902307 and 82072551) and the two funding supports for this article were sponsored by XL..

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Abd El-Kader S. M., Al-Jiffri O. H., Al-Shreef F. M. (2016). Plasma inflammatory biomarkers response to aerobic versus resisted exercise training for chronic obstructive pulmonary disease patients. Afr. Health Sci. 16, 507–515. doi:10.4314/ahs.v16i2.19

PubMed Abstract | CrossRef Full Text | Google Scholar

Accordini S., Calciano L., Marcon A., Pesce G., Antó J. M., Beckmeyer-Borowko A. B., et al. (2020). Incidence trends of airflow obstruction among European adults without asthma: A 20-year cohort study. Sci. Rep. 10, 3452. doi:10.1038/s41598-020-60478-5

PubMed Abstract | CrossRef Full Text | Google Scholar

Adolfo J. R., Dhein W., Sbruzzi G. (2019). Intensity of physical exercise and its effect on functional capacity in COPD: Systematic review and meta-analysis. J. Bras. Pneumol. 45 (6), e20180011. doi:10.1590/1806-3713/e20180011

PubMed Abstract | CrossRef Full Text | Google Scholar

Agustí A., Edwards L. D., Rennard S. I., MacNee W., Tal-Singer R., Miller B. E., et al. (2012). Persistent systemic inflammation is associated with poor clinical outcomes in COPD: A novel phenotype. PloS one 7, e37483. doi:10.1371/journal.pone.0037483

PubMed Abstract | CrossRef Full Text | Google Scholar

Alahmari A. D., Kowlessar B. S., Patel A. R., Mackay A. J., Allinson J. P., Wedzicha J. A., et al. (2016). Physical activity and exercise capacity in patients with moderate COPD exacerbations. Eur. Respir. J. 48 (2), 340–349. doi:10.1183/13993003.01105-2015

PubMed Abstract | CrossRef Full Text | Google Scholar

Alvarez-Peregrina C., Martinez-Perez C., Villa-Collar C., Sánchez-Tena M. Á. (2021). A bibliometric and citation network analysis of myopia genetics. Genes 12, 447. doi:10.3390/genes12030447

PubMed Abstract | CrossRef Full Text | Google Scholar

Baldi S., Jose P. E., Bruschi C., Pinna G. D., Maestri R., Rezzani A., et al. (2014). The mediating role of cytokine IL-6 on the relationship of FEV₁ upon 6-minute walk distance in chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 9, 1091–1099. doi:10.2147/COPD.S57845

PubMed Abstract | CrossRef Full Text | Google Scholar

Balnis J., Korponay T. C., Jaitovich A. (2020). AMP-activated protein kinase (AMPK) at the crossroads between CO₂ retention and skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD). Int. J. Mol. Sci. 21, 955. doi:10.3390/ijms21030955

CrossRef Full Text | Google Scholar

Barreiro E., Bustamante V., Cejudo P., Gáldiz J. B., Gea J., de Lucas P., et al. (2015). Guidelines for the evaluation and treatment of muscle dysfunction in patients with chronic obstructive pulmonary disease. Arch. Bronconeumol. 51, 384–395. doi:10.1016/j.arbres.2015.04.011

PubMed Abstract | CrossRef Full Text | Google Scholar

Barreiro E., Gea J. (2016). Molecular and biological pathways of skeletal muscle dysfunction in chronic obstructive pulmonary disease. Chron. Respir. Dis. 13, 297–311. doi:10.1177/1479972316642366

PubMed Abstract | CrossRef Full Text | Google Scholar

Beaumont M., Forget P., Couturaud F., Reychler G. (2018). Effects of inspiratory muscle training in COPD patients: A systematic review and meta-analysis. Clin. Respir. J. 12, 2178–2188. doi:10.1111/crj.12905

PubMed Abstract | CrossRef Full Text | Google Scholar

Bernardi E., Pomidori L., Bassal F., Contoli M., Cogo A. (2015). Respiratory muscle training with normocapnic hyperpnea improves ventilatory pattern and thoracoabdominal coordination, and reduces oxygen desaturation during endurance exercise testing in COPD patients. Int. J. Chron. Obstruct. Pulmon. Dis. 10, 1899–1906. doi:10.2147/COPD.S88609

PubMed Abstract | CrossRef Full Text | Google Scholar

Bernardi E., Pomidori L., Cassutti F., Cogo A. (2018). Home-based, moderate-intensity exercise training using a metronome improves the breathing pattern and oxygen saturation during exercise in patients with COPD. J. Cardiopulm. Rehabil. Prev. 38 (6), E16–E18. doi:10.1097/HCR.0000000000000360

PubMed Abstract | CrossRef Full Text | Google Scholar

Bisca G. W., Camillo C. A., Cavalheri V., Pitta F., Osadnik C. R. (2017). Peripheral muscle training in patients with chronic obstructive pulmonary disease: Novel approaches and recent advances. Expert Rev. Respir. Med. 11 (5), 413–423. doi:10.1080/17476348.2017.1317598

PubMed Abstract | CrossRef Full Text | Google Scholar

Bolton C. E., Singh S. J., Walker P. P. (2013). Commentary: The British thoracic society guideline on pulmonary rehabilitation in adults. Thorax 68 (9), 887–888. doi:10.1136/thoraxjnl-2013-203809

PubMed Abstract | CrossRef Full Text | Google Scholar

Bourbeau J., Lavoie K. L., Sedeno M. (2015). Comprehensive self-management strategies. Semin. Respir. Crit. Care Med. 36 (4), 630–638. doi:10.1055/s-0035-1556059

PubMed Abstract | CrossRef Full Text | Google Scholar

Braz Júnior D. S., Dornelas de Andrade A., Teixeira A. S., Cavalcanti C. A., Morais A. B., Marinho P. E., et al. (2015). Whole-body vibration improves functional capacity and quality of life in patients with severe chronic obstructive pulmonary disease (COPD): A pilot study. Int. J. Chron. Obstruct. Pulmon. Dis. 10, 125–132. doi:10.2147/COPD.S73751

PubMed Abstract | CrossRef Full Text | Google Scholar

Britto F. A., Gnimassou O., De Groote E., Balan E., Warnier G., Everard A., et al. (2020). Acute environmental hypoxia potentiates satellite cell-dependent myogenesis in response to resistance exercise through the inflammation pathway in human. FASEB J. 34 (1), 1885–1900. doi:10.1096/fj.201902244R

PubMed Abstract | CrossRef Full Text | Google Scholar

Buist A. S., McBurnie M. A., Vollmer W. M., Gillespie S., Burney P., Mannino D. M. (2007). BOLD collaborative research group, et alInternational variation in the prevalence of COPD (the BOLD study): A population-based prevalence study. Lancet (London, Engl. 370, 741–750. doi:10.1016/S0140-6736(07)61377-4

CrossRef Full Text | Google Scholar

Butler S. J., Desveaux L., Lee A. L., Beauchamp M. K., Brusco N. K., Wang W., et al. (2020). Randomized controlled trial of community-based, post-rehabilitation exercise in COPD. Respir. Med. 174, 106195. doi:10.1016/j.rmed.2020.106195

PubMed Abstract | CrossRef Full Text | Google Scholar

Catteau M., Passerieux E., Blervaque L., Gouzi F., Ayoub B., Hayot M., et al. (2021). Response to electrostimulation is impaired in muscle cells from patients with chronic obstructive pulmonary disease. Cells 10 (11), 3002. doi:10.3390/cells10113002

PubMed Abstract | CrossRef Full Text | Google Scholar

Chaillou T., Lanner J. T. (2016). Regulation of myogenesis and skeletal muscle regeneration: Effects of oxygen levels on satellite cell activity. FASEB J. 30 (12), 3929–3941. doi:10.1096/fj.201600757R

PubMed Abstract | CrossRef Full Text | Google Scholar

Chan C., Inskip J. A., Kirkham A. R., Ansermino J. M., Dumont G., Li L. C., et al. (2019). A smartphone oximeter with a fingertip probe for use during exercise training: Usability, validity and reliability in individuals with chronic lung disease and healthy controls. Physiotherapy 105 (3), 297–306. doi:10.1016/j.physio.2018.07.015

PubMed Abstract | CrossRef Full Text | Google Scholar

Chen C., Dubin R., Kim M. C. (2014). Emerging trends and new developments in regenerative medicine: A scientometric update (2000 - 2014). Expert Opin. Biol. Ther. 14, 1295–1317. doi:10.1517/14712598.2014.920813

PubMed Abstract | CrossRef Full Text | Google Scholar

Chen C. (2006). CiteSpace II: Detecting and visualizing emerging trends and transient patterns in scientific literature. J. Clin. Microbiol. 57, 359–365. doi:10.1128/JCM.44.2.359-365.2006

CrossRef Full Text | Google Scholar

Chen C. (2004). Searching for intellectual turning points: Progressive knowledge domain visualization. Proc. Natl. Acad. Sci. U. S. A. 101 (1), 5303–5310. doi:10.1073/pnas.0307513100

PubMed Abstract | CrossRef Full Text | Google Scholar

Cheng Y. Y., Lin S. Y., Hsu C. Y., Fu P. K. (2022). Respiratory muscle training can improve cognition, lung function, and diaphragmatic thickness fraction in male and non-obese patients with chronic obstructive pulmonary disease: A prospective study. J. Pers. Med. 12 (3), 475. doi:10.3390/jpm12030475

PubMed Abstract | CrossRef Full Text | Google Scholar

Dang Q., Luo Z., Ouyang C., Wang L. (2021). First systematic review on health communication using the CiteSpace software in China: Exploring its research hotspots and frontiers. Int. J. Environ. Res. Public Health 18, 13008. doi:10.3390/ijerph182413008

PubMed Abstract | CrossRef Full Text | Google Scholar

Daynes E., Greening N. J., Harvey-Dunstan T. C., Singh S. J. (2018). High-frequency airway oscillating device for respiratory muscle training in subjects with COPD. Respir. Care 63 (5), 584–590. doi:10.4187/respcare.05837

PubMed Abstract | CrossRef Full Text | Google Scholar

Dong J., Li L., Lu M., Cheng X., Zhai Y. (2021). Pressure ulcers in patients with diabetes: A bibliometrics analysis. Ann. Palliat. Med. 10, 10515–10526. doi:10.21037/apm-21-2757

PubMed Abstract | CrossRef Full Text | Google Scholar

Dong X., Wang X., Jia N., Chen X., Ding M. (2021). A comparison between qigong exercise and cycle ergometer exercise for the rehabilitation of chronic obstructive pulmonary disease: A pilot randomized controlled trial (CONSORT). Med. Baltim. 100 (21), e26010. doi:10.1097/MD.0000000000026010

CrossRef Full Text | Google Scholar

Doucet M., Russell A. P., Léger B., Debigaré R., Joanisse D. R., Caron M. A., et al. (2007). Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 176, 261–269. doi:10.1164/rccm.200605-704OC

PubMed Abstract | CrossRef Full Text | Google Scholar

Fiorentino G., Esquinas A. M., Annunziata A. (2020). Exercise and chronic obstructive pulmonary disease (COPD). Adv. Exp. Med. Biol. 1228, 355–368. doi:10.1007/978-981-15-1792-1_24

PubMed Abstract | CrossRef Full Text | Google Scholar

Fonseca J., Machado F. V. C., Santin L. C., Andrello A. C., Schneider L. P., Fernandes Belo L., et al. (2021). Handgrip strength as a reflection of general muscle strength in chronic obstructive pulmonary disease. COPD 18 (3), 299–306. doi:10.1080/15412555.2021.1919608

PubMed Abstract | CrossRef Full Text | Google Scholar

Franssen F. M., Sauerwein H. P., Ackermans M. T., Rutten E. P., Wouters E. F., Schols A. M., et al. (2011). Increased postabsorptive and exercise-induced whole-body glucose production in patients with chronic obstructive pulmonary disease. Metabolism. 60, 957–964. doi:10.1016/j.metabol.2010.09.004

PubMed Abstract | CrossRef Full Text | Google Scholar

Furness T., Bate N., Welsh L., Naughton G., Lorenzen C. (2012). Efficacy of a whole-body vibration intervention to effect exercise tolerance and functional performance of the lower limbs of people with chronic obstructive pulmonary disease. BMC Pulm. Med. 12, 71. doi:10.1186/1471-2466-12-71

PubMed Abstract | CrossRef Full Text | Google Scholar

GBD 2015 Chronic Respiratory Disease Collaborators (2017). Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: A systematic analysis for the global burden of disease study 2015. Lancet. Respir. Med. 5, 691–706. doi:10.1016/S2213-2600(17)30293-X

PubMed Abstract | CrossRef Full Text | Google Scholar

Gea J., Agustí A., Roca J. (2013). Pathophysiology of muscle dysfunction in COPD. J. Appl. Physiol., 114, 1222–1234. doi:10.1152/japplphysiol.00981.2012

PubMed Abstract | CrossRef Full Text | Google Scholar

Guo J. B., Chen B. L., Lu Y. M., Zhang W. Y., Zhu Z. J., Yang Y. J., et al. (2016). Tai chi for improving cardiopulmonary function and quality of life in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis. Clin. Rehabil. 30 (8), 750–764. doi:10.1177/0269215515604903

PubMed Abstract | CrossRef Full Text | Google Scholar

Haarmann H., Mohrlang C., Tschiesner U., Rubin D. B., Bornemann T., Rüter K., et al. (2015). Inhaled β-agonist does not modify sympathetic activity in patients with COPD. BMC Pulm. Med. 15, 46. doi:10.1186/s12890-015-0054-7

PubMed Abstract | CrossRef Full Text | Google Scholar

Habazettl H., Athanasopoulos D., Kuebler W. M., Wagner H., Roussos C., Wagner P. D., et al. (2010). Near-infrared spectroscopy and indocyanine green derived blood flow index for noninvasive measurement of muscle perfusion during exercise. J. Appl. Physiol. 108 (4), 962–967. doi:10.1152/japplphysiol.01269.2009

PubMed Abstract | CrossRef Full Text | Google Scholar

Iepsen U. W., Jørgensen K. J., Ringbæk T., Hansen H., Skrubbeltrang C., Lange P., et al. (2015). A combination of resistance and endurance training increases leg muscle strength in COPD: An evidence-based recommendation based on systematic review with meta-analyses. Chron. Respir. Dis. 12, 132–145. doi:10.1177/1479972315575318

PubMed Abstract | CrossRef Full Text | Google Scholar

Iepsen U. W., Munch G. D., Rugbjerg M., Rinnov A. R., Zacho M., Mortensen S. P., et al. (2016). Effect of endurance versus resistance training on quadriceps muscle dysfunction in COPD: A pilot study. Int. J. Chron. Obstruct. Pulmon. Dis. 11, 2659–2669. doi:10.2147/COPD.S114351

PubMed Abstract | CrossRef Full Text | Google Scholar

Jones A. V., Evans R. A., Man W. D., Bolton C. E., Breen S., Doherty P. J., et al. (2019). Outcome measures in a combined exercise rehabilitation programme for adults with COPD and chronic heart failure: A preliminary stakeholder consensus event. Chron. Respir. Dis. 16, 1–11. doi:10.1177/1479973119867952

CrossRef Full Text | Google Scholar

Kaur G., Maremanda K. P., Campos M., Chand H. S., Li F., Hirani N., et al. (2021). Distinct exosomal miRNA profiles from BALF and lung tissue of COPD and IPF patients. Int. J. Mol. Sci. 22 (21), 11830. doi:10.3390/ijms222111830

PubMed Abstract | CrossRef Full Text | Google Scholar

Kerti M., Balogh Z., Kelemen K., Varga J. T. (2018). The relationship between exercise capacity and different functional markers in pulmonary rehabilitation for COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 13, 717–724. doi:10.2147/COPD.S153525

PubMed Abstract | CrossRef Full Text | Google Scholar

Klooster K., ten Hacken N. H., Hartman J. E., Kerstjens H. A., van Rikxoort E. M., Slebos D. J., et al. (2015). Endobronchial valves for emphysema without interlobar collateral ventilation. N. Engl. J. Med. 373 (24), 2325–2335. doi:10.1056/NEJMoa1507807

PubMed Abstract | CrossRef Full Text | Google Scholar

Langer D., Ciavaglia C., Faisal A., Webb K. A., Neder J. A., Gosselink R., et al. (2018). Inspiratory muscle training reduces diaphragm activation and dyspnea during exercise in COPD. J. Appl. Physiol. 125 (2), 381–392. doi:10.1152/japplphysiol.01078.2017

PubMed Abstract | CrossRef Full Text | Google Scholar

Laughlin M. H., Roseguini B. (2008). Mechanisms for exercise training-induced increases in skeletal muscle blood flow capacity: Differences with interval sprint training versus aerobic endurance training. J. Physiol. Pharmacol. 59 (7), 71–88. doi:10.2170/physiolsci.RP013108

PubMed Abstract | CrossRef Full Text | Google Scholar

Leelarungrayub J., Puntumetakul R., Sriboonreung T., Pothasak Y., Klaphajone J. (2018). Preliminary study: Comparative effects of lung volume therapy between slow and fast deep-breathing techniques on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, 6-minute walking distance, and quality of life in persons with COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 13, 3909–3921. doi:10.2147/COPD.S181428

PubMed Abstract | CrossRef Full Text | Google Scholar

Lerner C. A., Sundar I. K., Rahman I. (2016). Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD. Int. J. Biochem. Cell Biol. 81, 294–306. doi:10.1016/j.biocel.2016.07.026

PubMed Abstract | CrossRef Full Text | Google Scholar

Liang G., Bowen J. P. (2016). Development of trypsin-like serine protease inhibitors as therapeutic agents: Opportunities, challenges, and their unique structure-based rationales. Curr. Top. Med. Chem. 16, 1506–1529. doi:10.2174/1568026615666150915121447

PubMed Abstract | CrossRef Full Text | Google Scholar

Liang Q. F., Zhou S. C., Fang C. P., Zou G. Y., Tang C. Z., Qi J., et al. (2021). Prostatitis studies in China from 2000 to 2020: A knowledge atlas-based study on the development trend of contemporary disciplines. Zhonghua Nan Ke Xue 27, 535–541.

PubMed Abstract | Google Scholar

Liao W. H., Chen J. W., Chen X., Lin L., Yan H. Y., Zhou Y. Q., et al. (2015). Impact of resistance training in subjects with COPD: A systematic review and meta-analysis. Respir. Care 60 (8), 1130–1145. doi:10.4187/respcare.03598

PubMed Abstract | CrossRef Full Text | Google Scholar

Lima V. P., Iamonti V. C., Velloso M., Janaudis-Ferreira T. (2016). Physiological responses to arm activity in individuals with chronic obstructive pulmonary disease compared with healthy controls: A SYSTEMATIC REVIEW. J. Cardiopulm. Rehabil. Prev. 36 (6), 402–412. doi:10.1097/HCR.0000000000000190

PubMed Abstract | CrossRef Full Text | Google Scholar

Lindenthaler J. R., Rice A. J., Versey N. G., McKune A. J., Welvaert M. (2018). Differences in physiological responses during rowing and cycle ergometry in elite male rowers. Front. Physiol. 9, 1010. doi:10.3389/fphys.2018.01010

PubMed Abstract | CrossRef Full Text | Google Scholar

Liu X., Fu C., Hu W., Hao S., Xie L., Wu X., et al. (2021b). The effect of tai chi on the pulmonary rehabilitation of chronic obstructive pulmonary disease: A systematic review and meta-analysis. Ann. Palliat. Med. 10 (4), 3763–3782. doi:10.21037/apm-20-940

PubMed Abstract | CrossRef Full Text | Google Scholar

Liu X., Hu Z., Zhou H. (2021a). N-acetylcysteine improves inflammatory response in COPD patients by regulating Th17/treg balance through hypoxia inducible factor-1α pathway. Biomed. Res. Int. 2021, 6372128. doi:10.1155/2021/6372128

PubMed Abstract | CrossRef Full Text | Google Scholar

Louvaris Z., Habazettl H., Wagner H., Zakynthinos S., Wagner P., Vogiatzis I., et al. (2018). Near-infrared spectroscopy using indocyanine green dye for minimally invasive measurement of respiratory and leg muscle blood flow in patients with COPD. J. Appl. Physiol. 25 (3), 947–959. doi:10.1152/japplphysiol.00959.2017

PubMed Abstract | CrossRef Full Text | Google Scholar

Louvaris Z., Rodrigues A., Dacha S., Gojevic T., Janssens W., Vogiatzis I., et al. (2021). High-intensity exercise impairs extradiaphragmatic respiratory muscle perfusion in patients with COPD. J. Appl. Physiol. 130 (2), 325–341. doi:10.1152/japplphysiol.00659.2020

PubMed Abstract | CrossRef Full Text | Google Scholar

Lozano R., Naghavi M., Foreman K., Lim S., Shibuya K., Aboyans V., et al. (2012). Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the global burden of disease study 2010. Lancet (London, Engl. 380, 2095–2128. doi:10.1016/S0140-6736(12)61728-0

CrossRef Full Text | Google Scholar

Man W. D., Chowdhury F., Taylor R. S., Evans R. A., Doherty P., Singh S. J., et al. (2016). Building consensus for provision of breathlessness rehabilitation for patients with chronic obstructive pulmonary disease and chronic heart failure. Chron. Respir. Dis. 13 (3), 229–239. doi:10.1177/1479972316642363

PubMed Abstract | CrossRef Full Text | Google Scholar

Mannino D. M., Buist A. S. (2007). Global burden of COPD: Risk factors, prevalence, and future trends. Lancet (London, Engl. 370, 765–773. doi:10.1016/S0140-6736(07)61380-4

CrossRef Full Text | Google Scholar

McCabe C., McCann M., Brady A. M. (2017). Computer and mobile technology interventions for self-management in chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 5 (5), CD011425. doi:10.1002/14651858.CD011425.pub2

PubMed Abstract | CrossRef Full Text | Google Scholar

McCarthy B., Casey D., Devane D., Murphy K., Murphy E., Lacasse Y., et al. (2015). Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 20 (2), CD003793. doi:10.1002/14651858.CD003793.pub3

PubMed Abstract | CrossRef Full Text | Google Scholar

Naranjo-Hernández D., Talaminos-Barroso A., Reina-Tosina J., Roa L. M., Barbarov-Rostan G., Cejudo-Ramos P., et al. (2018). Smart vest for respiratory rate monitoring of COPD patients based on non-contact capacitive sensing. Sensors (Basel) 18 (7), 2144. doi:10.3390/s18072144

CrossRef Full Text | Google Scholar

Neumeier A., Keith R. (2020). Clinical guideline highlights for the hospitalist: The GOLD and NICE guidelines for the management of COPD. J. Hosp. Med. 15, 240–241. doi:10.12788/jhm.3368

PubMed Abstract | CrossRef Full Text | Google Scholar

Neves L. F., Reis M. H., Plentz R. D., Matte D. L., Coronel C. C., Sbruzzi G., et al. (2014). Expiratory and expiratory plus inspiratory muscle training improves respiratory muscle strength in subjects with COPD: Systematic review. Respir. Care 59 (9), 1381–1388. doi:10.4187/respcare.02793

PubMed Abstract | CrossRef Full Text | Google Scholar

Østergaard E. B., Sritharan S. S., Kristiansen A. D., Thomsen P. M., Løkke A. (2018). Barriers and motivational factors towards physical activity in daily life living with COPD - an interview based pilot study. Eur. Clin. Respir. J. 5, 1484654. doi:10.1080/20018525.2018.1484654

PubMed Abstract | CrossRef Full Text | Google Scholar

Osthoff A. K., Taeymans J., Kool J., Marcar V., van Gestel A. J. (2013). Association between peripheral muscle strength and daily physical activity in patients with COPD: A systematic literature review and meta-analysis. J. Cardiopulm. Rehabil. Prev. 33 (6), 351–359. doi:10.1097/HCR.0000000000000022

PubMed Abstract | CrossRef Full Text | Google Scholar

Paneroni M., Simonelli C., Vitacca M., Ambrosino N. (2017). Aerobic exercise training in very severe chronic obstructive pulmonary disease: A systematic review and meta-analysis. Am. J. Phys. Med. Rehabil. 96 (8), 541–548. doi:10.1097/PHM.0000000000000667

PubMed Abstract | CrossRef Full Text | Google Scholar

Pedersen B. K., Saltin B. (2015). Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand. J. Med. Sci. Sports 25 (3), 1–72. doi:10.1111/sms.12581

PubMed Abstract | CrossRef Full Text | Google Scholar

Petersen A. M., Mittendorfer B., Magkos F., Iversen M., Pedersen B. K. (2008). Physical activity counteracts increased whole-body protein breakdown in chronic obstructive pulmonary disease patients. Scand. J. Med. Sci. Sports 18 (5), 557–564. doi:10.1111/j.1600-0838.2007.00727.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Pleguezuelos E., Esquinas C., Moreno E., Guirao L., Ortiz J., Garcia-Alsina J., et al. (2016). Muscular dysfunction in COPD: Systemic effect or deconditioning? Lung 194, 249–257. doi:10.1007/s00408-015-9838-z

PubMed Abstract | CrossRef Full Text | Google Scholar

Polhemus A., Ortiz L. D., Brittain G., Chynkiamis N., Salis F., GaBner H., et al. (2021). Walking on common ground: A cross-disciplinary scoping review on the clinical utility of digital mobility outcomes. NPJ Digit. Med. 4 (1), 149. doi:10.1038/s41746-021-00513-5

PubMed Abstract | CrossRef Full Text | Google Scholar

Puhan M. A., Chandra D., Mosenifar Z., Ries A., Make B., Hansel N. N., et al. (2011). The minimal important difference of exercise tests in severe COPD. Eur. Respir. J. 37 (4), 784–790. doi:10.1183/09031936.00063810

PubMed Abstract | CrossRef Full Text | Google Scholar

Qiu Z. H., Guo H. X., Lu G., Zhang N., He B. T., Zhou L., et al. (2016). Physiological responses to Tai Chi in stable patients with COPD. Respir. Physiol. Neurobiol. 221, 30–34. doi:10.1016/j.resp.2015.10.019

PubMed Abstract | CrossRef Full Text | Google Scholar

Reis L. F., Guimarães F. S., Fernandes S. J., Cantanhede L. A., Dias C. M., Lopes A. J., et al. (2013). A long-term pulmonary rehabilitation program progressively improves exercise tolerance, quality of life and cardiovascular risk factors in patients with COPD. Eur. J. Phys. Rehabil. Med. 49, 491–497. doi:10.1044/1092-4388(2013/er-0620)

PubMed Abstract | CrossRef Full Text | Google Scholar

Robles P., Araujo T., Brooks D., Zabjek K., Janaudis-Ferreira T., Marzolini S., et al. (2017). Cardiorespiratory responses to short bouts of resistance training exercises in individuals with chronic obstructive pulmonary disease: A COMPARISON OF EXERCISE INTENSITIES. J. Cardiopulm. Rehabil. Prev. 37 (5), 356–362. doi:10.1097/HCR.0000000000000282

PubMed Abstract | CrossRef Full Text | Google Scholar

Rozenberg D., Martelli V., Vieira L., OrchAnian-Cheff A., Keshwani N., Singer L. G., et al. (2017). Utilization of non-invasive imaging tools for assessment of peripheral skeletal muscle size and composition in chronic lung disease: A systematic review. Respir. Med. 131, 125–134. doi:10.1016/j.rmed.2017.08.007

PubMed Abstract | CrossRef Full Text | Google Scholar

Schaper-Magalhães F., Pinho J. F., Capuruço C. A. B., Rodrigues-Machado M. G. (2017). Positive end-expiratory pressure attenuates hemodynamic effects induced by an overload of inspiratory muscles in patients with COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 12, 2943–2954. doi:10.2147/COPD.S138737

CrossRef Full Text | Google Scholar

Sharanya A., Ciano M., Withana S., Kemp P. R., Polkey M. I., Sathyapala S. A., et al. (2019). Sex differences in COPD-related quadriceps muscle dysfunction and fibre abnormalities. Chron. Respir. Dis. 16, 1–13. 1479973119843650. doi:10.1177/1479973119843650

PubMed Abstract | CrossRef Full Text | Google Scholar

Silva B., Lira F. S., Rossi F. E., Ramos D., Uzeloto J. S., Freire A., et al. (2018). Inflammatory and metabolic responses to different resistance training on chronic obstructive pulmonary disease: A randomized control trial. Front. Physiol. 9, 262. doi:10.3389/fphys.2018.00262

PubMed Abstract | CrossRef Full Text | Google Scholar

Silverman E. K. (2020). Genetics of COPD. Annu. Rev. Physiol. 82, 413–431. doi:10.1146/annurev-physiol-021317-121224

PubMed Abstract | CrossRef Full Text | Google Scholar

Simmich J., Deacon A. J., Russell T. G. (2019). Active video games for rehabilitation in respiratory conditions: Systematic review and meta-analysis. JMIR Serious Games 7 (1), e10116. doi:10.2196/10116

PubMed Abstract | CrossRef Full Text | Google Scholar

Spruit M. A., Singh S. J., Garvey C., ZuWallack R., Nici L., Rochester C., et al. (2013). An official American thoracic society/European respiratory society statement: Key concepts and advances in pulmonary rehabilitation. Am. J. Respir. Crit. Care Med. 188, e13–e64. doi:10.1164/rccm.201309-1634ST

Google Scholar

Su J., Li P., Wu W. (2018). Manifestations and influencing factors of COPD skeletal muscle dysfunction. J. Clin. Pulm. Med. 23, 2313–2316.

CrossRef Full Text | Google Scholar

Sundar I. K., Li D., Rahman I. (2019b). Proteomic analysis of plasma-derived extracellular vesicles in smokers and patients with chronic obstructive pulmonary disease. ACS Omega 4, 10649–10661. doi:10.1021/acsomega.9b00966

PubMed Abstract | CrossRef Full Text | Google Scholar

Sundar I. K., Li D., Rahman I. (2019a). Small RNA-sequence analysis of plasma-derived extracellular vesicle miRNAs in smokers and patients with chronic obstructive pulmonary disease as circulating biomarkers. J. Extracell. Vesicles 8, 1684816. doi:10.1080/20013078.2019.1684816

PubMed Abstract | CrossRef Full Text | Google Scholar

Sundar I. K., Yao H., Rahman I. (2013). Oxidative stress and chromatin remodeling in chronic obstructive pulmonary disease and smoking-related diseases. Antioxid. Redox Signal. 18, 1956–1971. doi:10.1089/ars.2012.4863

PubMed Abstract | CrossRef Full Text | Google Scholar

Tan D. B. A., Armitage J., Teo T. H., Ong N. E., Shin H., Moodley Y. P., et al. (2017). Elevated levels of circulating exosome in COPD patients are associated with systemic inflammation. Respir. Med. 132, 261–264. doi:10.1016/j.rmed.2017.04.014

PubMed Abstract | CrossRef Full Text | Google Scholar

Tey C. K., An J., Chung W. Y. (2017). A novel remote rehabilitation system with the fusion of noninvasive wearable device and motion sensing for pulmonary patients. Comput. Math. Methods Med. 2017, 5823740. doi:10.1155/2017/5823740

PubMed Abstract | CrossRef Full Text | Google Scholar

van de Bool C., Rutten E. P. A., van Helvoort A., Franssen F. M. E., Wouters E. F. M., Schols A. M. W. J., et al. (2017). A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD. J. Cachexia Sarcopenia Muscle 8 (5), 748–758. doi:10.1002/jcsm.12219

PubMed Abstract | CrossRef Full Text | Google Scholar

van Doorslaer de Ten Ryen S., Warnier G., Gnimassou O., Belhaj M. R., Benoit N., Naslain D., et al. (2021). Higher strength gain after hypoxic vs normoxic resistance training despite no changes in muscle thickness and fractional protein synthetic rate. FASEB J. 35 (8), e21773. doi:10.1096/fj.202100654RR

PubMed Abstract | CrossRef Full Text | Google Scholar

van Eck N. J., Waltman L. (2010). Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics 84, 523–538. doi:10.1007/s11192-009-0146-3

PubMed Abstract | CrossRef Full Text | Google Scholar

van Helvoort H. A., Heijdra Y. F., de Boer R. C., Swinkels A., Thijs H. M., Dekhuijzen P. N., et al. (2007). Six-minute walking-induced systemic inflammation and oxidative stress in muscle-wasted COPD patients. Chest 131, 439–445. doi:10.1378/chest.06-1655

PubMed Abstract | CrossRef Full Text | Google Scholar

Van Helvoort H. A., Heijdra Y. F., Thijs H. M., Viña J., Wanten G. J., Dekhuijzen P. N., et al. (2006). Exercise-induced systemic effects in muscle-wasted patients with COPD. Med. Sci. Sports Exerc. 38, 1543–1552. doi:10.1249/01.mss.0000228331.13123.53

PubMed Abstract | CrossRef Full Text | Google Scholar

Vogiatzis I., Louvaris Z., Wagner P. D. (2020). Respiratory and locomotor muscle blood flow during exercise in health and chronic obstructive pulmonary disease. Exp. Physiol. 105 (12), 1990–1996. doi:10.1113/EP088104

PubMed Abstract | CrossRef Full Text | Google Scholar

Wang C. H., Chou P. C., Joa W. C., Chen L. F., Sheng T. F., Ho S. C., et al. (2014). Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: A pilot study. BMC Pulm. Med. 14, 142. doi:10.1186/1471-2466-14-142

PubMed Abstract | CrossRef Full Text | Google Scholar

Waqas A., Teoh S. H., Lapão L. V., Messina L. A., Correia J. C. (2020). Harnessing telemedicine for the provision of health care: Bibliometric and scientometric analysis. J. Med. Internet Res. 22, e18835. doi:10.2196/18835

CrossRef Full Text | Google Scholar

Wen H., Xie C., Wang L., Wang F., Wang Y., Liu X., et al. (2019). Difference in long-term trends in COPD mortality between China and the U.S., 1992⁻2017: An Age⁻Period⁻Cohort analysis. Int. J. Environ. Res. Public Health 16, 1529. doi:10.3390/ijerph16091529

PubMed Abstract | CrossRef Full Text | Google Scholar

Włodarczyk O. M., Barinow-Wojewódzki A. (2015). The impact of resistance respiratory muscle training with a SpiroTiger(®) device on lung function, exercise performance, and health-related quality of life in respiratory diseases. Kardiochir Torakochirurgia Pol. 12 (4), 386–390. doi:10.5114/kitp.2015.56796

PubMed Abstract | CrossRef Full Text | Google Scholar

Wu T. D., Fawzy A., Kinney G. L., Bon J., Neupane M., Tejwani V., et al. (2021). Metformin use and respiratory outcomes in asthma-COPD overlap. Respir. Res. 22, 70. doi:10.1186/s12931-021-01658-3

PubMed Abstract | CrossRef Full Text | Google Scholar

Wuytack F., Devane D., Stovold E., McDonnell M., Casey M., McDonnell T. J., et al. (2018). Comparison of outpatient and home-based exercise training programmes for COPD: A systematic review and meta-analysis. Respirology 23 (3), 272–283. doi:10.1111/resp.13224

PubMed Abstract | CrossRef Full Text | Google Scholar

Xu W., Li R., Guan L., Wang K., Hu Y., Xu L., et al. (2018). Combination of inspiratory and expiratory muscle training in same respiratory cycle versus different cycles in COPD patients: A randomized trial. Respir. Res. 19 (1), 225. doi:10.1186/s12931-018-0917-6