Interventions to Improve the Quality of Life of Patients with Chronic Obstructive Pulmonary Disease: A Global Mapping During 1990-2018.

Chronic obstructive pulmonary disease (COPD) has been considered a significant health challenge globally in recent years, which affects different aspects of the quality-of-life (QoL). A review was conducted of research output, research topics, and landscape to have a global view of the papers mentioning the interventions to increase QoL of patients with COPD. A total of 3242 research items from Web of Science during the period 1990–2018 were downloaded and analyzed. Analyses based on the different levels of data and methods using using VOSviewer software tool (version 1.16.15, Centre for Science and Technology Studies (CWTS), Leiden University, Leiden, The Netherlands) and Latent Dirichlet allocation. By exploring the trends in research productivity and topics, an increase was found in the number of papers mentioning non-pharmacological interventions as well as mental health illness and QoL among patients with COPD. In conclusion, the research on the interventions to increase the QoL of patients with COPD has attracted scientists globally. It is suggested that more research should be conducted on the effectiveness of non-pharmacological therapies to increase QoL of patients with COPD that can be applied broadly in the community. The collaboration and support from developed countries to developing countries are needed to increase the QoL of people living with COPD.


Introduction
Chronic obstructive pulmonary disease (COPD) is one of the chronic airway diseases, which characterized by the limitation in airflow and not fully reversible [1]. The reported prevalence of COPD is different among regions: 4% in Europe [2], 6.3% in the Asia Pacific region [3], from less than 4% to over 9% [4] in the US and predicted, with limited epidemiological evidence, to be at about 11% in 2010 in the African region [5,6].
This chronic disease has significant adverse effects on physical and mental conditions of those patients [7][8][9], as other systems and organs other than the lungs suffered the negative impacts, leading to pneumonia [10], pulmonary hypertension [11], and cardiovascular disease (CVD) [12]. A worsening mental status has been found in patients with COPD compared to non-COPD subjects, with higher rates of anxiety and depression [13,14], and the severity of fatigue [15]. Patients with COPD less frequently report a partner compared to others, and, when having a partner, they were less likely to be 'very satisfied' with the daily support and less often perceived emotional support from the partner [16]. They suffer worse quality of life with early-morning and nighttime symptoms compared to those without COPD [17,18]. COPD often results in a reduction in quality of life.
Quality of life (QoL) is defined by World Health Organization as a broad and complex concept of an individual about their physical health, mental health, social relationships and beliefs in the context of their living enviroment [19]. It is a "multidimensional measure" which focus on at least three domains: physics, psychology and society. Thus, several studies applied dimensions of QoL to to: (1) evaluate the efficiency of clinical therapies [20][21][22] or alternative therapies [23,24]; (2) identify factors associated with QoL [25] and increase health service quality [24]. In the case of COPD, improving QoL of patients with COPD becomes critical due to the incurables [26]. Medical methods have been used mainly to control COPD and strengthen prevention efforts, such as: (1) smoking cessation [27,28], (2) pharmacotherapy [29], and (3) Non-pharmacological therapy [30]. Therefore, measuring QoL could be useful in applying suitable interventions and preventing risk factors affected COPD.
Systematic reviews of interventions and treatments are considered as a reliable source of evidence to inform clinical practice and policy development [31]. Several systematic reviews and meta-analyses mentioning interventions to patients with COPD have been conducted. Gregersen et al. confirmed that telehealth showed promise for improving QoL of patients living with COPD, yet, this method call for more research to prove its effectiveness [32]. According to Coronini-Cronberg et al., psychosocial and pharmacological support is an effective intervention for smoking cessation [33], which raises the QoL in some health domains [34]. Moreover, breathing exercises can be used to improve the QoL of patients living with COPD, yet, the use of this method as a complementary therapy needs more research [35]. These literature review studies answer specific questions by gathering available empirical research evidence. However, a limitation of this approach is that it could review one method, which makes it difficult to compare the effects of all methods during a long period of study.
In addition, several researchers have used indicators of scientometric to review literature [36]. Prvevious studies used bibliometrics to explore research output, country collaboration, journal ranking or fundings of all papers mentioning COPD in European countries [37] or in Arab countries [38]. However, scientometric analyses may not have a deep understanding of the context of research or the landscape of research areas. Therefore, by combining scientometric and Latent Direcht allocation, topic modeling (in titles and abstracts), this study aims to describe the global trend in research outputs, countries collaboration, interdisciplinary research areas, as well as ten common topics among papers mentioning interventions to improve QoL of patients with COPD. The findings will emphasize research gaps, and make it possible to recommend some implications for future studies and policy.

Database and Search Strategy
The data were retrieved in the middle of 2019 from the Web of Science (WoS) Core Collection. It was decided to choose WoS because WoS (1) allows to download a large number of papers and (2) provides necessary information for scientometrics analysis, such as authors' affiliations, authors' keywords, the title of papers, publication year, research areas, as well as the number of citations and download times for each paper [39,40].
The search strategy was described as follow: • Step 1: With the use of Boolean operators "OR", the search query was developed to identify the number of published items related to "Quality of life" OR "well-being". Only English research articles and research reviews were included, while grey literature, conference proceedings, or books/book chapters in any other language were excluded. Papers having anonymous authors and publications in 2019 were also limited. This research began in the middle of 2019; thus, this data could not reflect the research trend for the whole year. Data in WoS databases under text format was downloaded and imported to STATA version 15.0 (STATACorp., Texas, TX, USA) for further extraction. (See Table A1) • Step 2: STATA syntax was applied to filter the papers in step 1 with the terms "Intervention" OR "Interventions" OR "trial" OR "trials" in titles or abstracts.

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Step 3: The COPD keywords were formed by COPD specialists and reviewing some papers and MeSH term library of PubMed. These terms were used to search in the title and keyword fields among papers in step 2 (see Table A1), and there were 5784 papers for further screening.

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Step 4: Two researchers separately screened the titles and abstracts of 5784 papers to exclude papers not related to COPD. A group discussion with a senior researcher was conducted if there were any contradictions. A total of 3242 papers were imported to STATA for further analysis. (See Figure A1).

Data Analysis
The corrected data after the screening was imported to STATA for further analysis using the following information of the articles: authors' affiliations, the title of papers, the journals' name, authors' keywords, the number of citations, research areas, and abstracts.
Several basic characteristics of the data sets were included publication year, the number of papers /per year, total citations up to 2018, average citation rate per year, total number of downloads in the last six months/five years, and average number of downloads (mean use rate) the last six months/five years. Two network graphs showing the countries collaboration and co-occurrence terms in title and abstracts were established by VOSviewer (version 1.16.15, Centre for Science and Technology Studies (CWTS), Leiden University, Leiden, The Netherlands). Latent dirichlet allocation (LDA) was used for classifying papers into topics [41][42][43][44][45]. The titles and abstracts of most cited papers within each group were reviewed. After discussing with COPD specialists, the labels for each topic were named. In addition to the number and percentage of publications of each topic, these topics were ranked based on the total number of publications in the past five years to explore the research interests. Table 1 shows the methods and results for each kind of data.

Results
Overall Growth and Essential Characteristics of Research Table 2 described the basic characteristics of publications. The first seven papers related to this health issues in dataset were published in 1991. There has been a gradual raise in the annual number of papers on intervention to improve the QoL of patients with COPD within the period 1991-2018, contributing to a total of 3242 papers. The papers in 2018 showed the reading interests of readers in last six month with the average times of download (mean use rate) was 1.8; meanwhile, the papers in 2013 received the highest concern in last five years with average times of download (the mean use rate) was 2.1. The papers in the year 2000 had the highest average citation with 6.9 citations per paper. The paper having the highest influence was the second report entitled Global Strategy for the Diagnosis, Management, and Prevention of COPD published in 2007 with 3456 citations [46]. Figure 1 shows countries collaboration network. In total, there were 89 countries contributing for the research field (automatically calculated by VOSviewer). In figure there were 64 countries with minimum of 5 papers. Of those, the United States of America led in the number of studies with 786 papers (24.2%), followed by England (452 papers, 13.9%), the Netherlands (322 papers, 9.9%), and Canada (268 papers, 8.3%). Although people living in low-and middle-income countries (LMICs) are more vulnerable to developing COPD [47], there was only China in the list of top 10 countries having the highest volume. As can ben seen, there were four main clusters in this countries network (1) Asia with the leadership of China in collaboration with two East European countries (Czech and Romania) (red cluster); (2) the U.S and South American countries (yellow cluster); (3) Canada, South Africa, New Zealandm and European countries (turquoise cluster); (4) European countries with three subgroups with the lead of France, the Netherlands, and England (the rest).
By analyzing abstracts and titles, the most co-occurrence terms were found to discover the scope of COPD research ( Figure 2). Three major clusters were formed by 279 most common terms in title and abstract with the minimum appearance of 95 times. The three significant clusters are: Cluster 1 (red) refers to comorbidity and COPD, among which mental health illness (depression and anxiety) was more vulnerable to developing COPD [47], there was only China in the list of top 10 countries having the highest volume. As can ben seen, there were four main clusters in this countries network (1) Asia with the leadership of China in collaboration with two East European countries (Czech and Romania) (red cluster); (2) the U.S and South American countries (yellow cluster); (3) Canada, South Africa, New Zealandm and European countries (turquoise cluster); (4) European countries with three subgroups with the lead of France, the Netherlands, and England (the rest). By analyzing abstracts and titles, the most co-occurrence terms were found to discover the scope of COPD research ( Figure 2). Three major clusters were formed by 279 most common terms in title and abstract with the minimum appearance of 95 times. The three significant clusters are: Cluster 1 (red) refers to comorbidity and COPD, among which mental health illness (depression and anxiety) was most frequently mentioned. Cluster 2 (blue) focuses on interventions and treatment to increase QoL of people with COPD. Cluster 3 (yellow) points out the risk and mortality of exacerbation of COPD.  Text mining using VOSviewer (titles and abstracts). Note: the colors of each node were automatically assigned by VOSviewer based on its score; the node size was based on the frequency of each term; the length and thickness of the lines reflected the association between two terms. Cluster 1 (red) refers to comorbidity and COPD; cluster 2 (blue) focuses on interventions and treatment to increase QoL of people with COPD, cluster 3 (yellow) points out the risk and mortality of exacerbation of COPD. Table 3 shows the most cited papers. Each had more than 100 citations during the study period. Based on the list, three main topics which have been recently attracted the attention of researchers were: (1) The Global Initiative for chronic obstructive lung disease (GOLD) reports and other national reports. GOLD was a consensus report published periodically since 2001. It included the latest evidence for diagnosis and prevention from experts, which were as "strategy documents" for Text mining using VOSviewer (titles and abstracts). Note: the colors of each node were automatically assigned by VOSviewer based on its score; the node size was based on the frequency of each term; the length and thickness of the lines reflected the association between two terms. Cluster 1 (red) refers to comorbidity and COPD; cluster 2 (blue) focuses on interventions and treatment to increase QoL of people with COPD, cluster 3 (yellow) points out the risk and mortality of exacerbation of COPD. Table 3 shows the most cited papers. Each had more than 100 citations during the study period. Based on the list, three main topics which have been recently attracted the attention of researchers were: (1) The Global Initiative for chronic obstructive lung disease (GOLD) reports and other national reports. GOLD was a consensus report published periodically since 2001. It included the latest evidence for diagnosis and prevention from experts, which were as "strategy documents" for adequate care for COPD at a global level [48] (paper 1, paper 7, paper 4, paper 9, paper 28, paper 36 ); (2) Exacerbations in patients with COPD (paper 2, paper 3, paper 12, paper 25, paper 29, paper 32); (3) Treatments and interventions of COPD (paper 5, paper 6, paper 11, paper 14, paper 15, paper 17, paper 19, paper 20, paper 23, paper 24, paper 27, paper 33, paper 34, paper 35, paper 39, paper 40), (4) QoL, health-related QoL and COPD (paper 26, paper 30, paper 31, and paper 41), others topic (rehabilitation-paper 8; COPD and comorbidity-paper 10; COPD and its effects to patient health and life-paper 22 and paper 37).
Applying latent dirichlet allocation in title and abstracts, ten major research topics were formed (Table 4). Topic 2 (n = 468 papers), Topic 1 (n = 436 papers), and topic 3 (n = 355 papers) were three topics with the highest volume of publications. Pulmonary rehabilitation has been a rapidly developed field in the last decades [49]. Further, improving QoL of patients living with COPD by pharmacological therapies (topic 6) or non-pharmacological therapies (topic 3, topic 10) has been a major area of focus. Notably, the domain of mental health received frequent attention from the scientific community with 436 papers. The reason for it could be that about 85% of people living with COPD were at high risk of developing anxiety disorders compared with healthy people [50].     Figure 4 shows the cluster of research areas in QoL of patients with COPD. The horizontal axis represents the distance between clusters, while the vertical axis displays the research areas [51]. The red lines show the depth for the cut-off of the analysis [52]. Research landscapes were divided into three main parts. The root (first group) in the top of the dendrogram included (a) respiratory system   Noninvasive Ventilation and Oxygen Therapy in patient with COPD 160 5.60% Topic 9 COPD Phenotype and quality of life 157 5.50% Figure 4 shows the cluster of research areas in QoL of patients with COPD. The horizontal axis represents the distance between clusters, while the vertical axis displays the research areas [51]. The red lines show the depth for the cut-off of the analysis [52]. Research landscapes were divided into three main parts. The root (first group) in the top of the dendrogram included (a) respiratory system and (b) critical care medicine. This cluster had a close relationship with (1) intervention and health care such as general & internal medicine, pharmacy, nursing, and cardiovascular system (second group); (2) comorbidities, for instance, psychiatry, clinical psychology, clinical neurology (third group). However, the first group did not have a strong relatedness to the cluster in the bottom, such as rehabiliation or the integration of public health, environmental and occupational health (health care science & services; health policy & services, occupational &public, environment, interdiscriplinary social sciences).

Discussion
This study investigated the global trend of 3242 research publications regarding interventions to increase QoL of patients with COPD. It was found that the publications of research related to in topic increased annually and gradually, and most of the contribution came from high income countries (HICs). Mental health issues and non-pharmacological therapy, including exercise, home care, self-care education, noninvasive ventilation, and oxygen therapy were common approaches. Current findings emphasize the importance of research that focuses on the effects of nonpharmacological therapy, which should be considered to increase QoL of people living with COPD. Additionally, mental health problems among people living with COPD have received more focus, especially in the last five years.
Notably, but unsurprisingly, a high number of research were conducted by authors from HICs

Discussion
This study investigated the global trend of 3242 research publications regarding interventions to increase QoL of patients with COPD. It was found that the publications of research related to in topic increased annually and gradually, and most of the contribution came from high income countries (HICs). Mental health issues and non-pharmacological therapy, including exercise, home care, self-care education, noninvasive ventilation, and oxygen therapy were common approaches. Current findings emphasize the importance of research that focuses on the effects of non-pharmacological therapy, which should be considered to increase QoL of people living with COPD. Additionally, mental health problems among people living with COPD have received more focus, especially in the last five years.
Notably, but unsurprisingly, a high number of research were conducted by authors from HICs than that of LMICs although more than 90% of COPD-related deaths occur in LMICs [53]. This work supports the conclusion of previous studies, which confirmed the main contribution of HICs in diabetes research [54] or HIV/AIDS research [55]. This phenomenon may be explained by the fact that risk factor prevention has not been fully recognized by the LMICs' governments and populations, including using biomass fuels indoors for cooking [56] or occupational exposure [57]. Moreover, many LMICs faced the barriers in research and implication planning, such as information and communication technology limitations [58], lack of human resources and finance, and scientific findings [59]. Therefore, the support of HICs and actively joining in collaboration network with HICs are critical to LMICs [60].
Chronic obstructive pulmonary disease is a chronic disorder, which requires a long-term treatment with complementary and alternative therapy to reduce exacerbation and improve patients' QoL [61]. Our finding were in line with the results of previous studies, which emphasized that pharmacological therapy [62], exercise [63], non-invasive ventilation [64], and oxygen therapy [65] increase the QoL of people living with COPD. In our study, the number of papers mentioning pharmacological treatment was in the top five of highest volume of work by LDA. It showed the concern of researchers and physicians on this therapy to control the symptoms in stable COPD as well as improve QoL of people suffered COPD. It confirmed the results of some papers which emphasize the effectiveness of pharmacotherapy in controlling symptoms to decrease recurrence and seriousness of exacerbations and improve QoL [66,67]. However, this topic rose at a lower level in the last five years compared with non-pharmacy therapies, such as mental health, or rehabilita. The results might be explained by the efficiency of the alternative therapies in improving the quality of life, controlling symptoms in daily life and when exacerbations occur [68], and reducing the frequency of hospitalization [69].
Furthermore, the topics receiving the most attention in the last five years were comorbidities and mental health issues in patients with COPD. A previous study showed that about one-third of patients living with COPD with depression or anxiety did not received appropriate treatment [50]. The comorbid condition of mental illness can increase the risk of exacerbations, reduce QoL, and raise the chance of mortality [70,71]. Thus, mental health illness should receive further piority, which may help to increase QoL among patients living with COPD [72].
The results provide some evidence to enhance designing interventions, health research, and policy. Most of the death cases related to COPD happened in LMICs, yet, most of the studies were conducted in HICs. The health research capacity in LMICs is lower than that of HICs could be explained by (1) the limitation of infrastructure and capacity [73], (2) a lack of investment funding in universities and research institutions, low wages for researchers [74], and (3) a lack of clear national research priorities [74]. Therefore, LMICs need to (1) actively create collaboration research networks with HICs and (2) prepare the national research priorities under the circumstance of understanding the local context. Moreover, the LMICs' national health research priorities should be considered when international organizations or donors from HICs invest in LMICs. Secondly, we call for multidisciplinary collaboration of researchers and physicians among research areas, especially between psychological and respiratory physiologists since the complexity of this disease and negatives effects of depression and anxiety to patients with COPD.
Several limitations of this study should be mentioned. Firstly, WOS was the only database used in the analysis. However, for a large number of papers for analysis, there was a high possibility that these articles were in other databases, including PubMed and Scopus. Secondly, only English publications were included. Thus, it was more likely that our study did not reflect the trend in COPD research where English is not used. Finally, only titles and abstracts were used for topic modeling. However, by applying a different level of data and alternative method, the trends and hidden themes of the research studies could be discovered [74].

Conclusions
The findings of the study show that the interventions to increase QoL of patients with COPD has attracted increasing research interest in the last two decades. Non-pharmacological therapy and mental health problems were two common approaches. In addition, increasing support from HICs to LMICs in research together with the multidisciplinary collaboration of research areas are needed to improve the QoL of people living with COPD in LMICs.

Conflicts of Interest:
The authors declare no conflict of interest.