Economic Burden of Chronic Obstructive Pulmonary Disease: A Systematic Review

Article information

Tuberc Respir Dis. 2024;87(3):234-251

Publication date (electronic) : 2024 February 16

doi : https://doi.org/10.4046/trd.2023.0100

¹Department of Health Economics, School of Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam

²Institute of Theoretical and Applied Research, Duy Tan University, Danang, Vietnam

³School of Business and Economics, Duy Tan University, Danang, Vietnam

⁴Can Tho University of Medicine and Pharmacy, Faculty of Public Health, Can Tho, Vietnam

⁵Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea

Address for correspondence Trang Huyen Thi Nguyen, M.P.H. Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Republic of Korea E-mail 2106201@ncc.re.kr

*These authors contributed equally to the manuscript as first author.

Received 2023 July 17; Revised 2023 November 30; Accepted 2024 February 5.

Abstract

Globally, providing evidence on the economic burden of chronic obstructive pulmonary disease (COPD) is becoming essential as it assists the health authorities to efficiently allocate resources. This study aimed to summarize the literature on economic burden evidence for COPD from 1990 to 2019. This study examined the economic burden of COPD through a systematic review of studies from 1990 to 2019. A search was done in online databases, including Web of Science, PubMed/Medline, Scopus, and the Cochrane Library. After screening 12,734 studies, 43 articles that met the inclusion criteria were identified. General study information and data on direct, indirect, and intangible costs were extracted and converted to 2018 international dollars (Int$). Findings revealed that the total direct costs ranged from Int$ 52.08 (India) to Int$ 13,776.33 (Canada) across 16 studies, with drug costs rannging from Int$ 70.07 (Vietnam) to Int$ 8,706.9 (China) in 11 studies. Eight studies explored indirect costs, while one highlighted caregivers’ direct costs at approximately Int$ 1,207.8 (Greece). This study underscores the limited research on COPD caregivers’ economic burdens, particularly in developing countries, emphasizing the importance of increased research support, particularly in high-resource settings. This study provides information about the demographics and economic burden of COPD from 1990 to 2019. More strategies to reduce the frequency of hospital admissions and acute care services should be implemented to improve the quality of COPD patients’ lives and reduce the disease’s rising economic burden.

Keywords: Chronic Obstructive Pulmonary Disease; Health Economics; Financial Stress; Systematic Review

Introduction

Chronic obstructive pulmonary disease (COPD) was ranked as the third highest contributor to global mortality in 2019, accounting for 3.23 million fatalities. Additionally, COPD held the seventh position among the leading causes of disability-adjusted life years lost worldwide [1]. In 2017, it was estimated that more than 300 million people were living with COPD worldwide, of which the major contributors were low- and middle-income countries [2]. Annually, COPD causes more than three million deaths globally [3]. In developed countries, the cost of COPD is estimated to range from 1,030 billion in 2010 to 2,200 billion US dollars (USD) in 2030, while in developing countries the cost is projected to be USD 2,600 billion in 2030. The cost of illness per person living with COPD will reach USD 4,800 in 2030 [4]. Additionally, approximately 10% of global productivity losses have been attributable to COPD, and this loss could equate to USD 6,700 per COPD patient [5].

The costs of COPD treatment and care are burdensome. Previous literature recorded a high rate of catastrophic health expenditure (CHE) among people with COPD [6,7]. A study in Australia observed that 46% of participants shared CHE [8]. This exceptionally high incidence of CHEs is likely due to the significant out-of-pocket payment for COPD treatment. Some studies indicated that COPD treatment cost (USD 236.2) [9] was superior to other severe non-communicable conditions such as mental health (USD 215) [10] and ischemic heart disease (USD 78) [11]. The average treatment cost of COPD increased from USD 6,300 in 2004 to USD 9,545 in 2010 [3]. Hospitalization is the major cost component. The mean cost of hospitalization exceeds USD 3,500, with medical expenses making up the majority (over 45.3% [USD 1,500]) [3]. Diagnosis and general medical expenses follow, totaling to more than USD 900 and USD 400, respectively [3]. In addition, a study in Greece showed that one-third of patients relied on support from family, relatives, or a supportive environment for daily activities, accounting for about 3.6 hours per day, across 4.1 days per week, of unpaid caregivers’ time [12].

Previous systematic reviews and meta-analyses of intervention and treatment provided appropriate evidence for clinical practice and policy development [13]. These studies collected available empirical research evidence to answer research questions regarding the treatments and interventions for COPD [14-16]. Although there is existing evidence concerning the economic implications of COPD, it predominantly consists of individual studies that are constrained by variables such as focusing only on a single nation [17,18], providing a concise overview of the economic impact of COPD [19], and conducting 10 years and drawing data from three databases [19]. Further rigorous investigation is warranted to achieve a more comprehensive understanding of the current COPD burden in settings adhering to globally recognized treatment guidelines, such as those outlined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). This review used studies from four databases to validate the COPD economic burden worldwide, providing direct, indirect, and intangible costs of COPD.

In conclusion, this study aimed to provide evidence on the burden of COPD, which is becoming globally urgent. Our results might help health authorities improve resource allocation and encourage people to have an adequate lifestyle [20].

Materials and Methods

This systematic review included studies on the economic burden of COPD in the period 1990 to 2019.

1. Eligible criteria

1) Inclusion criteria

We applied the Population–Indicator–Outcomes–Study types (PIO-S) question structure to develop an inclusion criteria and search strategy for articles as follows:

(1) Population (P): People with a diagnosis and treatment for COPD or who are the caregivers of COPD patients.

(2) Indicator (I): Studies mentioned patient characteristics, COPD symptoms, and treatment type.

(3) Outcomes (O): The economic burden among studies’ subjects:

ㆍ Direct cost is the cost of resources used direction for patient care: drugs or staff.

ㆍ Indirect cost is the expenses that cannot be directly attributed to a single, specific final cost objective. Rather, these costs are related to multiple final cost objectives or serve an intermediate cost objective (production loss, transportation).

ㆍ Intangible costs are indicators that cannot be measured or quantified. Therefore, in this study, intangible cost refers to pain, suffering, social stigma, and patient quality of life change.

(4) Study types (S): Every type of preliminary study, cross-sectional, case-control, and appropriate waves of longitudinal studies, and randomized clinical trials, were eligible for inclusion.

(5) The papers of our choice were research articles and research reviews in English.

(6) Period of included research articles was 1990 to 2019.

2) Exclusion criteria

(1) Research study is not written in English.

(2) Systematic review and meta-analysis studies.

2. Selection of studies and data extraction

The data selection was as follows:

Step 1: The following keywords were chosen based on the experts’ recommendations in the field and previous studies. The “search terms” were combined with Boolean operators “AND” to connect keywords related to COPD, population, and economic cost (Table 1).

Table 1.

Keywords for search strategy

Step 2: Web of Science, PubMed/Medline, Scopus, and the Cochrane Library were used to download the papers. Two researchers downloaded the data independently to ensure accuracy.

Step 3: The results were exported to Endnote 7 and duplicate records were removed. After that, the papers’ titles and abstracts were examined to see if they satisfied the eligibility criteria based on the structured PIO-S questions. Studies that were unrelated to the study’s goal were omitted. The full texts of studies that satisfied the selection criteria were downloaded.

Step 4: Two reviewers piloted a data extraction form, which was then used for all investigations. Each review author separately extracted: (1) author-date; (2) study design; (3) participant description; (4) sample size; (5) follow-up period; (6) outcomes; (7) study findings; and (8) quality evaluation. The data extraction results of the two reviewers were reviewed to ensure reliability and discrepancies were solved through discussion.

3. Data analysis

Two reviewers extracted direct and indirect costs data from the dataset. After that, purchasing power parities (PPPs) data was downloaded from the World Bank website (https://data.worldbank.org/indicator/NY.GDP.PCAP.PP.CD). PPPs represent currency conversion rates aimed at equalizing the purchasing power of diverse currencies by adjusting for variations in price levels among countries [21]. For comparative analysis, we gathered PPP data for the year 2018 to convert all costs into international data.

In this study, we also evaluated the burden and changes in the quality of life among COPD patients reported in the previous studies, which used the scales for the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire for COPD (SGRQ-C), and Caregiver Burden Questionnaire. CAT is a numerical scale questionnaire consisting of eight statements. It assesses various aspects by prompting respondents to assign a score from 0 to 5 for each of the eight areas. A score of 0 signifies no impairment in the respective area, while a score of 5 indicates severe impairment. The overall score, ranging from 0 to 40, reflects the extent to which COPD affects one’s overall health and well-being, with higher scores indicating a more significant impact [22]. The SGRQ-C is a condensed iteration of the SGRQ, crafted through the thorough analysis of extensive data from sizable studies in COPD. Since it is specifically designed using COPD data, the SGRQ-C is considered valid for assessing COPD. While its applicability to other conditions has not been formally established, it is expected to exhibit performance similar to the comprehensive SGRQ-C [23]. The Caregiver Burden Scale, developed by Elmstahl et al. [24] in 1996, is a 22-item questionnaire designed to assess the subjective burden experienced by caregivers across five domains: general strain, isolation, disappointment, emotional involvement, and environment. Respondents express the frequency with which each item applies to them using a 4-point scale, ranging from “not at all” to “often” [24].

The study applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to illustrate the search and screening flow.

Figure 1 indicates the screening process and the decisions taken during study selection. Initially, 12,734 documents were determined as relevant. After deduplication (n=3,848) and exclusion through screening the title and abstract (n=612), 342 records remained. Finally, out of the 342 studies, only 43 articles met the inclusion criteria.

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram of the searching and screening process.

Results

1. Study characteristics

A total of 43 studies met the inclusion criteria. Table 2 shows the descriptive characteristics of all the selected articles [5,12,25-65]. The main target populations were people living with COPD and caregivers. The majority of studies were conducted in developed countries: the USA (nine studies), followed by the United Kingdom (six studies), Italy (five studies), and Spain (five studies). The most common study design was retrospective study design (18 studies), followed by a cross-sectional study design (12 studies), and a cohort study design (six studies).

Table 2.

List of included studies

2. Direct cost

Total cost (10 studies), drug costs (10 studies), and nonmedical costs (three studies) were among the 16 reported direct costs. All the costs in Table 3 have been converted to international dollars (Int$; year 2018) [28-32,39-42,44,51,55,62,66,67]. The total direct cost, total medical direct cost, pharmaceutical therapy cost, outpatient cost, and total nonmedical cost were calculated. The total direct costs ranged from Int$ 1,098 (UK) to Int$ 43,994 (India). In terms of components of the nonmedical direct cost, we discovered differences between studies. There were also cost-effectiveness studies; therefore, there were differences in treatment techniques [26,47]. Results showed that, direct costs are much higher in developed countries than in developing countries. Hospital stays, medicine prices, and treatment expenses contribute to most of the direct costs. Nonmedical costs are typically low but can be higher in impoverished countries. The cost of immediate treatment varies substantially depending on the type and model of treatment. Notably, while the procedures might be the same, their efficiency may vary depending on the features of the health system and the resources available in each country. Indeed, the economic burden of COPD significantly differs depending on a country’s specific circumstances, including factors such as average income, access to health insurance, and gross domestic product (GDP) per capita.

Table 3.

Direct costs of COPD

3. Indirect cost

Table 4 described the indirect cost of COPD in ITN$. Nine studies reported indirect costs [5,12,28,30,31,41,51,55,67]. The survey of Kourlaba et al. [31] reported the most details when the study used the CAT score, modified Medical Research Council (mMRC) breathless scale, and GOLD for categories. The indirect cost ranged from Int$ 33.0 to ITN$ 3,265.3. Significant differences existed between levels in each scale and among the three scales. Dal Negro et al. [55] found out that there was no significant difference in total indirect cost between male and female patients. According to Souliotis et al. [12], over 33% of patients received daily assistance from family, friends, and a friendly environment, consuming 3.6 hours per day, 4.1 days per week, and accounting for Int$ 1,207.8 of nonpaid caregivers’ time and money.

Table 4.

The indirect cost of COPD

4. Intangible cost

Intangible costs are the unquantifiable impacts of an identifiable cause, such as pain, joy, or physical limitations, which can impact total productive performance. Intangible costs in this study were assessed using the patients’ and relatives’ variation of biopsychosocial quality of life after the diagnosis; quality of life in this context includes physical health, social contacts, and emotional health (Table 5). The research synthesizes six studies on the intangible cost in patients and caregivers. On all scales, the quality of life was reduced compared to before and after diagnosis. The caregiver’s burden increases as the time to care for the patient increases [68].

Table 5.

The burden and change in the quality of life

In Table 5, various health-related measures and their impact on individuals’ well-being are presented across different studies. The EuroQol 5-dimension 5-level (EQ5D-5L) scores show a slight decrease for family members of patients undergoing telephone coaching self-management compared to usual management [27,61]. Happiness scores, on a scale of 0 to 10, indicated a positive change for those in telephone coaching self-management but a decrease for those in usual management [27]. The CAT indicated an improvement in scores for patients using the modified inhaler combinations. However, it is noteworthy that this improvement was not statistically significant (95% confidence interval [CI], –3.57 to 1.89; p=0.525) [69].

The SGRQ-C highlights diverse impacts on quality of life, with different scores for continuity of care and routine care models and variations based on gender, education sections, and management types [70,71]. Lastly, the Caregiver Burden Questionnaire reveals increasing burden scores for caregivers with higher daily caregiving hours and those caring for COPD patients [68]. These findings provide insights into the multidimensional aspects of health and well-being in the context of COPD and its management.

Discussion

This study provided evidence of the economic burden and factors associated with the cost of COPD from 1990 to 2019. The outpatient visits and pharmaceutical therapy costs were the highest direct costs; meanwhile, the indirect costs were less researched. The findings of this study confirmed little research on economic burdens on caregivers of COPD patients and those conducted in developing countries.

In our dataset, four studies were conducted in lower-middle- and low-income countries [30,34,36,40], and seven for the upper-income countries [26,29,51,72,73]. Similar to results of several previous studies, these findings emphasize the lack of research on the economic costs of COPD in developing countries [26]. Probably due to human resources, finance, and infrastructure limitations in these countries [70]. This phenomenon calls for action from global researchers and the need to cooperate with researchers in high-resource settings.

The findings show that the most significant direct costs related to COPD were outpatient visits and pharmaceutical therapy costs [31,35,71]. As the disease worsens, patients need to spend more on palliative care, life maintenance, and hospital stay, which leads to an increase in the cost of hospitalization [58,74]. Other healthcare resources might contribute to COPD’s direct costs, such as home oxygen therapy and physician or specialist home visits [32,33]. In our dataset, no studies mentioned catastrophic costs due to COPD. However, the annual increase in COPD’s cost and long-term treatment characteristics could lead to a long-term economic burden on COPD patients.

Regarding indirect cost, our study included several dimensions of workforce participation, for instance, work and wage loss of COPD patients and caregivers, limitation, and disability in activities [75]. In our dataset, one study mentioned caregiver’s indirect cost [12]. Some studies also show that indirect costs can sometimes account for approximately 10% of the total economic burden [12,56]. However, the indirect cost of COPD is more challenging to control than the direct cost due to the various analytical components in indirect cost measurement [76]. The method of calculating the indirect cost burden is inconsistent among countries due to the different determinations of the workday value.

The study results indicate that the studies on the economic burden on caregivers of COPD patients are limited. Five studies in our dataset mentioned theme focusing on quality of life, the amount of time that caregivers spend for caring, family caregivers psychology, and burden [27,41,68,77,78]. Besides, there has been a lack of studies on mental or physical health of family caregivers’ of COPD patients.

This research found a link between the more significant reported burden of COPD (breathlessness, symptoms, and comorbidities) and higher overall societal expenses per patient [26,59,77,78]. Thus, the severity of the disease and symptoms might be one of the factors that influence the economic burden of COPD.

Health risk behaviors such as alcohol consumption have been proven to increase cross-reinforcement among COPD patients who struggle to achieve smoking cessation [79]. Regarding insurance and economic factors, developing countries have a wide range of community-based health insurance schemes and every insurance scheme aims to protect the vulnerable people in the system by sharing risk [80].

Finally, the management of the severity and symptoms of COPD is critical. Under well-controlled circumstances, the patient’s symptoms and health effects are slow and not frantic. However, when patients progress to exacerbation of COPD, their lives may be affected immediately. Preventing exacerbation in people with COPD can help them live healthier lives and reduce the risk of death [81]. Models of monitoring and telemedicine care, home-based models, and utilizing local primary care facilities are effective treatment and palliative care methods for COPD patients [27,69,78,82]. Our study found out that there have been valuable categorization methods in providing appropriate services to patients, such as GOLD, mMRC breathless scale, and CAT limiting the economic burden of COPD treatment [31,32,35,36,66]. However, future well-designed studies must compare these options with large populations to reach accurate conclusions.

The findings of this study have several implications. First, due to the insufficient economic burden of research related to caregivers, future research should focus on the characteristics and problems of caregivers. Therefore, suitable public health programs should be implemented to reduce the economic burden and negative impacts on caregivers. Second, there are differences in treatment costs of COPD among smokers, former smokers, and nonsmokers, which suggest the negative effects of smoking on progression COPD. Thus, smoking prevention and cessation programs should be implemented early at schools and universities to prevent high-risk behaviors. In addition, when managing symptoms and severity of COPD, it is essential to raise awareness about COPD and self-management COPD intervention among people. Due to limited financial resources, self-management COPD intervention should be implemented in developing countries such as Vietnam. Further cost-effectiveness research about options, drugs, and treatment models for COPD is required to identify the most optimal guideline for patients and relatives to reduce the economic burden of COPD.

In this study, dome limitations need to be considered. First, only English publications were selected, which restricted our sample. Second, our study focused on the economic burden of COPD with the results having many exact numbers regarding economic cost. Finally, the database was limited to the peer-review papers only. Grey literatures and proceedings were not included, which may effect the results.

In conclusion, our findings highlight the considerable variation in COPD-related costs worldwide. This study confirmed a wide variation in the total direct cost of COPD, a diverse drug cost, and a limited exploration of the indirect cost associated with COPD in different countries. In addition, our findings emphasize the limited research on the economic burdens COPD caregivers face. It advocates for increased research support, especially by high-resource settings. These results highlight the need for more studies to better understand and address the economic aspects of COPD, with a focus on caregivers and diverse global contexts.

Notes

Authors’ Contributions

Conceptualization: Pham HQ, Pham KHT, Ha GH, Nguyen THT. Methodology: Pham HQ, Ha GH, Nguyen THT. Formal analysis: Pham HQ, Ha GH, Nguyen THT. Data curation: Pham TT, Nguyen HT. Writing - original draft preparation: Pham HQ, Ha GH, Nguyen THT. Writing - review and editing: Pham KHT, Oh JK. Approval of final manuscript: all authors.

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Funding

This work was supported by the Domestic Master/PhD Scholarship Program of Vingroup Innovation Foundation.

One of the authors, Trang Huyen Thi Nguyen, received funding from the International Cooperation and Education Program (NCCRI·NCCI 52210-52211, 2023) of the National Cancer Center, Korea.

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Topic	Search terms
COPD	Chronic bronchitis OR pulmonary emphysema OR COPD OR chronic obstructive pulmonary disease OR chronic obstructive airway disease OR COAD OR chronic obstructive lung disease OR chronic airflow obstruction*
Population	Patients OR caregivers OR relates
Outcome	Cost OR economics OR economic burden OR cost analysis OR cost measures OR affordability OR productivity loss OR responsibility OR cost of illness OR quality of life

Table 2.

List of included studies

No.	Main objective	Year	Country	Sample size	Study design	Perspective	Reference
1	Assess the cost-effectiveness of a home-based disease management intervention compared to usual management (U.M.) in individuals participating in the COPD Patient Management European Trial (COMET).	2019	France, Italy, Germany, Spain	319	Health economic evaluation study	Patients	[25]
2	Examine the overall healthcare costs linked to nebulized budesonide (nBUD) versus systemic corticosteroids (SCS) in patients experiencing acute exacerbations of COPD (AECOPD).	2019	China	2,550	Post hoc study	Patients	[26]
3	Systematically gather prospective outcome data from household members and demonstrate how these data can be integrated into a cost-utility analysis of a behavior change intervention for individuals with COPD.	2019	UK	153	Randomized controlledtrial	Patients/Caregivers	[27]
4	Comprehensively investigate the socioeconomic impact and resource utilization associated with COPD.	2019	Italy	NA	Retrospective study	Patients	[28]
5	Compare the utilization of healthcare resources at the end of life among three distinct groups of patients based on their "do not resuscitate" (DNR) directive status: those without a DNR directive, those with an early DNR (EDNR) directive established before entering the terminal hospitalization phase, and those with a late DNR (LDNR) directive established during the terminal hospitalization phase.	2019	China	361	Cross-sectional study	Patients	[29]
6	Evaluate both the direct and indirect costs associated with severe AECOPD within a tertiary care healthcare environment located in a high-prevalence region of North India.	2019	India	129	Cross-sectional study	Patients	[30]
7	Evaluate the economic burden of COPD in Greece. Additionally, the study aimed to identify and analyze potential determinants of the COPD economic burden.	2019	Greece	351	Cross-sectional study	Patients	[31]
8	The main objective of this study was to assess the long-term economic burden and benefits of implementing a regular program of systematic active case-finding for COPD in comparison to routine practice.	2019	UK	-	Cost-utility analysis	Patients	[32]
9	Investigate the association between clinically important deterioration(CID) in COPD and its impact on future economic and quality of life (QoL) outcomes. In addition, utilize a novel composite endpoint, CID, which evaluates the stability of the disease in COPD patients.	2019	USA	3,769	Post hoc study	Patients	[33]
10	Investigate and quantify the health-seeking costs associated with chronic cough, a distressing symptom often indicative of underlying health conditions like tuberculosis and chronic airways diseases, in the context of developing countries, with a particular focuson Malawi.	2019	Malawi	608	Economic study	Patients	[34]
	Explore the coping mechanisms employed by individuals facing the financial burden of seeking care for chronic cough, such as borrowing money or selling household assets.
11	Describe the clinical and economic outcomes for patients with COPD based on their blood eosinophil (EOS) count.	2019	USA	48,090	Retrospective cohort study	Patients	[35]
12	Investigate healthcare resource utilization (HCRU) and related costs in patients COPD in a specialty care hospital setting in Finland	2019	Finland	9,042	Retrospective study	Patients	[36]
13	To explore and quantify the direct medical costs associated with COPD.	2018	Vietnam	33,617	Retrospective study	Patients	[37]
	To identify and understand the main factors or variables that drive the costs of managing COPD.						[38]
14	To evaluate the consequences of applying the GOLD 2017 grading system to existing patients in the UK primary care.	2018	UK	100	Cohort study	Patients	[39]
	To estimate the potential cost savings that could be achieved by implementing the treatment recommendations outlined in the GOLD 2017 guidelines for patients in the UK primary care.	2018	India	24
15	The objective of this research was to investigate the economic impact, encompassing both direct and indirect costs, experienced COPD patients who were receiving treatment at selected tertiary care hospitals in South India.	2018	India	24	Cross-sectional study	Patients	[40]
16	To investigate how these costs COPD’s cost vary across different dimensions, including time, age, and disease stage.	2018	Sweden	17,479	Retrospective study	Patients	[41]
17	Assess how COPD, a condition associated with numerous comorbidities and substantial healthcare resource utilization, influences the social and economic aspects in Spain.	2018	Spain	386	Retrospective study	Patients/Caregiver	[5]
18	Measure the comprehensive burden of COPD by calculating both incremental direct and indirect costs associated with COPD.	2018	USA	5,701	Retrospective study	Patients	[42]
	Assessing various aspects of cost, such as direct medical resource use, productivity metrics, and COPD-specific resource use and the associated expenses.	2018	Canada	47
19	Conduct a cost-effectiveness analysis comparing the use of free O2 technology to manual oxygen-titration technology in the treatment s COPD patients who are hospitalized for acute exacerbations.	2018	Canada	47	Health economic evaluation study	Patients	[43]
20	Estimate the annual cost incurred by patients with COPD during the maintenance phase in Greece.	2018	Greece	245	Retrospective study	Patients	[43]
21	Determine the prevalence of COPD and cost of medical conditions treated on general internal medicine (GIM) inpatient services in seven hospital sites located in Toronto, Canada.	2018	Canada	148,442	Retrospective study	Patients	[44]
22	Investigate the hypothesis that incorporating total healthcare cost into the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index would improve the prediction of mortality in patients with COPD.	2017	Italy	275	Cross-sectional study	Patients	[45]
23	Assess and understand the clinical characteristics, treatment patterns, and the socioeconomic burden of COPD in Eastern Europe, with a specific focus on Bulgaria.	2017	Bulgaria	426	Cross-sectional study	Patients	[46]
24	Provide understanding of the cost-effectiveness of antibiotic prescriptions for COPD exacerbations and demonstrate the applicability of electronic health records (EHRs) in conducting such economic evaluations, particularly in the context of pragmatic RCTs.	2017	UK	45,375	Cohort study	Patients	[47]
25	Explore the economic burden of COPD in Greece.	2017	Greece	NA	Retrospective study	Patients	[12]
26	Evaluate the cost of treatment for patients with COPD in the context of Greece and assess the impact of the financial crisis on COPD patients.	2017	Greece	189	Cross-sectional study	Patients	[48]
27	Analyze the association between frequent comorbidities and common symptoms and the annual direct and indirect costs incurred by patients with COPD in Germany.	2017	Germany	2,139	Cohort study	Patients	[49]
28	Understand the disease burden associated with respiratory disorders, including allergic rhinitis (AR), asthma, COPD, and rhinosinusitis.	2016	South Korea	999	Cross-sectional study	Patients	[50]
29	Quantify and assess the total costs associated with COPD management in urban areas of China.	2016	China	678	Cross-sectional study	Patients	[51]
	Explore and identify the factors that contribute to the high economic burden of COPD in these urban areas.
30	Quantify and analyze the annual cost of treating bronchiectasis (BE). in Spain, stratified by the severity of the disease as assessed by the FACED score.	2016	Spain	456	Cohort study	Patients	[52]
	Identify and examine the specific parameters or factors that are associated with increased costs in the treatment of BE.
31	Evaluate and compare the cost-effectiveness of tiotropium (TIO) and glycopyrronium (GLY) in the management of COPD.	2016	Canada, Sweden, Spain, UK	NA	Cohort study	Patients	[53]
	Consider the latest clinical evidence from the SPARK trial, which suggests that TIO is superior to GLY in reducing severe exacerbations.
32	Assess and report the prevalence and severity of respiratory symptoms in adults with a primary diagnosis of AR, asthma, COPD, and rhinosinusitis.	2016	Thailand	1,000	Cross-sectional study	Patients	[54]
	Evaluate the impact of these respiratory diseases on work productivity, including work-related impairment and activity limitations experienced by affected individuals.
	Analyze the economic burden associated with AR, asthma, COPD, and rhinosinusitis in terms of direct and indirect costs, including healthcare expenses and productivity losses.
33	Quantify and analyze the total economic burden of COPD in Italy.	2015	Italy	275	Retrospective study	Patients	[55]
34	Evaluate the economic implications of COPD in the period an official diagnosis.	2014	Denmark	131,881	Retrospective study	Patients	[56]
	Analyze the economic consequences of COPD after diagnosis.
35	Provide an overview of the economic and management aspects of COPD in the United States.	2013	USA		Retrospective study	Patients	[57]
36	Quantify and analyze the total costs associated with maintaining COPD therapy and managing acute exacerbations over a one-year timeframe.	2012	Canada	285	Retrospective study	Patients	[58]
37	Determine how the presence of anxiety and depression, as comorbidities, affect the utilization of healthcare resources and the associated costs among individuals with COPD.	2011	USA	3,761	Cohort study	Patients	[59]
38	Calculate and compare the annual COPD-related healthcare costs for each cohort, including both patient- and payer-paid costs.	2010	USA	37,089	Retrospective study	Patients	[60]
	Determine the adjusted episode-level costs for various types of COPD-related visits, including outpatient, urgent outpatient, emergency department, standard admission, and intensive care unit stays.
39	Estimate healthcare resources utilization and costs of patients with COPD at the Italian pneumology departments	2007	Italy	268	Prospective study	Patients	[61]
	Understand how the utilization of healthcare resources and costs vary among COPD patients at different stages of the disease.
40	Employing two different methods for cost estimation. The first method involved estimating the resources used and expenditures incurred by individuals with COPD that were directly attributable to the disease.	2005	USA	8,300	Retrospective study	Patient	[62]
	Determining the average direct costs of COPD per patient, including a breakdown of costs associated with hospitalization and other healthcare utilization.
41	Investigate and assess the economic burden of COPD in seven countries: Canada, France, Italy, the Netherlands, Spain, the UK, and the United States.	2003	Canada, France, UK, USA, Spain, Netherlands, France	3,265	Economic analysis	Patient	[63]
42	Assess the direct medical costs associated with the provision of respiratory care for COPD patients on long-term oxygen therapy, taking into consideration both not-for-profit (NP) and profit-making (PM) health organizations responsible for home oxygen delivery.	1996	France	234	Retrospective study	Patient	[64]
43	Assess the cost-effectiveness of bronchodilators, theophylline (T) and ipratropium bromide (IB) therapies, taking into consideration their impact on the outcome of COPD, healthcare costs, and their known toxicity profiles.	1993	USA	311	Retrospective cohort study	Patient	[65]

COPD: chronic obstructive pulmonary disease; NA: not available; GOLD: Global Initiative for Chronic Obstructive Lung Disease; FACED: assessment of severity tool, validated for people with non-cystic fibrosis bronchiectasis; SPARK: Effect of QVA149 Versus NVA237 and Tiotropium on COPD Exacerbations.

Study	Country	Population/subpopulation	Total cost	Total medical cost	Pharmaceutical therapy	Outpatient cost	Total nonmedical cost
Dal Negro (2019) [28]	Italy	Patients with COPD	3,988.09 (95% CI, 3,594.9–4,517.3)	2,594.26 (95% CI, 1,316.6–4,043.3)	678.15 (95% CI, 343.4–1,012.4)	630.00 (95% CI, 282.2–977.8)
Kourlaba et al. (2019) [31]	Greece	Patients with COPD	3,223.05 (95% CI, 2,816.8–3,662.3)	2,986.19 (95% CI, 260.8–3,368.5)	1,163.30 (95% CI, 1,077.8–1,248.7)
Corsico et al. (2019) [66]	Italy	Patients with COPD		3,600.19±6,391.0	1,549.16±1,668.7
Fu et al. (2019) [29]	China	Patients with COPD		7,685.23	7,685.23
Koul et al. (2019) [30]	India	Patients with COPD		1,404.38	258.71		108.49
Lambe et al. (2019) [32]	UK	Patients with COPD	1,098.29
Vo et al. (2018) [37]	Vietnam	Patients in Dong Nai Hospital		70.07
Vo et al. (2018) [37]	Vietnam	Patients in Pham Ngoc Thanh Hospital		1,291.55
Lakiang et al. (2018) [39]	India	Patients with COPD	1,131.99±534.8	514.42±324.1		52.08±6.3	331.82±99.5
Lisspers et al. (2018) [40]	Sweden	Patients with COPD	12,921.30
Merino et al. (2018) [41]	Spain	Patients with COPD		2,216.79±3,002.2	981.07±839.0	509.30±1,858.9	1,929.97±5,452.2
Poder et al. (2018) [42]	Canada	Patients with COPD	13766.33
Verma et al. (2018) [44]	Canada	Patients with COPD	10,180.53±15,842.7
Dzingina et al. (2017) [67]	Bulgaria	Patients with COPD	3,096.70
Chen et al. (2016) [51]	China	Patients with COPD	9,537.7±35,816.4	8,706.9±35,081.1		1,999.54±14,833.8
Dal Negro et al. (2015) [55]	Italy	Patients with COPD		2,679.95 (95% CI, 1,316.6–4,043.3)	678.15 (95% CI, 343.4–1,012.9)	630.00 (95% CI, 282.2–977.8)
		Male COPD patients		2,724.69 (95% CI, 2,053.2–3,396.2)	667.27 (95% CI, 525.1–809.4)	637.34 (95% CI, 462.7–810.6)
		Female COPD patients		2,473.76 (95% CI, 1,462.4–2,507.0)	688.48 (95% CI, 353.5–638.8)	599.67 (95% CI, 403.7–795.7)
Miller et al. (2005) [62]	USA	COPD patients	2,507.00		375.00

Study	Country	Population/subpopulation	Year	Indirect cost/Productivity loss	95% CI
Dal Negro (2019) [28]	Italy	Patients with COPD	2019	487.6	161.85–813.34
Koul et al. (2019) [30]	India	Patients with COPD	2019	94.8
Kourlaba et al. (2019) [31]	Greece	Patients with COPD	2019	236.9	149.91–350.79
		Patients with COPD and CAT score ≤10		45.0	7.5–98.94
		Patients with COPD and CAT score >10		274.3	163.40–411.25
		Patients with mild level on Medical Research Council breathless scale		199.4	80.95–370.28
		Patients with mild level on Medical Research Council breathless scale		290.8	148.41–473.71
		Patients with mild level on Medical Research Council breathless scale		269.8	92.94–454.22
		Patients with COPD at GOLD A		33.0	0–76.45
		Patients with COPD at GOLD B		97.4	47.97–157.40
		Patients with COPD at GOLD D		398.8	223.36–613.13
Merino et al. (2018) [41]	Spain	Patients with COPD	2018	900.7	399.40–1,403.25
Patel et al. (2018) [5]	USA	Patients with COPD	2018	1,150.0
Souliotis et al. (2017) [12]	Greece	Patients with COPD	2017	1,451.7
Souliotis et al. (2017) [12]	Greece	Nonpaid caregivers’ time	2017	1,207.8
Chen et al. (2016) [51]	China	Patients with COPD	2016	3,265.3
Dal Negro et al. (2015) [55]	Italy	Patients with COPD	2015	487.6	161.85–813.34
		Male COPD patient		496.2	353.49–638.84
		Female COPD patient		475.1	139.00–811.17

Scale	Study	Population/subpopulation	Difference	SD	95% CI
EQ-5D-5L score	Bhadhuri et al. (2019) [27]	Family members of patients on telephone coaching self-management	–0.029	0.14
	Bhadhuri et al. (2019) [27]	Family members of patients on usual management	–0.019	0.10
	O'Reilly et al. (2007) [61]	Patients on admissions	–0.24	0.373	–0.38 to –0.10
Happiness (scale 0 – 10)	Bhadhuri et al. (2019) [27]	Family members of patients on telephone coaching self-management	0.22	1.41
Happiness (scale 0 – 10)	Bhadhuri et al. (2019) [27]	Family member of patients with usual management	–0.11	1.24
The COPD Assessment Test	Ladziak et al. (2019) [69]	Patients with triple-therapy inhaler combinations	–0.84		–3.57 to 1.89
St George’s Respiratory Questionnaire for COPD	Bikmoradi et al. (2019) [72]	Patients with continuity of care model	11.93
	Bikmoradi et al. (2019) [72]	Patients with routine care model	–1.15
	Folch-Ayora et al. (2019) [82]	Male patients	–3.51
		Female patients	–2.24
		Patients who had telephone education session	–6.83
		Patient with usual management	–0.26
Caregiver burden questionnaire	Chu et al. (2019) [68]	Caregivers with <2 caregiving hours per day	34.5	15.1
		Caregivers with <3 caregiving hours per day	45.8	10.5
		Caregivers with <5 caregiving hours per day	59.8	5.1
		Caregivers with ≥6 caregiving hours per day	67.4	6.3
		Caregivers of COPD patient	57.3	14.6