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Modeling the Health and Economic Burden of Chronic Obstructive Pulmonary Disease in China From 2020 to 2039: A Simulation Study

Open AccessPublished:August 09, 2022DOI:https://doi.org/10.1016/j.vhri.2022.06.002

      Highlights

      • The burden of chronic obstructive pulmonary disease (COPD) in China is substantial. In 2011, 31% of global COPD mortality was estimated to occur in China. Nevertheless, limited data are available on the predicted long-term health and economic burden of COPD in China.
      • Our simulation estimated that the number of patients with COPD in China would increase from 88.3 million to 103.3 million between 2020 and 2039; the number of severe cases of COPD is estimated to increase by 31%, and 3.9 million deaths because of COPD are predicted over this period. The discounted total direct and indirect costs incurred because of COPD over 20 years are estimated to be $3.1 trillion and $360.5 billion, respectively.
      • This analysis quantified the epidemiological burden and the significant toll that COPD is expected to take on the Chinese healthcare system over a 20-year period. Effective strategies to help diagnose and manage COPD are warranted and may help to reduce the projected burden of disease.

      Abstract

      Objectives

      Despite a growing prevalence of respiratory diseases in recent decades in China, limited evidence is available on the health and economic burden of chronic obstructive pulmonary disease (COPD). We estimated the 20-year health and economic burden of COPD in China from 2020 to 2039.

      Methods

      We created a probabilistic dynamic open-cohort Markov model of COPD for the Chinese population aged ≥40 years. Projections of population growth and urbanization rates were obtained from the United Nations Population Division. Other parameter inputs including smoking prevalence, COPD prevalence and severity distributions, disease-related costs, and utility weights were obtained from the most recent published literature. We modeled number of COPD patients, excess mortality due to COPD, exacerbations, COPD-attributable losses of quality-adjusted life-years, and direct and indirect COPD costs over the 20 years.

      Results

      The number of COPD patients was projected to increase from 88.3 million in 2020 to 103.3 million in 2039. The projected total losses of quality-adjusted life-years and the excess mortality due to COPD were, respectively, estimated to be 253.6 million and 3.9 million over the 20 years. The projected 20-year total discounted direct and indirect costs of COPD were, respectively, $3.1 trillion and $360.5 billion. The projected health and economic burden was higher in males and urban areas.

      Conclusions

      COPD is projected to inflict a substantial burden to the society and the health care system in China. Effective strategies for prevention and early management of COPD are needed to mitigate the forthcoming disease burden.

      Keywords

      Introduction

      Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by progressive airway limitation that is not fully reversible and is associated with a significant deterioration in patients’ health-related quality of life.

      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global initiative for chronic obstructive lung disease (2021 report). Global Initiative for Chronic Obstructive Lung Disease. https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf. Accessed February 23, 2021.

      ,
      • Jones P.W.
      • Brusselle G.
      • Dal Negro R.W.
      • et al.
      Health-related quality of life in patients by COPD severity within primary care in Europe.
      According to the global burden of disease (GBD) 2015 study, COPD is the most common noncommunicable respiratory condition leading to death with 3.2 million deaths worldwide.
      • Wang H.
      • Naghavi M.
      • Allen C.
      Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet. 2017;389(10064):e1].
      ,
      • Soriano J.B.
      • Abajobir A.A.
      • Abate K.H.
      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.
      China accounts for a substantial proportion of the global burden of COPD. Thrity one percent of the global COPD mortality were estimated to have occurred in China in 2013.
      • Yin P.
      • Wang H.
      • Vos T.
      • et al.
      A subnational analysis of mortality and prevalence of COPD in China from 1990 to 2013.
      COPD has also posed a substantial burden within the country. COPD is ranked fifth in the causes of premature mortality in China,
      • Wang H.
      • Naghavi M.
      • Allen C.
      Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet. 2017;389(10064):e1].
      and the disease prevalence has increased by 66% in recent years, from 8.2% in 2004 to 13.6% in 2015, among Chinese adults aged 40 years or older.
      • Zhong N.
      • Wang C.
      • Yao W.
      • et al.
      Prevalence of chronic obstructive pulmonary disease in China: a large, population-based survey [published correction appears in Am J Respir Crit Care Med. 2007;176(11):1169].
      ,
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      Studies have attributed the increasing burden primarily to the aging population, high prevalence of smoking, and health disparities between urban and rural areas.
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      • Wang C.
      • Xu J.
      • Yang L.
      • et al.
      Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.
      • Fang X.
      • Wang X.
      • Bai C.
      COPD in China: the burden and importance of proper management.
      In terms of the economic burden of COPD in China, previous studies mostly have reported the cost burden at the individual level. A review study reported that the annual direct medical costs of COPD ranged from $726 to $3565 (US dollars) per patient in 2013 accounting for 33% to 118% of the local average annual income.
      • Zhu B.
      • Wang Y.
      • Ming J.
      • Chen W.
      • Zhang L.
      Disease burden of COPD in China: a systematic review.
      Another study based on a survey of patients with COPD in major urban areas reported that the COPD treatment costs accounted for 19.2% to 34.1% of the income of the study population.
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
      Some cost-of-illness studies have provided estimates of the economic burden of COPD at the country level using back-of-the-envelope calculations based on the prevalence and population size. For example, a prevalence study roughly estimated that the total annual costs of COPD in China could be between $151.6 billion and $266.3 billion using the prevalence levels observed in their study.
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      Nevertheless, these estimates did not capture changes in the population structure over time and variations in distributions of risk factors affecting the health and economic burden of COPD.
      As COPD has become an increasing threat to the medical and public health community in China, it is critical for policy makers to understand its long-term societal burden to plan for budget allocations accordingly. In this study, we quantified the 20-year health and economic burden of COPD in China, from 2020 to 2039, using a dynamic open-cohort Markov model that accounted for changes in the population structure and the smoking prevalence over time.

      Methods

      Model Overview and Structure

      We developed a probabilistic dynamic open-cohort Markov model to project the health and economic burden of COPD in China from 2020 to 2039 from a societal perspective.
      • Zafari Z.
      • Li S.
      • Eakin M.N.
      • Bellanger M.
      • Reed R.M.
      Projecting long-term health and economic burden of COPD in the United States.
      Our model consisted of 10 mutually exclusive health states, 9 of which were constructed based on the different combinations of smoking status (never smoker, current smoker, and former smoker) and COPD severity stages (mild, moderate, and severe or very severe). The tenth state was death as an absorbing state. The COPD severity was defined based on the lung function thresholds outlined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.

      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global initiative for chronic obstructive lung disease (2021 report). Global Initiative for Chronic Obstructive Lung Disease. https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf. Accessed February 23, 2021.

      We chose the time horizon of 20 years for the base case projections and the cycle length of 1 year. The schematic illustration of the model is presented in Figure 1.
      Figure thumbnail gr1
      Figure 1Schematic illustration of the Markov model.
      Because the key input parameters of the model such as the prevalence and severity of COPD are highly dependent on age, sex, and urbanicity of the individual’s residence, we constructed the model based on these demographic variables. Doing so allowed our model to capture the potential variations in the disease burden due to changes in the demographic structure over time. For each population subgroup of age, sex, and urbanicity, we modeled the subgroup-specific COPD prevalence, smoking prevalence, and severity distribution based on the published data (see Table 1
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      ,
      • Wang C.
      • Xu J.
      • Yang L.
      • et al.
      Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.
      ,
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
      ,
      • World population prospects - population division
      United Nations.
      • World urbanization prospects - population division
      United Nations.
      • Liu S.
      • Zhang M.
      • Yang L.
      • et al.
      Prevalence and patterns of tobacco smoking among Chinese adult men and women: findings of the 2010 national smoking survey.
      • Levy D.
      • Rodriguez-Buno R.L.
      • Hu T.-W.
      • Moran A.E.
      The potential effects of tobacco control in China: projections from the China SimSmoke simulation model.
      • Hoogendoorn M.
      • Rutten-van Mölken M.P.M.H.
      • Hoogenveen R.T.
      • et al.
      A dynamic population model of disease progression in COPD.
      • Hoogendoorn M.
      • Feenstra T.L.
      • Hoogenveen R.T.
      • Al M.
      • Mölken M.R.
      Association between lung function and exacerbation frequency in patients with COPD.
      GHO data repository. Life tables by country - China. World Health Organization.
      • Lan F.
      • Li J.
      • Yu C.
      • et al.
      [Associations between airflow obstruction and total and cause-specific mortality in adults in China].
      • Wu M.
      • Zhao Q.
      • Chen Y.
      • Fu C.
      • Xu B.
      Quality of life and its association with direct medical costs for COPD in urban China.
      • Yao Q.
      • Liu C.
      • Zhang Y.
      • Xu L.
      Changes in health-related quality of life of Chinese populations measured by the EQ-5D-3 L: a comparison of the 2008 and 2013 National Health Services Surveys.
      • Cai L.
      • Cui W.
      • He J.
      • Wu X.
      The economic burden of smoking and secondhand smoke exposure in rural South-West China.
      National data. NBS.
      ). The outcomes of the study are number of COPD patients, excess mortality due to COPD, COPD exacerbations, COPD-attributable losses of quality-adjusted life-years (QALYs), and direct and indirect costs of COPD. The list of parameter inputs used in the model and their corresponding distributions are provided in Table 1.
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      ,
      • Wang C.
      • Xu J.
      • Yang L.
      • et al.
      Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.
      ,
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
      ,
      • World population prospects - population division
      United Nations.
      • World urbanization prospects - population division
      United Nations.
      • Liu S.
      • Zhang M.
      • Yang L.
      • et al.
      Prevalence and patterns of tobacco smoking among Chinese adult men and women: findings of the 2010 national smoking survey.
      • Levy D.
      • Rodriguez-Buno R.L.
      • Hu T.-W.
      • Moran A.E.
      The potential effects of tobacco control in China: projections from the China SimSmoke simulation model.
      • Hoogendoorn M.
      • Rutten-van Mölken M.P.M.H.
      • Hoogenveen R.T.
      • et al.
      A dynamic population model of disease progression in COPD.
      • Hoogendoorn M.
      • Feenstra T.L.
      • Hoogenveen R.T.
      • Al M.
      • Mölken M.R.
      Association between lung function and exacerbation frequency in patients with COPD.
      GHO data repository. Life tables by country - China. World Health Organization.
      • Lan F.
      • Li J.
      • Yu C.
      • et al.
      [Associations between airflow obstruction and total and cause-specific mortality in adults in China].
      • Wu M.
      • Zhao Q.
      • Chen Y.
      • Fu C.
      • Xu B.
      Quality of life and its association with direct medical costs for COPD in urban China.
      • Yao Q.
      • Liu C.
      • Zhang Y.
      • Xu L.
      Changes in health-related quality of life of Chinese populations measured by the EQ-5D-3 L: a comparison of the 2008 and 2013 National Health Services Surveys.
      • Cai L.
      • Cui W.
      • He J.
      • Wu X.
      The economic burden of smoking and secondhand smoke exposure in rural South-West China.
      National data. NBS.
      Table 1Model input parameters for projecting the health and economic burden of COPD in China.
      Model parameterMean (SE)Distribution
      Population characteristics
       Annual population projections for population aged 40 years or olderPopulation projections based on age and sex for Mainland China from the UN Population Division
      • World population prospects - population division
      United Nations.
       Annual urbanization rate projections in ChinaUrbanization rate projections from the UN Population Division
      • World urbanization prospects - population division
      United Nations.
       Prevalence of smokingProjection of smoking prevalence in the Chinese population aged 15 years or older from the 2010 National Smoking Survey
      • Liu S.
      • Zhang M.
      • Yang L.
      • et al.
      Prevalence and patterns of tobacco smoking among Chinese adult men and women: findings of the 2010 national smoking survey.
      and the China SimSmoke model
      • Levy D.
      • Rodriguez-Buno R.L.
      • Hu T.-W.
      • Moran A.E.
      The potential effects of tobacco control in China: projections from the China SimSmoke simulation model.
       Background mortality ratesAge-specific mortality rates from the China Life Tables,
      GHO data repository. Life tables by country - China. World Health Organization.
      provided in Appendix Table 4 in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002
      COPD prevalence
      Data presented only for overall study population.
      ,
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      13.6%Beta
      GOLD severity distributions at baseline
      Data presented only for overall study population.
      ,
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      ,
      • Wang C.
      • Xu J.
      • Yang L.
      • et al.
      Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.
      Mild: 56.4%

      Moderate: 36.3%

      Severe/very severe: 7.4%
      Mortality rate ratios
      The reference group for the mortality rate ratio was individuals with normal lung function.
      for severe or very severe COPD
      • Lan F.
      • Li J.
      • Yu C.
      • et al.
      [Associations between airflow obstruction and total and cause-specific mortality in adults in China].
      1.77 (95% CI 1.66-1.89)Log-normal
      Transition probabilities
      A transition probability is defined as a probability of transition from one state to another during one cycle.
      between COPD severity stages
      • Hoogendoorn M.
      • Rutten-van Mölken M.P.M.H.
      • Hoogenveen R.T.
      • et al.
      A dynamic population model of disease progression in COPD.
       Mild to moderate COPDNever smoker: 1.8%

      Current smoker: 2.5%

      Former smoker: 2.1%
      -
       Moderate to severe/very severe COPDNever smoker: 3.0%

      Current smoker: 3.7%

      Former smoker: 3.4%
      -
      Transition probabilities
      A transition probability is defined as a probability of transition from one state to another during one cycle.
      between smoking states for COPD patients
      • Hoogendoorn M.
      • Rutten-van Mölken M.P.M.H.
      • Hoogenveen R.T.
      • et al.
      A dynamic population model of disease progression in COPD.
       Never smoker to current smoker0-
       Current smoker to former smoker4.7%-
       Former smoker to current smoker2.6%-
      COPD exacerbation rates
      A rate is defined as the number of events per person-year.
      ,
      • Hoogendoorn M.
      • Feenstra T.L.
      • Hoogenveen R.T.
      • Al M.
      • Mölken M.R.
      Association between lung function and exacerbation frequency in patients with COPD.
       Mild COPDTotal exacerbation
      Total exacerbations include both severe and nonsevere exacerbations.
      : 0.82 (0.26)

      Severe exacerbation: 0.11 (0.14)
      Gamma
       Moderate COPDTotal exacerbation
      Total exacerbations include both severe and nonsevere exacerbations.
      : 1.17 (0.15)

      Severe exacerbation: 0.16 (0.07)
      Gamma
       Severe/very severe COPDTotal exacerbation
      Total exacerbations include both severe and nonsevere exacerbations.
      : 1.66 (0.14)

      Severe exacerbation: 0.23 (0.04)
      Gamma
      Health-related quality of life for patients with COPD
      • Wu M.
      • Zhao Q.
      • Chen Y.
      • Fu C.
      • Xu B.
      Quality of life and its association with direct medical costs for COPD in urban China.
       Utility of mild COPD0.786 (0.085)Beta
       Utility of moderate COPD0.734 (0.158)Beta
       Utility of severe/very severe COPD0.682 (0.122)Beta
      Average health-state utility of adults in China
      • Yao Q.
      • Liu C.
      • Zhang Y.
      • Xu L.
      Changes in health-related quality of life of Chinese populations measured by the EQ-5D-3 L: a comparison of the 2008 and 2013 National Health Services Surveys.
      0.956
      COPD-attributable direct medical costs for urban residential areas (2020 USD per person-year)
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
       Mild COPD$995 ($100)Gamma
       Moderate COPD$1990 ($199)Gamma
       Severe/very severe COPD$3540 ($354)Gamma
      COPD-attributable direct nonmedical costs for urban residential areas (2020 USD per person-year)
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
       Mild COPD$114 ($11)Gamma
       Moderate COPD$101 ($10)Gamma
       Severe/very severe COPD$384 ($38)Gamma
      COPD-attributable indirect costs for urban residential areas (2020 USD per person-year)
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
       Mild COPD$214 ($21)Gamma
       Moderate COPD$509 ($51)Gamma
       Severe/very severe COPD$4048 ($405)Gamma
      COPD-attributable direct medical costs for rural residential areas (2020 USD per person-year)
      • Cai L.
      • Cui W.
      • He J.
      • Wu X.
      The economic burden of smoking and secondhand smoke exposure in rural South-West China.
      $1740 ($174)Gamma
      COPD-attributable direct nonmedical costs for rural residential areas (2020 USD per person-year)
      • Cai L.
      • Cui W.
      • He J.
      • Wu X.
      The economic burden of smoking and secondhand smoke exposure in rural South-West China.
      $109 ($11)Gamma
      COPD-attributable indirect costs for rural residential areas (2020 USD per person-year)
      • Cai L.
      • Cui W.
      • He J.
      • Wu X.
      The economic burden of smoking and secondhand smoke exposure in rural South-West China.
      $22 ($2)Gamma
      China consumer price index (urban household)
      National data. NBS.
      (from 2011 to 2020)
      +25.5%-
      China consumer price index (rural household)
      National data. NBS.
      (from 2011 to 2020)
      +25.0%-
      CI indicates confidence interval; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; SE, standard error; USD, US dollars.
      Data presented only for overall study population.
      The reference group for the mortality rate ratio was individuals with normal lung function.
      A transition probability is defined as a probability of transition from one state to another during one cycle.
      § A rate is defined as the number of events per person-year.
      ǁ Total exacerbations include both severe and nonsevere exacerbations.

      Modeling Population Growth and Smoking Prevalence

      We limited our study population to those who reside in Mainland China. Within the study population, subgroups were built based on different combinations of age groups (40-49, 50-59, 60-69, 70-79, and 80 years or older), sex, and urbanicity (urban or rural). The projections of the annual population growth and the urbanization rate (probability of living in urban areas) were obtained from the United Nations Population Division.
      • World population prospects - population division
      United Nations.
      ,
      • World urbanization prospects - population division
      United Nations.
      Age-specific urbanization rates were calculated using age distributions within urban and rural populations, which we obtained from the published literature.
      • Chen Q.
      • Dietzenbacher E.
      • Los B.
      The effects of ageing and urbanisation on China’s future rural and urban populations.
      The distributions of smoking status (never smoker, current smoker, and former smoker) within each subgroup were initially informed from the 2010 National Smoking Survey.
      • Liu S.
      • Zhang M.
      • Yang L.
      • et al.
      Prevalence and patterns of tobacco smoking among Chinese adult men and women: findings of the 2010 national smoking survey.
      Nevertheless, the prevalence of current smoking declined in more recent years in China. Therefore, to calibrate the prevalence of current smoking for the future decline, we derived a correction factor and applied to the subgroup-specific smoking prevalence calculated from the 2010 survey. A correction factor for a specific year was obtained by calculating a ratio between the prevalence of current smoking projected by the China SimSmoke simulation model for the year
      • Levy D.
      • Rodriguez-Buno R.L.
      • Hu T.-W.
      • Moran A.E.
      The potential effects of tobacco control in China: projections from the China SimSmoke simulation model.
      and the smoking prevalence from the 2010 survey. More technical details on the derivation of the subgroup-specific population projections and the smoking status distributions within the subgroups are provided in the Appendix in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002 (Section 1.1).

      Prevalence and Severity Distributions

      We derived the subgroup-specific prevalence and severity distributions of COPD using the prevalence estimates and the demographic information from 2 nationwide prevalence surveys in China.
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      ,
      • Wang C.
      • Xu J.
      • Yang L.
      • et al.
      Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.
      In both studies, COPD was defined as a post-bronchodilator forced expiratory volume in 1 second to forced vital capacity ratio of <0.70 based on the GOLD guidelines.

      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global initiative for chronic obstructive lung disease (2021 report). Global Initiative for Chronic Obstructive Lung Disease. https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf. Accessed February 23, 2021.

      Detailed methods used for the calculations of the subgroup-specific prevalence and severity distributions are provided in the Appendix in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002 (Section 1.2).

      Transition Probabilities and Dynamic Cohort Structure

      In each model cycle, patients had a chance to transition from one health state to another health state or die. The natural history of disease progression and the transition probabilities between the health states of our model were informed by previous studies.
      • Zafari Z.
      • Li S.
      • Eakin M.N.
      • Bellanger M.
      • Reed R.M.
      Projecting long-term health and economic burden of COPD in the United States.
      ,
      • Hoogendoorn M.
      • Rutten-van Mölken M.P.M.H.
      • Hoogenveen R.T.
      • et al.
      A dynamic population model of disease progression in COPD.
      For each subgroup, we started with an initial cohort of patients and followed them over the 20 years. Each year, some patients of the original cohort naturally died, and new patients were added to the model at the beginning of each cycle. To estimate the number of new patients to be added, we calculated the difference between the number of patients alive at the end of the previous cycle and the projected number of COPD patients for the current cycle, which is a product of the population size and the COPD prevalence of a subgroup for the current year.

      Outcomes

      Number of COPD patients, exacerbations, and mortality

      The number of COPD patients was modeled as a product of the population size of a subgroup and the subgroup-specific COPD prevalence. COPD exacerbations were defined as events of health care utilization because of worsening of COPD symptoms, which includes the use of short-acting bronchodilators with or without antibiotic agents, systemic steroids or hospitalization. Severe exacerbations were defined as events that required hospitalization, and nonsevere exacerbations were defined otherwise. The GOLD severity-specific exacerbation rates were obtained for total exacerbations (including both severe and nonsevere ones) and severe exacerbations from a published literature review.
      • Hoogendoorn M.
      • Feenstra T.L.
      • Hoogenveen R.T.
      • Al M.
      • Mölken M.R.
      Association between lung function and exacerbation frequency in patients with COPD.
      We calculated the number of exacerbations per cycle by multiplying the number of patients in each severity stage by the severity-specific exacerbation rate. To model the excess mortality due to COPD, the excess mortality rate was derived by subtracting the all-cause mortality rate in the general population from the all-cause mortality rate calculated for severe COPD. We obtained the baseline mortality rates from the Life Tables of China, and the GOLD severity-specific mortality rate ratio in the Chinese population, which we used for the all-cause mortality calculation for severe COPD, from the published literature.
      GHO data repository. Life tables by country - China. World Health Organization.
      ,
      • Lan F.
      • Li J.
      • Yu C.
      • et al.
      [Associations between airflow obstruction and total and cause-specific mortality in adults in China].

      Losses of QALYs and costs

      We calculated the losses of QALYs as a function of the GOLD severity-specific disutility weights for COPD and the distribution of the disease severity within the subgroup, assuming one's health-state utility is determined only by the disease severity. The severity-specific utility values were obtained from a published study that measured the health state utilities using the EQ-5D questionnaires in COPD patients in China.
      • Wu M.
      • Zhao Q.
      • Chen Y.
      • Fu C.
      • Xu B.
      Quality of life and its association with direct medical costs for COPD in urban China.
      The disutility values for the model input were calculated by getting the difference between the average health utility of the general Chinese population and the severity-specific utilities.
      • Wu M.
      • Zhao Q.
      • Chen Y.
      • Fu C.
      • Xu B.
      Quality of life and its association with direct medical costs for COPD in urban China.
      ,
      • Yao Q.
      • Liu C.
      • Zhang Y.
      • Xu L.
      Changes in health-related quality of life of Chinese populations measured by the EQ-5D-3 L: a comparison of the 2008 and 2013 National Health Services Surveys.
      The direct medical costs in our study included all medical costs (including out-of-pocket costs) incurred by outpatient visits, emergency department visits, hospitalizations, prescription drugs, and other medical services and products for treating COPD. The direct nonmedical costs included all nonmedical expenditures incurred by the use of transportation, accommodations, nutrition, and other services for treating COPD.
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
      The indirect costs included productivity losses of COPD patients and caregivers.
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
      All input costs were modeled as a function of underlying GOLD severity stages. The severity-specific cost estimates reported were obtained from the published cost studies conducted in China.
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
      ,
      • Cai L.
      • Cui W.
      • He J.
      • Wu X.
      The economic burden of smoking and secondhand smoke exposure in rural South-West China.
      All costs were inflated to 2020 values using the China Consumer Price Index and expressed in 2020 US dollars based on the average exchange rate in 2020.
      National data. NBS.
      More detailed descriptions on calculations of the severity-specific inputs for costs and the losses of QALYs are provided in the Appendix in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002 (Sections 1.3 and 1.4).

      Analysis Methods

      We used a probabilistic Monte Carlo simulation by running 1000 iterative simulations based on random draws from the statistical distributions of the model input parameters. The results were presented with the mean and the 95% credible interval (CrI) of the 1000 simulation runs. We projected both undiscounted and discounted outcomes, and we used an annual discount rate of 5% for the discounted outcomes.
      • Haacker M.
      • Hallett T.B.
      • Atun R.
      On discount rates for economic evaluations in global health.
      The 20-year total costs and the losses of QALYs were presented in net present values (See the Appendix in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002; for the details of discounting and net present value caculations (Section 1.5)), and the undiscounted outcomes were used to present the trends over time. Additionally, to account for the uncertainty around the long-term economic outlook in China, we performed a sensitivity analysis using an annual discount rate of 3%, the current standard for high-income countries.
      • Haacker M.
      • Hallett T.B.
      • Atun R.
      On discount rates for economic evaluations in global health.
      Another set of sensitivity analyses was performed varying the time horizons to 10 and 30 years to provide the disease burden estimates for different time horizons. All simulations were conducted using R version 3.6.3.
      R Core Team
      R: A Language and Environment for Statistical Computing.

      Dedicated Scenario Analysis for Modeling Future Declines in Smoking Prevalence in China

      To explore the potential effect of policy actions for tobacco control on the COPD burden, we conducted a scenario analysis assuming a further decline in the future smoking prevalence in case of implementation of stronger tobacco control policy measures in China. To reflect the hypothetical policy effects, we used the smoking prevalence projections by the SimSmoke model.
      • Levy D.
      • Rodriguez-Buno R.L.
      • Hu T.-W.
      • Moran A.E.
      The potential effects of tobacco control in China: projections from the China SimSmoke simulation model.
      Their model projected the potential impact of the complete implementation of policy actions recommended by the World Health Organization Framework Convention on Tobacco Control (FCTC) on the future smoking prevalence in China.
      • Levy D.
      • Rodriguez-Buno R.L.
      • Hu T.-W.
      • Moran A.E.
      The potential effects of tobacco control in China: projections from the China SimSmoke simulation model.
      The FCTC recommended policy actions included in the SimSmoke model were (1) tax at 75% of the retail price, (2) comprehensive smoke-free air laws, (3) comprehensive marketing ban, (4) high-intensity tobacco control campaigns, (5) strong health warnings, (6) youth access enforcement, and (7) cessation treatment policies.
      • Levy D.
      • Rodriguez-Buno R.L.
      • Hu T.-W.
      • Moran A.E.
      The potential effects of tobacco control in China: projections from the China SimSmoke simulation model.
      We assumed this policy change to start taking place in 2023.

      Results

      Number of COPD Patients

      The number of people with COPD in China was estimated to be 88.3 million (95% CrI 82.0 million-95.4 million) in 2020 and projected to increase to 103.3 million (95% CrI 95.2 million-112.0 million) in 2039 (see Appendix Fig. 1 in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002). The rate of increase was greater for severe and very severe cases than mild cases; the number of mild COPD cases was projected to increase by 12% by 2039, growing from 46.4 million to 52.1 million, whereas the number of severe and very severe cases was estimated to increase by 31%, growing from 7.1 million to 9.3 million, during the same period.

      COPD Exacerbations and Excess Mortality due to COPD

      The 20-year cumulative number of exacerbations was projected to be 2.0 billion (95% CrI 1.5 billion-2.7 billion), of which 273.0 million (95% CrI 101.4 million-665.3 million) were severe exacerbations requiring hospitalization. The number of exacerbations per year was projected to grow from 90.8 million (95% CrI 65.7 million-121.3 million) in 2020 to 107.4 million (95% CrI 78.9 million-142.2 million) in 2039 (Appendix Fig. 2A in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002). The 20-year cumulative number of excess deaths due to COPD was projected to be 3.9 million (95% CrI 3.3 million-4.7 million). The number of excess deaths due to COPD per year was estimated at 131.7 thousand (95% CrI 109.7 thousand-155.5 thousand) in 2020 and projected to increase to 275.7 thousand (95% CrI 228.8 thousand-327.8 thousand) in 2039 (Appendix Fig. 2B in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002).

      COPD-Attributable Losses of QALYs

      Both the discounted and the undiscounted health and economic burden of COPD over 20 years are presented in Table 2. The discounted 20-year total COPD-attributable losses of QALYs were projected to be 253.6 million (95% CrI 91.1 million-457.1 million). The annual losses of QALYs (undiscounted) attributable to mild cases were projected to increase by 12% from 8.1 million to 9.1 million over the 20-year, whereas the losses attributable to severe or very severe cases were projected to increase by 31% during the same period (from 1.9 million to 2.5 million) (Fig. 2A).
      Table 2Projected 20-year COPD-attributable losses of QALYs and costs of COPD from 2020 to 2039 in China.
      OutcomeUndiscounted 20-year total (95% CrI)Discounted 20-year total
      Annual discount rate of 5% was applied.
      (95% CrI)
      Losses of QALYs (million)393.78 (141.39-710.34)253.65 (91.09-457.12)
      Total direct costs (a + b + c) (billion USD
      2020 USD.
      )
      $4858.01 ($4226.15-$5546.99)$3113.47 ($2710.61-$3551.89)
       Direct medical costs (a + b) (billion USD
      2020 USD.
      )
      $4635.79 ($4007.33-$5313.21)$2969.68 ($2569.60-$3399.87)
      Hospitalization costs (a) (billion USD
      2020 USD.
      )
      $3526.43 ($2988.33-$4112.89)$2267.25 ($1922.86-$2641.47)
      Outpatient costs (b) (billion USD
      2020 USD.
      )
      $1109.36 ($887.94-$1364.14)$702.43 ($562.55-$862.79)
       Direct nonmedical costs (c) (billion USD
      2020 USD.
      )
      $222.22 ($188.97-$259.35)$143.79 ($122.39-$167.69)
      Indirect costs (billion USD
      2020 USD.
      )
      $570.24 ($460.72-$699.50)$360.47 ($291.35-$442.07)
      CrI indicates credible interval; COPD, chronic obstructive pulmonary disease; QALY, quality-adjusted life-year; USD, US dollars.
      Annual discount rate of 5% was applied.
      2020 USD.
      Figure thumbnail gr2
      Figure 2Trends of projected COPD-attributable losses of QALYs (A) and direct costs of COPD (B) from 2020 to 2039 in China.
      COPD indicates chronic obstructive pulmonary disease; QALY, quality-adjusted life-year.

      Direct and Indirect Costs of COPD

      The discounted 20-year total direct costs were projected to be $3.1 trillion (95% CrI $2.7 trillion-$3.6 trillion), of which $3.0 trillion (95% CrI $2.6 trillion-$3.4 trillion) were the direct medical costs (Table 2). The expenditures attributable to hospitalizations accounted for 73% ($2.3 trillion) of the total direct costs. The discounted 20-year total indirect costs were estimated to be $360.5 billion (95% CrI $291.4 billion-$442.1 billion). The trend of the annual direct costs (undiscounted) over time is presented in Figure 2B. The direct costs attributable to mild COPD were projected to increase by 20% over the 20 years (from $72.4 billion in 2020 to $86.8 billion in 2039), whereas the direct costs attributable to severe or very severe COPD were to increase by 37% during the same period (from $29.1 billion to $39.8 billion). The 20-year trends for other cost subcategories are provided in Supplemental Materials (Appendix Figs. 3-7 in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002).

      Subgroup Analyses

      The discounted total COPD-attributable losses of QALYs over the 20 years were estimated to be 175.9 million in males (112.2 million in urban areas and 63.7 million in rural areas) and 77.7 million in females (52.1 million in urban areas and 25.6 million in rural areas). The burden was the highest for people aged 50 to 59 years accounting for 29% of the total losses of QALYs (see Table 3 for all subgroup-specific estimates).
      Table 3Subgroup-specific projections of COPD-attributable losses of QALYs (discounted), number of COPD exacerbations, and number of excess deaths due to COPD in China from 2020 to 2039.
      MaleFemale
      AgeUrbanRuralAgeUrbanRural
      20-year total COPD-attributable losses of QALYs in million (95% CrI)
      40-4931.77 (10.48-59.38)16.97 (6.04-30.71)40-4913.77 (4.31-26.22)6.38 (1.93-11.98)
      50-5932.88 (11.66-58.98)19.02 (7.30-33.62)50-5914.34 (4.79-26.69)7.17 (2.33-13.27)
      60-6927.35 (9.43-50.12)15.85 (5.75-28.28)60-6912.67 (4.04-23.84)6.36 (2.04-11.89)
      70-7915.22 (5.60-27.16)9.04 (3.50-15.74)70-797.89 (2.82-14.52)4.06 (1.40-7.42)
      ≥805.00 (1.84-8.92)2.81 (1.09-4.90)≥ 803.42 (1.22-6.30)1.67 (0.57-3.05)
      20-year total number of COPD exacerbations (severe and nonsevere) in million (95% CrI)
      40-49253.38 (184.78-347.4)126.98 (90.25-174.29)40-49107.77 (72.48-150.58)46.69 (30.40-66.64)
      50-59260.28(194.68-351.58)141.03 (101.71-189.63)50-59110.55 (74.96-154.40)51.62 (33.95-73.35)
      60-69227.34 (169.21-306.27)123.16 (89.65-166.17)60-69103.30 (70.83-142.44)48.28 (32.00-68.05)
      70-79132.70 (103.12-172.00)73.96 (56.40-96.30)70-7966.73 (46.81-90.85)32.11 (22.03-44.28)
      ≥8045.04 (35.00-58.38)23.70 (18.08-30.86)≥ 8029.88 (20.96-40.69)13.58 (9.31-18.73)
      20-year total number of excess deaths due to COPD in thousand (95% CrI)
      40-4923.02 (18.62-27.78)11.77 (9.53-14.21)40-492.80 (2.16-3.59)1.19 (0.92-1.51)
      50-59114.5 (92.64-138.29)63.36 (51.38-76.49)50-5914.29 (11.05-18.17)6.57 (5.05-8.28)
      60-69286.59 (232.54-345.85)157.98 (128.59-190.61)60-6940.48 (31.41-51.33)18.58 (14.27-23.45)
      70-79909.62 (739.91-1097.33)514.50 (419.60-621.45)70-79166.18 (129.33-210.17)78.72 (61.10-98.47)
      ≥80777.50 (632.44-937.95)414.94 (338.40-501.19)≥80232.2 (180.67-293.53)103.85 (80.62-129.93)
      CrI indicates credible interval; COPD, chronic obstructive pulmonary disease; QALY, quality-adjusted life-year.
      The discounted total direct costs over the 20 years were $2.2 trillion in males and $0.9 trillion in females. Among male subgroups, urban residents were estimated to incur $1.6 trillion (72%), and rural residents $0.6 trillion (28%) over the 20 years. Similarly, among female subgroups, the discounted 20-year total direct costs were estimated to be $0.7 trillion in urban areas and $0.2 trillion in rural areas (25%). The direct cost burden was highest for those aged 50 to 59 years, accounting for 29% of the total burden, among all age groups. The 20-year total indirect costs were estimated to be $247.2 billion in males ($238.5 billion in urban areas and $8.7 billion in rural areas) and $113.3 billion in females ($109.8 billion in urban areas and $3.5 billion in rural areas). Twenty-eight percent of the total indirect cost burden was projected to be incurred by people aged 50 to 59 years (see Table 4 for all subgroup-specific estimates).
      Table 4Subgroup-specific projections of direct and indirect costs of COPD (discounted) in China from 2020 to 2039.
      MaleFemale
      AgeUrbanRuralAgeUrbanRural
      20-year total direct costs of COPD in billion (2020 USD) (95% CrI)
      Annual discount rate of 5% was applied.
      40-49$434.85 ($361.54-$526.06)$160.11 ($130.44-$194.10)40-49$183.25 ($142.34-$232.13)$57.69 ($44.45-$73.58)
      50-59$455.83 ($378.56-$552.12)$183.48 ($149.08-$222.16)50-59$190.88 ($148.30-$241.35)$65.10 ($50.08-$82.95)
      60-69$380.40 ($316.19-$459.37)$152.94 ($124.94-$184.88)60-69$170.78 ($133.39-$215.54)$58.47 ($44.87-$74.58)
      70-79$218.30 ($181.57-$264.1)$91.35 ($74.77-$111.01)70-79$108.54 ($85.45-$136.28)$38.47 ($29.74-$48.95)
      ≥80$71.73 ($59.66-$86.78)$28.41 ($23.25-$34.53)≥80$47.08 ($37.06-$59.11)$15.81 ($12.22-$20.12)
      20-year total indirect costs of COPD in billion (2020 USD) (95% CrI)
      Annual discount rate of 5% was applied.
      40-49$68.02 ($53.56-$84.80)$2.33 ($1.80-$2.88)40-49$29.09 ($21.59-$37.48)$0.86 ($0.65-$1.14)
      50-59$69.01 ($54.48-$86.12)$2.56 ($1.99-$3.17)50-59$29.80 ($22.35-$38.43)$0.95 ($0.72-$1.25)
      60-69$58.68 ($46.65-$73.09)$2.18 ($1.70-$2.70)60-69$26.97 ($20.25-$34.60)$0.86 ($0.65-$1.13)
      70-79$32.20 ($25.50-$40.11)$1.23 ($0.96-$1.52)70-79$16.72 ($12.50-$21.37)$0.55 ($0.42-$0.72)
      ≥80$10.58 ($8.38-$13.18)$0.38 ($0.30-$0.47)≥80$7.25 ($5.42-$9.27)$0.23 ($0.17-$0.30)
      CrI indicates credible interval; COPD, chronic obstructive pulmonary disease; USD, US dollars.
      Annual discount rate of 5% was applied.

      Sensitivity Analyses

      With an annual discount rate of 3% applied to the future losses of QALYs and cost outcomes, the 20-year total COPD-attributable losses of QALYs were estimated to be 298.9 million (95% CrI 107.3 million-538.8 million). The 20-year total direct and indirect costs were estimated to be $3.7 trillion (95% CrI $3.2 trillion-$4.2 trillion) and $427.9 billion (95% CrI $345.8 billion-$524.9 billion), respectively, using the 3% discount rate (see Appendix Table 1 in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002 for the results for other outcomes). The projections for 10-year and 30-year time horizons are presented in Appendix Tables 2 and 3 in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002.

      Scenario Analysis

      In the scenario analysis, where we assumed the full implementation of the World Health Organization FCTC-recommended policy actions, the smoking prevalence was projected to decline by 40% in males and 51% in females by 2039 compared with the 2020 levels. The number of excess deaths due to COPD was projected to be 3.4 million, which is a reduction of 13.9% from the base case estimate (See Appendix Fig. 8 in Supplemental Materials found at https://dx.doi.org/10.1016/j.vhri.2022.06.002 for the annual trend). The 20-year cumulative number of exacerbations was projected to be 1.9 billion, a 5% reduction from the base case estimate. The discounted 20-year total COPD-attributable losses of QALYs were projected to be 246.8 million (a reduction of 3% or 6.9 million). The discounted 20-year total direct costs were projected to be $3.0 trillion, a reduction of $158.2 billion (5.1%) from the base case estimate. The discounted 20-year total indirect costs were projected to be $343.0 billion, a reduction of $17.4 billion (4.8%) from the base case estimate.

      Discussion

      This study projected the health and economic burden of COPD in China from 2020 to 2039 based on the currently observed or projected patterns of the disease prevalence and progression, and changes in the key demographic characteristics of the population. Our simulation model showed that the number of COPD patients was projected to increase from 88.3 million in 2020 to 103.3 million in 2039, with a steeper rate of increase in the number of severe or very severe cases relative to mild or moderate cases. The projected number of excess deaths due to COPD and the COPD-attributable losses of QALYs (discounted) over the 20 years were estimated to be 3.9 million and 253.6 million, respectively. The discounted 20-year direct and indirect costs of COPD were, respectively, projected to be $3.1 trillion and $360.5 billion. Across all demographic subgroups, the health and economic burden was projected to be higher in males and urban residential areas.
      We simulated the disease burden with our model for a scenario where comprehensive tobacco control policy actions are fully implemented in China. Our simulation results showed that there would be a 14% reduction in the excess deaths due to COPD and approximately a 5% reduction in the discounted direct and indirect COPD costs by 2039. The projected reductions in the future disease burden shows the magnitude of potential return on investment for the comprehensive tobacco control policy actions. Nevertheless, our findings also suggest that the burden of COPD in China would be still high even after the prevalence of smoking has declined significantly. Additional measures to modify other risk factors in combination with cost-effective interventions to diagnose and treat COPD early in clinical settings can further help reduce the forthcoming burden of the disease.
      The burden of COPD in China has grown at an alarmingly rapid pace. A 2017 study by Chan et al
      • Chan K.Y.
      • Li X.
      • Chen W.
      • et al.
      Prevalence of chronic obstructive pulmonary disease (COPD) in China in 1990 and 2010.
      conducted a time trend analysis and found that the number of COPD patients in China increased by 67% between 1990 and 2010 (30.9 million to 51.5 million). Another study by Yin et al
      • Yin P.
      • Wang H.
      • Vos T.
      • et al.
      A subnational analysis of mortality and prevalence of COPD in China from 1990 to 2013.
      used the GBD framework and provided similar estimates for the growth of COPD cases in China. Recent studies pointed to a high COPD prevalence in China of 13.6%,
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      • Wang C.
      • Xu J.
      • Yang L.
      • et al.
      Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.
      which is an increase of approximately 5 percentage points from the prevalence estimate from the previous decade.
      • Zhong N.
      • Wang C.
      • Yao W.
      • et al.
      Prevalence of chronic obstructive pulmonary disease in China: a large, population-based survey [published correction appears in Am J Respir Crit Care Med. 2007;176(11):1169].
      A 2011 survey of COPD patients in major urban areas in China estimated the direct and the indirect costs of COPD to be, respectively, $31.7 billion and $5.3 billion (in 2011 US dollars).
      • Chen X.
      • Wang N.
      • Chen Y.
      • Xiao T.
      • Fu C.
      • Xu B.
      Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities.
      Fang et al
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      estimated the number of patients with COPD and the total annual costs of COPD in China to be, respectively, 77.2 million and $151.6 to $266.3 billion, using the 2010 population size (568 million adults aged 40 years or older) and the COPD prevalence rate from a 2015 survey (13.6%). Compared to the old estimates, our annual estimates were substantially higher, suggesting a continuing trend of increase in the burden of COPD.
      For the purpose of validation, when we used the same input parameters deployed by Fang et al
      • Fang L.
      • Gao P.
      • Bao H.
      • et al.
      Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
      in their study (eg, the 2010 population size and the 2015 prevalence rates in China), our model, which is more complex in nature, generated comparable estimates for the number of COPD cases and the direct costs of COPD.
      Our study has several strengths. To the best of our knowledge, it is the first study to project the long-term health and economic burden of COPD in China accounting for the population growth and changes in the demographic structure of the poulation over time. Our model is also the first dynamic open-cohort simulation model of COPD in China and can project the burden of disease for different population subgroups, reflecting subgroup-specific disease prevalence, severity distributions, and mortality, which provides information for policy decision making at the subgroup level. Our subgroup-specific projections quantified the heterogeneity in the disease burden across subgroups and may enable prioritizing subgroups for relevant policy decision making to reduce the burden. This is particularly important when the budget and resources are limited. In such circumstances, quantifying subgroups that can benefit the most from available resources helps with the efficient use of available budgets in optimizing societal health. For example, given that the smoking prevalence is higher in males, tobacco control interventions might contribute to reducing the disease burden in males to a greater extent. We also see from the sex-specific estimates that the disease burden in females was projected to be still substantial despite the smoking prevalence is significantly lower among females (50.4% in males vs 1.9% in females in 2020). This suggests the need for policy interventions on other modifiable risk factors such as air pollution or biomass fuel use to further reduce the disease burden. Our urban and rural projections of outcomes may also provide major implications for the health care system in China, given there are distinct health care systems in urban and rural areas that include separate health insurance programs and health care delivery systems.
      • Zhang C.
      • Lei X.
      • Strauss J.
      • Zhao Y.
      Health insurance and health care among the mid-aged and older Chinese: evidence from the national baseline survey of CHARLS: health insurance and health care among the mid-aged and older.
      Another strength of our study is the use of QALYs in quantifying the health burden. Although multiple previous studies used the GBD framework and estimated the COPD-attributable disability-adjusted life-years or age-standardized mortality,
      • Yin P.
      • Wang H.
      • Vos T.
      • et al.
      A subnational analysis of mortality and prevalence of COPD in China from 1990 to 2013.
      ,
      • Zhou M.
      • Wang H.
      • Zhu J.
      • et al.
      Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013.
      there is limited evidence on the long-term health burden of COPD in terms of QALYs. The QALYs can be a valuable metric and particularly important, as a growing body of economic evaluation literature in China has started to use QALYs as a measure of health for cost-effective budget allocations in recent years.
      • Butt T.
      • Liu G.G.
      • Kim D.D.
      • Neumann P.J.
      Taking stock of cost-effectiveness analysis of healthcare in China.
      In addition to QALYs, our model is capable to quantify other relevant clinical and epidemiological endpoints such as mortality and exacerbations.
      The major limitation of our study is that we did not have data to model future changes in the COPD prevalence, and our projections are based on the recent observed prevalence estimates. Although our model captures the population growth, changes in the demographic structures of the population, smoking prevalence, and disease progression over time, we did not have sufficient data to model other factors that may contribute to changes in the prevalence of disease. In addition, we only modeled input costs and health-state utility estimates as a function of underlying GOLD severity grades as suggested by previous studies.
      • Zafari Z.
      • Li S.
      • Eakin M.N.
      • Bellanger M.
      • Reed R.M.
      Projecting long-term health and economic burden of COPD in the United States.
      • Zafari Z.
      • Thorlund K.
      • FitzGerald J.M.
      • Marra C.A.
      • Sadatsafavi M.
      Network vs. pairwise meta-analyses: a case study of the impact of an evidence-synthesis paradigm on value of information outcomes.

      Conclusion

      The health and economic burden of COPD in China is projected to rise in the coming years taking heavy toll on the society and the health care system. The implementation of cost-effective strategies for the prevention of disease is necessary to mitigate the forthcoming burden of disease. Future research is needed to investigate the relative impacts of preventive strategies targeting different modifiable risk factors. In addition, early management of COPD can be instrumental in preventing the exacerbations and hospitalizations, particularly for patients with mild to moderate COPD when the lung function has not yet been lost significantly.
      • Zafari Z.
      • Sin D.D.
      • Postma D.S.
      • et al.
      Individualized prediction of lung-function decline in chronic obstructive pulmonary disease.
      • Zafari Z.
      • Lee T.Y.
      • Sadatsafavi M.
      External validation of lung function predictions in real-world cohorts of COPD.
      For patients with severe COPD, there have been recent advancements in therapeutic options, for instance, the introduction of triple therapies combining inhaled corticosteroids, long-acting β2-agonists, and long-acting muscarinic antagonists that are recommended for patients experiencing severe COPD exacerbations.

      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global initiative for chronic obstructive lung disease (2021 report). Global Initiative for Chronic Obstructive Lung Disease. https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf. Accessed February 23, 2021.

      Future studies should investigate the trade-offs between the higher relative costs of the novel therapeutic options and future reductions in health care resource use associated with these treatments for the management of severe COPD.

      Article and Author Information

      Author Contributions: Concept and design: Park, Ho, Liu, Alfonso-Cristancho, Ismaila, Zafari
      Acquisition of data: Park, Zhang, Ismaila, Zafari
      Analysis and interpretation of data: Park, Zhang, Ho, Liu, Alfonso-Cristancho, Ismaila, Zafari
      Drafting of the manuscript: Park, Alfonso-Cristancho, Ismaila, Zafari
      Critical revision of the paper for important intellectual content: Park, Zhang, Ho, Alfonso-Cristancho, Ismaila, Zafari
      Statistical analysis: Park, Zafari
      Provision of study materials or patients: Ismaila, Zafari
      Obtaining funding: Zafari
      Administrative, technical, or logistic support: Ismaila, Zafari
      Supervision: Zafari
      Conflict of Interest Disclosures: Drs Ho, Liu, Alfonso-Cristancho, and Ismaila are employees of and own stock in GlaxoSmithKline. No other disclosures were reported.
      Funding/Support: This work was supported by a research grant from GlaxoSmithKline to Dr Zafar Zafari and the University of Maryland School of Pharmacy.
      Role of the Funder/Sponsor: The funder was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

      Acknowledgment

      Medical writing support was provided by Tony Reardon of Aura, a division of Spirit Medical Communications Group Ltd, and funded by GlaxoSmithKline.

      Supplemental Materials

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