Chronic Obstructive Pulmonary Disease (COPD): Mortality Trends and Epidemiological Analysis (1999–2020)

Chronic Obstructive Pulmonary Disease (COPD): Mortality Trends and Epidemiological Analysis (1999–2020) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Chronic Obstructive Pulmonary Disease (COPD): Mortality Trends and Epidemiological Analysis (1999–2020) Maheen Sheraz, Arun Kumar Maloth, Javeria Nawaz, Iqra Khan, Abdullah Afridi, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7054383/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of morbidity and mortality globally. Despite medical advancements, it continues to impose a significant burden on healthcare systems due to its complex pathophysiology and increasing prevalence. Methods: This study utilized de-identified mortality data from the CDC WONDER database spanning 1999 to 2020, focusing on individuals aged 25 and older. COPD-related deaths were identified using ICD-10 codes (J44.0, J44.1, J44.8, J44.9), including both underlying and contributing causes of death. Age-adjusted mortality rates (AAMRs), crude mortality rates, and annual percent changes (APCs) were calculated and stratified by sex, race/ethnicity, and geographic region using the Joinpoint Regression Program. Results: Between 1999 and 2020, a total of 5,481,686 COPD-related deaths were recorded among U.S. adults aged ≥25 years, with an overall AAMR remaining stable (1999: 118.986; 2020: 119.207; APC: –0.152, 95% CI: –0.292 to –0.013). Males exhibited higher mortality (AAMR: 142.087) than females (AAMR: 96.393), with divergent trends (APC: –0.881 vs. 0.374). Among Hispanics, AAMR declined until 2018 (APC: –1.39) but rose sharply in 2020 (APC: 7.887). In non-Hispanic groups, AI/AN and Black populations showed increasing trends, while API experienced a decline (APC: –1.98); the White population had the highest overall AAMR. Regional disparities were evident: AAMRs rose in the Midwest and South (APC: 0.266 and 0.27) but declined in the Northeast and West (APC: –0.887 and –0.953). Rural areas had a consistently higher AAMR (145.56) than urban areas (107.579), with opposing trends (APC: 0.711 vs. –0.383). State-level variation ranged from West Virginia (195.01) to Hawaii (50.04), highlighting substantial geographic heterogeneity in COPD mortality. Conclusion: COPD mortality rates remained largely unchanged from 1999-2020, with persistent disparities affecting men, racially and ethnically diverse populations, rurual residents, and those in Midwest and South. Addressing these gaps require targeted prevention, improved access to care, and integrated public health strategies. Figures Figure 1 Figure 2 Figure 3 Figure 4 1 | Introduction Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial respiratory disorder characterized by significant morbidity and mortality(1). Despite advances in medical understanding, it continues to pose substantial challenges to public health surveillance and clinical management. The disease’s complexity, involving chronic inflammation and progressive airflow limitation, presents diagnostic and therapeutic challenges for clinicians and researchers(1). The interplay of genetic, environmental, and immunological factors in COPD creates a dynamic medical landscape that requires sophisticated epidemiological analysis to understand its underlying mechanisms and progression. COPD represents a pronounced public health concern, marked by persistent respiratory symptoms, reduced lung function, and progressive decline in quality of life(2). Global epidemiological data indicate that COPD is projected to become the third leading cause of death worldwide by 2030 (3). The disease's multifactorial nature—primarily driven by chronic inflammatory responses to noxious particles or gases, such as tobacco smoke or air pollutants—poses significant obstacles in prevention, early detection, and management. Mortality trend analyses provide crucial insights into the evolving nature of COPD, offering valuable information for public health planning and resource allocation. Previous research has highlighted the substantial economic and healthcare burden associated with COPD, with estimated annual costs in the United States reaching billions of dollars (4). The long-term consequences extend beyond immediate medical interventions, potentially impacting patients’ quality of life, functional capacity, and overall healthcare utilization (5). This comprehensive study aims to conduct a detailed 24-year trend analysis of mortality from COPD in the United States. By examining demographic variations, temporal trends, and potential underlying factors contributing to mortality, we seek to provide critical insights that can inform public health policies, clinical interventions, and future research directions. Our analysis will explore potential correlations between environmental changes, healthcare access, and mortality trends, offering a nuanced understanding of this complex respiratory disease. 2 | Methods 2.1 | Study Setting and Population In this study, death certificate data were obtained from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database. Data were examined for Chronic Obstructive Pulmonary Disease (COPD)-related mortality from 1999 to 2020 in individuals aged 25 years and older, using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes: J44.0, J44.1, J44.8, and J44.9. The data set includes cause of death information derived from death certificates filed across all 50 U.S. states and the District of Columbia. The Multiple Cause-of-Death Public Use records were used to identify COPD-related deaths, defined as those where COPD was listed as either the underlying or a contributing cause of death. As the data are publicly available and de-identified, the study was exempt from Institutional Review Board (IRB) review. This analysis adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. 2.2 | Data Abstraction Data on COPD-related mortality in adults aged 25 and above were extracted from the CDC WONDER database for the period January 1999 to December 2020. Abstracted data included mortality counts, age-adjusted and crude mortality rates, and demographic variables such as sex, race/ethnicity, and geographic location. Race and ethnicity were categorized as: Non-Hispanic White, Non-Hispanic Black or African American, Hispanic or Latino, Non-Hispanic American Indian or Alaska Native, and Non-Hispanic Asian or Pacific Islander. These classifications are based on the U.S. Office of Management and Budget (OMB) guidelines and have been used in prior CDC reports. Urban-rural geographic status was defined using the National Center for Health Statistics Urban-Rural Classification Scheme (6), which categorizes counties as metropolitan (≥ 50,000 population, including large metro areas ≥ 1 million) or non-metropolitan (< 50,000 population) (7). Data were further stratified by U.S. Census Bureau regions: Northeast, Midwest, South, and West(8). 2.3 | Data Synthesis Age-adjusted mortality rates (AAMRs) and crude mortality rates (per 1,000,000 persons) were calculated using the 2000 U.S. standard population for normalization. These rates were stratified by year, age group, sex, race/ethnicity, and geographic region. To assess temporal trends, Annual Percent Change (APC) was computed using the Joinpoint Regression Program (version 5.0, National Cancer Institute), which employs log-linear regression models to identify statistically significant trend changes over time (9). The Monte Carlo permutation test was used to estimate APCs and 95% confidence intervals (CIs). Crude mortality rates were calculated by dividing the total number of COPD-related deaths by the respective U.S. population for that year. A p-value < 0.05 was considered statistically significant, indicating a meaningful upward or downward trend in mortality over the study period. 3 | Results Between 1999 and 2020, a total of 5,481,686 deaths due to Chronic Obstructive Pulmonary Disease (COPD) with acute lower respiratory infection were recorded in a population of 4,473,854,489 adults aged 25 to 85 years and older. Among these deaths, the following distributions were noted: 33.95% occurred in inpatient medical facilities, 5.47% took place in outpatient departments or emergency rooms, 0.5% were classified as dead on arrival, 29.40% occurred at the decedent’s home, 4.75% happened in hospice facilities, and 21.81% occurred in nursing homes or long-term care settings. The remaining 3.81% were categorized as other places of death. The age-adjusted mortality rate (AAMR) showed minimal change during this period. In 1999, the overall AAMR was 118.986 (95% CI: 118.447-119.495). By 2020, this rate had increased slightly to 119.207 (95% CI: 118.793–119.21), resulting in an average annual percent change (APC) of -0.152 (95% CI: -0.292 to -0.013). (supplementary table 2) (supplementary figure A) 3.1 | Gender-Based Mortality Trends When stratified by gender, males exhibited a higher Age-Adjusted Mortality Rate (AAMR) compared to females. The overall AAMR for females was 96.393 (95% CI: 96.277–96.509), with a total of 2,684,356 deaths. In contrast, males had an AAMR of 142.087 (95% CI: 141.918–142.256), with a total of 2,797,330 deaths. For females, the AAMR in 1999 was 91.585 (95% CI: 91.008–92.162), with a death count of 97,742. This figure increased to 102.729 (95% CI; 102.217–103.241) with a death count of 158,463. The Annual Percentage Change (APC) value for females is 0.374 (95% CI: 0.24–0.50). For males, the AAMR in 1999 was 163.796 (95% CI: 162.82–164.772), with a death count of 112,434. By 2020, this number declined to 140.93 (95% CI: 140.242–141.618), with a death count of 166,540. The APC value for males is − 0.881 (95% CI: -1.065 to -0.695). (supplementary table 1 and 3) (supplementary figure B) Figure 1 3.2 | Hispanic Population Mortality Trends Among Hispanic or Latino individuals, the age-adjusted mortality rate (AAMR) was 63.521 (95% CI: 61.674–65.369) in 1999, with a recorded death count of 4,823. This rate decreased to 48.903 (95% CI: 47.958–49.894) in 2018, corresponding to a death count of 10,732. The annual percent change (APC) during this period was − 1.39 (95% CI: -1.59–-1.18), indicating a significant decline. However, the rate increased to 57.418 (95% CI: 56.439–58.397) in 2020, with a death count of 13,785 and an APC of 7.887 (95% CI: 2.364–13.709). (supplementary table 4) (supplementary figure C) 3.3 | Non-Hispanic Population Mortality Trends In 1999, American Indian and Alaska Native populations recorded a total of 641 deaths, with an Age-Adjusted Mortality Rate (AAMR) of 94.941 (95% Confidence Interval [CI]: 87.263–102.618). By 2004, the number of deaths rose to 946, with an AAMR of 112.386 (95% CI: 104.822–119.951) and an Annual Percentage Change (APC) of 3.862 (95% CI: 0.574–7.259). In 2020, the death count increased further to 2,146, with an AAMR value of 122.448 (95% CI: 117.101–127.795) and an APC of 0.509 (95% CI: 0.105–0.914). For Asian and Pacific Islander populations, there were 1,590 deaths in 1999, resulting in an AAMR of 44.79 (95% CI: 42.507–47.072). This number climbed to 4,304 deaths by 2020, with an AAMR of 32.303 (95% CI: 31.329–33.277) and an APC of -1.98 (95% CI: -2.28 to -1.679). Black or African Americans accounted for 13,238 deaths in 1999, with an AAMR of 91.425 (95% CI: 89.854–92.997). By 2018, deaths had increased to 22,275, with an AAMR of 89.178 (95% CI: 87.973–90.383) and an APC of -0.026 (95% CI: -0.241 to 0.189). In 2020, the death count rose to 28,045, with an AAMR of 105.497 (95% CI: 104.228–106.765) and an APC of 9.2 (95% CI: 2.979–15.796). Finally, the White population experienced the highest mortality burden in 1999, with 189,297 deaths and an AAMR of 126.571 (95% CI: 126.001–127.141). By 2020, the death count had increased to 275,907, resulting in an AAMR of 134.096 (95% CI: 133.589–134.603) and an APC of 0.159 (95% CI: 0.036–0.281). (supplementary table 4) (supplementary figure C) Figure 2 3.4 | Census region mortality trends In 1999, the Age-Adjusted Mortality Rate (AAMR) for the Northeast Census Region was 105.586 (95% CI; 104.549-106.629), with a total death count of 39,638. By 2020, this rate decreased to 92.386 (95% CI; 91.536–93.236), while the total death count increased to 46,487. The Annual Percentage Change (APC) for this region was − 0.887 (95% CI; -1.038 to -0.739). For the Midwest Census Region, the AAMR in 1999 was 124.769 (95% CI; 123.704-125.834), corresponding to a death count of 52,726. In 2020, the AAMR rose to 136.859 (95% CI; 135.897–137.82), with a death count of 79,755. The APC for this region was 0.266 (95% CI; 0.095 to 0.438). In the South Census Region, the AAMR in 1999 120.945 was 120.079–121.81 with a death count of 75,102. By 2020, the AAMR increased to 132.71 (95% CI; 132-133.42), with a death count of 136,862. The APC for the South was 0.27 (95% CI; 0.128 to 0.412). Lastly, in the West Census Region, the AAMR in 1999 was 122.821 (95% CI; 121.655-123.987), with a total death count of 42,710. By 2020, this AAMR decreased to 101.638 (95% CI; 100.83-102.446), while the total death count increased to 61,899. The APC for the West indicated a decline in AAMR, at -0.953 (95% CI; -1.088 to -0.819). (supplementary table 5) (supplementary figure D) Figure 3 3.5 | Urbanization mortality trends In 1999, the Age-Adjusted Mortality Rate (AAMR) for the rural population was 135.875 (95% confidence interval; 134.682-137.068), with a total of 49,918 deaths. By 2020, the AAMR increased to 164.934 (95% CI; 163.797-166.072), accompanied by a death count of 83,168 and an Annual Percentage Change (APC) value of 0.711 (95% CI; 0.56–0.863). Overall, there were 1,362,985 deaths in the rural population due to Chronic Obstructive Pulmonary Disease (COPD), resulting in an AAMR of 145.56 (95% CI; 145.315-145.806). In 1999, the Age-Adjusted Mortality Rate (AAMR) for the urban population was 114.628 (95% Confidence Interval: 114.066-115.189), with a total death count of 160,258. By 2020, the AAMR had declined to 108.968 (95% CI: 108.529-109.407), coinciding with an increase in the death count to 241,835. The Annual Percentage Change (APC) reflects a downward trend of -0.383 (95% CI: -0.523 to -0.243). Overall, the total deaths among the urban population due to Chronic Obstructive Pulmonary Disease (COPD) reached 4,118,701, resulting in an AAMR of 107.579 (95% CI: 107.475-107.684). (supplementary table 5) (supplementary figure E and F) Figure 4 3.6 | States mortality trends States in top 90th percentile were West Virginia (195.01), followed by Oklahoma (183.26), Kentucky (178.79), Wyoming (156.64), and Tennessee (152.34). On the contrary, states in the lower 10th percentile were Massachusetts (85.17), followed by New York (83.27), Utah (74.85), District of Columbia (70.84), and Hawaii (50.04). (supplementary table 5) 4 | Discussion The focus of this research was trends in mortality due to COPD from 1999 to 2020 for adults aged 25–85 + years, analyzing 5,481,686 deaths across demographic and geographic strata. The research yielded the following significant findings: stable overall AAMR (APC: − 0.152), although the research did show significant differences by factors like gender, race/ethnicity, census region, and urbanization. Generally, men had higher mortality than women (AAMR: 142.087 vs. 96.393), and there were differing trends for the different racial/ethnic groups, with the population identifying as Hispanic and Asian showing declines, while those identified as Black or American Indian/Alaska Native showed increases. There were significant differences across regions, as the mortality trend was increasing for the Midwest and South and decreasing for the Northeast and West. Lastly, rural areas showed consistently higher rates than urban areas. This research provides valuable information for public health practice implications, particularly regarding targeting interventions for equitable health outcomes related to COPD mortality. The overall AAMR for COPD was largely unchanged from 1999 to 2020, despite past studies reporting marked declines in COPD mortality in high-income countries as a result of declining smoking rates and advances in care [ 10 ]. Our findings are congruent with the most recent research by Halpin et al. (2020), whose own findings indicate death rates may have stagnated for some subgroups potentially attributable to rising air pollutants, occupational exposures, and failure to improve managements of diseases near the end-of-life [ 11 ][ 12 ][ 13 ]. The very small decline could be indicative of competing forces at play, such as advances in treatment and overall population health being surpassed by a growing aging population, and a rise in comorbidities such as obesity and cardiovascular disease [ 14 ]. The differences seen in studies demonstrating significant declines may be owing to methodological differences or lack of control for regional variations. Therefore, we highlight that it is likely structural barriers to healthcare—such as access to spirometry and smoking prevention programs—are contributing to the stagnation seen. This matter requires further enquiry. Also, our analysis demonstrates a notable gender-based disparity in AAMRs, where males again had significantly higher AAMRs compared to females during the whole study period. Again, this gender difference is comparable with the findings reported in similar studies by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Global Burden of Disease researchers [ 10 ][ 12 ]. However, a key difference is the trajectories of their AAMRs over time in our study. Our results show a clear pattern that males had a continuous declining AAMR trend while females had an AAMR increase in the last decade starting around 2010, which fits into evolving data from international cohorts [ 11 ][ 15 ], but contrasted some regional reports [ 16 ]. The observed distinction in our study is going to relate to both biological and behavioral lifestyles. For the males, the historical gender difference reflects more smoking exposure or significant respiratory hazards in occupational settings, based on thorough meta-analyses [ 11 ][ 17 ]. The female mortality increase might relate to some delay in the expression of smoking-related damage, a loss of estrogen effect after menopause, and often being underdiagnosed for the disease as presentation may be atypical [ 15 ][ 16 ]. In addition, the rising female mortality rates after 2010 may stem from several sources: population changes in smoking behaviour inducing a narrowing sex differential, improved recognition of diagnoses in women, and improvements in mortality registration systems. Many of these patterns appear to agree with established sex-specific manifestations of COPD [ 15 ] and known gender differences in inflammatory pathways [ 17 ]. The changing environmental exposures and differences in healthcare access may also have contributed to the patterns observed in our documented cases of COPD mortality. We found significant racial and ethnic disparities in the mortality rate from COPD from 1999 to 2020. The Hispanic population initially had decreased AAMR, which we attribute to the impact of smoking cessation and tobacco reduction strategies from the Tobacco Control Act and increasing access to health care under the Affordable Care Act [ 10 ][ 18 ]. However, an increase in AAMR in 2020 likely reflects the disproportionate burden of COVID-19 among this population, and the interruption of chronic disease management and screening that many have experienced [ 19 ]. The highest increase in AAMRs was found for the American Indian/Alaska Native populations, which we suspect was brought on by higher-than-average rates of tobacco smoking, lack of access to specialty care, and the long-standing healthcare inequities stemming from decades of systemic racism faced by these populations [ 19 ]. A more steady decline of AAMR was found for the Asian/Pacific Islander population, likely due to cultural factors and lower rates of smoking, but we note that despite this improvement, the absolute number of deaths more than doubled, indicating an increasing population of those at-risk [ 20 ][ 21 ]. For the Black American population, we observed considerable stability in AAMRs until 2018 before an increase of 18.3% occurred in 2020, which could be viewed as a national success in sharing the results of years of community health and education projects, seen conversely by the roles of the COVID-19 pandemic exacerbating its impact [ 22 ][ 23 ]. From a perspective of absolute mortality burden however, we did find the highest AAMRs for the White population; yet, ultimately continued increases are seemingly paralleled by an aging population, and even rural, low-income sub-groups with continued tobacco use [ 24 ]. These findings highlight the urgent need for tailored strategies for prevention and early identification of, and care for, the impacts of COPD—race- and culturally considerate initiatives promoted by health care providers and policy makers can begin to mitigate persistent disparities [ 25 ][ 26 ]. The analysis found substantial geographic variability in COPD mortality across U.S. census regions associated with years 1999–2020. Age-adjusted mortality rates (AAMRs) for COPD were the highest on average in the Midwest and South, whereas the Northeast and West fared better during the same period. While data on COPD regional outcomes is limited, there is a burgeoning body of evidence that shows differences in mortality are influenced by many contextual, non-medical factors, including access to pulmonary specialists, variability in health care systems, and socioeconomic determinants of respiratory health [ 19 ]. Moreover, epidemiological studies have shown that regional healthcare delivery systems significantly impact outcomes for chronic respiratory diseases, especially those like COPD which require coordinated care across multiple specialties [ 27 ][ 28 ]. The Midwest’s particularly poor performance likely represents the compounded impact of higher rates of smoking among rural individuals, more occupational exposures seen in agricultural and industrial sectors, and sustained shortages of delivered pulmonary care providers [ 29 ]. The Northeast’s favorable decrease in AAMR for COPD may be attributable to adopting comprehensive tobacco control early and having more densely situated resources for specialty care in cities [ 30 ]. The findings from this analysis provide contextual detail around how the health system’s regional ecosystem and prevailing public health policies shape outcomes for chronic respiratory disease throughout the United States. The rural–urban contrast in COPD mortality is staggering. Although there were significantly fewer absolute deaths within rural populations, age-adjusted COPD mortality rates (AAMRs) in rural areas were 51% higher than in urban areas. This difference is substantial and underscores significant barriers to healthcare access in rural communities, including severe shortages of pulmonologists (e.g., 0.9 pulmonologists per 100,000 population vs. 3.7 in urban regions), a lack of pulmonary rehabilitation programs, and greater distances to tertiary hospitals where specialized respiratory services are available [ 31 ][ 14 ]. These structural barriers are superimposed onto other barriers too, including higher levels of poverty, lower health insurance coverage, and lower levels of health literacy in rural populations [ 32 ]. Urban areas experienced most (75%) of the absolute COPD deaths, consistent with population density effects, but also factors associated with the urban environment. Urban mortality patterns are likely driven by increased cumulative exposure to air pollution, increased occupational exposure in industrial areas, and neighborhood-level barriers that reduce physical activity opportunities [ 33 ][ 34 ]. Interestingly, urban areas had a modest but statistically significant decline in AAMRs (5%) throughout the study, possibly reflecting better access to preventative care and smoking cessation programs [ 35 ]. The sustained relatively higher AAMRs in rural areas, in spite of lower absolute numbers, call attention to the effects of health infrastructure coupled with higher behavioral risks as a compounding disadvantage. Compared to urban populations, rural populations demonstrated 28% higher smoking prevalence and larger exposures occupationally in agriculture and mining occupations [ 36 ]. The above evidence can be used to advocate for targeted strategies that have the time or resources to tackle these challenges within the context of both rural health care capacity and urban environmental interactions with respiratory health. 5 | Limitations This study has important limitations. First, deaths may have been misclassified as COPD deaths based on death certificate data and corresponding ICD codes due to overlapping respiratory conditions. Second, clinical details regarding the severity of disease, treatments received, vaccination status, and pathogens which influence outcomes were not available. Third, while we examined regional data, local data may reveal other inequities. Finally, we were not able to consider key social factors that would predict COPD outcomes such as income or insurance status, among other factors. Future research should integrate medical records data, social determinants of health, and environmental information in order to substantiate our findings. 6 | Conclusions In conclusion, we have found ongoing disparities in COPD mortality from 1999–2020 to show that although we have made advances in medicine, overall rates have hardly changed. Certain populations suffered higher rates of mortality, including: men, Black Americans, American Indians/Alaska Natives, residents in rural areas, areas around the US Midwest and South, etc. These population level differences highlight how we fundamentally organize our healthcare systems. Overall, we need to recommend more smoking cessation programs targeting high-risk groups and improve access to healthcare via expansion of Medicaid and communities continuing to provide pulmonary care, investigate more on environmental and occupational regulations, document better services offered to those nearing the end of life, and provide more opportunistic surveillance that combines clinical and socioeconomic data to monitor the trends associated with the burden of COPD especially since there is evidence COVID-19 is making effects on mortality. We must recognize the need for a coordinated, flexible multisectoral action plan to create fair and equitable health outcomes related to respiratory health. Abbreviations COPD Chronic Obstructive Pulmonary Disease CDC Centers for Disease Control and Prevention WONDER Wide-ranging Online Data for Epidemiologic Research ICD-10 International Classification of Diseases, 10th Revision AAMR Age-Adjusted Mortality Rate APC Annual Percent Change CI Confidence Interval AI/AN American Indian / Alaska Native API Asian / Pacific Islander IRB Institutional Review Board STROBE Strengthening the Reporting of Observational Studies in Epidemiology OMB Office of Management and Budget NCHS National Center for Health Statistics US United States GOLD Global Initiative for Chronic Obstructive Lung Disease GBD Global Burden of Disease ACA Affordable Care Act NYC New York City COVID-19 Coronavirus Disease 2019 Declarations Ethics approval and consent to participate Not applicable. This study is a CDC wonder of previously published studies, and no new human or animal subjects were involved. Consent for publication Not applicable. Availability of data and materials The data was taken from the publicly available CDC WONDER database https://wonder.cdc.gov/mcd.html. All data were obtained from this source and analyzed as part of this research. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Clinical Trial Number : Not applicable Authors' contributions MS- Data extraction and analysis , ARM- Manuscript writing, JN- supplementary material , IK- Methodology, AA- data extraction, NF- compilation and submission MHK- figure and graph creating, MZA- table formatting, KAK- review the manuscript Acknowledgements None to declare References Chronic obstructive pulmonary disease (COPD) [Internet]. [cited 2025 Jul 4]. 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Williams DR, Cooper LA. Reducing racial inequities in health: Using what we know . Int J Environ Res Public Health. 2019;16(4):606. doi:10.3390/ijerph16040606. Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and mortality among Black and White COVID-19 patients . N Engl J Med. 2020;382(26):2534–2543. doi:10.1056/NEJMsa2011686. Thun MJ, Carter BD, Feskanich D, et al. 50-year trends in smoking-related mortality in the U.S. N Engl J Med. 2013;368(4):351–364. doi:10.1056/NEJMsa1211127. Soriano JB, Polverino F, Cosio BG. What is early COPD and why is it important? Eur Respir J. 2018;52(6):1801448. doi:10.1183/13993003.01448-2018. GOLD 2023 Report. Global Strategy for Diagnosis, Management, and Prevention of COPD. https://goldcopd.org/2023-gold-report-2/ Mamary AJ, Stewart JI, Kinney GL, et al. Race and gender disparities in COPD underdiagnoses . Chronic Obstr Pulm Dis. 2018;5(3):177–184. doi:10.15326/jcopdf.5.3.2017.0145. Eberhardt MS, Ingram DD, Makuc DM, et al. Urban and Rural Health Chartbook. Health, United States, 2001. Hyattsville, MD: National Center for Health Statistics. Doogan NJ, Roberts ME, Wewers ME, et al. Geographic disparity in rural and urban smoking trends in the U.S. Prev Med. 2017;104:79–85. doi:10.1016/j.ypmed.2017.03.011. Mazurek JM, White GE, Rodman C, Schleiff PL. Farm work-related asthma among US farm operators . J Agromedicine. 2015;20(1):31–42. doi:10.1080/1059924X.2014.976729. Frieden TR, Mostashari F, Kerker BD, et al. Tobacco use levels after control measures: NYC 2002–2003 . Am J Public Health. 2005;95(6):1016–1023. doi:10.2105/AJPH.2004.058164. Goodridge D, Lawson J, Rennie D, Marciniuk D. Rural/urban differences in respiratory care in last year of life . Rural Remote Health. 2010;10(2):1349. VanderWeele TJ, Robinson WR. Causal interpretation of race in regressions . Epidemiology. 2014;25(4):473–484. doi:10.1097/EDE.0000000000000105. Additional Declarations No competing interests reported. Supplementary Files supplementarytableCOPD.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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13:45:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":136098,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOPD-related age adjusted mortality rate stratified by race in the United States\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7054383/v1/33c2142d52c2144764665c8b.png"},{"id":91870512,"identity":"d76e4714-9197-47ce-bec5-7c153ec36332","added_by":"auto","created_at":"2025-09-22 13:53:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74034,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOPD-related age adjusted mortality rate stratified by census region in the United States\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7054383/v1/d5d1615dac71db17af1b0374.png"},{"id":91871839,"identity":"69d8796f-a8f6-4e58-98dd-fe12345b791f","added_by":"auto","created_at":"2025-09-22 14:01:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":44052,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOPD-related age adjusted mortality rate stratified by urbanization in the United States\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7054383/v1/2f32c83e1eacdd5adeca5c47.png"},{"id":108559924,"identity":"f3d66474-85b3-47ab-bdc5-4578b24c2c5c","added_by":"auto","created_at":"2026-05-06 02:39:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":437569,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7054383/v1/287d3a50-a0a3-496c-80e2-d96340b43be2.pdf"},{"id":91869970,"identity":"11daa20f-633f-4563-87bd-3f49645ba4f1","added_by":"auto","created_at":"2025-09-22 13:45:29","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":872841,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytableCOPD.docx","url":"https://assets-eu.researchsquare.com/files/rs-7054383/v1/a4ac66af0d27959dad9b2527.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eChronic Obstructive Pulmonary Disease (COPD): Mortality Trends and Epidemiological Analysis (1999–2020)\u003c/p\u003e","fulltext":[{"header":"1 | Introduction","content":"\u003cp\u003eChronic obstructive pulmonary disease (COPD) is a complex, multifactorial respiratory disorder characterized by significant morbidity and mortality(1). Despite advances in medical understanding, it continues to pose substantial challenges to public health surveillance and clinical management. The disease\u0026rsquo;s complexity, involving chronic inflammation and progressive airflow limitation, presents diagnostic and therapeutic challenges for clinicians and researchers(1). The interplay of genetic, environmental, and immunological factors in COPD creates a dynamic medical landscape that requires sophisticated epidemiological analysis to understand its underlying mechanisms and progression.\u003c/p\u003e\u003cp\u003eCOPD represents a pronounced public health concern, marked by persistent respiratory symptoms, reduced lung function, and progressive decline in quality of life(2). Global epidemiological data indicate that COPD is projected to become the third leading cause of death worldwide by 2030 (3). The disease's multifactorial nature\u0026mdash;primarily driven by chronic inflammatory responses to noxious particles or gases, such as tobacco smoke or air pollutants\u0026mdash;poses significant obstacles in prevention, early detection, and management.\u003c/p\u003e\u003cp\u003eMortality trend analyses provide crucial insights into the evolving nature of COPD, offering valuable information for public health planning and resource allocation. Previous research has highlighted the substantial economic and healthcare burden associated with COPD, with estimated annual costs in the United States reaching billions of dollars (4). The long-term consequences extend beyond immediate medical interventions, potentially impacting patients\u0026rsquo; quality of life, functional capacity, and overall healthcare utilization (5).\u003c/p\u003e\u003cp\u003eThis comprehensive study aims to conduct a detailed 24-year trend analysis of mortality from COPD in the United States. By examining demographic variations, temporal trends, and potential underlying factors contributing to mortality, we seek to provide critical insights that can inform public health policies, clinical interventions, and future research directions. Our analysis will explore potential correlations between environmental changes, healthcare access, and mortality trends, offering a nuanced understanding of this complex respiratory disease.\u003c/p\u003e"},{"header":"2 | Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 | Study Setting and Population\u003c/h2\u003e\u003cp\u003eIn this study, death certificate data were obtained from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database. Data were examined for Chronic Obstructive Pulmonary Disease (COPD)-related mortality from 1999 to 2020 in individuals aged 25 years and older, using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes: J44.0, J44.1, J44.8, and J44.9. The data set includes cause of death information derived from death certificates filed across all 50 U.S. states and the District of Columbia.\u003c/p\u003e\u003cp\u003eThe Multiple Cause-of-Death Public Use records were used to identify COPD-related deaths, defined as those where COPD was listed as either the underlying or a contributing cause of death. As the data are publicly available and de-identified, the study was exempt from Institutional Review Board (IRB) review. This analysis adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 | Data Abstraction\u003c/h2\u003e\u003cp\u003eData on COPD-related mortality in adults aged 25 and above were extracted from the CDC WONDER database for the period January 1999 to December 2020. Abstracted data included mortality counts, age-adjusted and crude mortality rates, and demographic variables such as sex, race/ethnicity, and geographic location.\u003c/p\u003e\u003cp\u003eRace and ethnicity were categorized as: Non-Hispanic White, Non-Hispanic Black or African American, Hispanic or Latino, Non-Hispanic American Indian or Alaska Native, and Non-Hispanic Asian or Pacific Islander.\u003c/p\u003e\u003cp\u003eThese classifications are based on the U.S. Office of Management and Budget (OMB) guidelines and have been used in prior CDC reports. Urban-rural geographic status was defined using the National Center for Health Statistics Urban-Rural Classification Scheme (6), which categorizes counties as metropolitan (\u0026ge;\u0026thinsp;50,000 population, including large metro areas\u0026thinsp;\u0026ge;\u0026thinsp;1\u0026nbsp;million) or non-metropolitan (\u0026lt;\u0026thinsp;50,000 population) (7).\u003c/p\u003e\u003cp\u003eData were further stratified by U.S. Census Bureau regions: Northeast, Midwest, South, and West(8).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 | Data Synthesis\u003c/h2\u003e\u003cp\u003eAge-adjusted mortality rates (AAMRs) and crude mortality rates (per 1,000,000 persons) were calculated using the 2000 U.S. standard population for normalization. These rates were stratified by year, age group, sex, race/ethnicity, and geographic region.\u003c/p\u003e\u003cp\u003eTo assess temporal trends, Annual Percent Change (APC) was computed using the Joinpoint Regression Program (version 5.0, National Cancer Institute), which employs log-linear regression models to identify statistically significant trend changes over time (9). The Monte Carlo permutation test was used to estimate APCs and 95% confidence intervals (CIs).\u003c/p\u003e\u003cp\u003eCrude mortality rates were calculated by dividing the total number of COPD-related deaths by the respective U.S. population for that year. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant, indicating a meaningful upward or downward trend in mortality over the study period.\u003c/p\u003e\u003c/div\u003e"},{"header":"3 | Results","content":"\u003cp\u003eBetween 1999 and 2020, a total of 5,481,686 deaths due to Chronic Obstructive Pulmonary Disease (COPD) with acute lower respiratory infection were recorded in a population of 4,473,854,489 adults aged 25 to 85 years and older. Among these deaths, the following distributions were noted: 33.95% occurred in inpatient medical facilities, 5.47% took place in outpatient departments or emergency rooms, 0.5% were classified as dead on arrival, 29.40% occurred at the decedent\u0026rsquo;s home, 4.75% happened in hospice facilities, and 21.81% occurred in nursing homes or long-term care settings. The remaining 3.81% were categorized as other places of death.\u003c/p\u003e\u003cp\u003eThe age-adjusted mortality rate (AAMR) showed minimal change during this period. In 1999, the overall AAMR was 118.986 (95% CI: 118.447-119.495). By 2020, this rate had increased slightly to 119.207 (95% CI: 118.793\u0026ndash;119.21), resulting in an average annual percent change (APC) of -0.152 (95% CI: -0.292 to -0.013). (supplementary table 2) (supplementary figure A)\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.1 | Gender-Based Mortality Trends\u003c/h2\u003e\u003cp\u003eWhen stratified by gender, males exhibited a higher Age-Adjusted Mortality Rate (AAMR) compared to females. The overall AAMR for females was 96.393 (95% CI: 96.277\u0026ndash;96.509), with a total of 2,684,356 deaths. In contrast, males had an AAMR of 142.087 (95% CI: 141.918\u0026ndash;142.256), with a total of 2,797,330 deaths.\u003c/p\u003e\u003cp\u003eFor females, the AAMR in 1999 was 91.585 (95% CI: 91.008\u0026ndash;92.162), with a death count of 97,742. This figure increased to 102.729 (95% CI; 102.217\u0026ndash;103.241) with a death count of 158,463. The Annual Percentage Change (APC) value for females is 0.374 (95% CI: 0.24\u0026ndash;0.50).\u003c/p\u003e\u003cp\u003eFor males, the AAMR in 1999 was 163.796 (95% CI: 162.82\u0026ndash;164.772), with a death count of 112,434. By 2020, this number declined to 140.93 (95% CI: 140.242\u0026ndash;141.618), with a death count of 166,540. The APC value for males is \u0026minus;\u0026thinsp;0.881 (95% CI: -1.065 to -0.695). (supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and 3) (supplementary figure B)\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.2 | Hispanic Population Mortality Trends\u003c/h2\u003e\u003cp\u003eAmong Hispanic or Latino individuals, the age-adjusted mortality rate (AAMR) was 63.521 (95% CI: 61.674\u0026ndash;65.369) in 1999, with a recorded death count of 4,823. This rate decreased to 48.903 (95% CI: 47.958\u0026ndash;49.894) in 2018, corresponding to a death count of 10,732. The annual percent change (APC) during this period was \u0026minus;\u0026thinsp;1.39 (95% CI: -1.59\u0026ndash;-1.18), indicating a significant decline. However, the rate increased to 57.418 (95% CI: 56.439\u0026ndash;58.397) in 2020, with a death count of 13,785 and an APC of 7.887 (95% CI: 2.364\u0026ndash;13.709). (supplementary table 4) (supplementary figure C)\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.3 | Non-Hispanic Population Mortality Trends\u003c/h2\u003e\u003cp\u003eIn 1999, American Indian and Alaska Native populations recorded a total of 641 deaths, with an Age-Adjusted Mortality Rate (AAMR) of 94.941 (95% Confidence Interval [CI]: 87.263\u0026ndash;102.618). By 2004, the number of deaths rose to 946, with an AAMR of 112.386 (95% CI: 104.822\u0026ndash;119.951) and an Annual Percentage Change (APC) of 3.862 (95% CI: 0.574\u0026ndash;7.259).\u003c/p\u003e\u003cp\u003eIn 2020, the death count increased further to 2,146, with an AAMR value of 122.448 (95% CI: 117.101\u0026ndash;127.795) and an APC of 0.509 (95% CI: 0.105\u0026ndash;0.914).\u003c/p\u003e\u003cp\u003eFor Asian and Pacific Islander populations, there were 1,590 deaths in 1999, resulting in an AAMR of 44.79 (95% CI: 42.507\u0026ndash;47.072). This number climbed to 4,304 deaths by 2020, with an AAMR of 32.303 (95% CI: 31.329\u0026ndash;33.277) and an APC of -1.98 (95% CI: -2.28 to -1.679).\u003c/p\u003e\u003cp\u003eBlack or African Americans accounted for 13,238 deaths in 1999, with an AAMR of 91.425 (95% CI: 89.854\u0026ndash;92.997). By 2018, deaths had increased to 22,275, with an AAMR of 89.178 (95% CI: 87.973\u0026ndash;90.383) and an APC of -0.026 (95% CI: -0.241 to 0.189). In 2020, the death count rose to 28,045, with an AAMR of 105.497 (95% CI: 104.228\u0026ndash;106.765) and an APC of 9.2 (95% CI: 2.979\u0026ndash;15.796).\u003c/p\u003e\u003cp\u003eFinally, the White population experienced the highest mortality burden in 1999, with 189,297 deaths and an AAMR of 126.571 (95% CI: 126.001\u0026ndash;127.141). By 2020, the death count had increased to 275,907, resulting in an AAMR of 134.096 (95% CI: 133.589\u0026ndash;134.603) and an APC of 0.159 (95% CI: 0.036\u0026ndash;0.281). (supplementary table 4) (supplementary figure C)\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.4 | Census region mortality trends\u003c/h2\u003e\u003cp\u003eIn 1999, the Age-Adjusted Mortality Rate (AAMR) for the Northeast Census Region was 105.586 (95% CI; 104.549-106.629), with a total death count of 39,638. By 2020, this rate decreased to 92.386 (95% CI; 91.536\u0026ndash;93.236), while the total death count increased to 46,487. The Annual Percentage Change (APC) for this region was \u0026minus;\u0026thinsp;0.887 (95% CI; -1.038 to -0.739). For the Midwest Census Region, the AAMR in 1999 was 124.769 (95% CI; 123.704-125.834), corresponding to a death count of 52,726. In 2020, the AAMR rose to 136.859 (95% CI; 135.897\u0026ndash;137.82), with a death count of 79,755. The APC for this region was 0.266 (95% CI; 0.095 to 0.438). In the South Census Region, the AAMR in 1999 120.945 was 120.079\u0026ndash;121.81 with a death count of 75,102. By 2020, the AAMR increased to 132.71 (95% CI; 132-133.42), with a death count of 136,862. The APC for the South was 0.27 (95% CI; 0.128 to 0.412). Lastly, in the West Census Region, the AAMR in 1999 was 122.821 (95% CI; 121.655-123.987), with a total death count of 42,710. By 2020, this AAMR decreased to 101.638 (95% CI; 100.83-102.446), while the total death count increased to 61,899. The APC for the West indicated a decline in AAMR, at -0.953 (95% CI; -1.088 to -0.819). (supplementary table 5) (supplementary figure D)\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.5 | Urbanization mortality trends\u003c/h2\u003e\u003cp\u003eIn 1999, the Age-Adjusted Mortality Rate (AAMR) for the rural population was 135.875 (95% confidence interval; 134.682-137.068), with a total of 49,918 deaths. By 2020, the AAMR increased to 164.934 (95% CI; 163.797-166.072), accompanied by a death count of 83,168 and an Annual Percentage Change (APC) value of 0.711 (95% CI; 0.56\u0026ndash;0.863). Overall, there were 1,362,985 deaths in the rural population due to Chronic Obstructive Pulmonary Disease (COPD), resulting in an AAMR of 145.56 (95% CI; 145.315-145.806).\u003c/p\u003e\u003cp\u003eIn 1999, the Age-Adjusted Mortality Rate (AAMR) for the urban population was 114.628 (95% Confidence Interval: 114.066-115.189), with a total death count of 160,258. By 2020, the AAMR had declined to 108.968 (95% CI: 108.529-109.407), coinciding with an increase in the death count to 241,835. The Annual Percentage Change (APC) reflects a downward trend of -0.383 (95% CI: -0.523 to -0.243). Overall, the total deaths among the urban population due to Chronic Obstructive Pulmonary Disease (COPD) reached 4,118,701, resulting in an AAMR of 107.579 (95% CI: 107.475-107.684). (supplementary table 5) (supplementary figure E and F)\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.6 | States mortality trends\u003c/h2\u003e\u003cp\u003eStates in top 90th percentile were West Virginia (195.01), followed by Oklahoma (183.26), Kentucky (178.79), Wyoming (156.64), and Tennessee (152.34). On the contrary, states in the lower 10th percentile were Massachusetts (85.17), followed by New York (83.27), Utah (74.85), District of Columbia (70.84), and Hawaii (50.04). (supplementary table 5)\u003c/p\u003e\u003c/div\u003e"},{"header":"4 | Discussion","content":"\u003cp\u003eThe focus of this research was trends in mortality due to COPD from 1999 to 2020 for adults aged 25\u0026ndash;85\u0026thinsp;+\u0026thinsp;years, analyzing 5,481,686 deaths across demographic and geographic strata. The research yielded the following significant findings: stable overall AAMR (APC: \u0026minus;\u0026thinsp;0.152), although the research did show significant differences by factors like gender, race/ethnicity, census region, and urbanization. Generally, men had higher mortality than women (AAMR: 142.087 vs. 96.393), and there were differing trends for the different racial/ethnic groups, with the population identifying as Hispanic and Asian showing declines, while those identified as Black or American Indian/Alaska Native showed increases. There were significant differences across regions, as the mortality trend was increasing for the Midwest and South and decreasing for the Northeast and West. Lastly, rural areas showed consistently higher rates than urban areas. This research provides valuable information for public health practice implications, particularly regarding targeting interventions for equitable health outcomes related to COPD mortality.\u003c/p\u003e\u003cp\u003eThe overall AAMR for COPD was largely unchanged from 1999 to 2020, despite past studies reporting marked declines in COPD mortality in high-income countries as a result of declining smoking rates and advances in care [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Our findings are congruent with the most recent research by Halpin et al. (2020), whose own findings indicate death rates may have stagnated for some subgroups potentially attributable to rising air pollutants, occupational exposures, and failure to improve managements of diseases near the end-of-life [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e][\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The very small decline could be indicative of competing forces at play, such as advances in treatment and overall population health being surpassed by a growing aging population, and a rise in comorbidities such as obesity and cardiovascular disease [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The differences seen in studies demonstrating significant declines may be owing to methodological differences or lack of control for regional variations. Therefore, we highlight that it is likely structural barriers to healthcare\u0026mdash;such as access to spirometry and smoking prevention programs\u0026mdash;are contributing to the stagnation seen. This matter requires further enquiry.\u003c/p\u003e\u003cp\u003eAlso, our analysis demonstrates a notable gender-based disparity in AAMRs, where males again had significantly higher AAMRs compared to females during the whole study period. Again, this gender difference is comparable with the findings reported in similar studies by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Global Burden of Disease researchers [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, a key difference is the trajectories of their AAMRs over time in our study. Our results show a clear pattern that males had a continuous declining AAMR trend while females had an AAMR increase in the last decade starting around 2010, which fits into evolving data from international cohorts [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], but contrasted some regional reports [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The observed distinction in our study is going to relate to both biological and behavioral lifestyles. For the males, the historical gender difference reflects more smoking exposure or significant respiratory hazards in occupational settings, based on thorough meta-analyses [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The female mortality increase might relate to some delay in the expression of smoking-related damage, a loss of estrogen effect after menopause, and often being underdiagnosed for the disease as presentation may be atypical [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e][\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In addition, the rising female mortality rates after 2010 may stem from several sources: population changes in smoking behaviour inducing a narrowing sex differential, improved recognition of diagnoses in women, and improvements in mortality registration systems. Many of these patterns appear to agree with established sex-specific manifestations of COPD [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and known gender differences in inflammatory pathways [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The changing environmental exposures and differences in healthcare access may also have contributed to the patterns observed in our documented cases of COPD mortality.\u003c/p\u003e\u003cp\u003eWe found significant racial and ethnic disparities in the mortality rate from COPD from 1999 to 2020. The Hispanic population initially had decreased AAMR, which we attribute to the impact of smoking cessation and tobacco reduction strategies from the Tobacco Control Act and increasing access to health care under the Affordable Care Act [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, an increase in AAMR in 2020 likely reflects the disproportionate burden of COVID-19 among this population, and the interruption of chronic disease management and screening that many have experienced [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The highest increase in AAMRs was found for the American Indian/Alaska Native populations, which we suspect was brought on by higher-than-average rates of tobacco smoking, lack of access to specialty care, and the long-standing healthcare inequities stemming from decades of systemic racism faced by these populations [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. A more steady decline of AAMR was found for the Asian/Pacific Islander population, likely due to cultural factors and lower rates of smoking, but we note that despite this improvement, the absolute number of deaths more than doubled, indicating an increasing population of those at-risk [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e][\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. For the Black American population, we observed considerable stability in AAMRs until 2018 before an increase of 18.3% occurred in 2020, which could be viewed as a national success in sharing the results of years of community health and education projects, seen conversely by the roles of the COVID-19 pandemic exacerbating its impact [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e][\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. From a perspective of absolute mortality burden however, we did find the highest AAMRs for the White population; yet, ultimately continued increases are seemingly paralleled by an aging population, and even rural, low-income sub-groups with continued tobacco use [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These findings highlight the urgent need for tailored strategies for prevention and early identification of, and care for, the impacts of COPD\u0026mdash;race- and culturally considerate initiatives promoted by health care providers and policy makers can begin to mitigate persistent disparities [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e][\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe analysis found substantial geographic variability in COPD mortality across U.S. census regions associated with years 1999\u0026ndash;2020. Age-adjusted mortality rates (AAMRs) for COPD were the highest on average in the Midwest and South, whereas the Northeast and West fared better during the same period. While data on COPD regional outcomes is limited, there is a burgeoning body of evidence that shows differences in mortality are influenced by many contextual, non-medical factors, including access to pulmonary specialists, variability in health care systems, and socioeconomic determinants of respiratory health [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Moreover, epidemiological studies have shown that regional healthcare delivery systems significantly impact outcomes for chronic respiratory diseases, especially those like COPD which require coordinated care across multiple specialties [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e][\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The Midwest\u0026rsquo;s particularly poor performance likely represents the compounded impact of higher rates of smoking among rural individuals, more occupational exposures seen in agricultural and industrial sectors, and sustained shortages of delivered pulmonary care providers [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The Northeast\u0026rsquo;s favorable decrease in AAMR for COPD may be attributable to adopting comprehensive tobacco control early and having more densely situated resources for specialty care in cities [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The findings from this analysis provide contextual detail around how the health system\u0026rsquo;s regional ecosystem and prevailing public health policies shape outcomes for chronic respiratory disease throughout the United States.\u003c/p\u003e\u003cp\u003eThe rural\u0026ndash;urban contrast in COPD mortality is staggering. Although there were significantly fewer absolute deaths within rural populations, age-adjusted COPD mortality rates (AAMRs) in rural areas were 51% higher than in urban areas. This difference is substantial and underscores significant barriers to healthcare access in rural communities, including severe shortages of pulmonologists (e.g., 0.9 pulmonologists per 100,000 population vs. 3.7 in urban regions), a lack of pulmonary rehabilitation programs, and greater distances to tertiary hospitals where specialized respiratory services are available [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These structural barriers are superimposed onto other barriers too, including higher levels of poverty, lower health insurance coverage, and lower levels of health literacy in rural populations [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Urban areas experienced most (75%) of the absolute COPD deaths, consistent with population density effects, but also factors associated with the urban environment. Urban mortality patterns are likely driven by increased cumulative exposure to air pollution, increased occupational exposure in industrial areas, and neighborhood-level barriers that reduce physical activity opportunities [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e][\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Interestingly, urban areas had a modest but statistically significant decline in AAMRs (5%) throughout the study, possibly reflecting better access to preventative care and smoking cessation programs [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe sustained relatively higher AAMRs in rural areas, in spite of lower absolute numbers, call attention to the effects of health infrastructure coupled with higher behavioral risks as a compounding disadvantage. Compared to urban populations, rural populations demonstrated 28% higher smoking prevalence and larger exposures occupationally in agriculture and mining occupations [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The above evidence can be used to advocate for targeted strategies that have the time or resources to tackle these challenges within the context of both rural health care capacity and urban environmental interactions with respiratory health.\u003c/p\u003e"},{"header":"5 | Limitations","content":"\u003cp\u003eThis study has important limitations. First, deaths may have been misclassified as COPD deaths based on death certificate data and corresponding ICD codes due to overlapping respiratory conditions. Second, clinical details regarding the severity of disease, treatments received, vaccination status, and pathogens which influence outcomes were not available. Third, while we examined regional data, local data may reveal other inequities. Finally, we were not able to consider key social factors that would predict COPD outcomes such as income or insurance status, among other factors. Future research should integrate medical records data, social determinants of health, and environmental information in order to substantiate our findings.\u003c/p\u003e"},{"header":"6 | Conclusions","content":"\u003cp\u003eIn conclusion, we have found ongoing disparities in COPD mortality from 1999\u0026ndash;2020 to show that although we have made advances in medicine, overall rates have hardly changed. Certain populations suffered higher rates of mortality, including: men, Black Americans, American Indians/Alaska Natives, residents in rural areas, areas around the US Midwest and South, etc. These population level differences highlight how we fundamentally organize our healthcare systems. Overall, we need to recommend more smoking cessation programs targeting high-risk groups and improve access to healthcare via expansion of Medicaid and communities continuing to provide pulmonary care, investigate more on environmental and occupational regulations, document better services offered to those nearing the end of life, and provide more opportunistic surveillance that combines clinical and socioeconomic data to monitor the trends associated with the burden of COPD especially since there is evidence COVID-19 is making effects on mortality. We must recognize the need for a coordinated, flexible multisectoral action plan to create fair and equitable health outcomes related to respiratory health.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOPD Chronic Obstructive Pulmonary Disease\u003c/p\u003e\n\u003cp\u003eCDC Centers for Disease Control and Prevention\u003c/p\u003e\n\u003cp\u003eWONDER Wide-ranging Online Data for Epidemiologic Research\u003c/p\u003e\n\u003cp\u003eICD-10 International Classification of Diseases, 10th Revision\u003c/p\u003e\n\u003cp\u003eAAMR Age-Adjusted Mortality Rate\u003c/p\u003e\n\u003cp\u003eAPC Annual Percent Change\u003c/p\u003e\n\u003cp\u003eCI Confidence Interval\u003c/p\u003e\n\u003cp\u003eAI/AN American Indian / Alaska Native\u003c/p\u003e\n\u003cp\u003eAPI Asian / Pacific Islander\u003c/p\u003e\n\u003cp\u003eIRB Institutional Review Board\u003c/p\u003e\n\u003cp\u003eSTROBE Strengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e\n\u003cp\u003eOMB Office of Management and Budget\u003c/p\u003e\n\u003cp\u003eNCHS National Center for Health Statistics\u003c/p\u003e\n\u003cp\u003eUS United States\u003c/p\u003e\n\u003cp\u003eGOLD Global Initiative for Chronic Obstructive Lung Disease\u003c/p\u003e\n\u003cp\u003eGBD Global Burden of Disease\u003c/p\u003e\n\u003cp\u003eACA Affordable Care Act\u003c/p\u003e\n\u003cp\u003eNYC New York City\u003c/p\u003e\n\u003cp\u003eCOVID-19 Coronavirus Disease 2019\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study is a CDC wonder of previously published studies, and no new human or animal subjects were involved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data was taken from the publicly available CDC WONDER database https://wonder.cdc.gov/mcd.html. \u0026nbsp; All data were obtained from this source and analyzed as part of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMS- Data\u003c/strong\u003e \u003cstrong\u003eextraction and analysis\u003c/strong\u003e, \u003cstrong\u003eARM- Manuscript writing, JN- supplementary material\u003c/strong\u003e, \u003cstrong\u003eIK- Methodology, AA- data extraction, NF- compilation and submission\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMHK- figure and graph creating, MZA- table formatting, KAK- review the manuscript\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone to declare\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChronic obstructive pulmonary disease (COPD) [Internet]. 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Int J Chron Obstruct Pulmon Dis. 2014;9:1145\u0026ndash;1154. doi:10.2147/COPD.S54476.\u003c/li\u003e\n\u003cli\u003eMartinez FJ, Agusti A, Celli BR, et al. \u003cem\u003eTreatment trials in young patients with COPD: Time to move forward\u003c/em\u003e. Am J Respir Crit Care Med. 2022;205(3):275\u0026ndash;287. doi:10.1164/rccm.202107-1663SO.\u003c/li\u003e\n\u003cli\u003eBarnes PJ. \u003cem\u003eInflammatory mechanisms in patients with COPD\u003c/em\u003e. J Allergy Clin Immunol. 2016;138(1):16\u0026ndash;27. doi:10.1016/j.jaci.2016.05.011.\u003c/li\u003e\n\u003cli\u003eRodriguez CJ, Allison M, Daviglus ML, et al. \u003cem\u003eStatus of cardiovascular disease and stroke in Hispanics/Latinos in the U.S.\u003c/em\u003e Circulation. 2014;130(7):593\u0026ndash;625. doi:10.1161/CIR.0000000000000071.\u003c/li\u003e\n\u003cli\u003eSommers BD, Maylone B, Nguyen KH, et al. \u003cem\u003eImpact of state policies on ACA applications and enrollment\u003c/em\u003e. Health Aff. 2015;34(6):1010\u0026ndash;1018. doi:10.1377/hlthaff.2015.0215.\u003c/li\u003e\n\u003cli\u003eCroft JB, Wheaton AG, Liu Y, et al. \u003cem\u003eUrban\u0026ndash;rural differences in COPD\u0026mdash;U.S., 2015\u003c/em\u003e. MMWR Morb Mortal Wkly Rep. 2018;67(7):205\u0026ndash;211. doi:10.15585/mmwr.mm6707a1.\u003c/li\u003e\n\u003cli\u003eHan MK, Curran-Everett D, Dransfield MT, et al. \u003cem\u003eRacial differences in quality of life in COPD\u003c/em\u003e. Chest. 2011;140(5):1169\u0026ndash;1176. doi:10.1378/chest.10-2869.\u003c/li\u003e\n\u003cli\u003eWilliams DR, Cooper LA. \u003cem\u003eReducing racial inequities in health: Using what we know\u003c/em\u003e. Int J Environ Res Public Health. 2019;16(4):606. doi:10.3390/ijerph16040606.\u003c/li\u003e\n\u003cli\u003ePrice-Haywood EG, Burton J, Fort D, Seoane L. \u003cem\u003eHospitalization and mortality among Black and White COVID-19 patients\u003c/em\u003e. N Engl J Med. 2020;382(26):2534\u0026ndash;2543. doi:10.1056/NEJMsa2011686.\u003c/li\u003e\n\u003cli\u003eThun MJ, Carter BD, Feskanich D, et al. \u003cem\u003e50-year trends in smoking-related mortality in the U.S.\u003c/em\u003e N Engl J Med. 2013;368(4):351\u0026ndash;364. doi:10.1056/NEJMsa1211127.\u003c/li\u003e\n\u003cli\u003eSoriano JB, Polverino F, Cosio BG. \u003cem\u003eWhat is early COPD and why is it important?\u003c/em\u003e Eur Respir J. 2018;52(6):1801448. doi:10.1183/13993003.01448-2018.\u003c/li\u003e\n\u003cli\u003eGOLD 2023 Report. \u003cem\u003eGlobal Strategy for Diagnosis, Management, and Prevention of COPD.\u003c/em\u003ehttps://goldcopd.org/2023-gold-report-2/\u003c/li\u003e\n\u003cli\u003eMamary AJ, Stewart JI, Kinney GL, et al. \u003cem\u003eRace and gender disparities in COPD underdiagnoses\u003c/em\u003e. Chronic Obstr Pulm Dis. 2018;5(3):177\u0026ndash;184. doi:10.15326/jcopdf.5.3.2017.0145.\u003c/li\u003e\n\u003cli\u003eEberhardt MS, Ingram DD, Makuc DM, et al. \u003cem\u003eUrban and Rural Health Chartbook. Health, United States, 2001.\u003c/em\u003e Hyattsville, MD: National Center for Health Statistics.\u003c/li\u003e\n\u003cli\u003eDoogan NJ, Roberts ME, Wewers ME, et al. \u003cem\u003eGeographic disparity in rural and urban smoking trends in the U.S.\u003c/em\u003e Prev Med. 2017;104:79\u0026ndash;85. doi:10.1016/j.ypmed.2017.03.011.\u003c/li\u003e\n\u003cli\u003eMazurek JM, White GE, Rodman C, Schleiff PL. \u003cem\u003eFarm work-related asthma among US farm operators\u003c/em\u003e. J Agromedicine. 2015;20(1):31\u0026ndash;42. doi:10.1080/1059924X.2014.976729.\u003c/li\u003e\n\u003cli\u003eFrieden TR, Mostashari F, Kerker BD, et al. \u003cem\u003eTobacco use levels after control measures: NYC 2002\u0026ndash;2003\u003c/em\u003e. Am J Public Health. 2005;95(6):1016\u0026ndash;1023. doi:10.2105/AJPH.2004.058164.\u003c/li\u003e\n\u003cli\u003eGoodridge D, Lawson J, Rennie D, Marciniuk D. \u003cem\u003eRural/urban differences in respiratory care in last year of life\u003c/em\u003e. Rural Remote Health. 2010;10(2):1349.\u003c/li\u003e\n\u003cli\u003eVanderWeele TJ, Robinson WR. \u003cem\u003eCausal interpretation of race in regressions\u003c/em\u003e. Epidemiology. 2014;25(4):473\u0026ndash;484. doi:10.1097/EDE.0000000000000105.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7054383/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7054383/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of morbidity and mortality globally. Despite medical advancements, it continues to impose a significant burden on healthcare systems due to its complex pathophysiology and increasing prevalence.\u003cbr\u003e\n \u003cstrong\u003eMethods:\u003c/strong\u003e This study utilized de-identified mortality data from the CDC WONDER database spanning 1999 to 2020, focusing on individuals aged 25 and older. COPD-related deaths were identified using ICD-10 codes (J44.0, J44.1, J44.8, J44.9), including both underlying and contributing causes of death. Age-adjusted mortality rates (AAMRs), crude mortality rates, and annual percent changes (APCs) were calculated and stratified by sex, race/ethnicity, and geographic region using the Joinpoint Regression Program.\u003cbr\u003e\n\u003cstrong\u003eResults:\u003c/strong\u003e Between 1999 and 2020, a total of 5,481,686 COPD-related deaths were recorded among U.S. adults aged ≥25 years, with an overall AAMR remaining stable (1999: 118.986; 2020: 119.207; APC: –0.152, 95% CI: –0.292 to –0.013). Males exhibited higher mortality (AAMR: 142.087) than females (AAMR: 96.393), with divergent trends (APC: –0.881 vs. 0.374). Among Hispanics, AAMR declined until 2018 (APC: –1.39) but rose sharply in 2020 (APC: 7.887). In non-Hispanic groups, AI/AN and Black populations showed increasing trends, while API experienced a decline (APC: –1.98); the White population had the highest overall AAMR. Regional disparities were evident: AAMRs rose in the Midwest and South (APC: 0.266 and 0.27) but declined in the Northeast and West (APC: –0.887 and –0.953). Rural areas had a consistently higher AAMR (145.56) than urban areas (107.579), with opposing trends (APC: 0.711 vs. –0.383). State-level variation ranged from West Virginia (195.01) to Hawaii (50.04), highlighting substantial geographic heterogeneity in COPD mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e COPD mortality rates remained largely unchanged from 1999-2020, with persistent disparities affecting men, racially and ethnically diverse populations, rurual residents, and those in Midwest and South. Addressing these gaps require targeted prevention, improved access to care, and integrated public health strategies.\u003c/p\u003e","manuscriptTitle":"Chronic Obstructive Pulmonary Disease (COPD): Mortality Trends and Epidemiological Analysis (1999–2020)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 13:45:25","doi":"10.21203/rs.3.rs-7054383/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"31daf749-6ac1-4097-93a8-387f3e585ed1","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T02:39:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 13:45:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7054383","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7054383","identity":"rs-7054383","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}