Investigating sex, race, and geographic disparities in bronchus and lung cancer mortality in the United States: a comprehensive longitudinal study (1999–2020) utilizing CDC WONDER data

Background: Lung and bronchus cancer has become the leading cause of cancer-related mortality in the United States. Understanding the patterns of mortality is an absolute requirement. Methods: This study analyzed Lung and Bronchus cancer-associated mortality rates from 1999 to 2020 using death certificate data from the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs), per 100 000 people, and annual percentage change (APCs) were also calculated. Results: 3 599 577 lung and bronchus cancer-related deaths occurred in patients aged younger than 1–85+ years between 1999 and 2020. Overall AAMRs declined from 59.1 in 1999 to 58.9 in 2001 (APC: −0.1364) then to 55.9 in 2005 (APC: −1.4388*) 50.5 by 2010 (APC: −2.0574*) 44.7 by 2014 (APC: −2.9497*) and 35.1 by 2020 (APC: −4.1040*). Men had higher AAMRs than women (overall AAMR men: 61.7 vs. women: 38.3). AAMRs were highest among non-Hispanic (NH) Black or African American (52.7) patients followed by NH White (51.8), NH American Indian or Alaska Native (38.6), NH Asian or Pacific Islander (24.7) and Hispanic or Latino race (20.2). AAMRs varied in region (overall AAMR; South: 52.4; Midwest: 52.3; Northeast: 46.3; West: 39.1). Non-metropolitan areas had a higher AAMR (55.9) as compared to metropolitan areas (46.7). The top 90th percentile states of Lung and Bronchus cancer AAMR were Arkansas, Kentucky, Mississippi, Tennessee, and West Virginia. Conclusion: An overall decreasing trend in AAMRs for lung and bronchus cancer was seen. Public health measures to regulate risk factors and precipitating events are needed.


Introduction
Cancer ranks as the second leading cause of mortality in the United States and is the primary cause of death among individuals under 85 years of age.The COVID-19 pandemic in 2019 led to setbacks in cancer detection and treatment due to closures in healthcare facilities, disruptions in employment and health insurance, and concerns about exposure to COVID-19.The longterm impact of these delays on cancer diagnosis at advanced stages and subsequent mortality rates will be understood

HIGHLIGHTS
• Trends in bronchus and lung cancer mortality: The study reveals a significant and consistent decrease in bronchus and lung cancer mortality rates over the course of two decades, from 1999 to 2020.• Sex disparities: Men consistently experienced higher ageadjusted mortality rates (AAMRs) compared to women, highlighting sex disparities in bronchus and lung cancer mortality.• Racial and ethnic variations: NH Black or African American individuals had the highest AAMRs among different racial and ethnic groups, followed by NH White, NH American Indian or Alaska Natives, NH Asian or Pacific Islanders and Hispanics populations.• Geographic disparities: The study found significant variations in AAMRs across different regions of the United States, with the South having the highest AAMRs, followed by the Midwest, Northeast, and Western regions.• Urban vs. non-metropolitan discrepancies: Non-metropolitan regions were shown to have higher AAMR values than metropolitan areas.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
gradually over several years.Projections for 2024 anticipate 2 001 140 new cancer cases and 611 720 cancer-related deaths in the United States.Lung cancer stands out as the primary cause of cancer-related mortality in the United States, representing approximately one-fifth of all cancer deaths.Annually, the number of lung cancer deaths surpasses the combined total of deaths from colon, breast, and prostate cancers.About 340 individuals succumb to lung cancer daily, a figure nearly 2.5 times higher than the number of deaths from colorectal cancer, which ranks second in cancer-related mortalities.It is estimated that around 81% of the 125 070 lung cancer deaths projected for 2024 will directly result from cigarette smoking, with an additional 3500 deaths attributed to exposure to second-hand smoke.
If classified separately, the ~20 300 lung cancer deaths not linked to smoking would rank as the eighth leading cause of cancer death across sexes [1][2][3] .The occurrence of lung cancer has shown a consistent decrease since 2006, with a yearly decline of 2.5% in men and 1% in women.This decline commenced later in women and has been less rapid compared to men, likely due to a delayed and slower decline in smoking habits among women, including increases in smoking prevalence among certain birth cohorts [1,4,5] .Understanding the demographic and regional patterns of mortality related to lung and bronchus malignant neoplasms is crucial for identifying high-risk populations and delivering targeted interventions promptly.Thus, we aimed to assess the demographic and regional variances in lung and bronchus malignant neoplasm mortality among U.S. adults from 1999 to 2020.

Study setting and population
To ascertain the mortality rates attributed to Lung and Bronchus cancer the following study made use of Previous studies have also made use of such an age range in patient categorization [6][7][8] .In addition, a sensitivity analysis considering neoplasms (C00-D48) as the underlying cause of death in the background of Lung and Bronchus cancer-related mortality was also carried out.This study complied with STROBE guidelines and since it utilized de-identified, government-released public use data, no regional institutional review board approval was required.

Data abstraction
Population size, year, location of death, demographics, geographic division, state state-specific data in addition to urban and rural classification included in the data abstracted.Location of death included homes, hospices, nursing homes, long-term care facilities, and hospitals with demographics referring to age, sex, and race or ethnicity.Furthermore, race was stratified into two types non-Hispanics (NH), defined as individuals who do not have ancestral ties to Spanish-speaking countries, particularly those in Latin America; and Latino or Hispanic, which is defined as a person of Cuban, Mexican, or Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.Additionally, the NH race was further sub-grouped into NH White people, NH Black or African American people, NH American Indians or Alaska Native people, and NH Asian or Pacific Island people.The data utilized in the analysis was death certificate reported information and has also been a source for earlier research using the aforementioned database [9] .The National Center for Health Statistics Urban-Rural Classification Scheme was used to divide the population into categories of urban and rural regions according to the 2013 U.S. Census [10] .Urban areas were subdivided into medium/small metropolitan areas, which had a population between 50 000 and 999 999, and large metropolitan areas, which had a population of one million or more.Rural regions were defined as having less than 50 000 people.Categorization of geographical areas into the Northeast, Midwest, South, and West regions was done via the United States Census Bureau's criteria [11] .

Statistical analysis
Trends in Lung and Bronchus Cancer-related mortality were analyzed by calculating mortality rates per 100 000 of the population for both age-adjusted and crude data, along with their respective 95% CIs, during the 1999-2020 period, categorizing them according to year, sex, race/ethnicity, state, urban/rural status.
In the calculation of crude mortality rates, the total number of deaths corresponding to Lung and Bronchus Cancer in a year was divided by the population for that year.For age-adjusted mortality rates (AAMR) calculations, Lung and Bronchus cancerrelated deaths in the United States population in 2000 were standardized [12] .The Joinpoint Regression Programme (Version 5.0.2,National Cancer Institute) was utilized to determine annual variations in Lung and Bronchus Cancer-related mortality by calculating annual percent changes (APC), along with their respective 95% CI, in age-adjusted AAMR [13] .This method makes use of log-linear regression models to recognize significant changes in AAMR over time.APCs were considered as increasing or decreasing when the two-tailed t-test indicated that the slope representing changes in mortality deviated significantly from zero.Lastly, a P value of P less than 0.05 was considered statistically significant.

Results
Lung and bronchus cancer between the years 1999 and 2020 caused a total of 3 599 577 deaths in patients aged younger than 1-85 + years (Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/MS9/A569).AAMRs for lung and bronchus Cancer-related mortalities in the United States stratified according to age groups are given in Table 1 with the 75-84 years age group having the highest AAMR at 361 (29.90% of deaths).Additionally, the age groups of younger than 1 year, 1-4 years, and 5-14 years presented with the lowest AAMR at 0 (0% of deaths) each.Other notable AAMRs include those for the 85 + year and 65-74 year age groups at 338 and 223.6, respectively.The overall AAMR for all age groups emphasizing the age-specific impact of Lung and Bronchus Cancer was revealed to be 53.4.The location of death was recorded for 3 588 558 deaths of which, 33.37% occurred at medical facilities, 13.64% at nursing homes, 7.00% at hospices, 40.83% at home, and 5.15% at other places that could not be included in the aforementioned categories, with the place of death of the remaining 11019 patients being unknown.(Supplementary Table 2, Supplemental Digital Content 1, http://links.lww.com/MS9/A569).
On sensitivity analysis considering neoplasms to be the underlying cause of death mortality rates were relatively constant with a slight decrease between 1999 and 2001 (APC: − 0.06; 95% CI: − 0.6538 to 0.4642) following which a trend of decreasing mortality at an increasing rate was seen consistently from  3 and 4, Supplemental Digital Content 1, http://links.lww.com/MS9/A569).
Lung and bronchus cancer-related AAMR stratified by race/ ethnicity AAMR stratification according to race/ethnicity revealed that total rates were highest among NH Black or African American   3 and 5, Supplemental Digital Content 1, http://links.lww.com/MS9/A569).African American patients and Hispanic or Latino patients had the highest and lowest total AAMRs, respectively.Compared to Hispanic or Latino, NH Black or African American, and NH Asian or Pacific Islander patients who demonstrated a continued decline in AAMR throughout the study period, NH American Indian or Alaskan Native and NH White patients demonstrated an increase in mortality trends between 1999-2010 and 1999-2002, respectively.Fourth, significant regional differences in lung and bronchus cancer mortality trends were observed, with the South and the West regions having the highest and lowest AAMRs, respectively.It was also noted that the Southern region had the highest AAMR from 1999 to 2010 while the Midwestern region reported the highest AAMR values from 2010 to 2020.(Fig. 6) Smoking patterns have a profound impact on the mortality trends of lung cancer, stratified by age, sex, socioeconomic status, and race or ethnicity [14] .Individuals belonging to low socioeconomic status have been found to have the highest prevalence of cigarette smoking [15] .The accessibility to lung and bronchus cancer screening is not equitable across states, which can be attributed to state-level differences in Medicaid coverage [16] .Moreover, the under-represented ethnic and racial minorities in the US have a greater likelihood of being uninsured, exacerbating disparities in lung cancer mortality and morbidity [16,17] .African Americans or NH Blacks are known to have the poorest survival rates among other racial or ethnic groups for the majority of cancers including lung cancer [18] .Richmond et al. [19] demonstrated that Black lung cancer patients had greater unadjusted odds of greater neighborhood deprivation and distant stage diagnosis in the Southeastern region.Racial and ethnic discrimination in the diagnostic experiences have significant ramifications on the treatment of lung cancer [20] .The sex-based differences in AAMRs of lung and bronchus cancer can be attributed to several mechanisms.Males tend to have an overall greater lung cancer mortality and a higher tumor grade at the time of diagnosis compared to their female counterparts.The sex-relevant considerations are also accounted for outcomes related to chemotherapies and immunotherapies with women and men demonstrating better treatment response, respectively [21] .The incidence of lung cancer is higher among men, however, women are more likely to be diagnosed at a younger age with earlier stage diagnosis [22] .Variability in the smoking patterns elucidates differences in the cancer histological subtype.Adenocarcinoma is more frequent in females compared to males [23] .During the first tobacco epidemic in industrialized countries, lung and bronchus cancer incidence, and mortality increased before declining for males and plateauing for females [24] .In our study, the decline in AAMRs in women was preceded by a rise in lung cancer mortality in women during 1999-2002.This can be explained by the comparatively later initiation of cigarette smoking among women [4,5,25] .The evidence can be forged to tailor public health campaigns, increase access to lung cancer screening programs, adopt sex-specific communication strategies, and address sex disparities in the treatment and prognostic outcomes of lung cancer.
In addition, we also observed higher AAMRs of lung and bronchus cancer in non-metropolitan areas than in metropolitan areas from 1990 to 2020.The mortality rates increased in nonmetropolitan areas during 1999-2001, after which a consistent decline was noted.The rate of decline in lung and bronchus cancer mortality was slower during 2001-2008 and relatively rapid during 2008-2014.The rural-urban disparity in lung and bronchus cancer mortality and burden can be represented by the area deprivation index in the rural and urban models [26,27] .Both localized and advanced forms of this cancer have a higher incidence in rural areas, with a comparatively higher disease burden [28] .The differences in lung and bronchus cancer mortality rates across metropolitan and non-metropolitan areas can be accounted for by relatively less access to specialized and routine care as well as worse survival and health outcomes in the latter [29] .The uneven geographic distribution of oncologists among metropolitan and non-metropolitan areas also contributes to the geographic disparities in lung cancer mortality rates [30][31][32][33] .The implementation of prevention and control measures including smoking cessation, smoke-free laws, and reduction of exposure to lung carcinogens not only addresses the urban-rural disparities but also decreases lung cancer incidence and mortality rates in non-metropolitan areas [34] .
Regarding the role of lung carcinogens in the environment and the associated risk of lung cancer, a research study demonstrated that non-metropolitan Utah counties had higher rates of incidence of lung cancer compared to metropolitan counties.After adjusting for smoking, the incidence rates were found to be significantly greater in high-radon counties compared to modern radon counties [35] .In addition to this, geographical variations in occupational hazards such as occupational coal and arsenic exposure.Local mitigation strategies and policies, however, determine the radon and arsenic levels in the environment and individual exposure levels [7] .Several other factors that contribute to the elevated lung cancer mortality rate include comorbidities and the disease stage.According to the literature, the majority of lung cancer patients visit hospitals when the disease is in advanced stages.Moreover, patients residing in rural areas have a higher mortality rate due to a lack of adequate healthcare facilities [36] .Lastly, the degree of adherence of individuals to screening programs and the type of screening programs also influence the incidence of lung cancer and the mortality benefits.Centralized surveillance programs tend to have a higher adherence rate compared to decentralized surveillance programs [37] .

Limitations
While the study has made significant contributions to understanding lung and bronchus cancer mortality trends and associated variables, it has several limitations.Firstly, the reliance on ICD-10 codes and death certificates is related to considerable variation across different healthcare settings, giving rise to misclassification bias and subsequent misinterpretation of data leading to the omission of lung and bronchus cancer as a cause of death.We also acknowledge that our dataset does not include information related to cancer biomarkers, smoking, lung and bronchus cancer prevalence in the family, therapeutic interventions, and duration between diagnosis and death of lung cancer patients.Data pertaining to the treatment of lung and bronchus neoplasms using medical therapy is unavailable.Additionally, data concerning the socioeconomic factors influencing health, which could impact access to care, is also lacking.

Conclusion
We thoroughly examined and presented the Centers for Disease Control and Prevention mortality data from 1999 to 2020.Our findings indicate a decreasing trend in the AAMR for lung and bronchus cancer in the overall U.S. population.The highest AAMRs were observed among non-Hispanic Black or African American adults, males, residents of the southern regions in earlier years while midwestern later on, and those living in nonmetropolitan areas across all age groups in the U.S. population.The study emphasizes the importance of addressing lung and bronchus cancer screening disparities and undertaking public health measures to regulate the risk factors and precipitating events.

Ethical approval
This study was exempted from the institutional review board's approval because it uses publicly available data that is deidentified.

Consent
Informed consent was not required for this review.

Source of funding
None.

Research registration unique identifying number (UIN)
This isn't needed as this paper is a comprehensive review and not a systematic review or meta-analysis.

Guarantor
Hafsah Alim Ur Rahman and Muhammad Ahmed Ali Fahim.

Figure 1 .Figure 2 .
Figure 1.Mortality rates for malignant neoplasm of bronchus and lung, stratified by sex in the population of all ages in the United States between 1999 and 2020, along with the associated age-adjusted mortality rates (AAMRs) per 100 000.The * denotes the annual percentage change (APC) that was found to be statistically significant at α = 0.05

Figure 4 .Figure 5 .
Figure 4. Mortality rates for malignant neoplasm of bronchus and lung, stratified by census region in population of all ages in the United States between 1999 and 2020, along with the associated age-adjusted mortality rates (AAMRs) per 100 000.The * denotes the annual percentage change (APC) that was found to be statistically significant at α = 0.05

Table 1
Demographic characteristics of deaths due to lung cancer among all ages in the USA from 1999 to 2020.