Association between low-dose aspirin and prevalence of chronic obstructive pulmonary disease (COPD): The mediating role of systemic immune inflammation index

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Low-dose aspirin is widely used as an anti-inflammatory medicine. However, the impact of low-dose aspirin on COPD is unclear. This article aims to investigate the association between low-dose aspirin and the prevalence of COPD. Methods A cohort study was conducted based on United States population data from the National Health and Nutrition Examination Survey (NHANES) data (2011–2012, 2013–2014, 2015–2016, 2017–2020, and 2021–2023). We examined pairwise associations between systemic immune inflammation index (SII), low-dose aspirin, and COPD prevalence by logistic regression analysis, the restricted cubic spline (RCS), and mediation analyses. Results In 5,668 people, 68% of them took low-dose aspirin. We found higher levels of SII in participants with COPD compared to those without COPD. Low-dose aspirin was significantly associated with COPD prevalence (β=-0.015, 95%CI=-0.026, -0.003, p < 0.001) and SII (β = 0.036, 95% CI = = 0.022, 0.050, p ≤ 0.001), even after considering a wide range of potential confounders (e.g., age, sex, race). SII was nonlinearly associated with COPD. SII mediated a marginal portion (PM, -0.039130; ACME = -0.000552, [95% CI = -0.001042, 0], p = 0.01) of the potential effects of low-dose aspirin on COPD prevalence. Conclusions Our research showed that SII, low-dose aspirin, and depression are pairwise correlated. Low-dose aspirin may decrease the risk of COPD, and Prophylactic use of low-dose aspirin may be advised in individuals at high risk of COPD. Aspirin COPD SII NHANES Figures Figure 1 Figure 2 Figure 3 Introduction Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of death worldwide, which is characterized by progressive airflow limitation and airway inflammation with great influence on high morbidity, mortality, and representing a substantial global health burden [ 1 , 2 ]. The World Health Organization (WHO) estimates that the prevalence of COPD is around 10%, resulting in approximately 3 million deaths annually attributed to the disease. [ 3 ]. Chronic inflammation of the airways is a key feature in the pathogenesis of COPD. One of the major challenges in treating COPD patients is the heterogeneous nature of the disease's pathogenesis, which involves the activation of various inflammatory cells, including lymphocytes, neutrophils, macrophages, and eosinophils, all of which contribute to the inflammatory response[ 4 ]. Meanwhile, counting inflammatory cells in the airway is not easy or convenient to detect [ 5 ]. Systemic inflammation is thought to play a significant role in COPD [ 6 ]. The systemic immune-inflammation index (SII), which is calculated using the formula (neutrophil count × platelet count) / lymphocyte count, serves as a novel and stable metric for assessing local immune responses and systemic inflammation [ 7 ]. Prior studies have indicated that the SII can be effective in predicting the risk of developing COPD [ 8 , 9 ]. Aspirin is extensively utilized and possesses a range of beneficial properties, including antipyretic, analgesic, and anti-inflammatory effects [ 10 , 11 ]. Evidence supports the chemo- preventive effect of low-dose aspirin in preventing atherosclerotic cardiovascular disease and other health conditions [ 12 – 14 ]. Furthermore, daily low-dose aspirin has been shown to decrease the incidence of colon cancer and to prevent or delay the development of atherosclerosis through its anti-inflammatory effects [ 15 , 16 ]. Based on the calculation method of SII, we hypothesized that low-dose aspirin might influence the value of SII. However, the relationship between low-dose aspirin and the prevalence of COPD remains unknown. In this particular context, our objective was to conduct a comprehensive investigation to determine whether a correlation exists between the administration of low-dose aspirin, SII, and COPD. Furthermore, we aimed to explore the potential mediating role of SII in the relationship between low-dose aspirin and COPD. Methods Study disign and population We conducted a continuous cross-sectional observational study using data from the 2011–2023 NHANES survey, which is carried out by the Centers for Disease Control and Prevention (CDC) to assess the health and nutritional status of the civilian, non-institutionalized population in the United States. The NHANES study protocol received approval from the Institutional Review Board of the National Center for Health Statistics (NCHS), and all participants provided written informed consent. Additional information about the NHANES program can be found on the CDC website ( http://www.cdc.gov/nchs/nhanes/index.htm ). A total of 57,395 participants were enrolled from five survey cycles (2011–2012, 2013–2014, 2015–2016, 2017–2020, and 2021–2023). Participants under the age of 18 (n = 21,580), as well as those with missing data on the diagnosis of COPD (n = 2,719), low-dose aspirin (n = 24,882), and the systemic immune inflammation index (SII; n = 2,546), were excluded from the analysis. Ultimately, 5,668 individuals were included in the final analysis (Fig. 1) Figure 1 Flow chart of the screening of the NHANES 2011–2023 participants Assessment of Asipin The definition of low-dose Aspirin in this study were based on some questions by trained interviewer using the Computer-Assisted Personal Interview (CAPI) system. Participants were asked “Dr told to take daily low-dose aspirin?” and “Followed advice, took low-dose aspirin?” Those who answered “Yes” were defined as low-dose aspirin. The other answers were excluded from the statistical analysis. Assessment of COPD COPD was diagnosed with the guidance from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024, and met the two criteria: 1) forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) < 0.7 following inhaled bronchodilator; 2) related respiratory symptoms and/or a history of exposure to risk factors for COPD (GOLD, 2024). In this study, participants suffered from COPD were defined as below: a) Based on the post-bronchodilator spirometry, FEV1/FVC < 0.7 following inhaled bronchodilator in the cycle 2011–2012; b) Answer Yes to the Problem “Has a doctor or other health professional ever told you that you had COPD?” in the cycle 2013–2023, because data on spirometry were unavailable in these cycles. Covariates The potential confounding variables were analysed in this study. Continuous covariates included age, systemic immune inflammation index (SII), body-mass index (BMI)(< 25, 25–30, ≥ 30), number of prescription medicines taken (RXD) ( 3.5). Categorical variables included gender (males and females), race (Non-Hispanic White, Non-Hispanic Black, Mexican American, Other Hispanic and Others), education (High school and below, high school graduate, and above high school), marital status (married/living with partners, widowed/divorced/separated, or never married), smoking status and self-reported diseases included hypertension and diabetes. Statistical analysis In accordance with the CDC guidelines, the statistical analyses in this study were conducted using a complex multi-stage weighted design. Statistical software (R version 4.1.1; https://cran.r-project.org/ ) was employed for the analyses. Doubled-sided P < 0.05 was considered as statistical significance. Continuous variables are presented as means with standard errers (SE) or medians and interquartile ranges, while categorical variables were convered through numerical counts and percentages frequencies (%). Logistic regression analysis was performed to investigate the relationship between low-dose aspirin and COPD. Crude model was unadjusted for any covariates, while the adjust model was adjusted for age, race/ethnicity, education level, marital status, BMI, smokinng status, FIR, BMI, hypertension, diabetes and RXD. Restricted cubic spline (RCS) was applied to assess the association between COPD prevalence and SII. The levels of SII were transformed into natural logarithms for all analyses. To explore the moderating effect of sex, we calculated the strength of the association between COPD prevalence and SII in both the male and female subgroups. Mediation analyses were performed to determine whether SII mediated the relationship between the low-dose aspirin and COPD prevalence. The potential mediating role of gender in the association between low-dose aspirin and COPD prevalence was also explored by Mediation analyses. Results Characteristics of Participants As shown in Table 1, a total of 5,668 individuals were analyzed in this study, of which 650 suffered from Chronic Obstructive Pulmonary Disease (COPD). The mean age of the participants was 63.9 years (standard error, 0.3), and 52.8% were male. Additionally, 69.8% of the individuals were taking low-dose aspirin. Compared to non-COPD individuals, COPD patients prone to be older, males, non-Hispanic White, High school and below, widowed/ divorced/separated and lower FIR (P<0.001). Besides, Significant differences were also found between the two groups in terms of smoking, hypertension, and diabetes. Notably, individuals with COPD had a higher level of Systemic Inflammation Index (SII), with values of 525.2 (range: 355.7-736.2) versus 451.3 (range: 316.6-644.6) in non-COPD individuals (P < 0.001). Furthermore, 17.4% of COPD patients reported taking more than ten different prescription medications in the past month, compared to only 3.6% of non-COPD individuals. Table 1 Characteristics of the NHANES 2011–2023 participants Overall COPD Non-COPD P -value N = 5668 N = 650 N = 5018 Age, y, mean(SE) 63.9 (0.3) 65.7(0.4) 63.7 (0.3) <0.001 Sex, n(%) <0.001 male 3033(52.8) 408 (60.8) 2625 (51.6) female 2635 (47.2) 242 (39.2) 2393 (48.4) Race/Ethnicity, n(%) < 0.001 Non-Hispanic White 2404 (72.6) 359 (81.6) 2045 71.8) Non-Hispanic Black 1429 (10.5) 168 (8.8) 1261 (10.7) Mexican American 600 (5.0) 32 (1.8) 568 (5.4) Other Hispanic 616 (5.0) 45 (2.8) 571 (5.1) Others 619 (6.9) 46 (5.0) 573 (7.0) Education, n(%) 0.010 High school and below 1332 (13.9) 173 (18.5) 1159 (13.9) High school graduate 1395 (26.2) 176 (29.6) 1219 (24.8) Above high school 2941 (59.9) 301 (51.9) 2640 (61.3) BMI, kg/m 2 , n(%) 0.196 <25 1434 (24.4) 171 (25.5) 1263 (24.7) 25–30 2020 (35.8) 211 (37.0) 1809 (36.0) ≥30 2214 (39.8) 268 (37.5) 1946 (39.3) Marital, n(%) <0.001 Married/living with partner 3351 (66.0) 339 (61.3) 3012 (66.3) Widowed/divorced/separated 2054 (29.7) 279 (34.9) 1775 (28.5) Never married 263 (4.3) 32 (3.8) 231 (5.1) FIR, n(%) 3.5 1578 (42.1) 134 (33.9) 1444 (43.0) Smoking, n(%) 916 (24.1) 185 (31.9) 731 (22.7) <0.001 Diabetes, n(%) 1927 (28.0) 257 (31.0) 1670 (27.3) 0.004 Hypertension, n(%) 3857 (62.5) 491 (72.5) 3366 (61.2) <0.001 Low-dose Aspirin, n(%) 3906 (69.8) 507 (77.5) 3399 (69.3) <0.001 RXD, n(%) <0.001 <5 3221 (60.3) 227 (43.2) 2994 (62.9) 5–10 2115 (34.4) 298 (39.3) 1817 (33.5) ≥10 332 (5.3) 125 (17.4) 207 (3.6) SII, median (IQR) 460.2 (320.8- 6297.6) 525.2 (355.7- 736.2) 451.3 (316.6- 644.6) <0.001 Data was shown as number (percentage), mean (SE) or median (25th-75th percentile). Abbreviations: BMI, body mass index; FIR, family income-poverty; SII, systemic immune inflammation index; RXD, the numbers of taking prescription medicine in past month. Correlations of low-dose aspirin with COPD prevalence and SII The prevalence of Chronic Obstructive Pulmonary Disease (COPD) was significantly lower in individuals taking low-dose aspirin. As indicated in Table 2, low-dose aspirin showed a significant association with COPD prevalence in the crude model (β= -0.027, 95% CI = -0.039, -0.016, p < 0.001). After adjusting for potential confounders included age, race/ethnicity, education level, marital status, BMI, smokinng status, FIR, BMI, hypertension, diabetes and RXD, low-dose aspirin was also associated with a 0.015 decrease in COPD prevalence(β=-0.015, 95%CI=-0.026, -0.003, p<0.001). When participants were categorized by sex, the positive correlation between low-dose aspirin and COPD prevalence was found to be stronger in males than in females within the crude model (β= 0.034, 95% CI = 0.015, 0.052 for males vs. β=0.018, 95% CI=0.004, 0.033 for females). Although low-dose aspirin use was slightly but significantly related to COPD in males, this relationship was not observed in females after adjusting for all covariates (β=0.020, 95% CI = 0.002, 0.038 for males vs. β=0.011, 95% CI=-0.003, 0.025 for females). Furthermore, low-dose aspirin was associated with SII ( β =0.047, 95% CI = 0.033, 0.061, p < 0.001)，as well as the adjust model (β =0.036, 95% CI = 0.022, 0.050, p < 0.001). Table 2 Associations of aspirin with SII and COPD prevalence(n=5668) Number of participants β(95% CI) P -Value Effect sizes of moderation effects P for interaction Associations of low-dose aspirin and COPD Crude Model 0.153 <0.001 Total 5668 -0.027 (-0.039,-0.016) <0.001 Male 3033 0.034(0.015,0.052) <0.001 Femal 2635 0.018(0.004,0.033) 0.014 Associations of low-dose aspirin and COPD Adjusted Model 0.104 0.030 Total 5668 -0.015 (-0.026,-0.003) 0.011 Male 3033 0.020(0.002,0.038) 0.028 Femal 2635 0.011(-0.003,0.025) 0.137 Associations of low-dose aspirin and SII Crude Model -0.175 <0.001 Total 5668 0.047(0.033,0.061) <0.001 Male 3033 -0.044(-0.064,-0.023) <0.001 Femal 2635 -0.053(-0.072,-0.034) <0.001 Associations of low-dose aspirin and SII Adjusted Model -0.2 0.002 Total 5668 0.036(0.022,0.050) <0.001 Male 3033 -0.032(-0.053,-0.012) 0.002 Femal 2635 -0.044(-0.063,-0,025) <0.001 Abbreviations: SII, systemic immune inflammation index, was calculated by Platelsts*Neutrophils /Lymphocytes. SII was transformed to natural logarithms in the analysis. Crude model was unadjust for any covariates, while the adjust model was adjusted for age, race/ethnicity, education level, marital status, BMI, smokinng status, FIR,BMI, hypertension, diabetes and RXD. Nonlinear association between SII and the prevalence of COPD Figure 3 illustrates the relationship between SII and COPD under both crude and adjusted models, utilizing the Restricted Cubic Splines (RCS) method. In this analysis, SII was transformed into natural logarithms (lnSII). Our findings indicate a nonlinear positive correlation between these variables. In the crude model, the odds ratio (OR) gradually increases with higher lnSII values. Notably, when lnSII approaches 5, the OR begins to rise significantly, and this rise accelerates when lnSII reaches 7 (as shown by the green curve). In comparison, the adjusted model demonstrates a more pronounced increase in the OR at higher lnSII values. Additionally, the curves for males and females in the subgroup analysis show similar trends; however, there are notable differences in specific values and the rates of increase, particularly at elevated lnSII levels. Mediating effect of SII on low-dose aspirin and COPD prevalence Table 3 presents the results of a mediation analysis of the relationship between low-dose aspirin and prevalence of COPD. SII significantly mediated the association between low-dose aspirin and COPD prevalence in both crude ( proportion mediated [PM], -0.04897; average causal mediation effects [ACME] = -0.00124 , [95% CI =-0.00196, 0], p = <2e-16) and adjusted model (PM, -0.039130; ACME = -0.000552, [95% CI = -0.001042, 0], p = 0.01). When stratifying by sex, the analysis shows that SII positively mediates the relationship between low-dose aspirin and COPD prevalence in males, but not in females, after adjusting for all covariates. In males, the mediation was significant (PM: -0.033229; ACME: -0.000642, with a 95% CI: -0.001383, 0; p = 0.020), while in females, the results were not statistically significant (PM: -0.046264; ACME: -0.000642, with a 95% CI: -0.001162, 0; p = 0.10). Table3 SII mediating the association between low-dose aspirin and COPD prevalence(n =5668). ACME ADE Total effect Proportion mediated Crude model Total -0.00124 -0.00196 0.00 <2e-16 0.02662 0.01544 0.04 <2e-16 0.02537 0.01467 0.04 <2e-16 -0.04897 -0.06514 -0.03 <2e-16 Male -0.00142 -0.00252 0.00 0.002 0.03303 0.01562 0.05 0.002 0.03161 0.01505 0.05 0.002 -0.04486 -0.06858 -0.02 <2e-16 Female -0.000917 -0.001818 0.00 0.006 0.017366 0.004265 0.03 0.006 0.016449 0.004082 0.03 0.006 -0.055742 -0.079025 -0.03 <2e-16 Adjusted model Total -0.000552 -0.001042 0.00 0.008 0.014648 0.004360 0.03 0.002 0.014096 0.003730 0.02 0.002 -0.039130 -0.172270 -0.01 0.01 Male -0.000642 -0.001383 0.00 0.020 0.019961 0.003113 0.04 0.018 0.019319 0.003028 0.04 0.018 -0.033229 -0.056796 -0.01 0.002 Female -0.000642 -0.001162 0.00 0.1 0.010587 -0.002930 0.02 0.1 0.010119 -0.002883 0.02 0.1 -0.046264 -0.070219 -0.02 <2e-16 Abbreviations: BMI, body mass index; SII, systemic immune inflammation index; ACME, average causal mediation effect; ADE, average direct effect. SII was transformed to natural logarithms in the analysis. Crude model was unadjusted for any covariates, while the adjust model was adjusted for age, race/ethnicity, education level, marital status, BMI, smoking status, FIR,BMI, hypertension, diabetes and RXD. Figure 3 illustrates the potential mediating role of gender in the relationship between low-dose aspirin and the prevalence of COPD. Our findings indicate that low-dose aspirin is significantly associated with COPD, but not with SII (P> 0.05). Additionally, SII does have an effect on COPD. Overall, gender does not appear to mediate the relationship between low-dose aspirin and COPD, as indicated by an ACME of 0.000 and a PM of -0.000. Discussion In this paper, we examined the relationship between low-dose aspirin intake and the prevalence of COPD in adults in the United States, specifically investigating whether this association is partially mediated by the Systemic Immune Inflammatory Index (SII). The primary conclusion drawn from the data is that low-dose aspirin intake decreases the prevalence of COPD, with stronger associations observed in males. This observation aligns with our findings, which indicated that the number of male patients with COPD exceeded that of female patients. As we know, cigarette smoke exposure is strongly associated with COPD [17], and the prevalence of tobacco in men is higher than women[18]. Previous studies have confirmed that inflammatory response of lung macrophages and epithelial cells from tobacco smoke[19,20]. These findings are consistent with research showing that aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways [21]. This may explain why low-dose aspirin, known for its anti-inflammatory properties, could reduce the incidence of COPD. However, it remains unclear whether the higher SII observed in men is responsible for low-dose aspirin's ability to reduce COPD prevalence. Additionally, there is insufficient evidence to suggest that smokers exhibit higher levels of SII. As anticipated, our results indicated a positive correlation between low-dose aspirin intake and SII levels. We utilized SII as a marker of inflammation due to its economical nature and ease of use in clinical settings. Comparisons with other studies confirm that aspirin can reduce the lymphocyte ratio (NLR) [22, 23], although few studies have explored the relationship between aspirin and SII. A potential explanation for this correlation may lie in aspirin's effects on platelet function and inflammation. Moreover, SII calculation is based on the counts of platelets, neutrophils, and lymphocytes. Another significant finding of this study is that SII level was associated with COPD in a nonlinear pattern, with SII positively correlating with COPD after surpassing a certain threshold. Prior studies have also identified nonlinear relationships between SII and COPD [24,25]. As a novel inflammatory biomarker, SII can be utilized to predict COPD risk and demonstrates superiority compared to NLR [8]. Furthermore, SII significantly mediated the association between low-dose aspirin and COPD prevalence. While direct studies on the effect of aspirin on SII are lacking, prior research has indicated that aspirin influences neutrophil function and lymphocyte proliferation [26]. Given that neutrophilic inflammation is a prominent feature of COPD [27]. it can be hypothesized that SII mediates the interactions between aspirin and COPD, and our results support this hypothesis. To advance precision approaches in COPD management, drug repurposing based on specific inflammatory biomarkers (e.g., type 2 inflammation) shows promise [28]. Although there are important discoveries revealed by these studies, there are also limitations. First, due to the cross-sectional nature of this study, we could not establish a causal relationship between low-dose aspirin, SII, and COPD. Additional randomized controlled studies are needed to validate our findings. Second, the data on low-dose aspirin intake and COPD status were primarily obtained from questionnaires, which may introduce potential memory bias. Longitudinal studies should implement stricter diagnostic criteria to further validate our results. Finally, while we adjusted for many confounding variables, some residual factors influencing COPD onset may remain unaccounted for. Conclusion In summary, the results of this study showed that SII, low-dose aspirin and COPD are pairwise correlated. Our findings highlight the importance of low-dose aspirin intake may decrease the risk of COPD, with SII playing a marginal role in mediating the relationship between low-dose aspirin and the prevalence of COPD. Further longitudinal studies are required to investigateh the specific mechanism behind it. Declarations Authors’ contributions Dandan Dai contributed to the conception, design and writing. Jiejun Shi and Chaochao Ding contributed to the Software and formal analysis. Jianmin Ren analyzed the data. Hongbin Xu edited and revised the manuscript. All authors contributed to the critical revision of the manuscript and approved the final version. Funding This study was supported by International Medical Exchange Foundation of China (Z-2017-24-2301), Ningbo medical science and technology project (2022Y06). Availability of data and materials The data utilized in this study is readily available from the U.S. Centers for Disease Control and Prevention through the National Center for Health Statistics, which effectively manages the National Health and Nutrition Examination Survey (NHANES). Ethical approval and consent to participate The studies involving humans were approved by the board of the National Center for Health Statistics (NCHS). All the participants signed the informed consent before participating in the study. Consent for publication Not applicable Competing interests No potential conflict of interest was reported by the authors. Author details 1 Department of Pharmacy, The First Affiliated Hospital of Ningbo University, Ningbo, China; 2 Department of Infectious disease, The First Affiliated Hospital of Ningbo University, Ningbo, China; References Francesca Polverino, Don D. Sin.Type 2 airway inflammation in COPD. Eur Respir J. 2024;63(5):2400150. 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Ma Q, Li WN, Liu HY et al. Expression of NLR and IL-1β and their predictive efficacy value in acute myocardial infarction patients treated with aspirin combined with clopidogrel. J Biol Regul Homeost Agents. 2021;35(4). Li W, Ren X, Zhang L. Clinical efficacy of atorvastatin calcium combined with aspirin in patients with acute ischemic stroke and effect on neutrophils, lymphocytes and IL-33. Exp Ther Med. 2020;20(2):1277–84. Kwok WC, Tam TCC, Lam DCL, et al. Systemic immune-inflammation index in predicting hospitalized bronchiectasis exacerbation risks and disease severity. J Thorac Dis. 2024;16(5):2767–75. Zhao Y, Li H, Wang Z, et al. Exploring the association between magnesium deficiency and chronic obstructive pulmonary diseases in NHANES 2005–2018. Sci Rep. 2024;14(1):25981. Chokshi R, Bennett O, Zhelay T, et al. NSAIDs Naproxen, Ibuprofen, Salicylate, and Aspirin Inhibit TRPM7 Channels by Cytosolic Acidification. Front Physiol. 2021;12:727549. Kwak N, Lee KH, Woo J, et al. Del-1 Plays a Protective Role against COPD Development by Inhibiting Inflammation and Apoptosis. Int J Mol Sci. 2024;25(4):1955. Moll M, Silverman EK. Precision Approaches to Chronic Obstructive Pulmonary Disease Management. Annu Rev Med. 2024;75:247–62. Additional Declarations No competing interests reported. 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. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5817670","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":402127216,"identity":"184c8178-aa9c-4695-949b-df19e13d8ddf","order_by":0,"name":"Dandan Dai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIie3PvarCQBCG4QmB2ERtN/h3CxFBkSDeShbBVAcsU1hElEmh4q1sqV0kEJsR27UzF3AKu3MKQcFSSWJnsU89Lx8DoCjfKNICBqADlDbXi+tPP0nMqGNfKCmSADwT5natdKHnF5VDPJP/W6fVM6OxzwMDquHSzUws4vP+mrz2LgwSybd1YHQUmYkdcWRljDVBe5ScDLDZT05yStG6YTwUcmRMOOoFEsmx9ljhQo4NKJRYMp07DfRGgkhnLiVm7i+Vk5eef9EZiMNKu/7502Y1XGcnL8zPzhVFUZS37jDtUwJ+W6hoAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":true,"prefix":"","firstName":"Dandan","middleName":"","lastName":"Dai","suffix":""},{"id":402127217,"identity":"e9f34e11-d52f-4f19-b0e0-d5993926c52a","order_by":1,"name":"Jiejun Shi","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Jiejun","middleName":"","lastName":"Shi","suffix":""},{"id":402127218,"identity":"89c7c5eb-fbcd-4948-84e8-83d757365cda","order_by":2,"name":"Chaochao Ding","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Chaochao","middleName":"","lastName":"Ding","suffix":""},{"id":402127219,"identity":"a94c37a2-3bb0-43bd-8fbd-12278d773966","order_by":3,"name":"Jianmin Ren","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Jianmin","middleName":"","lastName":"Ren","suffix":""},{"id":402127220,"identity":"a6d2e2b6-55cc-42b0-bc14-67251ed1113b","order_by":4,"name":"Hongbin Xu","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Hongbin","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-01-13 07:38:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5817670/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5817670/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73869765,"identity":"76f52f01-836a-40f9-8eee-84ffa356e852","added_by":"auto","created_at":"2025-01-15 12:10:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":192897,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the screening of the NHANES 2011-2023 participants\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5817670/v1/08934253b27b386e34e41ef3.png"},{"id":73869771,"identity":"36c000e2-4b11-4d08-afcb-a3ed15d46e0b","added_by":"auto","created_at":"2025-01-15 12:10:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":200500,"visible":true,"origin":"","legend":"\u003cp\u003eAssocation between SII with COPD prevalence by RCS.\u003c/p\u003e\n\u003cp\u003eAbbreviations: RCS, restricted cubic spline; SII, systemic immune inflammation index;\u003c/p\u003e\n\u003cp\u003eCrude model was unadjust for any covariates, while the adjust model was adjusted for age, race/ethnicity, education level, marital status, BMI, smokinng status, FIR,BMI, hypertension, diabetes and RXD.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5817670/v1/92597654286de890b76dd6ea.png"},{"id":73869767,"identity":"38f1aaab-c5d4-46aa-8a13-31e078730b30","added_by":"auto","created_at":"2025-01-15 12:10:11","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":106221,"visible":true,"origin":"","legend":"\u003cp\u003eMediation analysis of gender in the association between low-dose-aspirin and COPD. Abbreviations: ACME, average causal mediation effect; PM, proportion mediated.\u003c/p\u003e\n\u003cp\u003eModel was adjusted for age, race/ethnicity, education level, marital status, BMI, smoking status, FIR, BMI, hypertension, diabetes and RXD.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5817670/v1/908a2facef71210e03251d0a.png"},{"id":74296068,"identity":"4ac155cd-9d27-4de1-9c8f-84c3a923f610","added_by":"auto","created_at":"2025-01-20 18:08:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1266351,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5817670/v1/60716bdb-5ac1-4faf-937e-4f5d6e8fce8c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between low-dose aspirin and prevalence of chronic obstructive pulmonary disease (COPD): The mediating role of systemic immune inflammation index","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic obstructive pulmonary disease (COPD) ranks as the third leading cause of death worldwide, which is characterized by progressive airflow limitation and airway inflammation with great influence on high morbidity, mortality, and representing a substantial global health burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The World Health Organization (WHO) estimates that the prevalence of COPD is around 10%, resulting in approximately 3\u0026nbsp;million deaths annually attributed to the disease. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Chronic inflammation of the airways is a key feature in the pathogenesis of COPD. One of the major challenges in treating COPD patients is the heterogeneous nature of the disease's pathogenesis, which involves the activation of various inflammatory cells, including lymphocytes, neutrophils, macrophages, and eosinophils, all of which contribute to the inflammatory response[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Meanwhile, counting inflammatory cells in the airway is not easy or convenient to detect [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSystemic inflammation is thought to play a significant role in COPD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The systemic immune-inflammation index (SII), which is calculated using the formula (neutrophil count \u0026times; platelet count) / lymphocyte count, serves as a novel and stable metric for assessing local immune responses and systemic inflammation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Prior studies have indicated that the SII can be effective in predicting the risk of developing COPD [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAspirin is extensively utilized and possesses a range of beneficial properties, including antipyretic, analgesic, and anti-inflammatory effects [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Evidence supports the chemo- preventive effect of low-dose aspirin in preventing atherosclerotic cardiovascular disease and other health conditions [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, daily low-dose aspirin has been shown to decrease the incidence of colon cancer and to prevent or delay the development of atherosclerosis through its anti-inflammatory effects [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Based on the calculation method of SII, we hypothesized that low-dose aspirin might influence the value of SII. However, the relationship between low-dose aspirin and the prevalence of COPD remains unknown.\u003c/p\u003e \u003cp\u003eIn this particular context, our objective was to conduct a comprehensive investigation to determine whether a correlation exists between the administration of low-dose aspirin, SII, and COPD. Furthermore, we aimed to explore the potential mediating role of SII in the relationship between low-dose aspirin and COPD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy disign and population\u003c/h2\u003e \u003cp\u003eWe conducted a continuous cross-sectional observational study using data from the 2011\u0026ndash;2023 NHANES survey, which is carried out by the Centers for Disease Control and Prevention (CDC) to assess the health and nutritional status of the civilian, non-institutionalized population in the United States. The NHANES study protocol received approval from the Institutional Review Board of the National Center for Health Statistics (NCHS), and all participants provided written informed consent. Additional information about the NHANES program can be found on the CDC website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.cdc.gov/nchs/nhanes/index.htm\u003c/span\u003e\u003cspan address=\"http://www.cdc.gov/nchs/nhanes/index.htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA total of 57,395 participants were enrolled from five survey cycles (2011\u0026ndash;2012, 2013\u0026ndash;2014, 2015\u0026ndash;2016, 2017\u0026ndash;2020, and 2021\u0026ndash;2023). Participants under the age of 18 (n\u0026thinsp;=\u0026thinsp;21,580), as well as those with missing data on the diagnosis of COPD (n\u0026thinsp;=\u0026thinsp;2,719), low-dose aspirin (n\u0026thinsp;=\u0026thinsp;24,882), and the systemic immune inflammation index (SII; n\u0026thinsp;=\u0026thinsp;2,546), were excluded from the analysis. Ultimately, 5,668 individuals were included in the final analysis (Fig.\u0026nbsp;1)\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;1 Flow chart of the screening of the NHANES 2011\u0026ndash;2023 participants\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAssessment of Asipin\u003c/h3\u003e\n\u003cp\u003eThe definition of low-dose Aspirin in this study were based on some questions by trained interviewer using the Computer-Assisted Personal Interview (CAPI) system. Participants were asked \u0026ldquo;Dr told to take daily low-dose aspirin?\u0026rdquo; and \u0026ldquo;Followed advice, took low-dose aspirin?\u0026rdquo; Those who answered \u0026ldquo;Yes\u0026rdquo; were defined as low-dose aspirin. The other answers were excluded from the statistical analysis.\u003c/p\u003e\n\u003ch3\u003eAssessment of COPD\u003c/h3\u003e\n\u003cp\u003eCOPD was diagnosed with the guidance from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024, and met the two criteria: 1) forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC)\u0026thinsp;\u0026lt;\u0026thinsp;0.7 following inhaled bronchodilator; 2) related respiratory symptoms and/or a history of exposure to risk factors for COPD (GOLD, 2024). In this study, participants suffered from COPD were defined as below:\u003c/p\u003e \u003cp\u003ea) Based on the post-bronchodilator spirometry, FEV1/FVC\u0026thinsp;\u0026lt;\u0026thinsp;0.7 following inhaled bronchodilator in the cycle 2011\u0026ndash;2012;\u003c/p\u003e\u003cp\u003eb) Answer Yes to the Problem \u0026ldquo;Has a doctor or other health professional ever told you that you had COPD?\u0026rdquo; in the cycle 2013\u0026ndash;2023, because data on spirometry were unavailable in these cycles.\u003c/p\u003e \n\u003ch3\u003eCovariates\u003c/h3\u003e\n\u003cp\u003eThe potential confounding variables were analysed in this study. Continuous covariates included age, systemic immune inflammation index (SII), body-mass index (BMI)(\u0026lt;\u0026thinsp;25, 25\u0026ndash;30, \u0026ge;\u0026thinsp;30), number of prescription medicines taken (RXD) (\u0026lt;\u0026thinsp;5, 5\u0026ndash;10, \u0026ge;\u0026thinsp;10) and family income-poverty ratio (FIR) (\u0026thinsp;≦\u0026thinsp;1.3, 1.3\u0026ndash;3.5, and \u0026gt;\u0026thinsp;3.5). Categorical variables included gender (males and females), race (Non-Hispanic White, Non-Hispanic Black, Mexican American, Other Hispanic and Others), education (High school and below, high school graduate, and above high school), marital status (married/living with partners, widowed/divorced/separated, or never married), smoking status and self-reported diseases included hypertension and diabetes.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003e In accordance with the CDC guidelines, the statistical analyses in this study were conducted using a complex multi-stage weighted design. Statistical software (R version 4.1.1; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cran.r-project.org/\u003c/span\u003e\u003cspan address=\"https://cran.r-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was employed for the analyses. Doubled-sided \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as statistical significance. Continuous variables are presented as means with standard errers (SE) or medians and interquartile ranges, while categorical variables were convered through numerical counts and percentages frequencies (%).\u003c/p\u003e \u003cp\u003eLogistic regression analysis was performed to investigate the relationship between low-dose aspirin and COPD. Crude model was unadjusted for any covariates, while the adjust model was adjusted for age, race/ethnicity, education level, marital status, BMI, smokinng status, FIR, BMI, hypertension, diabetes and RXD.\u003c/p\u003e \u003cp\u003eRestricted cubic spline (RCS) was applied to assess the association between COPD prevalence and SII. The levels of SII were transformed into natural logarithms for all analyses. To explore the moderating effect of sex, we calculated the strength of the association between COPD prevalence and SII in both the male and female subgroups. Mediation analyses were performed to determine whether SII mediated the relationship between the low-dose aspirin and COPD prevalence. The potential mediating role of gender in the association between low-dose aspirin and COPD prevalence was also explored by Mediation analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCharacteristics of Participants\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 1, a total of 5,668 individuals were analyzed in this study, of which 650 suffered from Chronic Obstructive Pulmonary Disease (COPD). The mean age of the participants was 63.9 years (standard error, 0.3), and 52.8% were male. Additionally, 69.8% of the individuals were taking low-dose aspirin. Compared to non-COPD individuals, COPD patients prone to be older, males, non-Hispanic White, High school and below, widowed/ divorced/separated and lower FIR (P\u0026lt;0.001). Besides, Significant differences were also found between the two groups in terms of smoking, hypertension, and diabetes. Notably, individuals with COPD had a higher level of Systemic Inflammation Index (SII), with values of 525.2 (range: 355.7-736.2) versus 451.3 (range: 316.6-644.6) in non-COPD individuals (P \u0026lt; 0.001). Furthermore, 17.4% of COPD patients reported taking more than ten different prescription medications in the past month, compared to only 3.6% of non-COPD individuals.\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cp class=\"CaptionNumber\"\u003eTable 1\u003c/p\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCharacteristics of the NHANES 2011\u0026ndash;2023 participants\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eOverall\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eCOPD\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003eNon-COPD\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u003cem\u003eP\u003c/em\u003e-value\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;5668\u003c/em\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;650\u003c/em\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;5018\u003c/em\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eAge, y, mean(SE)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e63.9 (0.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e65.7(0.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e63.7 (0.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eSex, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003emale\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3033(52.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e408 (60.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2625 (51.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003efemale\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2635 (47.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e242 (39.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2393 (48.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eRace/Ethnicity, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;\u0026thinsp;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNon-Hispanic White\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2404 (72.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e359 (81.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2045 71.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNon-Hispanic Black\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1429 (10.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e168 (8.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1261 (10.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMexican American\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e600 (5.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e32 (1.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e568 (5.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eOther Hispanic\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e616 (5.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e45 (2.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e571 (5.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eOthers\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e619 (6.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e46 (5.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e573 (7.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eEducation, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.010\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eHigh school and below\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1332 (13.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e173 (18.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1159 (13.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eHigh school graduate\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1395 (26.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e176 (29.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1219 (24.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eAbove high school\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2941 (59.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e301 (51.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2640 (61.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.196\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026lt;25\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1434 (24.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e171 (25.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1263 (24.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e25\u0026ndash;30\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2020 (35.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e211 (37.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1809 (36.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026ge;30\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2214 (39.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e268 (37.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1946 (39.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMarital, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eMarried/living with partner\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3351 (66.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e339 (61.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3012 (66.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eWidowed/divorced/separated\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2054 (29.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e279 (34.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1775 (28.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eNever married\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e263 (4.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e32 (3.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e231 (5.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eFIR, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026le;1.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1486 (15.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e224 (23.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1262 (14.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e1.3\u0026ndash;3.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2604 (42.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e292 (42.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2312 (42.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026gt;3.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1578 (42.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e134 (33.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1444 (43.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eSmoking, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e916 (24.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e185 (31.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e731 (22.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eDiabetes, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1927 (28.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e257 (31.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1670 (27.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e0.004\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eHypertension, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3857 (62.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e491 (72.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3366 (61.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eLow-dose Aspirin, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3906 (69.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e507 (77.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3399 (69.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eRXD, n(%)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026lt;5\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e3221 (60.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e227 (43.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2994 (62.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e5\u0026ndash;10\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e2115 (34.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e298 (39.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e1817 (33.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026ge;10\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e332 (5.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e125 (17.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e207 (3.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003eSII, median (IQR)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e460.2 (320.8-\u003cbr\u003e6297.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e525.2 (355.7-\u003cbr\u003e736.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e451.3 (316.6-\u003cbr\u003e644.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eData was shown as number (percentage), mean (SE) or median (25th-75th percentile).\u003c/p\u003e\n\u003cp\u003eAbbreviations: BMI, body mass index; FIR, family income-poverty; SII, systemic immune inflammation index; RXD, the numbers of taking prescription medicine in past month.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCorrelations of low-dose aspirin with COPD prevalence and SII\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe prevalence of Chronic Obstructive Pulmonary Disease (COPD) was significantly lower in individuals taking low-dose aspirin. As indicated in Table 2, low-dose aspirin showed a significant association with COPD prevalence in the crude model (\u0026beta;= -0.027, 95% CI = -0.039, -0.016, p \u0026lt; 0.001). After adjusting for potential confounders included age, race/ethnicity, education level, marital status, BMI, smokinng status, FIR, BMI, hypertension, diabetes and RXD, low-dose aspirin was also associated with a 0.015 decrease in COPD prevalence(\u0026beta;=-0.015, 95%CI=-0.026, -0.003, p\u0026lt;0.001). When participants were categorized by sex, the positive correlation between low-dose aspirin and COPD prevalence was found to be stronger in males than in females within the crude model (\u0026beta;= 0.034, 95% CI = 0.015, 0.052 for males vs. \u0026beta;=0.018, 95% CI=0.004, 0.033 for females). Although low-dose aspirin use was slightly but significantly related to COPD in males, this relationship was not observed in females after adjusting for all covariates (\u0026beta;=0.020, 95% CI = 0.002, 0.038 for males vs. \u0026beta;=0.011, 95% CI=-0.003, 0.025 for females). Furthermore, low-dose aspirin was associated with SII ( \u0026beta; =0.047, 95% CI = 0.033, 0.061, p \u0026lt; 0.001)，as well as the adjust model (\u0026beta; =0.036, 95% CI = 0.022, 0.050, p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eTable 2 Associations of aspirin with SII and COPD prevalence(n=5668)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003eNumber of participants\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026beta;(95% CI)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u003cem\u003eP\u003c/em\u003e-Value\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003eEffect sizes of moderation effects\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003eP for interaction\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 630px;\"\u003eAssociations of\u0026nbsp;low-dose aspirin\u0026nbsp;and COPD\u003cbr\u003eCrude Model\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e0.153\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eTotal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e5668\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e-0.027 (-0.039,-0.016)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eMale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e3033\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.034(0.015,0.052)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eFemal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e2635\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.018(0.004,0.033)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.014\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 630px;\"\u003eAssociations of\u0026nbsp;low-dose aspirin\u0026nbsp;and COPD\u003cbr\u003eAdjusted Model\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e0.104\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e0.030\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eTotal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e5668\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e-0.015\u003cbr\u003e(-0.026,-0.003)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.011\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eMale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e3033\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.020(0.002,0.038)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.028\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eFemal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e2635\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.011(-0.003,0.025)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.137\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 630px;\"\u003eAssociations of\u0026nbsp;low-dose aspirin\u0026nbsp;and SII\u003cbr\u003eCrude Model\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e-0.175\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eTotal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e5668\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.047(0.033,0.061)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eMale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e3033\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e-0.044(-0.064,-0.023)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eFemal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e2635\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e-0.053(-0.072,-0.034)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 630px;\"\u003eAssociations of\u0026nbsp;low-dose aspirin\u0026nbsp;and SII\u003cbr\u003eAdjusted Model\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e-0.2\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eTotal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e5668\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.036(0.022,0.050)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eMale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e3033\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e-0.032(-0.053,-0.012)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003eFemal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 182px;\"\u003e2635\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e-0.044(-0.063,-0,025)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: SII, systemic immune inflammation index, was calculated by Platelsts*Neutrophils /Lymphocytes. SII was transformed to natural logarithms in the analysis.\u003c/p\u003e\n\u003cp\u003eCrude model was unadjust for any covariates, while the adjust model was adjusted for age, race/ethnicity, education level, marital status, BMI, smokinng status, FIR,BMI, hypertension, diabetes and RXD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eNonlinear association between SII and the prevalence of COPD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 3 illustrates the relationship between SII and COPD under both crude and adjusted models, utilizing the Restricted Cubic Splines (RCS) method. In this analysis, SII was transformed into natural logarithms (lnSII). Our findings indicate a nonlinear positive correlation between these variables. In the crude model, the odds ratio (OR) gradually increases with higher lnSII values. Notably, when lnSII approaches 5, the OR begins to rise significantly, and this rise accelerates when lnSII reaches 7 (as shown by the green curve). In comparison, the adjusted model demonstrates a more pronounced increase in the OR at higher lnSII values. Additionally, the curves for males and females in the subgroup analysis show similar trends; however, there are notable differences in specific values and the rates of increase, particularly at elevated lnSII levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMediating effect of SII on low-dose aspirin and COPD prevalence\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 presents the results of a mediation analysis of the relationship between low-dose aspirin and prevalence of COPD. SII significantly mediated the association between low-dose aspirin and COPD prevalence in both crude ( proportion mediated [PM], -0.04897; average causal mediation effects [ACME] = -0.00124 , [95% CI =-0.00196, 0], p = \u0026lt;2e-16) and adjusted model (PM, -0.039130; ACME = -0.000552, [95% CI = -0.001042, 0], p = 0.01). When stratifying by sex, the analysis shows that SII positively mediates the relationship between low-dose aspirin and COPD prevalence in males, but not in females, after adjusting for all covariates. In males, the mediation was significant (PM: -0.033229; ACME: -0.000642, with a 95% CI: -0.001383, 0; p = 0.020), while in females, the results were not statistically significant (PM: -0.046264; ACME: -0.000642, with a 95% CI: -0.001162, 0; p = 0.10).\u003c/p\u003e\n\u003cp\u003eTable3 SII mediating the association between low-dose aspirin and COPD prevalence(n =5668).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003eACME\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003eADE\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003eTotal effect\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003eProportion mediated\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003eCrude \u0026nbsp;model\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003eTotal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.00124\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.00196\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.00\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026lt;2e-16\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.02662\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.01544\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.04\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026lt;2e-16\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.02537\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.01467\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.04\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026lt;2e-16\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.04897\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.06514\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e-0.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026lt;2e-16\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003eMale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.00142\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.00252\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.00\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.03303\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.01562\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.05\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.002\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.03161\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.01505\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.05\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.002\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.04486\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.06858\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e-0.02\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026lt;2e-16\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003eFemale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.000917 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.001818 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.00\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.006\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.017366 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;0.004265 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.03 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.006\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.016449\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.004082\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.03\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.006 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.055742 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.079025 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e-0.03\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026lt;2e-16\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003eAdjusted \u0026nbsp;model\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003eTotal\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.000552\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.001042 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.00\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.008\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.014648\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.004360 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.014096\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.003730 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.02\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.039130 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\u0026nbsp;-0.172270 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e-0.01 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.01\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003eMale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.000642\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.001383\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.00 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.020\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.019961 \u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.003113\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.04\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.018\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.019319\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.003028\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.04\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.018\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.033229\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.056796\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e-0.01\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003eFemale\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.000642\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.001162\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.00\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.010587\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.002930\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.02\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e0.010119\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.002883\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e0.02\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e0.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.046264\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e-0.070219\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4px;\"\u003e-0.02\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\u0026lt;2e-16\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: BMI, body mass index; SII, systemic immune inflammation index; ACME, average causal mediation effect; ADE, average direct effect.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSII was transformed to natural logarithms in the analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCrude model was unadjusted for any covariates, while the adjust model was adjusted for age, race/ethnicity, education level, marital status, BMI, smoking status, FIR,BMI, hypertension, diabetes and RXD.\u003c/p\u003e\n\u003cp\u003eFigure 3 illustrates the potential mediating role of gender in the relationship between low-dose aspirin and the prevalence of COPD. Our findings indicate that low-dose aspirin is significantly associated with COPD, but not with SII (P\u0026gt; 0.05). Additionally, SII does have an effect on COPD. Overall, gender does not appear to mediate the relationship between low-dose aspirin and COPD, as indicated by an ACME of 0.000 and a PM of -0.000.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this paper, we examined the relationship between low-dose aspirin intake and the prevalence of COPD in adults in the United States, specifically investigating whether this association is partially mediated by the Systemic Immune Inflammatory Index (SII).\u003c/p\u003e\n\u003cp\u003eThe primary conclusion drawn from the data is that low-dose aspirin intake decreases the prevalence of COPD, with stronger associations observed in males. This observation aligns with our findings, which indicated that the number of male patients with COPD exceeded that of female patients. As we know, cigarette smoke exposure is strongly associated with COPD [17], and the prevalence of tobacco in men is higher than women[18]. Previous studies have confirmed that inflammatory response of lung macrophages and epithelial cells from tobacco smoke[19,20]. These findings are consistent with research showing that aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways [21]. This may explain why low-dose aspirin, known for its anti-inflammatory properties, could reduce the incidence of COPD. However, it remains unclear whether the higher SII observed in men is responsible for low-dose aspirin\u0026apos;s ability to reduce COPD prevalence. Additionally, there is insufficient evidence to suggest that smokers exhibit higher levels of SII.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs anticipated, our results indicated a positive correlation between low-dose aspirin intake and SII levels. We utilized SII as a marker of inflammation due to its economical nature and ease of use in clinical settings. Comparisons with other studies confirm that aspirin can reduce the lymphocyte ratio (NLR) [22, 23], although few studies have explored the relationship between aspirin and SII. A potential explanation for this correlation may lie in aspirin\u0026apos;s effects on platelet function and inflammation. Moreover, SII calculation is based on the counts of platelets, neutrophils, and lymphocytes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnother significant finding of this study is that SII level was associated with COPD in a nonlinear pattern, with SII positively correlating with COPD after surpassing a certain threshold. Prior studies have also identified nonlinear relationships between SII and COPD [24,25]. As a novel inflammatory biomarker, SII can be utilized to predict COPD risk and demonstrates superiority compared to NLR [8]. Furthermore, SII significantly mediated the association between low-dose aspirin and COPD prevalence. While direct studies on the effect of aspirin on SII are lacking, prior research has indicated that aspirin influences neutrophil function and lymphocyte proliferation [26].\u0026nbsp;Given that neutrophilic inflammation is a prominent feature of COPD [27]. it can be hypothesized that SII mediates the interactions between aspirin and COPD, and our results support this hypothesis. To advance precision approaches in COPD management, drug repurposing based on specific inflammatory biomarkers (e.g., type 2 inflammation) shows promise [28].\u003c/p\u003e\n\u003cp\u003eAlthough there are important discoveries revealed by these studies, there are also limitations. First, due to the cross-sectional nature of this study, we could not establish a causal relationship between low-dose aspirin, SII, and COPD. Additional randomized controlled studies are needed to validate our findings. Second, the data on low-dose aspirin intake and COPD status were primarily obtained from questionnaires, which may introduce potential memory bias. Longitudinal studies should implement stricter diagnostic criteria to further validate our results. Finally, while we adjusted for many confounding variables, some residual factors influencing COPD onset may remain unaccounted for.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, the results of this study showed that SII, low-dose aspirin and COPD are pairwise correlated. Our findings highlight the importance of low-dose aspirin intake may decrease the risk of COPD, with SII playing a marginal role in mediating the relationship between low-dose aspirin and the prevalence of COPD. Further longitudinal studies are required to investigateh the specific mechanism behind it.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDandan Dai contributed to the conception, design and writing. Jiejun Shi and Chaochao Ding contributed to the Software and formal analysis. Jianmin Ren analyzed the data. Hongbin Xu edited and revised the manuscript. All authors contributed to the critical revision of the manuscript and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by International Medical Exchange Foundation of China (Z-2017-24-2301), Ningbo medical science and technology project (2022Y06).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data utilized in this study is readily available from the U.S. Centers for Disease Control and Prevention through the National Center for Health Statistics, which effectively manages the National Health and Nutrition Examination Survey (NHANES).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by the board of the National Center for Health Statistics (NCHS). All the participants signed the informed consent before participating in the study.\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\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo potential conflict of interest was reported by the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Pharmacy, The First Affiliated Hospital of Ningbo University, Ningbo, China; \u003csup\u003e2\u003c/sup\u003e Department of Infectious disease, The First Affiliated Hospital of Ningbo University, Ningbo, China;\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFrancesca Polverino, Don D. Sin.Type 2 airway inflammation in COPD. 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The association between systemic immune-inflammation index and chronic obstructive pulmonary disease in adults aged 40 years and above in the United States: a cross-sectional study based on the NHANES 2013\u0026ndash;2020. Front Med (Lausanne).2023;10:1270368.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYe C, Li Y, KL. Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study. BMC Pulm Med. 2023;23(1):295.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHall DCN, Benndorf RA. Aspirin sensitivity of PIK3CA-mutated colorectal cancer: Potential mechanisms revisited. Cell Mol Life Sci. 2022;79(7):393.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMontinari MR, Minelli S, De Caterina R. The first 3500 years of aspirin history from its roots - a concise summary. Vascul Pharmacol. 2019;113:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatrono C. 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Low-Dose\u0026ensp;Aspirin\u0026ensp;and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway.\u0026ensp;Am. J Gastroenterol. 2024;119(7):1402\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNelson MR, Black JA. Aspirin: latest evidence and developments. Heart. 2024;110(17):1069\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManevski M, Devadoss D, Long C et al. Increased Expression of LASI lncRNA Regulates the Cigarette Smoke and COPD Associated Airway Inflammation and Mucous Cell Hyperplasia.Front Immunol. 2022; 14(13):803362.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaul B, Jean Simon D, Kondo Tokpovi VC, et al. Tobacco use in Haiti: findings from demographic and health survey. BMC Public Health. 2023;23(1):2504.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrzelak A, Ratajczak A, Adamiec A, et al. Tobacco Smoke Induces and Alters Immune Responses in the Lung Triggering Inflammation, Allergy, Asthma and Other Lung Diseases: A Mechanistic Review. Int J Environ Res Public Health. 2018;15(5):1033.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonzalez DH, Soukup JM, Madden MC, et al. A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. Chem Res Toxicol. 2020;33(4):999\u0026ndash;1009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Oliveira JR, Pereira ABM, et al. Anti-inflammatory actions of aspirin-triggered resolvin D1 (AT-RvD1) in bronchial epithelial cells stimulated by cigarette smoke extract. Prostaglandins Other Lipid Mediat. 2024;172:106833.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa Q, Li WN, Liu HY et al. Expression of NLR and IL-1β and their predictive efficacy value in acute myocardial infarction patients treated with aspirin combined with clopidogrel. J Biol Regul Homeost Agents. 2021;35(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi W, Ren X, Zhang L. Clinical efficacy of atorvastatin calcium combined with aspirin in patients with acute ischemic stroke and effect on neutrophils, lymphocytes and IL-33. Exp Ther Med. 2020;20(2):1277\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwok WC, Tam TCC, Lam DCL, et al. Systemic immune-inflammation index in predicting hospitalized bronchiectasis exacerbation risks and disease severity. J Thorac Dis. 2024;16(5):2767\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao Y, Li H, Wang Z, et al. Exploring the\u0026ensp;association\u0026ensp;between magnesium deficiency and\u0026ensp;chronic\u0026ensp;obstructive\u0026ensp;pulmonary\u0026ensp;diseases in NHANES 2005\u0026ndash;2018. Sci Rep. 2024;14(1):25981.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChokshi R, Bennett O, Zhelay T, et al. NSAIDs Naproxen, Ibuprofen, Salicylate, and\u0026ensp;Aspirin\u0026ensp;Inhibit TRPM7 Channels by Cytosolic Acidification. Front Physiol. 2021;12:727549.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwak N, Lee KH, Woo J, et al. Del-1 Plays a Protective Role against\u0026ensp;COPD\u0026ensp;Development by Inhibiting Inflammation and Apoptosis. Int J Mol Sci. 2024;25(4):1955.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoll M, Silverman EK. Precision Approaches to Chronic Obstructive Pulmonary Disease Management. Annu Rev Med. 2024;75:247\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\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":"Aspirin, COPD, SII, NHANES","lastPublishedDoi":"10.21203/rs.3.rs-5817670/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5817670/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCOPD is a respiratory disease with significant inflammatory characteristics. Low-dose aspirin is widely used as an anti-inflammatory medicine. However, the impact of low-dose aspirin on COPD is unclear. This article aims to investigate the association between low-dose aspirin and the prevalence of COPD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA cohort study was conducted based on United States population data from the National Health and Nutrition Examination Survey (NHANES) data (2011\u0026ndash;2012, 2013\u0026ndash;2014, 2015\u0026ndash;2016, 2017\u0026ndash;2020, and 2021\u0026ndash;2023). We examined pairwise associations between systemic immune inflammation index (SII), low-dose aspirin, and COPD prevalence by logistic regression analysis, the restricted cubic spline (RCS), and mediation analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn 5,668 people, 68% of them took low-dose aspirin. We found higher levels of SII in participants with COPD compared to those without COPD. Low-dose aspirin was significantly associated with COPD prevalence (β=-0.015, 95%CI=-0.026, -0.003, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and SII (β\u0026thinsp;=\u0026thinsp;0.036, 95% CI\u0026thinsp;=\u0026thinsp;=\u0026thinsp;0.022, 0.050, p\u0026thinsp;\u0026le;\u0026thinsp;0.001), even after considering a wide range of potential confounders (e.g., age, sex, race). SII was nonlinearly associated with COPD. SII mediated a marginal portion (PM, -0.039130; ACME = -0.000552, [95% CI = -0.001042, 0], p\u0026thinsp;=\u0026thinsp;0.01) of the potential effects of low-dose aspirin on COPD prevalence.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur research showed that SII, low-dose aspirin, and depression are pairwise correlated. Low-dose aspirin may decrease the risk of COPD, and Prophylactic use of low-dose aspirin may be advised in individuals at high risk of COPD.\u003c/p\u003e","manuscriptTitle":"Association between low-dose aspirin and prevalence of chronic obstructive pulmonary disease (COPD): The mediating role of systemic immune inflammation index","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-15 12:10:06","doi":"10.21203/rs.3.rs-5817670/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":"d6041acf-acf2-41e7-9377-a1c9b5e5883e","owner":[],"postedDate":"January 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-20T18:08:36+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-15 12:10:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5817670","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5817670","identity":"rs-5817670","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}