C-Reactive Protein to Lymphocyte Ratio is associated with asthma risk:A Cross-Sectional Study

C-Reactive Protein to Lymphocyte Ratio is associated with asthma risk:A Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article C-Reactive Protein to Lymphocyte Ratio is associated with asthma risk:A Cross-Sectional Study yun Guo, wei zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8150143/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 17 You are reading this latest preprint version Abstract BACKGROUND CLR, a recently identified inflammatory biomarker, has been associated with various inflammatory conditions. Asthma is an inflammatory airway disease heavily influenced by inflammation. The primary goal of this study was to examine the impact of CLR on the risk of asthma. Methods This study conducted a retrospective analysis of 22,339 participants from the NHANES dataset between 1999 and 2010. To investigate the relationship between CLR and asthma risk, we employed logistic regression and restricted cubic spline analysis. Additionally, subgroup and sensitivity analyses were performed to validate the robustness of the identified associations. Results Analysis using a multivariate logistic regression models revealed a significant positive correlation between ln-transformed CLR and asthma risk (OR: 1.07,95% CI 1.03–1.11; P < 0.001). Compared to participants in the first tertile of ln-transformed CLR values ( T1), those in the T2 and T3 showed increased asthma risk by 1.07 times and 1.21 times, respectively. The risk demonstrated a statistically significant upward trend with higher ln-transformed CLR (trend test P < 0.001). RCS analysis confirmed no nonlinear relationship between CLR values and asthma risk. Subgroup and sensitivity analyses further validated the robustness and consistency of these findings. Conclusions As the CLR level improved, the risk of asthma increased correspondingly, exhibiting a linear correlation. C-Reactive Protein to Lymphocyte Ratio asthma NHANES risk inflammation Figures Figure 1 Figure 2 Introduction Asthma is a chronic inflammatory disorder of the airways that leads to symptoms such as coughing, wheezing, shortness of breath, and chest tightness. These symptoms arise from airway inflammation, which triggers mucus production, remodeling of the airway walls, and bronchial hyperresponsiveness 1 . In 2021, approximately 260 million individuals worldwide were affected by asthma, a number projected to rise to 275 million by 2050. Asthma presents considerable public health challenges due to its health impacts, economic burdens, and the distress experienced by patients 2 . In many asthma patients, chronic airway inflammation is mediated by Th2 cells or ILC2 cells that produce IL-4, IL-5, and IL-13 4 . Consequently, asthma involves a variety of immune cells and inflammatory cytokines, with intricate immune mechanisms playing a vital role 1 . C-reactive protein (CRP) is widely recognized as a sensitive biomarker for inflammation. The correlation between elevated plasma or serum CRP levels and various disease states has attracted considerable attention 3 .Recently, the C-reactive protein to lymphocyte ratio (CLR), an emerging inflammatory biomarker, has been shown to effectively indicate the balance between systemic inflammatory response and immune activation 5 . Numerous studies have established that elevated CLR levels are significantly associated with poor prognosis in a range of diseases, including Chronic Obstructive Pulmonary Disease 6 ,myocardial infarction 7 , chronic kidney disease 8 and Non-alcoholic fatty liver disease (NAFLD) 9 . As a biomarker, CLR holds substantial promise for predicting disease outcomes and enhancing diagnostic evaluations. Asthma, characterized as an inflammatory airway disease, is associated with inflammatory processes, indicating a possible link to CLR levels. This study seeks to examine the relationship between CLR levels and the risk of asthma in American adults through a cross-sectional design. Methods Study Population The National Health and Nutrition Examination Survey (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), serves as a nationally representative study aimed at evaluating the health status and nutritional levels of non-institutionalized populations in the United States. Employing a multi-stage stratified probability sampling strategy, the survey gathers extensive data through standardized questionnaires, physical examinations, and laboratory tests. This dataset offers valuable insights into demographic characteristics, chronic disease profiles, biomarkers, lifestyle behaviors, and environmental exposures. To maintain data relevance and national representativeness, findings are released biennially. The NHANES protocol has received approval from the National Center for Health Statistics Research Ethics Review Board, with all participants providing written informed consent upon enrollment. (This study utilizes publicly available standardized data, https://www.cdc.gov/nchs/nhanes/irba98.htm; ethical approval or consent is required.) This research employed a cross-sectional design, utilizing data from the National Health and Nutrition Examination Survey (NHANES) collected from 1999 to 2010. The study focused exclusively on adult participants. Additionally, individuals who were pregnant (n=1294), those without relevant asthma survey data (n=31), and participants with incomplete records for CLR (n=3515) or covariates (n=5285) were excluded (Figure 1). Incomplete data on demographic characteristics (age, gender, race, BMI), prior medical history (alcohol or tobacco use, hypertension, diabetes, cardiovascular disease), and laboratory test indicators (neutrophil differential count, eosinophils, monocytes, platelets, red blood cells) led to the exclusion of 5,285 study participants, resulting in the inclusion of 22,339 eligible research subjects. C-Reactive Protein to Lymphocyte Ratio Blood samples were collected at the NHANES Mobile Examination Center (MEC) and subsequently analyzed in the laboratory. In this study, CLR denotes the ratio of C-reactive protein (CRP) concentration (mg/L) to lymphocyte count (1000 cells/L) 10 . NHANES maintains rigorous data quality control procedures during both data collection and laboratory analysis. Asthma Asthma diagnosis was rigorously established through a comprehensive standardized questionnaire aimed at capturing detailed medical histories. Participants were classified as having asthma if they answered affirmatively to the critical question, "Have you ever been told by a healthcare professional that you have asthma?" This question was designed to elicit clear and definitive responses. This method ensured that the diagnosis was both reliable and consistent, accurately reflecting the participants' self-reported medical histories. The structured nature of the questionnaire facilitated an efficient process for identifying individuals with asthma, thereby enhancing the overall validity of the study's findings. Covariates Investigators with specialized training conducted the data collection and documentation processes. The study encompassed demographic characteristics (age, gender, race/ethnicity, education, marital status, alcohol and tobacco use, poverty-income ratio, and body mass index), comorbid conditions (cardiovascular disease, hypertension, diabetes), and laboratory parameters (segmented neutrophil, eosinophil, monocyte, platelet, and red blood cell counts). Gender is primarily classified into two categories: male and female. Ethnicity is further subdivided into the following groups: non-Hispanic white participants, non-Hispanic black participants, Mexican American participants, and others. Educational attainment is categorized into three levels: high school or higher, high school or equivalent, and high school or below. Marital status is classified into two types: married or living with a partner, and single. Alcohol consumption is divided into three categories: current drinkers, former drinkers, and non-drinkers. Smoking status is classified into two groups: smokers and non-smokers. The Poverty-Income Ratio (PIR) is divided into three ranges: ≤1.30, 1.31-3.50, and >3.50. Body Mass Index (BMI) is calculated by dividing weight by height squared. The diagnosis of asthma was confirmed through interviews utilizing a standardized questionnaire aimed at assessing medical conditions. This questionnaire included the question: “Have you ever been told you have asthma?” A participant was classified as having asthma if they answered "yes" to any of the questions posed. 11 Hypertension is diagnosed when subjects meet any of the following criteria: an average systolic blood pressure of 140 mmHg or higher, an average diastolic blood pressure of 90 mmHg or higher, a history of using antihypertensive medication, or a confirmed hypertension diagnosis 12 . The diagnosis of diabetes mellitus is based on the following criteria: a fasting blood glucose level of ≥7.0 mmol/L, a random blood glucose level of ≥11.1 mmol/L, an oral glucose tolerance test indicating a post-2-hour blood glucose level of ≥11.1 mmol/L, a glycated hemoglobin level of ≥6.5%, or a confirmed diabetes mellitus diagnosis in patients receiving insulin therapy or diabetes medications 13 . Statistical Analysis In accordance with established literature and clinical practice, we compiled demographic indicators and laboratory data from the participants 7,14 . The substantial sample size of the study resulted in a proportion of missing covariate values of less than 10%. Given the minimal extent of missing data, we chose to exclude these values directly. We considered the distribution characteristics of continuous variables, presenting normally distributed data as mean ± standard deviation (SD) and summarizing skewed data using the median and interquartile range (IQR). Differences among groups were assessed using one-way ANOVA, the Kruskal–Wallis test, or chi-square tests. Given the asymmetric distribution of the CLR data, this study first applied a natural logarithm (LN) transformation to the dataset before conducting statistical analyses. In the subsequent exploratory analyses, CLR was treated as a continuous variable; within the transformed dataset, analyses were performed using increments of 1 unit or by grouping based on three-tenths quantiles. A multiple logistic regression model was employed to compute odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs). This study developed five analytical models. Model 1, the baseline model, included no covariates. Model 2 adjusted for demographic variables, such as age, gender, and race/ethnicity. Model 3 expanded this adjustment to include socioeconomic and lifestyle factors, including education level, marital status, alcohol consumption patterns, smoking habits, poverty income ratio (PIR), and body mass index (BMI). Model 4 additionally accounted for major comorbidities, such as cardiovascular disease, hypertension, and diabetes. Model 5 functioned as the comprehensive adjustment model, incorporating all previously identified variables. To investigate the dose-response relationship between log-transformed CLR and asthma, we utilized a three-knot restricted cubic spline (RCS) for our analysis. Additionally, this association was assessed using a piecewise logistic regression model, which included adjustments for all covariates in Model 5. Moreover, this study conducted subgroup analyses for sensitivity assessment. Stratified analyses were carried out according to variables including gender, age (20-65 years vs. ≥65 years), body mass index (BMI, <18.5 vs. 18.5-24.9, 25-29.9, or ≥30 kg/m²), smoking status (non-smokers vs. smokers), coronary heart disease, hypertension, and diabetes, aiming to assess the consistency of the association between logarithmically transformed CLR and asthma across various subgroups. Statistical analyses were performed using R4.2.2 (http:// www.R-project.org, The R Foundation) and Free Statistics software version 2.2. A P-value <0.05 (two-sided) was regarded as statistically significant in all analyses. Results Baseline Characteristics Between 1999 and 2010, this study successfully enrolled 22,339 participants (shown in Fig. 1). The participants were categorized into three groups—T1, T2, and T3—according to their CLR levels. An examination of Table 1 reveals baseline disparities between the T1 and T2 groups in comparison to the T3 group, with all variables demonstrating significant differences. Higher levels of C-reactive protein (CRP) in the upper tertiles correlated with increased age, a higher proportion of females, elevated body mass index (BMI), and a greater burden of comorbidities. Hematological parameters revealed progressive increases in segmented neutrophils and platelets across the tertiles. The prevalence of asthma exhibited a graded increase from the first quartile (Q1) to the third quartile (Q3) (Table 1). Logit analysis Given the skewed distribution characteristics of the CLR data, this study utilized a natural logarithm (ln) transformation method to standardize the data. Table 2 presents the analysis results regarding the association between CLR and asthma following ln transformation across five models. In Model 1, when treating the ln-transformed CLR as a continuous variable, a significant positive correlation with asthma risk was observed (OR=1.1; 95% CI=1.07-1.14; P<0.001). Notably, this association remained significant even after adjusting for multiple covariates. The results in Model 5 indicate that for each 1-unit increase in ln-transformed CLR, the risk of asthma increased by 7% (OR=1.07; 95% CI=1.03-1.11; P<0.001). When performing a three-way grouping analysis on natural ln-transformed CLR data, the association with asthma revealed trends consistent with those found in continuous analysis. Individuals in the third quartile (T3) exhibited a higher risk of asthma compared to those in the first quartile (T1) (OR=1.21; 95% CI 1.09-1.36; P=0.001; Table 2, Model 5). Importantly, across all models, the risk of asthma showed a progressive increase corresponding to the advancement of the three-way grouping in natural ln-transformed CLR data (all trend P-values <0.001). Non-linear relationships Another key finding of this study is the lack of a nonlinear relationship. As shown in Fig. 2, no nonlinear association was detected between CLR and asthma risk (nonlinear test p-value = 0.331). The asthma risk demonstrated an increasing trend with rising CLR values, indicating a significant positive correlation between the two variables. Sensitivity analysis Table 3 consolidates the findings from the stratified and interaction analyses. As shown in Table 3, no interaction was observed between age, sex, smoking history, coronary heart disease, hypertension, and CLR. This indicates that, regardless of age being over 65 years, sex, smoking history, or a history of coronary heart disease and hypertension, the risk of asthma increased with elevated CLR. An interaction may exist among Body Mass Index (BMI), diabetes, and CRP levels. However, it is important to emphasize that regardless of whether an individual's BMI is 30 or higher or whether they have comorbid diabetes, the risk of asthma rises with increased CRP levels. The analysis of all subgroups in this study is consistent with the trend observed in the overall population, suggesting that elevated CRP levels are a significant risk factor for the onset of asthma. Discussion Using national adult sample data from the National Health and Nutrition Examination Survey (NHANES), this study identified a significant positive correlation between CLR levels and asthma risk, after carefully controlling for multiple covariates. Subgroup analysis of the sensitivity analysis further confirmed the robustness of the results. Additionally, a progressive linear relationship was observed between CLR and asthma risk, offering new insights into the complex interaction mechanisms between the two. C-reactive protein (CRP), a well-established marker of systemic inflammation, is strongly associated with asthma. Multiple clinical studies have reported that plasma CRP levels are significantly higher in patients with asthma than in those without 15 . Notably, inhaled glucocorticoids have been shown to reduce CRP levels effectively 15 .Moreover, Mendelian randomization analyses provide evidence for a causal relationship, indicating that elevated circulating CRP directly increases the risk of asthma. 16 17 Lymphocyte-mediated immune dysregulation significantly contributes to the pathology of asthma. Clinical studies indicate that patients with asthma exhibit a reduction in T lymphocytes and a Th2 immune bias, characterized by elevated IgE levels and increased eosinophil counts. 18 Research on nocturnal asthma has demonstrated that the circadian rhythm of lymphocyte activity correlates with fluctuations in symptoms 19 . Transgenic mouse models have confirmed that the expression of human MMP-9 can mitigate airway hyperresponsiveness and lymphocyte aggregation 20 . Furthermore, genome-wide studies have revealed that genes associated with lymphocyte count are enriched in regions linked to asthma susceptibility, suggesting that genetic factors may influence asthma risk by modulating lymphocyte function. 21 These findings suggest that the C-reactive protein–to–lymphocyte count ratio (CLR) may serve as a novel clinical biomarker for asthma progression. The study found a significant association between higher CLR and increased asthma risk, and this association remained statistically significant after adjustment for multiple potential confounders. This study's strength is that it provides new evidence linking CLR to asthma risk. It analyzed a strictly defined, highly homogeneous adult population drawn from a nationally representative sample of U.S. adults. The study design also adjusted effectively for confounders, thereby substantially reducing their potential influence on the results. This study provides useful insights but has several important limitations. First, its retrospective design limits control over confounding and prevents causal inference. Second, because the NHANES database records asthma diagnosis only by self-report, the outcome is vulnerable to reporting bias. Third, C-reactive protein levels and lymphocyte markers can be altered by immune status or recent acute infections, and these influences were not fully controlled. Although we applied regression models, subgroup analyses, and sensitivity tests, unmeasured or unknown confounders may still have affected the results. Therefore, future work should use longitudinal designs to test causality and perform mechanistic experiments to elucidate the underlying biology. Conclusion This study revealed a correlation between CLR levels and asthma risk: elevated CLR levels were proportional to an increased risk of asthma. Declarations Statement of Ethics The NHANES protocol has been reviewed and approved by the National Center for Health Statistics Research Ethics Review Board, with all participants signing written informed consent forms upon enrollment. (This study utilizes publicly available standardized data, https://www.cdc.gov/nchs/nhanes/irba98.htm.thus no ethical approval or consent is required.) Competing interests The authors have no conflicts of interest to declare. Funding This study was not funded by any external source Authors’ contributions Yun Guo was responsible for data collection and analysis, interpreting results, writing the thesis, and designing the research. Wei Zhou participated in the manuscript review. Data Availability Statement This study utilized the NHANES public databases. The National Health and Nutrition Examination Survey (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), is a nationally representative study designed to assess the health status and nutritional levels of non-institutionalized populations in the United States. 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17:00:44","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":119067,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8150143/v1/85df5af12ad08c9c7c2d108a.html"},{"id":100613238,"identity":"3d71954d-899a-4ac1-8e6c-f67bba272262","added_by":"auto","created_at":"2026-01-19 17:02:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":105467,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBaseline Characteristics of Participants in the NHANES 1999–2010 Cycles\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8150143/v1/7d07c6d7a737836ca863fd5a.png"},{"id":100613222,"identity":"4a4083ac-38ae-44c1-a456-1df54a742db6","added_by":"auto","created_at":"2026-01-19 17:01:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":63958,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNon-linear relationship between ln-CLR and asthma risk.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdjustment factors included age, sex, race/ethnicity,marital status, poverty income ratio, educational level, smoking status, drinking status, body mass index,cardiovascular disease, hypertension, diabetes,segmented neutrophils number, platelet count, eosinophils number, monocyte number, red blood cell count.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe red line and orange line represent the estimated values and their corresponding 95% confidence intervals.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8150143/v1/8b46b586b81a9b088261d00f.png"},{"id":100615780,"identity":"5555b32b-5dc9-4f43-b02a-53125d043e3f","added_by":"auto","created_at":"2026-01-19 17:36:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":816925,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8150143/v1/7c2d3196-b284-4c1a-beba-59e6cfac4e30.pdf"},{"id":100613216,"identity":"e8c6f7b9-b5e2-4b5a-a672-c1af1b9c44c9","added_by":"auto","created_at":"2026-01-19 17:01:31","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13835,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialSectionS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8150143/v1/6d5fb52b6d368dcd4e136a62.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eC-Reactive Protein to Lymphocyte Ratio is associated with asthma risk:A Cross-Sectional Study\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAsthma is a chronic inflammatory disorder of the airways that leads to symptoms such as coughing, wheezing, shortness of breath, and chest tightness. These symptoms arise from airway inflammation, which triggers mucus production, remodeling of the airway walls, and bronchial hyperresponsiveness\u003csup\u003e1\u003c/sup\u003e. In 2021, approximately 260 million individuals worldwide were affected by asthma, a number projected to rise to 275 million by 2050. Asthma presents considerable public health challenges due to its health impacts, economic burdens, and the distress experienced by patients\u003csup\u003e2\u003c/sup\u003e. In many asthma patients, chronic airway inflammation is mediated by Th2 cells or ILC2 cells that produce IL-4, IL-5, and IL-13\u003csup\u003e4\u003c/sup\u003e. Consequently, asthma involves a variety of immune cells and inflammatory cytokines, with intricate immune mechanisms playing a vital role\u003csup\u003e1\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eC-reactive protein (CRP) is widely recognized as a sensitive biomarker for inflammation. The correlation between elevated plasma or serum CRP levels and various disease states has attracted considerable attention\u003csup\u003e3\u003c/sup\u003e.Recently, the C-reactive protein to lymphocyte ratio (CLR), an emerging inflammatory biomarker, has been shown to effectively indicate the balance between systemic inflammatory response and immune activation\u003csup\u003e5\u003c/sup\u003e. Numerous studies have established that elevated CLR levels are significantly associated with poor prognosis in a range of diseases, including Chronic Obstructive Pulmonary Disease \u003csup\u003e6\u003c/sup\u003e,myocardial infarction\u003csup\u003e7\u003c/sup\u003e, chronic kidney disease\u003csup\u003e8\u003c/sup\u003eand Non-alcoholic fatty liver disease (NAFLD)\u003csup\u003e9\u003c/sup\u003e. As a biomarker, CLR holds substantial promise for predicting disease outcomes and enhancing diagnostic evaluations.\u003c/p\u003e\n\u003cp\u003eAsthma, characterized as an inflammatory airway disease, is associated with inflammatory processes, indicating a possible link to CLR levels. This study seeks to examine the relationship between CLR levels and the risk of asthma in American adults through a cross-sectional design.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe National Health and Nutrition Examination Survey (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), serves as a nationally representative study aimed at evaluating the health status and nutritional levels of non-institutionalized populations in the United States. Employing a multi-stage stratified probability sampling strategy, the survey gathers extensive data through standardized questionnaires, physical examinations, and laboratory tests. This dataset offers valuable insights into demographic characteristics, chronic disease profiles, biomarkers, lifestyle behaviors, and environmental exposures. To maintain data relevance and national representativeness, findings are released biennially. The NHANES protocol has received approval from the National Center for Health Statistics Research Ethics Review Board, with all participants providing written informed consent upon enrollment. (This study utilizes publicly available standardized data, https://www.cdc.gov/nchs/nhanes/irba98.htm; ethical approval or consent is required.)\u003c/p\u003e\n\u003cp\u003eThis research employed a cross-sectional design, utilizing data from the National Health and Nutrition Examination Survey (NHANES) collected from 1999 to 2010. The study focused exclusively on adult participants. Additionally, individuals who were pregnant (n=1294), those without relevant asthma survey data (n=31), and participants with incomplete records for CLR (n=3515) or covariates (n=5285) were excluded (Figure 1).\u003c/p\u003e\n\u003cp\u003eIncomplete data on demographic characteristics (age, gender, race, BMI), prior medical history (alcohol or tobacco use, hypertension, diabetes, cardiovascular disease), and laboratory test indicators (neutrophil differential count, eosinophils, monocytes, platelets, red blood cells) led to the exclusion of 5,285 study participants, resulting in the inclusion of 22,339 eligible research subjects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC-Reactive Protein to Lymphocyte Ratio\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBlood samples were collected at the NHANES Mobile Examination Center (MEC) and subsequently analyzed in the laboratory. In this study, CLR denotes the ratio of C-reactive protein (CRP) concentration (mg/L) to lymphocyte count (1000 cells/L)\u003csup\u003e10\u003c/sup\u003e. NHANES maintains rigorous data quality control procedures during both data collection and laboratory analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAsthma\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAsthma diagnosis was rigorously established through a comprehensive standardized questionnaire aimed at capturing detailed medical histories. Participants were classified as having asthma if they answered affirmatively to the critical question, \u0026quot;Have you ever been told by a healthcare professional that you have asthma?\u0026quot; This question was designed to elicit clear and definitive responses. This method ensured that the diagnosis was both reliable and consistent, accurately reflecting the participants\u0026apos; self-reported medical histories. The structured nature of the questionnaire facilitated an efficient process for identifying individuals with asthma, thereby enhancing the overall validity of the study\u0026apos;s findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCovariates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInvestigators with specialized training conducted the data collection and documentation processes. The study encompassed demographic characteristics (age, gender, race/ethnicity, education, marital status, alcohol and tobacco use, poverty-income ratio, and body mass index), comorbid conditions (cardiovascular disease, hypertension, diabetes), and laboratory parameters (segmented neutrophil, eosinophil, monocyte, platelet, and red blood cell counts).\u003c/p\u003e\n\u003cp\u003eGender is primarily classified into two categories: male and female. Ethnicity is further subdivided into the following groups: non-Hispanic white participants, non-Hispanic black participants, Mexican American participants, and others. Educational attainment is categorized into three levels: high school or higher, high school or equivalent, and high school or below. Marital status is classified into two types: married or living with a partner, and single. Alcohol consumption is divided into three categories: current drinkers, former drinkers, and non-drinkers. Smoking status is classified into two groups: smokers and non-smokers. The Poverty-Income Ratio (PIR) is divided into three ranges:\u0026nbsp;\u0026le;1.30, 1.31-3.50, and \u0026gt;3.50. Body Mass Index (BMI) is calculated by dividing weight by height squared.\u003c/p\u003e\n\u003cp\u003eThe diagnosis of asthma was confirmed through interviews utilizing a standardized questionnaire aimed at assessing medical conditions. This questionnaire included the question:\u0026nbsp;\u0026ldquo;Have you ever been told you have asthma?\u0026rdquo;\u0026nbsp;A participant was classified as having asthma if they answered \u0026quot;yes\u0026quot; to any of the questions posed.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eHypertension is diagnosed when subjects meet any of the following criteria: an average systolic blood pressure of 140 mmHg or higher, an average diastolic blood pressure of 90 mmHg or higher, a history of using antihypertensive medication, or a confirmed hypertension diagnosis \u003csup\u003e12\u003c/sup\u003e. The diagnosis of diabetes mellitus is based on the following criteria: a fasting blood glucose level of\u0026nbsp;\u0026ge;7.0 mmol/L, a random blood glucose level of\u0026nbsp;\u0026ge;11.1 mmol/L, an oral glucose tolerance test indicating a post-2-hour blood glucose level of\u0026nbsp;\u0026ge;11.1 mmol/L, a glycated hemoglobin level of\u0026nbsp;\u0026ge;6.5%, or a confirmed diabetes mellitus diagnosis in patients receiving insulin therapy or diabetes medications\u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with established literature and clinical practice, we compiled demographic indicators and laboratory data from the participants\u003csup\u003e7,14\u003c/sup\u003e. The substantial sample size of the study resulted in a proportion of missing covariate values of less than 10%. Given the minimal extent of missing data, we chose to exclude these values directly. We considered the distribution characteristics of continuous variables, presenting normally distributed data as mean \u0026plusmn; standard deviation (SD) and summarizing skewed data using the median and interquartile range (IQR). Differences among groups were assessed using one-way ANOVA, the Kruskal\u0026ndash;Wallis test, or chi-square tests.\u003c/p\u003e\n\u003cp\u003eGiven the asymmetric distribution of the CLR data, this study first applied a natural logarithm (LN) transformation to the dataset before conducting statistical analyses. In the subsequent exploratory analyses, CLR was treated as a continuous variable; within the transformed dataset, analyses were performed using increments of 1 unit or by grouping based on three-tenths quantiles. A multiple logistic regression model was employed to compute odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs).\u003c/p\u003e\n\u003cp\u003eThis study developed five analytical models. Model 1, the baseline model, included no covariates. Model 2 adjusted for demographic variables, such as age, gender, and race/ethnicity. Model 3 expanded this adjustment to include socioeconomic and lifestyle factors, including education level, marital status, alcohol consumption patterns, smoking habits, poverty income ratio (PIR), and body mass index (BMI). Model 4 additionally accounted for major comorbidities, such as cardiovascular disease, hypertension, and diabetes. Model 5 functioned as the comprehensive adjustment model, incorporating all previously identified variables.\u003c/p\u003e\n\u003cp\u003eTo investigate the dose-response relationship between log-transformed CLR and asthma, we utilized a three-knot restricted cubic spline (RCS) for our analysis. Additionally, this association was assessed using a piecewise logistic regression model, which included adjustments for all covariates in Model 5.\u003c/p\u003e\n\u003cp\u003eMoreover, this study conducted subgroup analyses for sensitivity assessment. Stratified analyses were carried out according to variables including gender, age (20-65 years vs. \u0026ge;65 years), body mass index (BMI, \u0026lt;18.5 vs. 18.5-24.9, 25-29.9, or \u0026ge;30 kg/m\u0026sup2;), smoking status (non-smokers vs. smokers), coronary heart disease, hypertension, and diabetes, aiming to assess the consistency of the association between logarithmically transformed CLR and asthma across various subgroups.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using R4.2.2 (http:// www.R-project.org, The R Foundation) and Free Statistics software version 2.2. A P-value \u0026lt;0.05 (two-sided) was regarded as statistically significant in all analyses.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween 1999 and 2010, this study successfully enrolled 22,339 participants (shown in Fig. 1). The participants were categorized into three groups\u0026mdash;T1, T2, and T3\u0026mdash;according to their CLR levels. An examination of Table 1 reveals baseline disparities between the T1 and T2 groups in comparison to the T3 group, with all variables demonstrating significant differences.\u003c/p\u003e\n\u003cp\u003eHigher levels of C-reactive protein (CRP) in the upper tertiles correlated with increased age, a higher proportion of females, elevated body mass index (BMI), and a greater burden of comorbidities. Hematological parameters revealed progressive increases in segmented neutrophils and platelets across the tertiles. The prevalence of asthma exhibited a graded increase from the first quartile (Q1) to the third quartile (Q3) (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLogit analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the skewed distribution characteristics of the CLR data, this study utilized a natural logarithm (ln) transformation method to standardize the data. Table 2 presents the analysis results regarding the association between CLR and asthma following ln transformation across five models. In Model 1, when treating the ln-transformed CLR as a continuous variable, a significant positive correlation with asthma risk was observed (OR=1.1; 95% CI=1.07-1.14; P\u0026lt;0.001). Notably, this association remained significant even after adjusting for multiple covariates. The results in Model 5 indicate that for each 1-unit increase in ln-transformed CLR, the risk of asthma increased by 7% (OR=1.07; 95% CI=1.03-1.11; P\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eWhen performing a three-way grouping analysis on natural ln-transformed CLR data, the association with asthma revealed trends consistent with those found in continuous analysis. Individuals in the third quartile (T3) exhibited a higher risk of asthma compared to those in the first quartile (T1) (OR=1.21; 95% CI 1.09-1.36; P=0.001; Table 2, Model 5). Importantly, across all models, the risk of asthma showed a progressive increase corresponding to the advancement of the three-way grouping in natural ln-transformed CLR data (all trend P-values \u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNon-linear relationships\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnother key finding of this study is the lack of a nonlinear relationship. As shown in Fig. 2, no nonlinear association was detected between CLR and asthma risk (nonlinear test p-value = 0.331). The asthma risk demonstrated an increasing trend with rising CLR values, indicating a significant positive correlation between the two variables.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Table 3 consolidates the findings from the stratified and interaction analyses. As shown in Table 3, no interaction was observed between age, sex, smoking history, coronary heart disease, hypertension, and CLR. This indicates that, regardless of age being over 65 years, sex, smoking history, or a history of coronary heart disease and hypertension, the risk of asthma increased with elevated CLR.\u003c/p\u003e\n\u003cp\u003eAn interaction may exist among Body Mass Index (BMI), diabetes, and CRP levels. However, it is important to emphasize that regardless of whether an individual\u0026apos;s BMI is 30 or higher or whether they have comorbid diabetes, the risk of asthma rises with increased CRP levels. The analysis of all subgroups in this study is consistent with the trend observed in the overall population, suggesting that elevated CRP levels are a significant risk factor for the onset of asthma.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eUsing national adult sample data from the National Health and Nutrition Examination Survey (NHANES), this study identified a significant positive correlation between CLR levels and asthma risk, after carefully controlling for multiple covariates.\u003c/p\u003e\n\u003cp\u003eSubgroup analysis of the sensitivity analysis further confirmed the robustness of the results. Additionally, a progressive linear relationship was observed between CLR and asthma risk, offering new insights into the complex interaction mechanisms between the two.\u003c/p\u003e\n\u003cp\u003eC-reactive protein (CRP), a well-established marker of systemic inflammation, is strongly associated with asthma. Multiple clinical studies have reported that plasma CRP levels are significantly higher in patients with asthma than in those without\u003csup\u003e15\u003c/sup\u003e. Notably, inhaled glucocorticoids have been shown to reduce CRP levels effectively\u003csup\u003e15\u003c/sup\u003e.Moreover, Mendelian randomization analyses provide evidence for a causal relationship, indicating that elevated circulating CRP directly increases the risk of asthma.\u003csup\u003e16\u003c/sup\u003e\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eLymphocyte-mediated immune dysregulation significantly contributes to the pathology of asthma. Clinical studies indicate that patients with asthma exhibit a reduction in T lymphocytes and a Th2 immune bias, characterized by elevated IgE levels and increased eosinophil counts.\u003csup\u003e18\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eResearch on nocturnal asthma has demonstrated that the circadian rhythm of lymphocyte activity correlates with fluctuations in symptoms\u003csup\u003e19\u003c/sup\u003e. Transgenic mouse models have confirmed that the expression of human MMP-9 can mitigate airway hyperresponsiveness and lymphocyte aggregation\u003csup\u003e20\u003c/sup\u003e. Furthermore, genome-wide studies have revealed that genes associated with lymphocyte count are enriched in regions linked to asthma susceptibility, suggesting that genetic factors may influence asthma risk by modulating lymphocyte function.\u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThese findings suggest that the C-reactive protein\u0026ndash;to\u0026ndash;lymphocyte count ratio (CLR) may serve as a novel clinical biomarker for asthma progression. The study found a significant association between higher CLR and increased asthma risk, and this association remained statistically significant after adjustment for multiple potential confounders.\u003c/p\u003e\n\u003cp\u003eThis study\u0026apos;s strength is that it provides new evidence linking CLR to asthma risk. It analyzed a strictly defined, highly homogeneous adult population drawn from a nationally representative sample of U.S. adults. The study design also adjusted effectively for confounders, thereby substantially reducing their potential influence on the results.\u003c/p\u003e\n\u003cp\u003eThis study provides useful insights but has several important limitations. First, its retrospective design limits control over confounding and prevents causal inference. Second, because the NHANES database records asthma diagnosis only by self-report, the outcome is vulnerable to reporting bias. Third, C-reactive protein levels and lymphocyte markers can be altered by immune status or recent acute infections, and these influences were not fully controlled. Although we applied regression models, subgroup analyses, and sensitivity tests, unmeasured or unknown confounders may still have affected the results. Therefore, future work should use longitudinal designs to test causality and perform mechanistic experiments to elucidate the underlying biology.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study revealed a correlation between CLR levels and asthma risk: elevated CLR levels were proportional to an increased risk of asthma.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatement of Ethics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe NHANES protocol has been reviewed and approved by the National Center for Health Statistics Research Ethics Review Board, with all participants signing written informed consent forms upon enrollment. (This study utilizes publicly available standardized data, https://www.cdc.gov/nchs/nhanes/irba98.htm.thus no ethical approval or consent is required.)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp id=\"_Toc472330568\"\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not funded by any external source\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYun Guo was responsible for data collection and analysis, interpreting results, writing the thesis, and designing the research. Wei Zhou participated in the manuscript review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study utilized the NHANES public databases.\u003c/p\u003e\n\u003cp\u003eThe National Health and Nutrition Examination Survey (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), is a nationally representative study designed to assess the health status and nutritional levels of non-institutionalized populations in the United States. Utilizing a multi-stage stratified probability sampling strategy, the survey collects comprehensive data through standardized questionnaires, physical examinations, and laboratory tests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHammad, H. \u0026amp; Lambrecht, B. N. The basic immunology of asthma. \u003cem\u003eCell\u003c/em\u003e \u003cstrong\u003e184\u003c/strong\u003e, 2521-2522, doi:10.1016/j.cell.2021.04.019 (2021).\u003c/li\u003e\n\u003cli\u003eGlobal, regional, and national burden of asthma and atopic dermatitis, 1990-2021, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. \u003cem\u003eLancet Respir Med\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 425-446, doi:10.1016/s2213-2600(25)00003-7 (2025).\u003c/li\u003e\n\u003cli\u003eRizo-T\u0026eacute;llez, S. A., Sekheri, M. \u0026amp; Filep, J. G. C-reactive protein: a target for therapy to reduce inflammation. \u003cem\u003eFront Immunol\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 1237729, doi:10.3389/fimmu.2023.1237729 (2023).\u003c/li\u003e\n\u003cli\u003eCaramori, G.\u003cem\u003e et al.\u003c/em\u003e COPD immunopathology. \u003cem\u003eSemin Immunopathol\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, 497-515, doi:10.1007/s00281-016-0561-5 (2016).\u003c/li\u003e\n\u003cli\u003eCill\u0026oacute;niz, C.\u003cem\u003e et al.\u003c/em\u003e The Value of C-Reactive Protein-to-Lymphocyte Ratio in Predicting the Severity of SARS-CoV-2 Pneumonia. \u003cem\u003eArch Bronconeumol\u003c/em\u003e \u003cstrong\u003e57\u003c/strong\u003e, 79-82, doi:10.1016/j.arbres.2020.07.038 (2021).\u003c/li\u003e\n\u003cli\u003eZhou, J.\u003cem\u003e et al.\u003c/em\u003e Association of CALLY index and CLR with COPD risk in middle-aged and older Americans: evidence from NHANES 2017-2020. \u003cem\u003eFront Med (Lausanne)\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 1535415, doi:10.3389/fmed.2025.1535415 (2025).\u003c/li\u003e\n\u003cli\u003eHe, L., Xie, H., Du, Y., Xie, X. \u0026amp; Zhang, Y. The relationship between C-reactive protein to lymphocyte ratio and the prevalence of myocardial infarction in US adults: A cross-sectional study. \u003cem\u003eHeliyon\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, e17776, doi:10.1016/j.heliyon.2023.e17776 (2023).\u003c/li\u003e\n\u003cli\u003eHe, P.\u003cem\u003e et al.\u003c/em\u003e The relationship between C-reactive protein to lymphocyte ratio and the prevalence of chronic kidney disease in US adults: a cross-sectional study. \u003cem\u003eFront Endocrinol (Lausanne)\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 1469750, doi:10.3389/fendo.2024.1469750 (2024).\u003c/li\u003e\n\u003cli\u003eXi, J.\u003cem\u003e et al.\u003c/em\u003e The role of C-reactive protein to lymphocyte ratio in NAFLD and mortality among NAFLD patients. \u003cem\u003eBMC Gastroenterol\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 327, doi:10.1186/s12876-025-03924-w (2025).\u003c/li\u003e\n\u003cli\u003eHuang, C. Y.\u003cem\u003e et al.\u003c/em\u003e Assessing the Predictive Utility of the C-Reactive Protein-to-Lymphocyte Ratio for Mortality in Isolated Traumatic Brain Injury: A Single-Center Retrospective Analysis. \u003cem\u003eDiagnostics (Basel)\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, doi:10.3390/diagnostics14182065 (2024).\u003c/li\u003e\n\u003cli\u003eDing, J., Zhang, Y. \u0026amp; Chen, X. Red cell distribution width to albumin ratio is associated with asthma risk: a population-based study. \u003cem\u003eFront Med (Lausanne)\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 1493463, doi:10.3389/fmed.2024.1493463 (2024).\u003c/li\u003e\n\u003cli\u003eWu, D.\u003cem\u003e et al.\u003c/em\u003e Water Intake and Handgrip Strength in US Adults: A Cross-Sectional Study Based on NHANES 2011-2014 Data. \u003cem\u003eNutrients\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, doi:10.3390/nu15204477 (2023).\u003c/li\u003e\n\u003cli\u003eLiu, H., Wang, D., Wu, F., Dong, Z. \u0026amp; Yu, S. Association between inflammatory potential of diet and self-reported severe headache or migraine: A cross-sectional study of the National Health and Nutrition Examination Survey. \u003cem\u003eNutrition\u003c/em\u003e \u003cstrong\u003e113\u003c/strong\u003e, 112098, doi:10.1016/j.nut.2023.112098 (2023).\u003c/li\u003e\n\u003cli\u003eCai, C., Zeng, W., Wang, H. \u0026amp; Ren, S. Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Monocyte-to-Lymphocyte Ratio (MLR) as Biomarkers in Diagnosis Evaluation of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Retrospective, Observational Study. \u003cem\u003eInt J Chron Obstruct Pulmon Dis\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 933-943, doi:10.2147/copd.S452444 (2024).\u003c/li\u003e\n\u003cli\u003eKasayama, S.\u003cem\u003e et al.\u003c/em\u003e Asthma is an independent risk for elevation of plasma C-reactive protein levels. \u003cem\u003eClin Chim Acta\u003c/em\u003e \u003cstrong\u003e399\u003c/strong\u003e, 79-82, doi:10.1016/j.cca.2008.09.013 (2009).\u003c/li\u003e\n\u003cli\u003eMou, Y.\u003cem\u003e et al.\u003c/em\u003e The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis. \u003cem\u003ePostgrad Med J\u003c/em\u003e \u003cstrong\u003e100\u003c/strong\u003e, 555-561, doi:10.1093/postmj/qgae019 (2024).\u003c/li\u003e\n\u003cli\u003eWang, T. N.\u003cem\u003e et al.\u003c/em\u003e The polymorphisms of C-reactive protein gene modify the association between central obesity and lung function in taiwan asthmatics. \u003cem\u003eScand J Immunol\u003c/em\u003e \u003cstrong\u003e74\u003c/strong\u003e, 482-488, doi:10.1111/j.1365-3083.2011.02599.x (2011).\u003c/li\u003e\n\u003cli\u003eGupta, S., Frenkel, R., Rosenstein, M. \u0026amp; Grieco, M. H. Lymphocyte subpopulations, serum IgE and total eosinophil counts in patients with bronchial asthma. \u003cem\u003eClin Exp Immunol\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 438-445 (1975).\u003c/li\u003e\n\u003cli\u003eOosterhoff, Y., Hoogsteden, H. C., Rutgers, B., Kauffman, H. F. \u0026amp; Postma, D. S. Lymphocyte and macrophage activation in bronchoalveolar lavage fluid in nocturnal asthma. \u003cem\u003eAm J Respir Crit Care Med\u003c/em\u003e \u003cstrong\u003e151\u003c/strong\u003e, 75-81, doi:10.1164/ajrccm.151.1.7812576 (1995).\u003c/li\u003e\n\u003cli\u003eMehra, D.\u003cem\u003e et al.\u003c/em\u003e Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma. \u003cem\u003eAm J Physiol Lung Cell Mol Physiol\u003c/em\u003e \u003cstrong\u003e298\u003c/strong\u003e, L189-196, doi:10.1152/ajplung.00042.2009 (2010).\u003c/li\u003e\n\u003cli\u003eCusanovich, D. A.\u003cem\u003e et al.\u003c/em\u003e The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes. \u003cem\u003eHum Mol Genet\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 2111-2123, doi:10.1093/hmg/dds021 (2012).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-bronchology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Bronchology](https://ejb.springeropen.com/)","snPcode":"43168","submissionUrl":"https://submission.nature.com/new-submission/43168/3","title":"The Egyptian Journal of Bronchology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"C-Reactive Protein to Lymphocyte Ratio, asthma, NHANES, risk, inflammation","lastPublishedDoi":"10.21203/rs.3.rs-8150143/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8150143/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBACKGROUND\u003c/b\u003e\u003c/p\u003e \u003cp\u003eCLR, a recently identified inflammatory biomarker, has been associated with various inflammatory conditions. Asthma is an inflammatory airway disease heavily influenced by inflammation. The primary goal of this study was to examine the impact of CLR on the risk of asthma.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study conducted a retrospective analysis of 22,339 participants from the NHANES dataset between 1999 and 2010. To investigate the relationship between CLR and asthma risk, we employed logistic regression and restricted cubic spline analysis. Additionally, subgroup and sensitivity analyses were performed to validate the robustness of the identified associations.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAnalysis using a multivariate logistic regression models revealed a significant positive correlation between ln-transformed CLR and asthma risk (OR: 1.07,95% CI 1.03\u0026ndash;1.11; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared to participants in the first tertile of ln-transformed CLR values ( T1), those in the T2 and T3 showed increased asthma risk by 1.07 times and 1.21 times, respectively. The risk demonstrated a statistically significant upward trend with higher ln-transformed CLR (trend test P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). RCS analysis confirmed no nonlinear relationship between CLR values and asthma risk. Subgroup and sensitivity analyses further validated the robustness and consistency of these findings.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAs the CLR level improved, the risk of asthma increased correspondingly, exhibiting a linear correlation.\u003c/p\u003e","manuscriptTitle":"C-Reactive Protein to Lymphocyte Ratio is associated with asthma risk:A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-19 15:59:15","doi":"10.21203/rs.3.rs-8150143/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-22T15:51:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-22T01:23:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-21T10:22:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"17288798322489867073595417629425418672","date":"2026-01-19T08:27:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T19:35:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"151081090769538599870709915107420961737","date":"2026-01-16T14:40:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-15T01:22:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160603287055395648561337897669899574863","date":"2026-01-14T12:05:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-14T10:50:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321486099697645600501194304765835725305","date":"2026-01-14T08:59:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"151862321398235491350884897675887130410","date":"2026-01-14T08:45:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"205314937044532799410898209774856534533","date":"2026-01-14T08:42:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"177058849548181746286799627757731998506","date":"2026-01-14T08:28:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-14T08:18:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-07T06:04:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-06T04:19:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Journal of Bronchology","date":"2025-12-31T06:52:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-bronchology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Bronchology](https://ejb.springeropen.com/)","snPcode":"43168","submissionUrl":"https://submission.nature.com/new-submission/43168/3","title":"The Egyptian Journal of Bronchology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f354724c-38c1-4347-aba9-6dc905eb891b","owner":[],"postedDate":"January 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-12T04:24:27+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-19 15:59:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8150143","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8150143","identity":"rs-8150143","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}