Abstract Background: Lung cancer exhibits disparities in incidence, disease prevalence, and treatment outcomes. Chemokines and their corresponding receptors have been shown to be associated with these observed disparities within different ethnic groups. In this study, we have demonstrated that the differential signaling of chemokine receptor CCR6 and its natural ligand is associated with the observed disparity, and this differential CCR6 signaling is primarily due to the diversity in CCL20. Methods: Bulk RNA-seq data (BioProject ID: PRJNA1039495) from lung cancer cell lines derived from African American (AA) and European American (EA) individuals were analyzed to identify and quantify different isoforms of CCL20. MD simulations were performed to evaluate the binding affinity of CCL20, hydrogen-bond stability, and conformational behavior upon interaction with the CCR6 receptor. Downstream pathway activation potential was inferred by comparing the expression of signaling molecules that support oncogenic pathways and are associated with poor therapeutic outcomes. Furthermore, smoking habits, including higher nicotine intake, distinct metabolite patterns, and alterations in basic cytokine levels, were incorporated into the model as external factors that may influence CCL20 isoforms and CCR6 signaling. Results: Out of 5 CCL20 isoforms, Isoform-1 (24 TPM) and Isoform-2 (36 TPM) showed stronger interactions with CCR6 compared to EA cells (Isoform-1: 7.5 TPM; Isoform-2: 11.2 TPM). Across smoking groups, AA cells showed higher Isoform-2 levels than EA cells, increasing from non-smokers (Isoform-1: 18 TPM; Isoform-2: 18 TPM) to smokers (Isoform-1: 24 TPM; Isoform-2: 40 TPM), while EA cells showed lower increases from non-smokers (Isoform-1: 18 TPM; Isoform-2: 19 TPM) to smokers (Isoform-1: 24 TPM; Isoform-2: 30 TPM). MD simulations revealed that lung-cancer-cell CCR6 binds both CCL20 Isoform-1 & 2 from AA-derived cell lines with significantly stronger affinity compared to EA-derived cells, reflected by lower binding free energies, more stable hydrogen-bonds, and longer ligand-receptor contact durations. Isoform-2 showed the strongest overall binding affinity, indicating that it may be the dominant activator of CCR6 signaling. Population-level behavioral data, including All of Us cohort metrics, showed that AA smokers tend to use cigarettes with higher nicotine content, inhale more deeply, and exhibit slower nicotine and cotinine clearance, which corresponded with increased Isoform-2 expression. Conclusion: Lung cancer cells derived from AA exhibit a ligand-rich and affinity-enhanced CCL20-CCR6 signaling axis driven primarily by Isoform-2. Isoform-specific expression, receptor affinity, and smoking-associated inflammation together highlight the significance of Isoform-2 in disparity observation in Lung cancer, as a key player in contributing to disparity. Citation Format: Murugesh Eswaran, Briana Alicia Brock, Hina Mir, Sejong Bae, Gabriella M. Oprea-Ilies, Eric L. Flenaugh, Sanjay R. Jain, Brian M. Rivers, Rick A. Kittles, James W. Lillard, Rajesh Singh, Shailesh Singh. Health behavior associated CCL20 ligand variation contributes to the disparity in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1507.

Chronic obstructive pulmonary disease (COPD) is optimally managed through a comprehensive, individualized, and adaptable treatment approach. This review summarizes current and emerging strategies in COPD care, emphasizing both pharmacologic and non-pharmacologic interventions aimed at relieving symptoms, reducing exacerbations, and improving quality of life. Long-acting bronchodilators remain the cornerstone of pharmacologic therapy, with combination long-acting β-agonists (LABA) and long-acting muscarinic antagonist (LAMA) therapy preferred as initial treatment for most patients with persistent dyspnea or exercise intolerance. Inhaled corticosteroids (ICS) are recommended for select patient phenotypes, particularly individuals with frequent exacerbations or elevated blood eosinophil levels. Triple therapy (LABA+LAMA+ICS) demonstrates significant benefits in reducing exacerbations and may provide mortality benefits in appropriately selected patients. Personalized treatment strategies guided by exacerbation history, blood eosinophil counts, and symptom burden have become central to contemporary COPD management. Novel biologic therapies targeting type 2 inflammation, including dupilumab and mepolizumab, have demonstrated efficacy in reducing exacerbations in patients with eosinophilic phenotypes who remain symptomatic despite optimized triple inhaler therapy. Bronchoscopic interventions, particularly endobronchial valve placement for lung volume reduction, offer meaningful improvements in lung function and quality of life for carefully selected patients. Despite these advances, significant challenges persist, especially in resource-limited settings. Barriers include limited access to guideline-recommended therapies, difficulties in managing comorbidities, inadequate implementation of pulmonary rehabilitation programs, and broader health system constraints continue to impact optimal disease management.

Lung cancer remains the leading cause of cancer-related morbidity and mortality worldwide. African Americans (AA) are disproportionally affected by the disease, and mortality is higher in AA compared to European Americans (EA). The mortality rate among AA is higher than EA even when diagnosed at an early stage, implying biological differences associated with health behaviors such as smoking and its impact on microbial dysbiosis. A higher mortality rate in AA diagnosed at an early stage compared to EA highlights the biological differences in AA are primarily due to health behaviors such as smoking and its impact on microbial dysbiosis, making AA predisposed to higher risk and mortality. Microbial dysbiosis in lung cancer was analyzed using GEO and All of Us data repositories. Our analysis provides compelling evidence of the interplay between microbial dysbiosis, health behaviors, and racial disparities in lung cancer outcomes. Our study shows that smoking exacerbates microbial imbalances, particularly with the prevalence of Streptococcus and its differential impact on AA and EA. Dysbiosis correlates strongly with lung cancer pathogenesis, particularly the abundance of Streptococcus, Haemophilus, Neisseria, and Pseudomonas. AA participants show higher susceptibility to Streptococcus invasion, with detectable levels in the blood at just 7 cigars daily compared to 23 cigars in EAs. Urine samples of AAs smoking only 17 cigars per day are positive for streptococcus, while for EAs the bacteria is detected only when they smoke 20 cigars daily. These findings underscore a biological predisposition that amplifies cancer risk for AAs at lower smoking intensities. The lower thresholds for Streptococcus detection among AA populations suggest a heightened biological vulnerability, emphasizing the need for tailored public health interventions and early screening programs in these communities. These results underscore the importance of integrating microbial profiling in personalized medicine approaches and addressing underlying health inequities to improve lung cancer outcomes across diverse populations. Murugesh Eswaran, Briana A. Brock, Hina Mir, Gabriela Oprea-Ilies, Eric Flenaugh, James W. Lillard, Brian M. Rivers, Rajesh Singh, Shailesh Singh. The role of health behaviors in microbial dysbiosis and lung cancer inequities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6528.

Introduction: We present a rare case of two malignancies in the same surgical resection, one primary and the other with a metastatic lesion in the same location. Case Summary: This is a 60-year-old woman with a history of type II diabetes, metastatic papillary thyroid cancer s/p thyroidectomy and radioactive iodine therapy in 2011, and treated latent tuberculosis who was found to have an incidental cavitary lesion in the left lower lobe (LLL) 13 years later. The patient was evaluated for suspected cardiac chest pain by CT coronary angiography where an incidental 5.1 cm cavitary lesion with diffuse asymmetric wall thickening and consolidation was found. Polymerase chain reaction for mycobacterium tuberculosis was negative. A navigational bronchoscopy with tip-tracked transbronchial biopsy, fine needle aspiration and brush biopsy of the cavitary lesion were performed which showed lepidic-predominate adenocarcinoma(LPA). A PET-CT showed a LLL FDG avid (SUV 6.31) lesion and two sub centimeter lesions abutting the diaphragm on the left lower lobe (SUV 1.34 and 1.83) and the patient was then referred to thoracic surgery for resection. The patient underwent a robotic-assisted left lower lobectomy with mediastinal dissection of lymph nodes 5, 7, 9, 10L, 11L and 12L. Positive tumor markers: TTF1 and CK7. The cavitary lesion was analyzed using next-generation sequencing (NGS) testing and confirmed using molecular studies showing lung adenocarcinoma and papillary thyroid carcinoma. Discussion: Secondary primary malignancies (SPMs) occur in 8.1% of patients diagnosed with cancer, with concurrent malignancies less common. Primary malignancies diagnosed less than 6 months apart are synchronous or if greater than six months are metachronous. Some malignancies have overlapping markers, which is important to distinguish. In this case the patient had a known history of papillary thyroid carcinoma, though originally thought to be in remission for 13 years. SPMs located in the lungs are associated with radiation, chemotherapy, genetics and smoking. Metachronous cancers make up 70.87% of secondary cancers, secondary cancers after diagnosis of thyroid cancer occur in 3.38% of patients. The identification of the second malignancy occurs on average 2.7 years after the diagnosis of thyroid cancer. The median survival of patients with primary thyroid cancer is 23.28 years, but in patients with a SPM the median is 4.73 years. Conclusion: SPMs are challenging to detect especially with overlapping tumor markers between both malignancies. NSG provides additional diagnostic help to detect multiple malignancies in the sample biopsy.

Importance:Individuals at risk for chronic obstructive pulmonary disease (COPD) but without spirometric airflow obstruction can have respiratory symptoms and structural lung disease on chest computed tomography. Current guidelines recommend COPD diagnostic schemas that do not incorporate imaging abnormalities. Objective:To determine whether a multidimensional COPD diagnostic schema that includes respiratory symptoms and computed tomographic imaging abnormalities identifies additional individuals with disease. Design, Setting, and Participants:This cohort study included 2 longitudinal cohorts: the Genetic Epidemiology of COPD (COPDGene), which enrolled 10 305 participants between November 9, 2007, and April 15, 2011, with longitudinal follow-up through August 31, 2022; and the Canadian Cohort Obstructive Lung Disease (CanCOLD), which enrolled 1561 participants between November 26, 2009, and July 15, 2015, with follow-up through December 31, 2023. Exposure:Exposure included the new multidimensional COPD diagnostic schema, defined by (1) major diagnostic category: presence of the major criterion (airflow obstruction based on postbronchodilator forced expiratory volume in the first second of expiration [FEV1]/forced vital capacity ratio <0.70) and at least 1 of 5 minor criteria (emphysema or bronchial wall thickening on computed tomography, dyspnea, poor respiratory quality of life, and chronic bronchitis); or (2) minor diagnostic category: presence of least 3 of 5 minor criteria (which must include emphysema and bronchial wall thickening for individuals with respiratory symptoms potentially due to other causes). Main Outcomes and Measures:All-cause mortality, respiratory cause-specific mortality, exacerbations, and annualized change in FEV1. Results:Among 9416 adults in COPDGene (mean [SD] age at enrollment, 59.6 [9.0] years; 5035 [53.5%] were men; 3071 [32.6%] were Black; 6345 (67.4%) were White; 4943 [52.5%] currently smoked), 811 of 5250 individuals (15.4%) without airflow obstruction were newly classified as having COPD by minor diagnostic category, and 282 of 4166 individuals (6.8%) with airflow obstruction were classified as not having COPD. Reclassified individuals with a new COPD diagnosis had greater all-cause mortality (adjusted hazard ratio, 1.98; 95% CI, 1.67-2.35; P < .001) and respiratory-specific mortality (adjusted hazard ratio, 3.58; 95% CI, 1.56-8.20; P = .003), more exacerbations (adjusted incidence rate ratio, 2.09; 95% CI, 1.79-2.44; P < .001), and more rapid FEV1 decline (adjusted β = -7.7 mL/y; 95% CI, -13.2 to -2.3; P = .006) compared with individuals classified as not having COPD. Among individuals with airflow obstruction on spirometry, those no longer classified as having COPD based on this new diagnostic schema had outcomes similar to those without airflow obstruction. Among 1341 adults in CanCOLD, individuals newly classified as having COPD experienced more exacerbations (adjusted incidence rate ratio, 2.09; 95% CI, 1.25-3.51; P < .001). Conclusions and Relevance:A new COPD diagnostic schema integrating respiratory symptoms, respiratory quality of life, spirometry, and structural lung abnormalities on computed tomographic imaging newly classified some individuals as having COPD. These individuals had an increased risk of all-cause and respiratory-related death, frequent exacerbations, and rapid lung function decline compared with individuals classified as not having COPD. Some individuals with airflow obstruction without respiratory symptoms or evidence of structural lung disease were no longer classified as having COPD.

Non-small cell lung cancer (NSCLC) exhibits notable disparities between African American (AA) and European American (EA) populations, both in incidence and clinical outcomes. Among the molecular regulators of NSCLC, the CCL20–CCR6 chemokine axis is known to promote tumor progression, metastasis, and immune evasion. CCL20, the natural ligand for CCR6, binds to its receptor CCR6 to recruit immune cells, including regulatory T cells and myeloid suppressor cells. Smoking alters chemokine expression and mutation patterns, but the race-specific impact of CCL20 mutations on receptor engagement and immune signaling remains poorly understood. Genomic variants of CCL20 were retrieved from the AllofUs and ClinVar databases, categorized by smoking status and race, and modeled using the 6WWZ PDB structure. A split MD strategy in Desmond was implemented to simulate longer-timescale interactions and potential ligand dissociation events, running multiple consecutive trajectories for 1 microsecond (1000ns) per variant. This enabled measurement of residence time through contact duration and structural stability. Key structural metrics were used to compare AA- and EA-derived mutations, including RMSF, average contacts per frame, binding cavity retention (Å3), and SASA. Kinetic metrics such as radius of gyration and ligand-receptor center-of-mass distance were analyzed to quantify the dynamic stability. CCR6 membrane topology was annotated using TMHMM to contextualize variant positions and their functional implications. Our data show a positive correlation between smoking status and mutation frequency in CCL20, which is a natural ligand of CCR6. Mutations in CCL20 (TYR36HIS and GLN26ARG) are significantly more frequent in AA smokers compared to European Americans (EA). AA smoking induced variants showed increased binding cavity volume (412.3 ± 18.6 Å3 vs. 364.7 ± 16.1 Å3 in EA), reduced RMSF at the binding interface (1.12 Å vs. 1.57 Å), and a higher average of hydrogen bonds (>4 persistent contacts per frame) with CCR6 across 1-microsecond cumulative simulation window. CCR6-CCL20 contact duration was higher in AA (750 ms) compared to EA (420 ms). Binding interface area retention was higher in AA profiles (3125.9 Å2) than in EA (2758.4 Å2). Our study reveals that smoking-associated CCL20 mutations contribute to higher ligand diversity in AA compared to EA; hence, observed disparities in NSCLC may be due to differential activation of CCR6. Murugesh Eswaran, Briana A. Brock, Hina Mir, Sejong Bae, Gabriela Oprea-Ilies, Eric L. Flenaugh, Sanjai Jain, Brian M. Rivers, Rick Kittles, James W. Lillard Jr, Rajesh Singh, Shailesh Singh. Differential binding affinity of CCL20 with CCR6 due to smoking-induced mutation contributes to disparity in non-small cell lung cancer [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C011.

Introduction: A 72-year-old man with a history of clear cell renal cell carcinoma(ccRCC), prostate cancer, Chronic Kidney Disease stage IV, type II diabetes, and heart failure, insidiously developed acute hypoxic respiratory failure. Two years prior the patient was diagnosed with stage III ccRCC, WHO/ISUP grade 4. He underwent a radical nephrectomy at the time, and attained clear margins. A subsequent Computed Tomography (CT) scan of the chest, after completing 11 cycles of pembrolizumab, revealed worsening lung nodules and ground glass opacities concerning for malignancy or organizing pneumonia. The patient was started on cabozantinib for presumed recurrence or progression of his ccRCC. A CT with pulmonary angiography was later attained to evaluate for insidious shortness of breath, and showed worsening ground glass and nodular opacities concerning for organizing pneumonia. A navigational bronchoscopy with tip-tracked transbronchial needle aspiration and biopsy of multiple nodules, and bronchoalveolar lavage were performed, which were negative for malignancy and positive for reactive bronchial cells. The patient was diagnosed with pembrolizumab-induced pneumonitis and was started on a 4-month steroid taper. However, three months later new pleural effusions and nodules on the diaphragm were seen on point of care ultrasound (POCUS). Two thoracenteses of the right-sided pleural effusions produced >1.0L of serosanguinous fluid, which were positive for reactive mesothelial cells and negative for malignancy. There was continued high suspicion for malignancy and a VATS was performed with biopsy of a pleural nodule and diaphragmatic nodule, followed by talc pleurodesis to prevent further development of pleural effusions. The biopsies were positive for ccRCC and the patient's therapy was transitioned to levatinib and everolimus. Discussion: Immunomodulators such as Pembrolizumab are well known to cause pneumonitis, which can decrease the diagnostic yield from a bronchoscopic biospy. Additional modalities to evaluate metastatic disease spread can be essential for a timely diagnosis. The use of thoracentesis to diagnose malignancy is approximately 60% sensitive, which increases 27% with a second thoracentesis, but without further diagnostic yield thereafter. In a patient with a highly metastatic cancer such as grade 4 ccRCC, negative fluid studies require additional examination. In this case, the use of POCUS in the hands of a skilled operator can provide additional imaging details about metastatic disease involving the diaphragm, visceral and parietal pleural. Conclusion: Patients with highly metastatic malignancies require further investigation of abnormal chest imaging. When thoracentesis is negative, additional investigation with PCOUS and VATS may be necessary to confirm a diagnosis.

Middle lobe syndrome (MLS) is a rare entity defined as recurrent or chronic collapse of the right middle lobe (RML) of the lung. It can be caused by extrinsic compression, such as tumors or peribronchial lymphadenopathy, or chronic inflammatory and infectious changes. Symptoms typically include chronic cough, shortness of breath, and chest discomfort. However, the diagnosis of MLS can be challenging, particularly when imaging findings are atypical. We present a case of an elderly woman evaluated for malignancy with surgical biopsy resulting in the diagnosis of middle-lobe-syndrome. A 62-year-old woman with history of chronic obstructive lung disease, hypertension, and prior tobacco use disorder(44 pack years) was referred to the Lung Nodule clinic due to an abnormal chest computed tomography done for lung cancer screening, revealing a 13 x 18 x 24 mm nodular density on a background of moderate emphysema. On evaluation, her vital signs were stable, and her physical examination was unremarkable. She reported chronic dyspnea on exertion but denied fever, chills, cough, chest pain or unexplained weight loss. Given concern for malignancy, a positron emission tomography (PET) scan was pursued demonstrating increased uptake in the RML opacification, and PET-avid left gastric lymph nodes. Pulmonary function tests done showed a flow-volume loop supporting obstruction but FEV1 was 84% and the diffusing capacity of the lungs for carbon monoxide (DLCO) was 89% of predicted, suggesting adequate lung function. The patient was then referred to Thoracic Surgery for right robotic-assisted right middle lobe wedge resection and to Gastroenterology for endoscopic ultrasound-guided fine needle aspiration (FNA) of the perigastric lymph node. The patient tolerated the procedures without immediate complications. The surgical biopsy revealed clusters of histiocytes forming non-necrotizing granulomas supporting chronic inflammation, bronchiectasis with peribronchial fibrosis, and prominent lymphocytic infiltrates (Figure 1), favoring middle lobe syndrome. The lymph node FNA only revealed benign lymphoid hyperplasia. After clinical monitoring in the hospital, she was discharged with Clinic follow-up. While there are two forms of middle lobe syndrome, obstructive and nonobstructive, the most common etiology is chronic inflammation, leading to fibrosis or granuloma formation, causing RML collapse. In this case, the patient's significant history of smoking and chronic obstructive lung disease likely contributed to her susceptibility to chronic inflammatory lung changes resulting in the development of right middle lobe syndrome with nodular presentation. In cases where malignancy is suspected, clinical history along with histopathological findings are crucial for accurate diagnosis.

Lung cancer remains a leading cause of death in the United States and globally, despite progress in treatment and screening efforts. While mortality rates have decreased in recent years, long-term survival of patients with lung cancer continues to be a challenge. Notably, African American (AA) men experience significant disparities in lung cancer compared to European Americans (EA) in terms of incidence, treatment, and survival. Previous studies have explored factors such as smoking patterns and complex social determinants, including socioeconomic status, personal beliefs, and systemic racism, indicating their role in these disparities. In addition to social factors, emerging evidence points to variations in tumor biology, immunity, and comorbid conditions contributing to racial disparities in this disease. This review emphasizes differences in smoking patterns, screening, and early detection and the intricate interplay of social, biological, and environmental conditions that make African Americans more susceptible to developing lung cancer and experiencing poorer outcomes.

Abstract The persistent gap in cancer incidence and outcomes between African American (AA) and European American (EA) populations remains a significant public health challenge. Understanding these discrepancies is pivotal for crafting targeted interventions to mitigate health disparities. To comprehensively assess these inequalities, this study delves into the association between smoking and lung cancer incidence within a diverse cohort of 5270 participants, comprising both AA (868 participants) and EA (3137 participants) individuals. Among the 2901 lung cancer patients identified in our analysis, diagnoses ranged from Malignant Tumors of the Lung to various subtypes of Non-Small Cell and Small Cell Lung Cancer. Surprisingly, only a significant subset of these patients were smokers, with statistical analysis indicating a p<0.001, pointing to other influential demographic factors. Employing the Chi-Square Test of Independence, Logistic Regression, and Multivariate Analysis, we evaluated the impact of smoking alongside additional variables on lung cancer incidence. Factors such as Age, Gender, Socioeconomic Status, Occupational Exposures, Geographic Location, Family History of Cancer, Comorbidities, and Lifestyle Factors were considered in the multivariate analyses to ascertain their contribution to lung cancer risks. Our findings from Relative Risk (RR) and Attributable Risk (AR) assessments suggest that while smoking constitutes a notable risk factor, a substantial proportion of lung cancer cases in this cohort were not linked to smoking. Stratified and Sensitivity Analyses further unveiled nuanced risk profiles within subgroups, elucidating the intricate interplay between lifestyle factors and genetic predispositions. Our study highlights that a significant portion of lung cancer cases, particularly among EA and AA populations, occur in non-smokers, with smoking often associated with other comorbidities rather than solely lung- specific diseases. This underscores the multifaceted nature of lung cancer risk factors across different racial groups, advocating for public health strategies that address a broader spectrum of influences beyond smoking to combat cancer disparities within these communities effectively. Citation Format: Murugesh Eswaran, Briana A Briana A Brock, Hina Abdulrehman Mir, Eric L. Flenaugh, Oprea M. Gabriela, Brian Rivers, Rajesh Singh, Shailesh Singh. Influence of Socio-Demographic and Lifestyle Factors on Lung Cancer Incidence Among African American and European American [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C173.

Rationale:Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need. Objective:Identify prognostic and dynamic plasma protein biomarkers of COPD progression. Methods:We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung. Using SPIROMICS as a discovery cohort, linear mixed models identified baseline proteins that predicted future change in FEV1 (prognostic model) and proteins whose expression changed with change in lung function (dynamic model). Findings were replicated in COPDGene and MESA-Lung. Using the COPD-enriched cohorts, Gene Set Enrichment Analysis (GSEA) identified proteins shared between COPDGene and SPIROMICS. Metascape identified significant associated pathways. Measurements and Main Results:The prognostic model found 7 significant proteins in common (p < 0.05) among all 3 cohorts. After applying false discovery rate (adjusted p < 0.2), leptin remained significant in all three cohorts and growth hormone receptor remained significant in the two COPD cohorts. Elevated baseline levels of leptin and growth hormone receptor were associated with slower rate of decline in FEV1. Twelve proteins were nominally but not FDR significant in the dynamic model and all were distinct from the prognostic model. Metascape identified several immune related pathways unique to prognostic and dynamic proteins. Conclusion:We identified leptin as the most reproducible COPD progression biomarker. The difference between prognostic and dynamic proteins suggests disease activity signatures may be different from prognosis signatures.

ABSTRACTPurposeLow-dose computed tomography lung cancer screening is effective for reducing lung cancer mortality. It is critical to understand the lung cancer screening practices for screen-eligible individuals living in Alabama and Georgia where lung cancer is the leading cause of cancer death. High lung cancer incidence and mortality rates are attributed to high smoking rates among underserved, low income, and rural populations. Therefore, the purpose of this study: (1) to define sociodemographic and clinical characteristics of patients who were screened for lung cancer at an Academic Medical Center (AMC) in Alabama and a Safety Net Hospital (SNH) in Georgia.MethodsA retrospective cohort study of patient electronic health records who received lung cancer screening between 2015 to 2020 was performed to identify the study population and outcome variable measures. Chi-square tests and Student t-tests were used to compare screening uptake across patient demographic and clinical variables. Bivariate and multivariate logistic regressions determined significant predictors of lung cancer screening uptake.ResultsAt the AMC, 67,355 were identified as eligible for LCS and 1,129 were screened. In bivariate analyses, there were several differences between those who were screened and those who were not screened. Screening status in the site at Alabama varied significantly by age (P<0.01), race (P<0.001), marital status (P<0.01), smoking status (P<0.01) health insurance (P<0.01), median income (P<0.01), urban status (P<0.01) and distance from UAB (P<0.01). Those who were screened were more likely to have lesser comorbidities (2.31 vs. 2.53; P<0.001). At the SNH, 11,011 individuals were identified as screen-eligible and 500 were screened. In the site at Georgia, screening status varied significantly by race (P<0.01), health insurance (P<0.01), and distance from site (P<0.01). At the AMC, the odds of being screened increased significantly if the individual was a current smoker compared to former smoker (OR=3.21; P<0.01). At the SNH, the odds of being screened for lung cancer increased significantly with every unit increase in co-morbidity count (OR = 1.12; P=0.01)ConclusionThe study provides evidence that LCS has not reached all subgroups and that additional targeted efforts are needed to increase lung cancer screening uptake. Furthermore disparity was noticed between adults living closer to screening institutions and those who lived farther.

Aim: Increasing evidence suggests that the inclusion of self -identified race in clinical decision algorithms may perpetuate longstanding inequities. Until recently, most pulmonary function tests utilized separate reference equations that are race/ethnicity based. Purpose: We assess the magnitude and scope of the available literature on the negative impact of race -based pulmonary function prediction equations on relevant outcomes in African Americans with COPD. Methods: We performed a scoping review utilizing an English language search on PubMed/Medline, Embase, Scopus, and Web of Science in September 2022 and updated it in December 2023. We searched for publications regarding the effect of race -specific vs race -neutral, race -free, or race -reversed lung function testing algorithms on the diagnosis of COPD and COPD-related physiologic and functional measures. Joanna Briggs Institute (JBI) guidelines were utilized for this scoping review. Eligibility criteria: The search was restricted to adults with COPD. We excluded publications on other lung disorders, non-English language publications, or studies that did not include African Americans. The search identified publications. Ultimately, six peer -reviewed publications and four conference abstracts were selected for this review. Results: Removal of race from lung function prediction equations often had opposite effects in African Americans and Whites, specifically regarding the severity of lung function impairment. Symptoms and objective findings were better aligned when racespecific reference values were not used. Race -neutral prediction algorithms uniformly resulted in reclassifying severity in the African Americans studied. Conclusion: The limited literature does not support the use of race -based lung function prediction equations. However, this assertion does not provide guidance for every specific clinical situation. For African Americans with COPD, the use of race -based prediction equations appears to fall short in enhancing diagnostic accuracy, classifying severity of impairment, or predicting subsequent clinical events. We do not have information comparing race -neutral vs race -based algorithms on prediction of progression of COPD. We conclude that the elimination of race -based reference values potentially reduces underestimation of disease severity in African Americans with COPD.