Smoking Index Research Articles

Genetically Proxied Autoimmune Diseases and the Risk of Facial Aging.

Previous studies have suggested a relationship between autoimmune diseases and the risk of facial skin aging. However, evidence from population-based studies on this topic is limited, leaving the causal association between these factors unknown. This study aimed to systematically evaluate the causal effects of 18 autoimmune diseases on the risk of facial skin aging, aim of providing strategies to mitigate early facial aging in patients with autoimmune diseases. We conducted univariate Mendelian randomization (UVMR) analyses to examine the causal relationship between 18 autoimmune diseases and facial aging using publicly available summary data from genome-wide association studies (GWASs). We also conducted multivariate Mendelian randomization (MVMR) analyses to adjust for confounding factors, including smoking, alcohol consumption, and body mass index (BMI). The main inverse variance weighted (IVW) method revealed that genetically proxied ankylosing spondylitis (AS) (OR 1.017; 95% CI: 1.003-1.031; P=0.018), sicca syndrome (SS) (OR 1.008; 95% CI: 1.005-1.011; P= 2.66×10-6), systemic lupus erythematosus (SLE) (OR 1.006; 95% 1.001-1.011; P=0.014), multiple sclerosis (MS) (OR 1.004; 95% CI: 1.001-1.007; P=0.021), primary sclerosing cholangitis (PSC) (OR 1.002; 95% CI: 1.000-1.004; P=0.023), and celiac disease (CeD) (OR 1.002; 95% CI: 1.001-1.004; P=0.009) were significantly associated with higher risk of facial aging. After adjusting for potential confounding factors, the association persisted between AS, SLE, and CeD. These findings indicated that autoimmune diseases play a causal role in facial skin aging. Therefore, patients with autoimmune diseases should take appropriate measures to prevent early facial aging.

Protein Programmed Death-Ligand 1 Expression in Non-Small Cell Lung Cancer (NSCLC) and Its Correlation to Smoking Status in North Sumatera Population

Tobacco smoking is associated to the increase risk of lung cancer, and smoking could also trigger the tumour proportion score from programmed death ligand (PD-L1). This study aims to identify the correlation of non-small cell lung cancer (NSCLC) with the PD-L1 expression and smoking profile on the North Sumatra Population. Lung cancer is a significant health issue worldwide, where it is the leading cause of death in men. In Indonesia, lung cancer ranks second in terms of incidence overall and first in men. The 5-year prevalence of lung cancer in Indonesia is 10.85 per 100,000 population. The case fatality rate (CFR) for lung cancer in Indonesia is 86.91%. This research implemented a descriptive study with cross-sectional design. 100 of patients with lung cancer were recruited, however; only 52 patients were diagnosed with NSCLC based on histopathological results. Subsequently, 35 samples were included in accordance to inclusion criteria. Staining on Ventana 22C3 platform was performed in Dharmais Cancer Hospital, and tumour proportion score was assessed by two experts of Pathologist. This study was carried out from August 2019 to September 2020. Results: Characteristics of patients with NSCLC to the PD-L1 expression were found more in male patients with percentage of 88.6%, whereas the most common type of cancer is adenocarcinoma, accounting for 97.14% of cases with mild degree smoking index for 45.7% (Brinkman index) and IV-stage of clinical status for 68.6%. The tumour proportion score with 1-49% was 51.4% with high expression of PD-L1 (positive) for 74.28%, while lower expression of PD-L1 accounted for 45%. There is a correlation between PD-L1 expression and smoking status in NSCLC patients, with p-value of 0.037 (<0.05).

Abstract 3117: Cannabis Use Disorder And The Risk Of Atherosclerotic Cardiovascular Diseases

Introduction: With the legalization of cannabis, concerns have emerged regarding the long-term health impact of excessive use. The current literature has struggled to address questions about the adverse effects of cannabis, particularly in the context of atherosclerotic cardiovascular disease (ASCVD). Using genetic approaches to causal inference, we explored the relationship between cannabis use disorder (CUD) and ASCVD. Methods: Genetic instruments were constructed from a multi-population GWAS comprising 64,314 individuals with and 990,051 without CUD. Outcome data for coronary artery disease (CAD), ischemic stroke, peripheral artery disease (PAD), and abdominal aortic aneurysms (AAA) were derived from multi-population GWAS. Univariable Mendelian randomization (MR) was performed using the inverse-variance weighted (IVW) method to test the association of CUD with each outcome. Multivariable MR (MVMR) was performed to assess if the impact of cardiometabolic risk factors accounted for the association of CUD with ASCVD using summary statistics from publicly available GWAS of cardiometabolic risk factors. Results: CUD was associated with increased risk of CAD (OR 1.27; 95% CI 1.17-1.38; P=<0.01), ischemic stroke (OR 1.10; 95%CI 1.03-1.19; P=<0.01), PAD (OR 1.31; 95% CI 1.17-1.46; P=<0.01), and AAA (OR 1.37; 95% CI 1.21-1.55; P=<0.01). CUD also had a significant impact on cardiometabolic risk factors including triglycerides, waist-to-hip ratio, BMI, type 2 diabetes, obesity, and heart failure. The effect of CUD on ASCVD, other than stroke, remained largely independent of traditional risk factors except for lipids and tobacco smoking. Controlling for lifetime smoking index attenuated all associations between CUD and ASCVD except CAD, which remained significant (OR 1.21; 95% CI 1.11-1.31). Conclusion: Excessive cannabis use has the potential to increase ASCVD risk, independent of cardiometabolic risk factors, although this risk may in part be attributable to shared susceptibility to lipids and tobacco use. Awareness of the long-term risks of excessive cannabis use should be considered when formulating medical advice and public policy.

Burden of hypertension and associated risk factors among the Nicobarese tribe of Car Nicobar Island, India

Background: Hypertension, a significant risk factor for various non-communicable diseases, poses a preventable threat to mortality and disease burden. However, there remains a lack of data on hypertension within Indian tribes, particularly those residing in impoverished areas. Determining the prevalence of hypertension and identifying associated risk factors among the Nicobarese tribes. A cross-sectional survey was conducted, involving 2600 tribal individuals aged 18 years and above from ten randomly selected villages on Car Nicobar Island. Methods: A structured questionnaire was utilized to gather data on blood pressure (BP), anthropometric measurements, and detailed participant characteristics. Prevalence of hypertension was determined and analyzed in relation to various identified risk factors using chi-square, Karl Pearson coefficient of correlation, and generalized linear models. Prevalence ratio and adjusted risk ratio calculated, along with their corresponding confidence intervals. Results: Prevalence of hypertension was 57.9%. Several factors, including age, male gender, illiteracy, diabetes, smoking, alcohol consumption, and higher body mass index (BMI), were significantly associated with hypertension. Systolic and diastolic BP levels increased significantly with age, socio-economic scores, BMI, and weight. Conclusions: The prevalence of hypertension among the Nicobarese tribes is significantly higher compared to the general population. Adapting preventive strategies based on an understanding of the tribe's specific culture and lifestyle is important for controlling hypertension. However, it is also crucial to consider genetic and environmental influences that may contribute to the high prevalence of hypertension in this tribe.

A causal relationship between educational attainment and risk of infectious diseases: A Mendelian randomisation study.

Previous observational studies have investigated the association between educational attainment and sepsis, pneumonia, and urinary tract infections (UTIs). However, their findings have been susceptible to reverse causality and confounding factors. Furthermore, no study has examined the effect of educational level on the risk of infections of the skin and subcutaneous tissue (SSTIs). Thus, we aimed to evaluate the causal relationships between educational level and the risk of four infectious diseases using Mendelian randomisation (MR) techniques. We used univariable MR analysis to investigate the causal associations between educational attainment (years of schooling (n = 766 345) and holding college or university degree (n = 334 070)) and four infectious diseases (sepsis (n = 486 484), pneumonia (n = 486 484), UTIs (n = 463 010), and SSTIs (n = 218 792)). We included genetic instrumental variables with a genome-wide significance (P < 5 × 10-8) in the study. We used inverse variance-weighted estimation in the primary analysis and explored the stability of the results using multivariable MR analysis after adjusting for smoking, alcohol consumption, and body mass index. Genetically predicted years of schooling were associated with a reduced risk of sepsis (odds ratio (OR) = 0.763; 95% confidence interval (CI) = 0.668-0.870, P = 5.525 × 10-5), pneumonia (OR = 0.637; 95% CI = 0.577-0.702, P = 1.875 × 10-19), UTIs (OR = 0.995; 95% CI = 0.993-0.997, P = 1.229 × 10-5), and SSTIs (OR = 0.696; 95% CI = 0.605-0.801, P = 4.034 × 10-7). We observed consistent results for the correlation between qualifications and infectious diseases. These findings remained stable in the multivariable MR analyses. Our findings suggest that increased educational attainment may be causally associated with a decreased risk of sepsis, pneumonia, UTIs, and SSTIs.

Cognitive Function, Healthy Lifestyle, and All-Cause Mortality among Chinese Older Adults: A Longitudinal Prospective Study.

Both cognitive decline and unhealthy lifestyles have been linked to an elevated risk of mortality in older people. We aimed to investigate whether a healthy lifestyle might modify the association between cognitive function and all-cause mortality in Chinese older populations. The final analysis included 5124 individuals free of dementia, selected from the Chinese Longitudinal Healthy Longevity Survey from 2011 to 2018. Cognitive function was assessed in 2011 using the Mini-Mental State Examination (MMSE). A lifestyle score was calculated based on five lifestyle factors, including smoking, alcohol consumption, physical activity, diet, and body mass index. Cox proportional hazards models were performed to evaluate the association between baseline cognitive function and the risk of all-cause mortality, with an interaction term of cognitive function and lifestyle score being added to the models. The average age of participants was 81.87 years old at baseline. During a median follow-up of 6.4 years, 1461 deaths were documented. Both higher cognitive function (HR: 0.96; 95% CI: 0.96-0.97) and a healthier lifestyle (HR: 0.92; 95% CI: 0.87-0.97) were significantly associated with a reduced risk of mortality. We found that lifestyle significantly modified the association of cognitive function with mortality (p for interaction = 0.004). The inverse relation between cognitive function and mortality was found to be more pronounced among participants with a healthier lifestyle. Of note, among the lifestyle scores component, diet showed a significant interaction with mortality (p for interaction = 0.003), and the protective HR of the all-cause mortality associated with higher MMSE scores was more prominent among participants with healthy diets compared with unhealthy diets. Our study indicates that cognitive decline is associated with a higher risk of mortality, and such associations are attenuated by maintaining a healthy lifestyle, with a particular emphasis on healthy diet.

The Removal of Total Knee Arthroplasty From the Inpatient-Only List has Improved Patient Optimization.

On January 1, 2018, the Centers for Medicare and Medicaid Services removed total knee arthroplasty (TKA) from the inpatient-only (IPO) list, expanding outpatient TKA (oTKA) to include patients with insurance coverage through their programs. These regulatory changes reinforced the need for preoperative optimization to ensure a safe and timely discharge after surgery. This study compared modifiable preoperative optimization metrics in patients who underwent oTKA pre-IPO and post-IPO removal. The authors hypothesized that patients post-IPO removal would demonstrate improvement in the selected categories. Outpatient TKA in a national database was identified and stratified by surgical year (2015 to 2017 versus 2018 to 2020). Preoperative optimization thresholds were established for the following modifiable risk factors: albumin, hematocrit, sodium, smoking, and body mass index. The percentage of patients who did not meet thresholds pre-IPO and post-IPO removal were compared. In total, 2,074 patients underwent oTKA from 2015 to 2017 compared with 46,480 from 2018 to 2020. Patients undergoing oTKA after IPO removal were significantly older (67.0 versus 64.4 years; P < 0.01). A lower percentage of patients in the post-IPO cohort fell outside the threshold for all modifiable risk factors. Results were significant for preoperative sodium (10.7% versus 8.8%; P < 0.01), body mass index (12.4% versus 11.0% P = 0.05), and smoking history (9.9% versus 6.6%; P < 0.01). Outpatient TKA has increased considerably post-IPO removal. As this regulatory change has allowed older patients with increased comorbidities to undergo oTKA, the need for appropriate preoperative optimization has increased. The current data set demonstrates that surgeons have improved preoperative optimization efforts for select modifiable risk factors.

Mendelian Randomization Analysis of the Causal Effect of Cigarette Smoking on Hospital Costs.

Knowledge of the impact of smoking on health care costs is important for establishing the external effects of smoking and for evaluating policies intended to modify this behavior. Conventional analysis of this association is difficult because of omitted variable bias, reverse causality, and measurement error. We approached these challenges using a Mendelian Randomization study design; genetic variants associated with smoking behaviors were used in instrumental variables models with inpatient hospital costs (calculated from electronic health records) as the outcome. We undertook genome-wide association studies to identify genetic variants associated with smoking initiation and a composite smoking index (reflecting cumulative health impacts of smoking) on up to 300 045 individuals (mean age: 57 years at baseline, range 39-72 years) in the UK Biobank. We followed individuals up for a mean of 6 years. Genetic liability to initiate smoking (ever vs. never smoking) was estimated to increase mean per-patient annual inpatient hospital costs by £477 (95% confidence interval (CI): £187 to £766). A one-unit change in genetic liability to the composite smoking index (range: 0-4.0) increased inpatient hospital costs by £204 (95% CI: £105 to £303) per unit increase in this index. There was some evidence that the composite smoking index causal models violated the instrumental variable assumptions, and all Mendelian Randomization models were estimated with considerable uncertainty. Models conditioning on risk tolerance were not robust to weak instrument bias. Our findings have implications for the potential cost-effectiveness of smoking interventions. We report the first Mendelian Randomization analysis of the causal effect of smoking on health care costs. Using two smoking phenotypes, we identified substantial impacts of smoking on inpatient hospital costs, although the causal models were associated with considerable uncertainty. These results could be used alongside other evidence on the impact of smoking to evaluate the cost-effectiveness of antismoking interventions and to understand the scale of externalities associated with this behavior.

Analysis of prognostic and predictive factors in neovascular age-related macular degeneration Kuopio cohort.

The aim of the study was to explore factors affecting the progression of neovascular age-related macular degeneration (nAMD) and identify predictive factors that can estimate the duration of intravitreal treatments. This retrospective real-world study included 421 nAMD patients treated at the Kuopio University Hospital during years 2007-2021. The collected data included background demographics, treatment history, visual acuity and retinal biomarker analysis. Impact of baseline factors on age at diagnosis, treatment duration, received treatment intensity and visual acuity gains were analysed. Heavy smoking and high body mass index (BMI) were associated with an earlier onset, while the use of anticoagulation and anti-aggregation medication were associated with a later onset of nAMD. A low number of injections during the first year of treatment and the presence of intraretinal fluid (IRF) at baseline were associated with shorter treatment duration. Interestingly, when IRF only patients were compared to subretinal fluid (SRF) only patients, IRF patients showed higher occurrences of subretinal drusenoid deposits (43.5% vs. 15%, p = 0.04). In addition, when all patients with IRF were compared to SRF only patients, more hyperreflective foci (HRF) and complete RPE and outer retinal atrophy (cRORA; 20.7% vs. 5%, p = 0.02) were observed in patients with IRF. Our results reveal that heavy smoking and high BMI are accelerating factors for earlier emergence of nAMD, while the presence of IRF results in a fast-progressing disease. More intriguingly, the link between IRF and appearance of subretinal drusenoid deposits, HRF, and increased retinal atrophy was observed.

Analysis of changes in intrinsic neural timescales in male smoking addicts based on whole brain resting-state functional magnetic resonance imaging

Objective: To investigate the abnormal changes of intrinsic neural time scale (INT) in male smoking addicts based on whole brain resting state functional magnetic resonance imaging (rs-fMRI). Methods: A case-control study. The clinical data and whole brain rs-fMRI data of 139 male subjects, aged (34.1±8.8) years, recruited through the online platform from January 2019 to December 2021 were retrospectively analyzed. According to the existence of smoking addiction, they were divided into smoking addiction group (n=83) and healthy control group (n=56).INT was calculated to reflect the brain neural activity dynamics. Single sample t test was used to obtain the whole brain spatial distribution maps of INT in smoking addiction group and the control group. Then two-sample t test was conducted to explore the difference of INT between the smoking addition group and the healthy control group, with age and years of education as covariates. Finally, Spearman correlation analysis was used to explore the relationship between INT and nicotine dependence scale score and smoking index. Results: Subjects with smoking addiction and healthy control group showed a similar pattern of hierarchical neural timescales, namely shorter INT in sensorimotor areas and longer INT in parietal lobe, posterior cingulate cortex. In addition, in the smoking addiction group, the left medial occipital gyrus (peak t=-3.18), left suproccipital gyrus (peak t=-3.66), bilateral pericalar cleft cortex (left: peak t=-3.02, right: peak t=-3.22), bilateral lingual gyrus (left: peak t=-3.10, right: t peak=-3.04), left cuneus (peak t=-2.97), default network associated brain region [left anterior cuneus(peak t=-3.23), left angular gyrus (peak t=-3.07), and left posterior cingulate cortex (peak t=-3.54) were significantly lower than those of healthy controls (gaussian random field correction, voxel level all P<0.005, mass level all P<0.05). However, there was no significant correlation between INT and nicotine dependence scale score and smoking index (both P>0.05 after Bonferroni correction). Conclusion: Compared with healthy controls, smoking addicts showed abnormal changes in the dynamics of neural activity in the visual cortex and the default network.

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders

BackgroundEndothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. MethodsThe study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. ResultsThe total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. ConclusionsIn our study, patients with schizophrenia – including the drug-naïve – have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

Prevalence of hyperthyroidism and hypothyroidism in liver transplant recipients and associated risk factors

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05–4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43–1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients

BackgroundObservational studies have shown that smoking is related to the diffusing capacity of the lungs for carbon monoxide (DLCO) in individuals with idiopathic pulmonary fibrosis (IPF). Nevertheless, further investigation is needed to determine the causal effect between these two variables. Therefore, we conducted a study to investigate the causal relationship between smoking and DLCO in IPF patients using two-sample Mendelian randomization (MR) analysis.MethodsLarge-scale genome-wide association study (GWAS) datasets from individuals of European descent were analysed. These datasets included published lifetime smoking index (LSI) data for 462,690 participants and DLCO data for 975 IPF patients. The inverse-variance weighting (IVW) method was the main method used in our analysis. Sensitivity analyses were performed by MR‒Egger regression, Cochran’s Q test, the leave-one-out test and the MR-PRESSO global test.ResultsA genetically predicted increase in LSI was associated with a decrease in DLCO in IPF patients [ORIVW = 0.54; 95% CI 0.32–0.93; P = 0.02].ConclusionsOur study suggested that smoking is associated with a decrease in DLCO. Patients diagnosed with IPF should adopt an active and healthy lifestyle, especially by quitting smoking, which may be effective at slowing the progression of IPF.

Clinical Value of the Diagonal Earlobe Crease in Patients with Chest Pain for Diagnosing Coronary Heart Disease.

To investigate the clinical application value of diagonal earlobe crease (DELC) in patients with chest pain for the diagnosis of coronary heart disease (CHD) and to construct a risk model by multivariate logistic regression. Our trial enrolled prospectively and consecutively 706 chest pain patients with suspected CHD between January 2021 to June 2023 from Chengde Central Hospital. According to coronary angiography results, they were categorized into the CHD (n=457) and non-CHD groups (n=249). The trial demonstrated a significant positive relationship between DELC and CHD. Independent risk factors were sex, age, hypertension, diabetes mellitus, LP (a), Cys C, and DELC, whilst HDL-C was a protective factor, for CHD. Patients with-DELC were older than those in the without-DELC arm (P<0.001) and had a higher proportion of males than females (61.6% vs 50.0%, P=0.026). After multifactorial correction, independent risk factors for CHD included DELC (OR=1.660, 95% CI:1.153 to 2.388, P=0.006), age (OR=1.024, 95% CI:1.002 to 1.045, P=0.030), gender (OR=1.702, 95% CI:1.141 to 2.539, P=0.009), hypertension (OR=1.744, 95% CI:1.226 to 2.482, P=0.002), diabetes mellitus (OR=2.113, 95% CI:1.404 to 3.179, P<0.001), LP(a) (OR=1.010, 95% CI:1.003 to 1.017, P=0.005), Cys C (OR=3.549, 95% CI:1.605 to 7.846, P=0.002). The Hosmer and Lemeshow (H-L) test (P=0.818) suggests a high goodness of fit, and the area under the ROC curve was calculated to be 0.721 (95% CI:0.682 to 0.760, P<0.001), which demonstrates that the model has a superior diagnostic value for CHD. DELC is an independent risk factor for CHD after adjusting for sex, age, hypertension, diabetes mellitus, smoking index, LP (a), Cys C, and HDL-C. Our model can be used clinically for assessing the risk of CHD.

Promising Intestinal Microbiota Associated with Clinical Characteristics of COPD Through Integrated Bioinformatics Analysis.

Chronic obstructive pulmonary disease (COPD), an incurable chronic respiratory disease, has become a major public health problem. The relationship between the composition of intestinal microbiota and the important clinical factors affecting COPD remains unclear. This study aimed to identify specific intestinal microbiota with high clinical diagnostic value for COPD. The fecal microbiota of patients with COPD and healthy individuals were analyzed by 16S rDNA sequencing. Random forest classification was performed to analyze the different intestinal microbiota. Spearman correlation was conducted to analyze the correlation between different intestinal microbiota and clinical characteristics. A microbiota-disease network diagram was constructed using the gut MDisorder database to identify the possible pathogenesis of intestinal microorganisms affecting COPD, screen for potential treatment, and guide future research. No significant difference in biodiversity was shown between the two groups but significant differences in microbial community structure. Fifteen genera of bacteria with large abundance differences were identified, including Bacteroides, Prevotella, Lachnospira, and Parabacteroides. Among them, the relative abundance of Lachnospira and Coprococcus was negatively related to the smoking index and positively related to lung function results. By contrast, the relative abundance of Parabacteroides was positively correlated with the smoking index and negatively correlated with lung function findings. Random forest classification showed that Lachnospira was the genus most capable of distinguishing between patients with COPD and healthy individuals suggesting it may be a potential biomarker of COPD. A Lachnospira disease network diagram suggested that Lachnospira decreased in some diseases, such as asthma, diabetes mellitus, and coronavirus disease 2019 (COVID-19), and increased in other diseases, such as irritable bowel syndrome, hypertension, and bovine lichen. The dominant intestinal microbiota with significant differences is related to the clinical characteristics of COPD, and the Lachnospira has the potential value to identify COPD.

Assessment of hyaluronic acid in COPD patients as a prognostic biomarker

BackgroundOne essential element of the extracellular matrix is hyaluronic acid (HA). It has been claimed that HA and its metabolism are different in the lungs of patients with chronic obstructive pulmonary disease (COPD). The present study investigated the predictive significance of serum level of HA in patients with COPD and monitored changes in its level in these patients because of therapy.MethodsHA was assessed in 60 patients with stable COPD (divided into subgroups I and II) and 20 healthy controls and then repeated after 3 and 6 months in COPD patients.ResultsMost of the patients were males (63.3%), and their ages ranged from 30 to 90. The serum level of HA was significantly increased in subgroups I and II (269.33 ± 4, 290 ± 4, respectively), compared to the control group (147.5 ± 1) with a significant difference in its level between both (p < 0.0001). The serum level of HA was significantly decreased in both subgroups 3 and 6 months later following adjustment of treatment and associated with improvement in pulmonary function test. There were significant positive correlations between HA and age as well as smoking index. Its level correlated negatively with forced expiratory volume in the first second (FEV1%), forced vital capacity (FVC%), and FEV1/FVC.ConclusionsHA is a useful marker for identifying clinical stability in COPD patients and for follow-up in the efficacy of treatment.

Contribution of Nutritional, Lifestyle, and Metabolic Risk Factors to Parkinson's Disease.

Modifiable risk factors for Parkinson's disease (PD) are poorly known. The aim is to evaluate independent associations of different nutritional components, physical activity, and sedentary behavior and metabolic factors with the risk of PD. In this population-based prospective cohort study using the data of the United Kingdom Biobank (from 2006-2010), 502,017 men and women who were free from PD (International Classification of Diseases 10th edition; "G20") at baseline were included. We implemented a Cox proportion hazard's model to evaluate the associations of different levels of physical activity, sitting time, sleep habits, diet quality, alcohol and coffee consumption, smoking, and body mass index with PD risk, adjusting for several confounding variables. During a median follow-up of 12.8 years, lifestyle factors including vigorous physical activity (hazard ration [HR] = 0.84; 95% confidence interval [CI], 0.75-0.94), low-to-moderate sitting time (HR = 0.89; 95% CI, 0.81-0.97), and high sleep quality (HR = 0.89; 95% CI, 0.80-0.99) were associated with a reduced risk of PD. Small amounts of coffee (HR = 0.88; 95% CI, 0.82-0.95), red meat (HR = 0.86; 95% CI, 0.76-0.97), and current smoking (HR = 0.65; 95% CI, 0.56-0.75) were also associated with a lower risk of PD, whereas alcohol intake (HR = 1.29; 95% CI, 1.06-1.56) with higher PD risk. Secondary analysis, including metabolic risk factors, confirmed these findings and highlighted the potential protective effect of plasma vitamin D and uric acid, but of low-density lipoprotein-cholesterol, triglycerides, and C-reactive protein as well. Vigorous physical activity, reduced sitting time, good sleep quality together with small coffee intake and vitamin D supplementation are potentially neuroprotective lifestyle interventions for the prevention of PD. © 2024 International Parkinson and Movement Disorder Society.

Early smoking lead to worse prognosis of COPD patients: a real world study

BackgroundSmoking remains a major risk factor for the development and progression of chronic obstructive pulmonary disease (COPD). Due to the adolescent smoking associated with worse health state, the age, at which an individual started smoking, might play a key role in shaping the trajectory of COPD development and the severity.MethodsWe conducted an observational study from September 2016 through January 2023 of eligible patients hospitalized with COPD. Patients who started smoking during the alveolar development stage (ADS, smoking initiation ≤ 24 years old) were defined as early smoking patients, and patients who started smoking after ADS (smoking initiation > 24 years old) were defined as late smoking patients. We collected demographic and clinical data characterizing the patients and documented their condition from hospital discharge to follow-up. The primary endpoints were short-term (within one year), 3-year, and long-term (beyond 3 years) all-cause mortality after discharge.ResultsAmong 697 COPD patients, early smoking patients had a lower smoking cessation rate (P < 0.001) and a higher smoking index (P < 0.001) than late smoking patients. Although adjusted smoking index, early smoking patients still had poorer lung function (P = 0.023), thicker left ventricular diameters (P = 0.003), higher frequency of triple therapy use during stable stage (P = 0.049), and more acute exacerbations in the past year before enrollment (P < 0.05). Survival analysis showed that they had a higher risk of death after discharge within three years (P = 0.004) and beyond three years (P < 0.001). Furthermore, even in early smoking COPD patients who quit smoking after adjusting the smoking index had poorer lung function (P < 0.05) and thicker left ventricular diameters (P = 0.003), and survival analysis also showed that they had a higher long-term mortality rate (P = 0.010) and shorter survival time (P = 0.0128).ConclusionEarly smoking COPD patients exhibited multiple adverse clinical outcomes, including heavy cigarette addiction, compromised pulmonary function, augmented left ventricular diameter, and elevated mortality risk. Additional, smoking cessation could not bring enough improvement of health state in early smoking COPD patients as late smoking COPD patients. Consequently, early intervention and specialized cessation approaches for younger smokers are of paramount importance in this context.

Abstract 6123: Validating cancer modulated allostatic load as a composite biomarker for mortality in patients with cancer

Abstract Allostatic load (AL) is the cumulative burden of chronic stress and life events typically measured by lab and vital values routinely collected during standard care. AL has been associated with adverse socioenvironmental stressors and increased mortality rates including risk of cancer death. Despite modifications of AL as a result of progressing cancer and anti-cancer treatments, AL may serve as a valuable biomarker for cancer outcomes, and highlight similar disparities across sociodemographic groups agnostic of a history of cancer diagnosis. Recent investigations have shown associations of AL with overall mortality rates in patients with non-small cell lung cancer (NSCLC) and breast cancer, as well as various social determinants of health. The impact of AL on different malignancies, particularly in the context of genetic variations identified through genomic profiling, is yet to be thoroughly investigated. We identified a pan-cancer cohort of 29,433 patients sequenced with the MSK-IMPACT targeted panel sequencing assay, and collected clinical, genomic, and lab data. We first studied the association of AL with patient and tumor characteristics such as tumor type, stage, cancer genomics, comorbidities, social deprivation defined by the Yost index, and genetic ancestry. We derived AL using 10 standard biomarkers across cardiovascular, metabolic, renal, and immune systems, and created a composite AL summary score with a range between 0 and 10. Composite AL summary score into quartiles for comparisons. We found that AL was increased with higher cancer stage, older age, smoking, multiple comorbidities, African ancestry, and Yost index. Multivariate logistic regression analysis showed that AL was correlated with mutations e in KRAS and anti-correlated with EGFR mutations (FDR&amp;lt;0.02). Next, we investigated AL as a biomarker for mortality in patients with cancer and compared its prognostic value to other biomarkers. Using a Cox proportional hazard model we found that AL was significantly associated with shorter overall survival, controlling for stage and socioeconomic variables (HR=1.7, 2.2, 2.7 in AL Quartiles 2-4 respectively). Finally, we decomposed AL into its individual markers to quantify the most important features driving outcomes. Using a Random Survival Forest model with a focus on NSCLC patients, we found that albumin and alkaline phosphatase were the strongest features of shorter survival in our AL composite model. Our findings suggest that elevated AL is associated with a poorer prognosis across multiple cancer types, a trend observable across different stages of cancer. The association between AL and clinically actionable mutations highlights the importance of understanding the relationship between somatic alterations and social/environmental factors. The study underscores the utility of AL as a powerful prognostic tool that can be routinely collected in a clinical setting. Citation Format: Christopher J. Fong, Kaicheng U, Cheryl Phua, Xuechun Bai, Michele Waters, Tom Fu, Kanika Arora, Tomin Perea-Chamblee, Devika Jutagir, Michael Berger, Nikolaus Schultz, Adam Schoenfeld, Francesca Gany, Justin Jee, Jian Carrot-Zhang. Validating cancer modulated allostatic load as a composite biomarker for mortality in patients with cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6123.

Abstract 3635: Insulin-like growth factor receptor predicts poor prognosis in early-stage non-small cell lung cancer

Abstract Introduction: Insulin like growth factor receptor (IGF1R) is involved in the proliferation and metastasis of various cancers. However, the clinical significance of IGF1R in non-small cell lung cancer (NSCLC) remains to be unclear. In this study, we retrospectively evaluated the correlation between IGF1R expression and clinicopathological features of NSCLC. Method: A total of 782 specimens of NSCLC patients who underwent surgical resection of primary lung cancer between 2010 and 2019 at Osaka Metropolitan University Hospital was enrolled in this study. Immunohistochemical staining of IGF1R were performed, and the correlation between IGF1R expression and clinicopathological features of NSCLC, especially in recurrence free survival (RFS) and overall survival (OS), was evaluated. We also evaluated an association between IGF1R and programmed death ligand 1 (PD-L1) expression. Results: IGF1R expression was positive in 279 (35.8%) patients. IGF1R-positive group had significantly longer smoking histories (median smoking index, 1,000 vs 600, p &amp;lt;0.01) and a higher proportion of squamous cell carcinomas (35.1% vs 14.1 %, p &amp;lt;0.01). IGF1R-positive group also significantly expressed PD-L1 (24.4% vs 6.4%, p&amp;lt;0.01). IGF1R-positive group had significantly worse RFS (10-year recurrence-free rate; 42.7% vs 53.7%, p &amp;lt;0.01) and OS (10-year survival rate; 54.4% vs 67.3%, p &amp;lt;0.01). RFS and OS were significantly worse in the IGF1R-positive NSCLC patients at stage 0 and stage I (10-year recurrence-free rate; 49.0% vs 62.9%, p &amp;lt;0.01, 10-year survival rate; 57.4% vs 74.2%, p&amp;lt;0.01), but not in stage II (10-year recurrence-free rate; 52.0% vs 43.8%, p=0.68, 10-year survival rate; 63.4% vs 47.5%, p=0.95) and III (10-year recurrence-free rate; 20.7% vs 20.8%, p=0.77, 10-year survival rate; 38.3% vs 54.6%, p=0.18). IGF1R expression was associated with poorer RFS and OS in early-stage NSCLC. Conclusion: IGF1R is a predictor of poor prognosis in resected early-stage NSCLC. Citation Format: Hiroaki nagamine, Masakazu Yashiro, Megumi Mizutani, Akira Sugimoto, Yoshiya Matsumoto, Yoko Tani, Kenji Sawa, Kazuhiro Yamada, Hiroyasu Kaneda, Tetsuya Watanabe, Kazuhisa Asai, Satoshi Suzuki, Tomoya Kawaguchi. Insulin-like growth factor receptor predicts poor prognosis in early-stage non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3635.