Chronic Obstructive Pulmonary Disease Smokers Research Articles

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis

BackgroundVolatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample.MethodsWe assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin.ResultsIn the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers.ConclusionsOur findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Factors Associated with Patient Education in Patients with Chronic Obstructive Pulmonary Disease (COPD) - A Primary Health Care Register-Based Study.

Patient education in chronic obstructive pulmonary disease (COPD) is recommended in treatment strategy documents, since it can improve the ability to cope with the disease. Our aim was to identify the extent of and factors associated with patient education in patients with COPD in a primary health care setting. In this nationwide study, we identified 29,692 COPD patients with a registration in the Swedish National Airway Register (SNAR) in 2019. Data on patient education and other clinical variables of interest were collected from SNAR. The database was linked to additional national registers to obtain data about pharmacological treatment, exacerbations and educational level. Patient education had been received by 44% of COPD patients, 72% of whom had received education on pharmacological treatment including inhalation technique. A higher proportion of patients who had received education were offered smoking cessation support, had performed spirometry and answered the COPD Assessment Test (CAT), compared with patients without patient education. In the adjusted analysis, GOLD grade 2 (OR 1.29, 95% CI 1.18-1.42), grade 3 (OR 1.41, 95% CI 1.27-1.57) and grade 4 (OR 1.79, 95% CI 1.48-2.15), as well as GOLD group E (OR 1.17, 95% CI 1.06-1.29), ex-smoking (OR 1.70, 95% CI 1.56-1.84) and current smoking (OR 1.45, 95% CI 1.33-1.58) were positively associated with having received patient education, while cardiovascular disease (OR 0.92, 95% CI 0.87-0.98) and diabetes (OR 0.93, 95% CI 0.87-1.00) were negatively associated with receipt of patient education. Fewer than half of the patients had received patient education, and the education had mostly been given to those with more severe COPD, ex- and current smokers and patients with fewer comorbidities. Our study highlights the need to enhance patient education at an earlier stage of the disease.

Air Pollution Exposure and Interstitial Lung Features in SPIROMICS Participants with COPD.

It is unknown whether air pollution is associated with radiographic features of interstitial lung disease in individuals with chronic obstructive pulmonary disease (COPD). To determine whether air pollution increases prevalence of interstitial lung abnormalities (ILA) or percent high-attenuation area (HAA) on computed tomography (CT) in individuals with a heavy smoking history and COPD. We performed a cross-sectional study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), focused on current or former smokers with COPD. 10-year exposure to particulate matter < 2.5 µm (PM2.5), nitrogen oxides (NOx), nitrogen dioxide (NO2), and ozone (O3) prior to enrollment CTs (completed between 2010-2015) were estimated with validated spatiotemporal models at residential addresses. We applied adjusted multivariable modified Poisson regression and linear regression to investigate associations between pollution exposure and relative risk of ILA or increased percent HAA (between -600 and -250 Hounsfield units) respectively. We assessed for effect modification by MUC5B-promoter polymorphism (GT/TT vs GG at rs3705950), smoking status, sex, and percent emphysema. Among 1272 participants with COPD assessed for HAA, 424 were current smokers, 249 were carriers of the variant MUC5B allele (GT/TT). 519 participants were assessed for ILA. We found no association between pollution exposure and ILA or HAA. Associations between pollutant exposures and risk of ILA were modified by the presence of MUC5B polymorphism (p-value interaction term for NOx = 0.04 and PM2.5 = 0.05) and smoking status (p-value interaction term for NOx = 0.05, NO2 = 0.01, and O3 = 0.05). With higher exposure to NOx and PM2.5, MUC5B variant carriers had increased risk of ILA (Relative Risk [RR] per 26ppb NOx 2.41; 95% Confidence Interval [CI] 0.97 to 6.0) and RR per 4 μg·m-3 PM2.5 1.43; 95% CI 0.93 to 2.2). With higher exposure to NO2, former smokers had increased risk of ILA (RR per 10ppb 1.64; 95% CI 1.0 to 2.7). Exposure to ambient air pollution was not associated with interstitial features on CT in this population of heavy smokers with COPD. MUC5B modified the association between pollution and ILA, suggesting that gene-environment interactions may influence prevalence of interstitial lung features in COPD.

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.

Diagnostic insights from chemometric analysis of hemogram inflammatory indexes in male smokers with and without asthma or chronic obstructive pulmonary disease.

Diagnosis of asthma and chronic obstructive pulmonary disease (COPD) becomes difficult in a primary healthcare center due to ambiguous interpretation of spirometry and lack of facility to access established biomarkers. While routine hematological indices are easily available and accessible. The study aimed to evaluate the role of different hemogram indexes in males in COPD, asthma, and healthy smokers. Lung function tests and complete blood count (CBC) were done for 50 male subjects each from asthma, COPD, and healthy smokers. Multivariate analysis (MVA) was performed on blood indices data set. Receiver operating characteristic (ROC) curve was plotted to observe the performance of indexes. Pearson correlation was used to establish association between the lung function and blood indices. Most of the indices were elevated in COPD. Whereas, asthma patients showed a significant increase in eosinophil basophil ratio (EBR), lymphocyte-monocyte ratio (LMR), and mean platelet volume-platelet count ratio (MPR). Orthogonal (O)- Partial Least-Squares Discriminant Analysis (PLSDA) and variable importance in projection (VIP) score established EBR, neutrophil-lymphocyte ratio (NLR) and LMR, as discriminants for asthma. Whereas, Systemic Inflammatory Response Index (SIRI), NLR and EBR were the key variables for COPD. NLR (r = -0.73, p < 0.001) and SIRI (r = -0.71, p < 0.001) were found to be negatively correlated with forced expiratory volume in 1 s (FEV1) percentage of the predicted value (%pred) in asthma and COPD, respectively. EBR showed the sensitivity and specificity of 96% and 86% respectively in asthma. NLR was having sensitivity of 82% and 90% specificity in COPD. Our study in males shows routine hematological indices as being cost-effective, feasible, and seem to have tremendous potential as screening markers among chronic respiratory diseases in a primary healthcare center.

A prospective study on association between sleep duration and the risk of chronic obstructive pulmonary disease in adults in Suzhou

Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Oxidative Damage and Telomere Length as Markers of Lung Cancer Development among Chronic Obstructive Pulmonary Disease (COPD) Smokers.

Lung cancer (LC) constitutes an important cause of death among patients with Chronic Obstructive Pulmonary Disease (COPD). Both diseases may share pathobiological mechanisms related to oxidative damage and cellular senescence. In this study, the potential value of leucocyte telomere length, a hallmark of aging, and 8-OHdG concentrations, indicative of oxidative DNA damage, as risk biomarkers of LC was evaluated in COPD patients three years prior to LC diagnosis. Relative telomere length measured using qPCR and serum levels of 8-OHdG were determined at the baseline in 99 COPD smokers (33 with LC and 66 age-matched COPD without LC as controls). Of these, 21 COPD with LC and 42 controls had the biomarkers measured 3 years before. Single nucleotide variants (SNVs) in TERT, RTEL, and NAF1 genes were also determined. COPD cases were evaluated, which showed greater telomere length (p < 0.001) and increased serum 8-OHdG levels (p = 0.004) three years prior to LC diagnosis compared to the controls. This relationship was confirmed at the time of LC diagnosis. No significant association was found between the studied SNVs in cases vs. controls. In conclusion, this preliminary study shows that longer leucocyte telomere length and increased 8-OHdG serum levels can be useful as early biomarkers of the risk for future lung cancer development among COPD patients.

Neglecting the neglected: Tobacco cessation support is essential for the management of asthma and COPD.

Asthma and COPD management have a broad framework, and smoking cessation plays an essential role. We examine the management of asthma and COPD patients not only for inhaler treatment options but also for essential interventions, such as smoking cessation support. Data were collected cross-sectionally from pulmonology departments of three government hospitals in Türkiye between May and September 2022. Patients aged ≥18 years who had been diagnosed with asthma or COPD for at least a year, were included in the study. The demographic and clinical characteristics of the patients were investigated. Routine cessation interventions were implemented for current smokers, and they were followed via phone calls after one month regarding their quit status and access to cessation clinics. Data from 145 patients with asthma and 148 patients with COPD were analyzed. The rate of current smoking among patients with asthma and COPD was 18.8% and 34.5%, respectively. Current smoking was negatively associated with age (<65 years) and disease duration (years) for both diseases (p<0.05). In addition, for asthmatics, presence of pulmonary disease in the family (OR:0.28, 95% CI: 0.10-0.79) and for COPD patients presence of hospitalization (OR: 0.26, 95% CI: 0.07-0.93) were negatively associated with current smoking. After one month, 85.1% of current asthmatic smokers had not tried to call a quitline, while 14.8% had tried to contact a quitline. Among current smoker COPD patients, only 1.9% had visited a smoking cessation clinic. Tobacco cessation support seems to be neglected in asthma and COPD management. Instead, pulmonologists and patients focus on pharmaceutical treatments, which constitute the other component of care.

The Molecular Blueprint for Chronic Obstructive Pulmonary Disease (COPD): A New Paradigm for Diagnosis and Therapeutics.

The global prevalence of chronic obstructive pulmonary disease (COPD) has increased over the last decade and has emerged as the third leading cause of death worldwide. It is characterized by emphysema with prolonged airflow limitation. COPD patients are more susceptible to COVID-19 and increase the disease severity about four times. The most used drugs to treat it show numerous side effects, including immune suppression and infection. This review discusses a narrative opinion and critical review of COPD. We present different aspects of the disease, from cellular and inflammatory responses to cigarette smoking in COPD and signaling pathways. In addition, we highlighted various risk factors for developing COPD apart from smoking, like occupational exposure, pollutants, genetic factors, gender, etc. After the recent elucidation of the underlying inflammatory signaling pathways in COPD, new molecular targeted drug candidates for COPD are signal-transmitting substances. We further summarize recent developments in biomarker discovery for COPD and its implications for disease diagnosis. In addition, we discuss novel drug targets for COPD that could be explored for drug development and subsequent clinical management of cardiovascular disease and COVID-19, commonly associated with COPD. Our extensive analysis of COPD cause, etiology, diagnosis, and therapeutic will provide a better understanding of the disease and the development of effective therapeutic options. In-depth knowledge of the underlying mechanism will offer deeper insights into identifying novel molecular targets for developing potent therapeutics and biomarkers of disease diagnosis.

Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC.

Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC). Smoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4-/CD8-, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA-/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA-/CD45RO+/CD197-) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups. Our focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients. The applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC.

Breathlessness and "exacerbation" questions predictive for incident COPD (MARKO study): data after two years of follow-up.

To determine the predictability of the MARKO questionnaire and/or its domains, individually or in combination with other markers and characteristics (age, gender, smoking history, lung function, 6-min walk test (6 MWT), exhaled breath temperature (EBT), and hsCRP for the incident chronic obstructive pulmonary disease (COPD) in subjects at risk over 2 years follow-up period). Patients, smokers/ex-smokers with >20 pack-years, aged 40-65 years of both sexes were recruited and followed for 2 years. After recruitment and signing the informed consent at the GP, a detailed diagnostic workout was done by the pulmonologist; they completed three self-assessment questionnaires-MARKO, SGRQ and CAT, detailed history and physical, laboratory (CBC, hsCRP), lung function tests with bronchodilator and EBT. At the 2 year follow-up visit they performed: the same three self-assessment questionnaires, history and physical, lung function tests and EBT. A sample of 320 subjects (41.9% male), mean (SD) age 51.9 (7.4) years with 36.4 (17.4) pack-years of smoking was reassessed after 2.1 years. Exploratory factor analysis of MARKO questionnaire isolated three distinct domains (breathlessness and fatigue, "exacerbations", cough and expectorations). We have determined a rate for incident COPD that was 4.911/100 person-years (95% CI [3.436-6.816]). We found out that questions about breathlessness and "exacerbations", and male sex were predictive of incident COPD after two years follow-up (AUC 0.79, 95% CI [0.74-0.84], p < 0.001). When only active smokers were analyzed a change in EBT after a cigarette (ΔEBT) was added to a previous model (AUC 0.83, 95% CI [0.78-0.88], p < 0.001). Our preliminary data shows that the MARKO questionnaire combined with EBT (change after a cigarette smoke) could potentially serve as early markers of future COPD in smokers.

Bronchodilator reversibility in the GAN severe asthma cohort.

Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit negative BDR test.To describe frequency of positive and negative BDR in patients with severe asthma and associations with phenotypic characteristics. Positive BDR was defined as FEV1 increase > 200 ml AND > 12% upon testing with a short-acting beta-agonist (SABA). Out of 2013 patients included in the German Asthma Net (GAN) severe asthma registry, 793 had data on BDR. Hereof, 250 (31.5%) had a positive and 543 (68.5%) had a negative BDR test. Comorbidities significantly associated with negative BDR were gastro-esophageal reflux (GERD) (28.0% vs 40.0%, p<0.01) and EGPA (0.4% vs 3.0%; p<0.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and COPD comorbidity (5.2% vs 7.2%) were similar in both groups. Patients with positive BDR had worse asthma control (median ACQ-5 3.4 vs 3.0, p<0.05), reported dyspnea at rest (26.8% vs 16.4%, p<0.001) and chest tightness (36.4% vs 26.2%, p<0.001) more frequently, had more severe airway obstruction at baseline (FEV1% pred: 56 vs 64, p<0.001) and higher FeNO levels (41 vs 33 ppb, p<0.05), while diffusion capacity did not differ (DLCO-SB % pred. 70% vs 71%). Multivariate linear regression analysis identified association of lower baseline FEV1% (p<0.001) and chest tightness (p<0.05) with positive, and GERD (p<0.05) with negative BDR. In this real-life setting the majority of patients with severe asthma exhibited negative BDR. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.

Systematic analysis of various RNA transcripts and construction of biological regulatory networks at the post-transcriptional level for chronic obstructive pulmonary disease

BackgroundAlthough chronic inflammation, oxidative stress, airway remodeling, and protease-antiprotease imbalance have been implicated in chronic obstructive pulmonary disease (COPD), the exact pathogenesis is still obscure. Gene transcription and post-transcriptional regulation have been taken into account as key regulators of COPD occurrence and development. Identifying the hub genes and constructing biological regulatory networks at the post-transcriptional level will help extend current knowledge on COPD pathogenesis and develop potential drugs.MethodsAll lung tissues from non-smokers (n = 6), smokers without COPD (smokers, n = 7), and smokers with COPD (COPD, n = 7) were collected to detect messenger RNA (mRNA), microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) expression and identify the hub genes. Biological regulatory networks were constructed at the post-transcriptional level, including the RNA-binding protein (RBP)-hub gene interaction network and the competitive endogenous RNA (ceRNA) network. In addition, we assessed the composition and abundance of immune cells in COPD lung tissue and predicted potential therapeutic drugs for COPD. Finally, the hub genes were confirmed at both the RNA and protein levels.ResultsAmong the 20 participants, a total of 121169 mRNA transcripts, 1871 miRNA transcripts, 4244 circRNA transcripts, and 122130 lncRNA transcripts were detected. There were differences in the expression of 1561 mRNAs, 48 miRNAs, 33 circRNAs, and 545 lncRNAs between smokers and non-smokers, as well as 1289 mRNAs, 69 miRNAs, 32 circRNAs, and 433 lncRNAs between smokers and COPD patients. 18 hub genes were identified in COPD. TGF-β signaling and Wnt/β-catenin signaling may be involved in the development of COPD. Furthermore, the circRNA/lncRNA-miRNA-mRNA ceRNA networks and the RBP-hub gene interaction network were also constructed. Analysis of the immune cell infiltration level revealed that M2 macrophages and activated NK cells were increased in COPD lung tissues. Finally, we identified that the ITK inhibitor and oxybutynin chloride may be effective in treating COPD.ConclusionsWe identified several novel hub genes involved in COPD pathogenesis. TGF-β signaling and Wnt/β-catenin signaling were the most dysregulated pathways in COPD patients. Our study constructed post-transcriptional biological regulatory networks and predicted small-molecule drugs for the treatment of COPD, which enhanced the existing understanding of COPD pathogenesis and suggested an innovative direction for the therapeutic intervention of the disease.

An explainable artificial intelligence framework for risk prediction of COPD in smokers

BackgroundSince the inconspicuous nature of early signs associated with Chronic Obstructive Pulmonary Disease (COPD), individuals often remain unidentified, leading to suboptimal opportunities for timely prevention and treatment. The purpose of this study was to create an explainable artificial intelligence framework combining data preprocessing methods, machine learning methods, and model interpretability methods to identify people at high risk of COPD in the smoking population and to provide a reasonable interpretation of model predictions.MethodsThe data comprised questionnaire information, physical examination data and results of pulmonary function tests before and after bronchodilatation. First, the factorial analysis for mixed data (FAMD), Boruta and NRSBoundary-SMOTE resampling methods were used to solve the missing data, high dimensionality and category imbalance problems. Then, seven classification models (CatBoost, NGBoost, XGBoost, LightGBM, random forest, SVM and logistic regression) were applied to model the risk level, and the best machine learning (ML) model’s decisions were explained using the Shapley additive explanations (SHAP) method and partial dependence plot (PDP).ResultsIn the smoking population, age and 14 other variables were significant factors for predicting COPD. The CatBoost, random forest, and logistic regression models performed reasonably well in unbalanced datasets. CatBoost with NRSBoundary-SMOTE had the best classification performance in balanced datasets when composite indicators (the AUC, F1-score, and G-mean) were used as model comparison criteria. Age, COPD Assessment Test (CAT) score, gross annual income, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), anhelation, respiratory disease, central obesity, use of polluting fuel for household heating, region, use of polluting fuel for household cooking, and wheezing were important factors for predicting COPD in the smoking population.ConclusionThis study combined feature screening methods, unbalanced data processing methods, and advanced machine learning methods to enable early identification of COPD risk groups in the smoking population. COPD risk factors in the smoking population were identified using SHAP and PDP, with the goal of providing theoretical support for targeted screening strategies and smoking population self-management strategies.

Profiling of Microbial Landscape in Lung of Chronic Obstructive Pulmonary Disease Patients Using RNA Sequencing.

The aim of the study was to use RNA sequencing (RNA-seq) data of lung from chronic obstructive pulmonary disease (COPD) patients to identify the bacteria that are most commonly detected. Additionally, the study sought to investigate the differences in these infections between normal lung tissues and those affected by COPD. We re-analyzed RNA-seq data of lung from 99 COPD patients and 93 non-COPD smokers to determine the extent to which the metagenomes differed between the two groups and to assess the reliability of the metagenomes. We used unmapped reads in the RNA-seq data that were not aligned to the human reference genome to identify more common infections in COPD patients. We identified 18 bacteria that exhibited significant differences between the COPD and non-COPD smoker groups. Among these, Yersinia enterocolitica was found to be more than 30% more abundant in COPD. Additionally, we observed difference in detection rate based on smoking history. To ensure the accuracy of our findings and distinguish them from false positives, we double-check the metagenomic profile using Basic Local Alignment Search Tool (BLAST). We were able to identify and remove specific species that might have been misclassified as other species in Kraken2 but were actually Staphylococcus aureus, as identified by BLAST analysis. This study highlighted the method of using unmapped reads, which were not typically used in sequencing data, to identify microorganisms present in patients with lung diseases such as COPD. This method expanded our understanding of the microbial landscape in COPD and provided insights into the potential role of microorganisms in disease development and progression.

Immunohistochemical Study of Airways Fibrous Remodeling in Smoking Mice.

The fibrotic remodeling in chronic obstructive pulmonary disease (COPD) is held responsible for narrowing of small airways and thus for disease progression. Oxidant damage and cell senescence factors are recently involved in airways fibrotic remodeling. Unfortunately, we have no indications on their sequential expression at anatomical sites in which fibrotic remodeling develops in smoking subjects. Using immunohistochemical techniques, we investigated in two strains of mice after cigarette smoke (CS) exposure what happens at various times in airway areas where fibrotic remodeling occurs, and if there also exists correspondence among DNA damage induced by oxidants, cellular senescence, the presence of senescence-secreted factors involved in processes that affect transcription, metabolism as well as apoptosis, and the onset of fibrous remodeling that appears at later times in mice exposed to CS. A clear positivity for fibrogenic cytokines TGF-β, PDGF-B, and CTGF, and for proliferation marker PCNA around airways that will be remodeled is observed in both strains. Increased expression of p16ink4A senescence marker and MyoD is also seen in the same areas. p16ink4A and MyoD can promote cell cycle arrest, terminal differentiation of myofibroblasts, and can oppose their dedifferentiation. Of interest, an early progressive attenuation of SIRT-1 is observed after CS exposure. This intracellular regulatory protein can reduce premature cell senescence. These findings suggest that novel agents, which promote myofibroblast dedifferentiation and/or the apoptosis of senescent cells, may dampen progression of airway changes in smoking COPD subjects.

Risk Factors for Chronic Obstructive Pulmonary Disease Exacerbations among Individuals without a History of Recent Exacerbations: A COPDGene Analysis.

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are detrimental events in the natural history of COPD, but the risk factors associated with future exacerbations in the absence of a history of recent exacerbations are not fully understood. Objectives: To identify risk factors for COPD exacerbations among participants in the Genetic Epidemiology of COPD Study (COPDGene) without a history of exacerbation in the previous year. Methods: We identified participants with a smoking history enrolled in COPDGene who had COPD (defined as forced expiratory volume in 1 second [FEV1]/forced vital capacity < 0.70), no exacerbation in the year before their second study site visit, and who completed at least one longitudinal follow-up questionnaire in the following 36 months. We used univariable and multivariable zero-inflated negative binomial regression models to identify risk factors associated with increased rates of exacerbation. Each risk factor's regression coefficient (β) was rounded to the nearest 0.25 and incorporated into a graduated risk score. Results: Among the 1,528 participants with a smoking history and COPD enrolled in COPDGene without exacerbation in the year before their second study site visit, 508 participants (33.2%) had at least one moderate or severe exacerbation in the 36 months studied. Gastroesophageal reflux disease, chronic bronchitis, high symptom burden (as measured by Modified Medical Research Council Dyspnea Scale and COPD Assessment Test), and lower FEV1% predicted were associated with an increased risk of exacerbation. Each 1-point increase in our graduated risk score was associated with a 25-30% increase in exacerbation rate in the 36 months studied. Conclusions: In patients with COPD without a recent history of exacerbations, gastroesophageal reflux disease, chronic bronchitis, high symptom burden, and lower lung function are associated with increased risk of future exacerbation using a simple risk score that can be used in clinical practice.

Smoking index and COPD duration as potential risk factors for development of osteoporosis in patients with non-small cell lung cancer – A retrospective case control study evaluated by CT Hounsfield unit

ObjectiveTo investigate the effect of smoking index (calculated as number of cigarettes per day × smoking years) and chronic obstructive pulmonary disease (COPD) duration on osteoporosis (OP)evaluated by opportunistic chest CT in patients with non-small cell lung cancer (NSCLC). MethodsA total of 101 patients diagnosed with NSCLC were included in our cohort study. Among them, 50 patients with a history of smoking and COPD were assigned to the experimental group, while 51 patients without a history of smoking and COPD were assigned to the control group. Hounsfield unit (HU) value was measured by conventional chest CT to investigate the bone mineral density; and the mean values of axial HU value in the upper, middle and lower parts of T4, T7, T10 and L1 vertebral bodies were measured as the study variables. ResultsThere were no significant differences in gender, age, body mass index, type of lung cancer, clinical stage of lung cancer and comorbidities between the two groups (P = 0.938，P = 0.158，P = 0.722,P = 0.596,P = 0.813,P = 0.655). The overall mean HU values of T4, T7, T10, L1 in the experimental group were 116.60 ± 30.67, 110.56 ± 30.03, 109.18 (96.85–122.95), 94.63 (85.20–104.12) and 106.86 ± 22.26, respectively, which were significantly lower than those in the control group (189.55 ± 34.57, 174.54 ± 35.30, 172.73 (156.33–199.50), 158.20 (141.60–179.40) and 177.50 ± 33.49) (P ＜0.05). And in the experimental group, smoking index and COPD duration were significantly and negatively correlated with HU values (r = −0.627, −0.542, P ＜0.05, respectively). ConclusionPatients with NSCLC who have a history of smoking and COPD exhibit a notably lower HU value compared to the control groups. Additionally, it has been observed that the smoking index and duration of COPD may be influential factors affecting bone mineral density in NSCLC patients.

Endothelin-1 Gene Polymorphism in Chronic Obstructive Pulmonary Disease: A Case-Control Study

Abstract&#x0D; Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common multifactorial disease which has heterogeneous pathogenesis. The most important risk factor is smoking. In addition to many pathogenic mechanisms taking part in inflammatory process, Our study group does research on the relation of COPD with single nucleotide gene polymorphism at ET-1 gene. In the current studies there being a high ratio of Endotelin-1 (ET-1) in BAL liquid of COPD cases made researchers think ET-1 may have an important role in pathogenesis of COPD. &#x0D; Methods: This prospective case-control study included 89 patients admitted with COPD and 87 control patients. In our study, we search for the density of single nucleotide gene polymorphism (+134 insA/delA) in ET-1 gene in the 87 smoking COPD and 89 healthy cases. Allele ratio and genotype distribution, distribution amongst three genotype in the COPD patient and healthy control group was analyzed. In this study, for endothelin gene -3A/-4A (-138 insertion/deletion) polymorphism analysis, PCR-RFLP method was used. &#x0D; Results: In comparison with the healthy group, the COPD group has higher ratio of ET-1 gene (+134 insA/delA) polymorphism (p&lt; 0,001). &#x0D; Conclusion: Endotelin-1 gene polymorphism (+134 insA/delA) significantly increased in the patients than healthy ones (p

Levels of Urinary Mercapturic Acids of Acrolein, Methacrolein, Crotonaldehyde, and Methyl Vinyl Ketone in Relationship to Chronic Obstructive Pulmonary Disease in Cigarette Smokers of the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Cigarette smoking is an established cause of chronic obstructive pulmonary disease (COPD). Numerous studies implicate acrolein, which occurs in relatively high concentrations in cigarette smoke and reacts readily with proteins, as one causative factor for COPD in smokers. Far less is known about the possible roles in COPD of the related α,β-unsaturated carbonyl compounds of cigarette smoke crotonaldehyde, methacrolein, and methyl vinyl ketone. In the study reported here, we analyzed mercapturic acids of these α,β-unsaturated compounds in the urine of 413 confirmed cigarette smokers in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)─202 with COPD and 211 without COPD. The mercapturic acids analyzed were 3-hydroxypropyl mercapturic acid (3-HPMA) from acrolein, 3-hydroxy-1-methylpropyl mercapturic acid (HMPMA-1) from crotonaldehyde, 3-hydroxy-2-methylpropyl mercapturic acid (HMPMA-2) from methacrolein, and 3-hydroxy-3-methylpropyl mercapturic acid (HMPMA-3) from methyl vinyl ketone. In models adjusting for age, sex, race, pack years of tobacco use, and BMI, all four mercapturic acids were increased in individuals with COPD but not significantly. Stratified by the GOLD status, there were increased levels of the metabolites associated with GOLD 3-4 compared to that with GOLD 0, with the methacrolein metabolite HMPMA-2 reaching statistical significance (adjusted odds ratio 1.23 [95% CI: 1.00-1.53]). These results highlight the possible role of methacrolein, which has previously received little attention in this regard, as a causative factor in COPD in cigarette smokers.