International Journal of Chronic Obstructive Pulmonary Disease最新文献

Background: The Aryl Hydrocarbon Receptor (AHR) is a ligand-activated transcription factor that regulates gene expression, including those involved in metabolizing xenobiotic chemicals. The association of AHR with the onset and severity of Chronic Obstructive Pulmonary Disease (COPD) has not yet been elucidated. This study aimed to investigate the correlation between two AHR polymorphisms and the expression levels of this gene in COPD patients compared to healthy controls.

Methods: The AHR gene expression level and frequency of two polymorphisms, rs2066853 and rs2074113, were studied in 154 COPD patients and 145 healthy individuals using RT-PCR and AS-PCR methods respectively.

Results: The findings showed a significant difference in the frequencies of G and A, as well as GG and GA genotypes in rs2066853 between patients and healthy controls [G: OR: 0.4, CI: 0.24-0.67, (p=0.0002); A: OR: 2.44, CI: 1.48-4.03, (p=0.0002); genotypes GG: OR: 0.37, CI: 0.21-0.65, (p=0.0002) and GA: OR: 2.42, CI: 1.40-4.18 (p=0.001)]. Additionally, the GT genotype frequency in the rs2074113 was different between two groups [GT: OR: 0.23, CI: 0.07-0.72, (p=0.008)]. Moreover, AHR gene expression was significantly lower in COPD patients compared to healthy controls (P=0.03). Noteworthy, individuals with the GA genotype in rs2066853 exhibited lower AHR expression levels than those with the GG genotype.

Conclusion: The presence of allele A and the GA genotype of the rs2066853 polymorphism in the AHR gene is significantly associated with COPD, suggesting a genetic predisposition. Moreover, reduced AHR expression in patients supports its key role in COPD pathogenesis.

Background: Communication about sexuality is neglected in chronic obstructive pulmonary disease (COPD). This study evaluated the effectiveness of the Communication about Sexuality intervention (COSY) on quality of life (QoL) and physical activity (PA) and its acceptability in people with COPD.

Methods: People with COPD (GOLD I-IV) were recruited from pulmonary rehabilitation and primary care settings and randomly allocated (1:1 ratio) to the COSY intervention group (IG) or usual care control group (CG). The primary endpoint was change in QoL, assessed with the Control, Autonomy, Self-realization and Pleasure scale (CASP- 12) between baseline and 3 months. The implementation of the intervention was assessed by review of study documents and questionnaires and acceptability by an interview with IG participants at study end.

Results: Thirty-six persons (28% of target sample size), median age 72 years, 44% female, were included and randomized (CG, n=19, IG, n=17). 33 completed the 3-month-follow-up (CG, n=17, IG, n=16). There was no difference in change between the two groups in CASP-12 (mean difference 0.02, 95% CI -2.01 to 2.06). The COSY intervention increased self-efficacy and adherence for PA. All IG participants appreciated the communication about the topic and study participation. Most participants expressed their need for closeness, intimacy and tenderness.

Conclusion: Communication about sexual wellbeing using the COSY instruments was well received by people with COPD and enable healthcare professionals to comfortably address an often-ignored topic. Recruitment challenges limited study power, but the findings offer strong justification for further research into this promising and needed holistic care approach.

Background: The activation of dendritic cells, which is atypical, is vital for triggering the acquired immune response in people afflicted with chronic obstructive pulmonary disease (COPD). This research seeks to pinpoint significant genes linked to dendritic cells within the lung tissues of COPD patients by utilizing bioinformatics predictions and experimental validation.

Methods: Differentially expressed genes of classical dendritic cells (cDCs) were identified using single-cell RNA sequencing (scRNA-seq) data from GSE196638, and their biological functions and regulatory signaling pathways were thoroughly explored. Additionally, RNA sequencing (RNA-seq) data from GSE26296 was utilized to analyze differentially expressed genes in myeloid dendritic cells (mDCs) of emphysema patients. The RNA-seq data from GSE38974 underwent weighted gene co-expression network analysis (WGCNA) along with differential analysis to pinpoint genes that are differentially expressed and modules linked to COPD. Validation was performed using a mouse model of emphysema induced by cigarette smoke (CS) and bone marrow-derived dendritic cells (BMDCs) exposed to 3% cigarette smoke extract (CSE).

Results: The genes that showed differential expression in cDCs and mDCs were mainly associated with immune responses, the reaction to interferon-gamma, the differentiation of Th1 and Th2 cells, along with the signaling pathways of TNF and IL-17. The WGCNA results revealed that the green-yellow and red modules exhibited the highest correlation coefficients with the COPD phenotype. An assessment of the genes that are expressed differently between cDCs and mDCs, combined with the intersection of GSE38974 module genes and differentially expressed genes, results in the identification of four dendritic cells (DCs)-related genes: one upregulated signature gene (RASGRP3) and three downregulated signature genes (C1QB, BLOC1S2, VSIG4). In both the lung tissues of mice with CS-induced emphysema and in CSE-treated BMDCs, RT-qPCR validated the expression trends of these four genes. Concomitantly, Western blot revealed a reduction in VSIG4 protein level in the lung tissues of emphysema mice compared with the control group.

Conclusion: RASGRP3, C1QB, BLOC1S2, and VSIG4 may represent DCs-related genes in the lung tissue of COPD patients, potentially involved in the development and progression of emphysema.

Purpose: To understand the current situation of respiratory and community physicians in China regarding the initial treatments for patients with chronic obstructive pulmonary disease (COPD).

Patients and methods: A multivariate discrete choice model was applied to simulate patients with stable COPD, and an online questionnaire was randomly provided to respiratory physicians and community physicians. The questionnaire responses and medications prescribed to the simulated patients by the doctors in the different groups were analyzed and compared.

Results: (1) This study surveyed 109 doctors who made prescription decisions for 872 simulated COPD patients. (2) The results of the questionnaire revealed that the percentages of LAMA, LAMA/LABA and triple therapies that could be prescribed in community health care centers were 40.6%, 25%, and 34.4%, respectively. More than 60% of the physicians in the CHC and SH groups prescribed ICS/LABA as an initial regimen for maintenance therapy. (3) Triple therapy accounted for the highest proportion of prescriptions at 49%, followed by dual bronchodilator therapy (29.6%), whereas LAMA monotherapy represented the smallest share, with only 4.9% of prescriptions. Notably, ICS/LABA combination therapy represented a clinically relevant proportion of prescriptions (14.3%). A total of 58.9% of the 170 simulated COPD patients without asthma in the current study were prescribed triple therapy by their physicians. Approximately 60% of the COPD patients in Groups A and B were prescribed triple therapy as an initial treatment regimen, despite blood EOS counts of 100-300 cells/µL in both groups.

Conclusion: Although most respiratory physicians follow guidelines for the choice of initial therapy for COPD, there are still irregularities in the use of triple therapy. A clinically relevant percentage of physicians, especially community physicians, selected ICS+LABA as the initial treatment choice. These practice irregularities should be the focus of future guidelines for promotion and education.

Background: Chronic obstructive pulmonary disease (COPD) poses a major global health burden with high morbidity. Relative fat mass (RFM), as a novel body fat measurement indicator, can reflect the distribution of body fat. This study aims to elucidate its associations with COPD prevalence and severity in two cohorts to enhance prevention and treatment strategies.

Methods: We retrospectively investigated the medical records of 166 patients with COPD and the data of 2654 subjects from two cohorts. To explore the relative importance of factors in COPD prevalence and severity, we built an extreme gradient boosting (XGBoost) machine-learning model. Logistic regression models were used to assess the relationship between COPD and RFM, with subgroup analysis to clarify the difference across diverse subgroups. Furthermore, restricted cubic spline (RCS) curves were used to explore the exposure-response relationship.

Results: Multivariate logistic regression analysis revealed a significant positive association between RFM and COPD prevalence (OR = 1.043, 95% CI: 1.004-1.083, p = 0.030) and a negative association with COPD severity (OR = 0.892, 95% CI: 0.813-0.978, p = 0.015). According to the RCS curves, there was no nonlinear association between RFM and COPD prevalence or severity (p for nonlinear = 0.703, p for nonlinear = 0.348).

Conclusion: RFM was positively associated with the prevalence of COPD but inversely associated with its severity. Specifically, RFM predicted COPD prevalence more accurately in individuals aged 40-60 and smokers, while it predicted COPD severity more effectively in those aged ≥ 60.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Hemoglobin (HGB) abnormalities, including anemia and secondary polycythemia, are common comorbidities in COPD patients, yet their association with mortality remains less clear. This study aimed to investigate the relationship between HGB levels and all-cause mortality in COPD patients and to evaluate whether HGB could serve as a treatable trait in COPD.

Methods: We conducted a retrospective observational cohort study using data from the National Health and Nutrition Examination Survey (NHANES, 2013-2018). A total of 544 COPD patients were included. Multivariable Cox regression was conducted to assess HGB-mortality associations, adjusting for age, sex, BMI, smoking status, and comorbidities. Nonlinear relationships were examined using generalized additive models with threshold effect analysis. Stratified analyses were performed by sex, age, and comorbidity status.

Results: Among 544 COPD patients, HGB levels demonstrated a significant nonlinear association with all-cause mortality, with a critical inflection point identified at 14.2 g/dL. Below this threshold, each 1g/dL in HGB was associated with reduced mortality (adjusted HR=0.73, 95% CI: 0.61-0.79, P<0.0001). Above 14.2g/dL, however, no significant association was observed (HR=1.24, 95% CI: 0.98-1.55, P=0.0775). Although stratified analyses suggested variation in HR across subgroups (including males, elderly >65 years, smokers, and those with cardiovascular disease), interaction tests did not reach statistical significance (all P-interaction >0.05), indicating no evidence of effect modification. Smoothing curves supported this nonlinear relationship, showing decreasing mortality risk with rising HGB until the threshold, beyond which risk stabilized with a slight non-significant upward trend.

Conclusion: This study identifies a nonlinear relationship between HGB levels and mortality in COPD, establishing 14.2 g/dL as a critical threshold that supports anemia's inclusion in the COPD "treatable traits" framework. Below this value, increasing HGB is associated with reduced mortality, whereas above it no further benefit is observed. Clinicians should prioritize HGB monitoring in high-risk subgroups (elderly males, smokers, and cardiac comorbidities).

Purpose: Chronic obstructive pulmonary disease (COPD) is a common condition with respiratory obstructive impairment, and is often treated by primary care physicians. Because COPD is a high-risk factor for lung cancer, chest computed tomography (CT) is used to screen for early cancer detection. However, it is difficult for primary care physicians to conduct regular CT examinations. In the western Yokohama area, we have established a system of collaboration between primary care physicians and our hospital to manage COPD patients. We hypothesized that routine standard-dose CT examinations could detect lung cancer at early stage in COPD patients managed by primary care physicians via COPD coordinated system.

Patients and methods: From 114 COPD patients who visited Yokohama Seibu Hospital between January 2013 and March 2020 for the purpose of COPD consultation, we selected the 70 in whom either abnormal shadows had been detected or negative imaging findings confirmed on chest CT over a 5-year period.

Results: Nodules were detected in 15 patients (21.4%) during the course of the study, with six of these founded to have lung cancer. Five of the six had were operable as early-stage cancer, and one had advanced small cell lung cancer and received chemotherapy. Detection of operable cases was difficult with chest X-rays.

Conclusion: Routine chest CT may contribute to the early-stage detection of cancer in patients with COPD managed by primary care physicians in collaboration with hospitals.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory respiratory disorder characterized by persistent respiratory symptoms that negatively impact quality of life, reduce survival, and increase the risk of cardiovascular events. It is one of the leading causes of global morbidity and mortality.

Methods: A retrospective cohort study was conducted in patients with a confirmed diagnosis of COPD based on spirometry (FEV1/FVC < 0.7), who received care between 2005 and 2020. Adults over 40 years of age were included. Clinical, sociodemographic, and treatment-related variables were collected. Five-year survival was estimated using Kaplan-Meier curves and stratified by age, sex, comorbidities, use of oxygen therapy, FEV1 ≤ 35%, and GOLD 2025 classification. The Log rank test was used to compare survival differences.

Results: A total of 350 COPD patients were included; the mean age was 75.3 years (SD 11.77); 82.3% were over 65 years old and 56.6% were male. Five-year survival was 89.7%. No differences were observed between sexes (p = 0.558). Survival was lower in those over 65 years (87.9% vs 98.5%; p = 0.015), in patients with heart failure (78.4% vs 91.1%; p = 0.014), those using oxygen therapy (82.2% vs 94.6%; p = 0.002), and those with FEV1 ≤ 35% (88.8% vs 96.5%; p = 0.035). A trend toward lower survival was found in GOLD group E (84.9%) compared to GOLD A (93.3%) and B (87.7%) (p = 0.186).

Conclusion: The five-year survival rate in this cohort was 89.7%. Lower survival was observed in patients over 65 years of age, with heart failure, on home oxygen therapy, and with FEV1 ≤ 35%. A trend toward lower survival was identified in the GOLD group E.

Purpose: To systematically explore the potential causal relationships among gene expression, DNA methylation, and chronic obstructive pulmonary disease (COPD) susceptibility using a multi-omics Mendelian randomization (MR) framework, and to further investigate key regulatory genes and methylation sites potentially involved in COPD pathogenesis.

Patients and methods: We integrated genome-wide association study (GWAS) data from 635,145 individuals, expression quantitative trait loci (eQTL) data (N=15,695) from the eQTLGen Consortium, and methylation quantitative trait loci (mQTL) data from the Genetics of DNA Methylation Consortium (GoDMC). Two-sample Mendelian randomization was performed using genome-wide significant, linkage disequilibrium (LD)-independent (P < 5×10^-⁸, r² < 0.1) instruments filtered by Steiger analysis. Sensitivity analyses included inverse-variance weighted (IVW), MR-Egger, weighted median, and leave-one-out approaches. Colocalization analysis (posterior probability H₄ ≥ 0.75) and summary data-based Mendelian randomization (SMR) with heterogeneity in dependent instruments (HEIDI) test (P > 0.05) were used to validate shared causal variants. A three-step Mendelian randomization assessed mediation through methylation, gene expression, and COPD risk.

Results: We identified eight putative causal genes for COPD based on Mendelian randomization and colocalization analyses. SDK1 demonstrated consistent statistical significance across all subsequent steps. Increased SDK1 expression was significantly associated with a reduced risk of COPD (β = -0.124, P = 0.002). Methylation at the intronic CpG site cg07526904 within SDK1 was associated with lower SDK1 expression (β = -0.148, P = 0.002) and elevated COPD susceptibility (β = 0.036, P = 0.038). Mediation analysis indicated that SDK1 expression mediated approximately 51.9% of the total effect of cg07526904 on COPD risk (β = 0.018, P = 0.038), supporting a potential epigenetic pathway.

Conclusion: This analysis suggests that SDK1 methylation may affect COPD risk by regulating gene expression, highlighting a potential epigenetic mechanism. These findings offer preliminary insights into COPD pathogenesis and may help identify targets for future biomarker-based interventions.