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1.
Inflammation ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954261

ABSTRACT

Peroxiredoxin 6 (PRDX6) has a protective effect on pulmonary epithelial cells against cigarette smoke (CS)-induced ferroptosis. This study investigates the role of PRDX6 in the development of chronic obstructive pulmonary disease (COPD) and its possibility as a target. We observed that PRDX6 was downregulated in lung tissues of COPD patients and in CS-stimulated cells. The degradation of PRDX6 could be through the lysosomal pathway. PRDX6 deficiency exacerbated pulmonary inflammation and mucus hypersecretion in vivo. Overexpression of PRDX6 in Beas-2B cells ameliorated CS-induced cell death and inflammation, suggesting its protective role against CS-induced damage. Furthermore, PRDX6 deficiency promoted ferroptosis by adding the content of iron and reactive oxygen species, while iron chelation with deferoxamine mitigated CS-induced ferroptosis, cell death, and inflammatory infiltration both in vitro and in vivo. The critical role of PRDX6 in regulating ferroptosis suggests that targeting PRDX6 or iron metabolism may represent a promising strategy for COPD treatment.

2.
Arch Gerontol Geriatr ; 126: 105539, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38954987

ABSTRACT

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

3.
Aging Cell ; : e14266, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958042

ABSTRACT

Age-related chronic inflammatory lung diseases impose a threat on public health, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, their etiology and potential targets have not been clarified. We performed genome-wide meta-analysis for IPF with the largest sample size (2883 cases and 741,929 controls) and leveraged the summary statistics of COPD (17,547 cases and 617,598 controls). Transcriptome-wide and proteome-wide Mendelian randomization (MR) designs, together with genetic colocalization, were implemented to find robust targets. The mediation effect was assessed using leukocyte telomere length (LTL). The single-cell transcriptome analysis was performed to link targets with cell types. Individual-level data from UK Biobank (UKB) were used to validate our findings. Sixteen genetically predicted plasma proteins were causally associated with the risk of IPF and 6 proteins were causally associated with COPD. Therein, genetically-elevated plasma level of SCARF2 protein should reduce the risk of both IPF (odds ratio, OR = 0.9974 [0.9970, 0.9978]) and COPD (OR = 0.7431 [0.6253, 0.8831]) and such effects were not mediated by LTL. Genetic colocalization further corroborated these MR results of SCARF2. The transcriptome-wide MR confirmed that higher expression level of SCARF2 was associated with a reduced risk of both. However, the single-cell RNA analysis indicated that SCARF2 expression level was only relatively lower in epithelial cells of COPD lung tissue compared to normal lung tissue. UKB data implicated an inverse association of serum SCARF2 protein with COPD (hazard ratio, HR = 1.215 [1.106, 1.335]). The SCARF2 gene should be a novel target for COP.

4.
Int J Chron Obstruct Pulmon Dis ; 19: 1421-1431, 2024.
Article in English | MEDLINE | ID: mdl-38948906

ABSTRACT

Objective: To determine the association of urinary phthalate metabolites with chronic obstructive pulmonary disease (COPD), airflow obstruction, lung function and respiratory symptoms. Methods: Our study included a total of 2023 individuals aged ≥ 40 years old in the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was conducted to explore the correlation of eleven urinary phthalate metabolites (MCNP, MCOP, MECPP, MnBP, MCPP, MEP, MEHHP, MEHP, MiBP, MEOHP, and MBzP) with COPD, airflow obstruction and respiratory symptoms. Linear regression analyses were used to evaluate the relationship between urinary phthalate metabolites and lung function. Results: When compared to the first tertile, the third tertile of MEHHP was associated with the risk of COPD [OR: 2.779; 95% confidence interval (CI): 1.129-6.840; P = 0.026]. Stratified analysis showed that MEHHP increased the risk of COPD by 7.080 times in male participants. Both MCPP and MBzP were positively correlated with the risk of airflow obstruction. The third tertile of MBzP increased the risk of cough by 1.545 (95% CI: 1.030-2.317; P = 0.035) times. Both FEV1 and FVC were negatively associated with MEHHP, MECPP, MnBP, MEP, MiBP and MEOHP. Conclusion: Higher levels of MEHHP are associated with increased risk of COPD, and lower measures of FEV1 and FVC. MBzP is positively related to airflow obstruction and cough.


Subject(s)
Biomarkers , Lung , Nutrition Surveys , Phthalic Acids , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/urine , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Male , Cross-Sectional Studies , Female , Middle Aged , Risk Factors , Lung/physiopathology , Forced Expiratory Volume , Phthalic Acids/urine , Adult , Biomarkers/urine , United States/epidemiology , Vital Capacity , Aged , Multivariate Analysis , Odds Ratio , Linear Models , Logistic Models , Cough/physiopathology , Cough/urine , Cough/epidemiology
5.
Int J Chron Obstruct Pulmon Dis ; 19: 1433-1445, 2024.
Article in English | MEDLINE | ID: mdl-38948907

ABSTRACT

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) were reported less frequently during the COVID-19 pandemic. We report real-world data on COPD exacerbation rates before and during this pandemic. Methods: Exacerbation patterns were analysed using electronic medical records or claims data of patients with COPD before (2017-2019) and during the COVID-19 pandemic (2020 through early 2022) in France, Germany, Italy, the United Kingdom and the United States. Data from each country were analysed separately. The proportions of patients with COPD receiving maintenance treatment were also estimated. Results: The proportion of patients with exacerbations fell 45-78% across five countries in 2020 versus 2019. Exacerbation rates in most countries were reduced by >50% in 2020 compared with 2019. The proportions of patients with an exacerbation increased in most countries in 2021. Across each country, seasonal exacerbation increases seen during autumn and winter in pre-pandemic years were absent during the first year of the pandemic. The percentage of patients filling COPD prescriptions across each country increased by 4.53-22.13% in 2019 to 9.94-34.17% in 2021. Conclusion: Early, steep declines in exacerbation rates occurred in 2020 versus 2019 across all five countries and were accompanied by a loss of the seasonal pattern of exacerbation.


Subject(s)
COVID-19 , Disease Progression , Pulmonary Disease, Chronic Obstructive , Humans , COVID-19/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Female , Aged , Middle Aged , SARS-CoV-2 , United States/epidemiology , France/epidemiology , United Kingdom/epidemiology , Pandemics , Italy/epidemiology , Time Factors , Seasons
6.
Int J Chron Obstruct Pulmon Dis ; 19: 1447-1456, 2024.
Article in English | MEDLINE | ID: mdl-38948908

ABSTRACT

Purpose: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea. Patients and Methods: This population-based cohort study enrolled adults aged ≥40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan-Meier curves. Results: Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P <0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P <0.001). Conclusion: The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.


Subject(s)
Cardiovascular Diseases , Databases, Factual , Metabolic Syndrome , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/diagnosis , Metabolic Syndrome/epidemiology , Metabolic Syndrome/mortality , Metabolic Syndrome/diagnosis , Male , Female , Republic of Korea/epidemiology , Middle Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Aged , Incidence , Risk Assessment , Adult , Time Factors , Proportional Hazards Models , Prognosis , Risk Factors , Heart Disease Risk Factors , Comorbidity
7.
Dysphagia ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951236

ABSTRACT

Patients with chronic obstructive pulmonary disease (COPD) in pulmonary rehabilitation programs (PRPs) are not routinely screened for dysphagia. An Australian regional health service audit revealed that patients with COPD are frequently referred to speech pathology during acute admissions, rather than proactively to mitigate the risk of dysphagia-related consequences. Referral patterns to speech pathology using a novel transdisciplinary approach for identifying at risk for dysphagia patients in a PRP were explored. The aim of this study was to investigate the impact of a transdisciplinary dysphagia screening questionnaire on speech pathology referrals within a cohort of patients with COPD enrolled in a PRP. This quasi-experimental study introduced a dysphagia screening questionnaire in a PRP using a transdisciplinary approach. A retrospective audit of PRP patients (n = 563) between 01/01/2014 and 31/12/2018 was conducted to identify the frequency of referrals to speech pathology for dysphagia. Data was compared to a cohort of patients (n = 50) enrolled in the PRP (from 01/02/21 to 30/11/21) after introduction of the questionnaire using Fisher's exact test. Less than 1% (n = 4/563) of PRP patients were referred to speech pathology prior to implementation of the questionnaire. Following the implementation, referrals to speech pathology significantly increased to 16% (8/50) (X2 = 7.72, P < 0.05; odds ratio = 7.89 95% CI [1.94, 32.1]). Introducing a dysphagia screening questionnaire increased referrals to speech pathology from a PRP. This study demonstrated the potential for a transdisciplinary approach in early screening for patients at risk of dysphagia for patients with COPD. Further research is encouraged to explore patient motivation towards speech pathology input with COPD-related dysphagia and clinicians' perceived self-efficacy in using the questionnaire.

8.
Yale J Biol Med ; 97(2): 125-139, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38947110

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a significant respiratory disease and is globally ranked as the third leading cause of death. In Canada, the direct healthcare costs associated with COPD are estimated to be $1.5 billion annually. This study utilized quantitative analyses to examine the impact of specific dimensions of social support, namely, guidance, reliable alliance, reassurance of worth, attachment, and social integration within a clinically identified population of individuals with COPD who exhibit symptoms of depression and anxiety. The study was based on the Social Provisions Theory and stress-buffering hypothesis, utilizing large-scale population data from Statistics Canada's 2012 Canadian Community Health Survey (CCHS) Mental Health component. On a national scale, individuals were more likely to report a decreased sense of belonging to a group of friends (social integration) and struggle to depend on others in stressful times (reliable alliance) while experiencing symptoms of anxiety and depression. These findings underscore the potential benefits of integrating peer support, socialization initiatives, and caregiver training into clinical programs designed for individuals with COPD.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Social Support , Humans , Pulmonary Disease, Chronic Obstructive/psychology , Pulmonary Disease, Chronic Obstructive/epidemiology , Canada/epidemiology , Male , Female , Middle Aged , Mental Health/statistics & numerical data , Depression/epidemiology , Depression/psychology , Aged , Anxiety/epidemiology , Anxiety/psychology , Adult , Psychological Well-Being
9.
Cureus ; 16(6): e63277, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38947141

ABSTRACT

Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple bodily systems. Elderly individuals often face a multitude of chronic illnesses and geriatric syndromes, which can complicate the diagnosis and treatment of CD in this demographic. This case study details the presentation of an elderly patient with adrenocorticotropic hormone (ACTH)-dependent CD, who initially presented with an acute exacerbation of chronic obstructive pulmonary disease. The article delves into the unique onset characteristics and treatment strategies for CD in the elderly, providing valuable insights for the comprehensive management of similar clinical cases.

10.
Int J Chron Obstruct Pulmon Dis ; 19: 1491-1513, 2024.
Article in English | MEDLINE | ID: mdl-38957709

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes. Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal. Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them. Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.


Subject(s)
Databases, Genetic , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive , Pyroptosis , Humans , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/immunology , Pyroptosis/genetics , Gene Expression Profiling , Lung/immunology , Male , Female , Middle Aged , Genetic Markers , Case-Control Studies , Transcriptome , Aged , Reproducibility of Results , Genetic Predisposition to Disease , Prognosis
12.
Article in English | MEDLINE | ID: mdl-38966505

ABSTRACT

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of hospital admissions. Coronavirus disease 2019 (COVID-19) has large impact on patients with pulmonary diseases. The purpose of the study is to evaluate the impact of COVID-19 on patients with AECOPD. Method: Retrospective study with two cohorts, the first period included patients with AECOPD before COVID-19 pandemic; the second period included patients with AECOPD since the beginning of COVID-19 pandemic. The length of stay (LOS), number of patients requiring mechanical ventilation, and allcause mortality were calculated. Results: There was a total of 55 (44.72%) patients in the pre-COVID period compared to 68 (55.28%) patients in the COVID period. In the pre-COVID period: 14 (19.44%) had hypertension, 26(36.11%) had diabetes, 27(37.50%) had ischemic heart disease, 3(4.17%) had myocardial infarction; in the COVID period: 20 (29.41%) had hypertension, 24(35.29%) had diabetes, 27(39.71%) had ischemic heart disease, 1(1.47) had myocardial infarction. The LOS was shorter in pre-COVID period compared to COVID period, 6.51(SD 5.02) days vs 8.91(SD7.88) days with P-value of 0.042 respectively. The total number of patients needing mechanical ventilation in pre-COVID period was similar to the COVID period with P-value of 0.555. All-cause mortality number was 2 (3.64%) in the pre-COVID period compared to 6 (8.82%) in COVID period with P-value of 0.217. Conclusion: Study results revealed significant difference in length of stay for patients with AECOPD, patient in COVID period had increased LOS compared to pre-COVID period. There was no significant difference in the other parameters.

13.
Front Med (Lausanne) ; 11: 1359347, 2024.
Article in English | MEDLINE | ID: mdl-38966524

ABSTRACT

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterized primarily by airflow obstruction, significantly impacting patients' quality of life. Traditional mind-body exercises, as a non-pharmacological intervention for COPD, have become a new research focus. Objective: To assess the impact of traditional mind-body exercises (Tai Chi, Qigong, Yoga) on pulmonary function, exercise capacity, and quality of life in COPD patients. Additionally, to identify the most suitable form of traditional mind-body exercise for different indicators. Methods: Searches were conducted in databases such as Web of Science, PubMed, EBSCOhost, CNKI, etc., to collect randomized controlled trials (RCTs) evaluating the intervention of traditional mind-body exercises (Tai Chi, Yoga, Qigong) in COPD. The Cochrane evaluation tool was applied for methodological quality assessment of the included literature. Statistical analysis and sensitivity analysis were performed using Revman 5.4 software, while publication bias was assessed using R software. Results: This study included 23 studies with a total of 1862 participants. Traditional mind-body exercises improved patients' FEV1% index (WMD = 4.61, 95%CI [2.99, 6.23]), 6-min walk distance (SMD = 0.83, 95%CI [0.55, 1.11]), and reduced patients' SGRQ score (SMD = -0.79, 95%CI [-1.20, -0.38]) and CAT score (SMD = -0.79, 95%CI [-1.20, -0.38]). Qigong showed the most significant improvement in FEV1% and 6MWT, while Tai Chi primarily improved 6MWT, and the effect of Yoga was not significant. Sensitivity analysis indicated stable and reliable research conclusions. Conclusion: Traditional mind-body exercises are effective rehabilitation methods for COPD patients, significantly improving pulmonary function, exercise capacity, and quality of life. They are suitable as complementary interventions for standard COPD treatment. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display-record.php?ID=CRD42023495104], identifier [CRD42023495104].

14.
Article in English | MEDLINE | ID: mdl-38967536

ABSTRACT

Background: This present work focused on predicting prognostic outcome of inpatients developing acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and enhancing patient monitoring and treatment by using objective clinical indicators. Methods: The present retrospective study enrolled 322 AECOPD patients. Registry data downloaded based on COPD Pay-for-Performance Program database from January 2012 to December 2018 were used to check whether the enrolled patients were eligible. Our primary and secondary outcomes were ICU admission and in-hospital mortality, respectively. The best feature subset was chosen by recursive feature elimination. Moreover, seven machine learning (ML) models were trained for forecasting ICU admission among AECOPD patients, and the model with the most excellent performance was used. Results: According to our findings, random forest (RF) model showed superb discrimination performance, and the values of area under curve (AUC) were 0.973 and 0.828 in training and test cohorts, separately. Additionally, according to decision curve analysis, the net benefit of RF model was higher when differentiating patients with a high risk of ICU admission at a <0.55 threshold probability. Moreover, the ML-based prediction model was also constructed to predict in-hospital mortality, and it showed excellent calibration and discrimination capacities. Conclusion: The ML model was highly accurate in assessing the ICU admission and in-hospital mortality risk for AECOPD cases. Maintenance of model interpretability helped effectively provide accurate and lucid risk prediction of different individuals.

15.
Cell Biochem Biophys ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967902

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high death rates. Aucubin is an iridoid glycoside extracted from Eucommia ulmoides with antioxidative and anti-inflammatory properties in human diseases. This study aimed to investigate its specific function in mouse and cell models of COPD. METHODS: The COPD mouse model was established by exposing mice to a long-term cigarette smoke (CS). The number of inflammatory cells and the contents of inflammatory factors tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-8 in bronchoalveolar lavage fluid (BALF) of CS-exposed mice were measured. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) in the lung tissues were estimated. Masson staining and hematoxylin-eosin (H&E) staining were utilized to evaluate pulmonary fibrosis and emphysema in CS-treated mice. Cell apoptosis in the lung tissues was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Western blot was applied to quantify protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and apoptotic markers. COPD cell model was established by exposing mouse lung epithelial cells (MLE12) with cigarette smoke extract to further verify the properties of aucubin in vitro. RESULTS: Aucubin reduced the number of inflammatory cells and decreased the contents of TNF-α, IL-6, and IL-8 in BALF of CS-treated mice. The oxidative stress, lung emphysema, fibrosis, and lung cell apoptosis induced by CS exposure were ameliorated by aucubin administration. Aucubin activated the Nrf2/HO-1 signaling pathway in vitro and in vivo. Pretreatment with ML385, a specific Nrf2 inhibitor, antagonized the protective effects of aucubin on inflammation, oxidative stress, fibrosis, and cell apoptosis in COPD. CONCLUSION: Aucubin alleviates inflammation, oxidative stress, apoptosis, and pulmonary fibrosis in COPD mice and CSE-treated MLE12 cells by activating the Nrf2/HO-1 signaling pathway.

16.
Gene ; 927: 148736, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950687

ABSTRACT

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity, disability, and mortality rates worldwide. RNA-binding proteins (RBPs) might regulate genes involved in oxidative stress and inflammation in COPD patients. Single-cell transcriptome sequencing (scRNA-seq) offers an accurate tool for identifying intercellular heterogeneity and the diversity of immune cells. However, the role of RBPs in the regulation of various cells, especially AT2 cells, remains elusive. MATERIALS AND METHODS: A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out. RESULTS: RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD. CONCLUSION: RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.

17.
Respir Med ; 231: 107731, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38969026

ABSTRACT

INTRODUCTION: Coexistence of chronic obstructive pulmonary disease(COPD) and heart failure(HF) is associated with systemic inflammation, myocardial injury, and arterial stiffening, impacting cardiovascular risk and prognosis in patients. Arterial stiffness, reduced nitric oxide synthesis, and altered cardiac autonomic control further link COPD and HF pathophysiology, emphasizing the need for comprehensive cardiovascular assessment. OBJECTIVE: To investigate a cardiovascular profile in patients hospitalized with exacerbation COPD(ECOPD) in coexistence with HF compared with isolated diseases. METHODS: A cross-sectional study including patients diagnosed with ECOPD and decompensated HF, approached between 24 and 48 h after hospital admission. Assessments included: endothelial function by brachial artery flow-mediated vasodilation(FMD); hemodynamic through analysis of pulse wave and arterial stiffness by carotid-femoral pulse wave velocity(cfPWV) and cardiac autonomic modulation(CAM) by heart rate variability(HRV). RESULTS: The mean FMD was 4.45 %, indicating endothelial dysfunction in all patients. Date is present in mean(confidence interval) sequency COPD(n = 12), COPD-HF(n = 21) and HF(n = 21). FMD: 5.47(3.96-6.91); 2.66(0.09-3.48); 4.60(2.30-6.43) p < 0.01. However, COPD-HF had worse FMD. Arterial stiffens (AIx: 29.0(19.0-42.6); 34.6(24.3-43.2); 14.5(8.0-24.0)p < 0.01; cfPWV: (6.5(5.4-7.2); 7.7(7.0-8.5); 6.0(5.0-6.5)); COPD-HF also showed greater activation of the sympathetic nervous system compared to patients with isolated diseases (PNS: 1.32(-2.53 to -0.62); -2.33(-2.60 to -2.12); -1.32(-1.42 to -1.01) p < 0.01; SNS: 3.50(1.40-8.55); 7.11(5.70-8.29); 2.32(1.78-5.01) p < 0.01). In addition, rMSSD, NN50, pNN50, and TINN also indicate worse CAM in the COPD-HF group compared to isolated diseases. CONCLUSION: During hospitalization, the worst impairment in vascular function and cardiac autonomic modulation were found in patients with COPD and HF comorbidity compared to the isolated diseases(HF or COPD).

18.
Int J Chron Obstruct Pulmon Dis ; 19: 1547-1559, 2024.
Article in English | MEDLINE | ID: mdl-38979101

ABSTRACT

Purpose: This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. Participants and Methods: This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. Results: The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. Conclusion: These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.


Subject(s)
Absorptiometry, Photon , Asian People , Lung , Postmenopause , Spirometry , Humans , Female , Cross-Sectional Studies , Middle Aged , Japan/epidemiology , Aged , Forced Expiratory Volume , Risk Factors , Vital Capacity , Prevalence , Lung/physiopathology , Osteoporosis, Postmenopausal/physiopathology , Osteoporosis, Postmenopausal/ethnology , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/epidemiology , Predictive Value of Tests , Logistic Models , Risk Assessment , Bone Density , Linear Models , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/ethnology , Pulmonary Disease, Chronic Obstructive/epidemiology , Diagnostic Self Evaluation , Odds Ratio , East Asian People
19.
Front Neurol ; 15: 1363225, 2024.
Article in English | MEDLINE | ID: mdl-38988597

ABSTRACT

Introduction: Although acupuncture is recommended by chronic obstructive pulmonary disease (COPD) treatment guidelines owing to its effects on dyspnea, the underlying neurobiological mechanisms of these effects remain unclear. This study aims to evaluate the efficacy of acupuncture in patients with stable COPD and explore the possible involvement of specific brain regions. Methods: This is a prospective, multicenter, single-blind, randomized controlled trial. A total of 90 participants will be recruited from three centers and will be randomly assigned in a 1:1 ratio to undergo acupuncture at acupoints on the disease-affected meridian (DAM) or non-acupoints on the non-affected meridian (NAM), in addition to routine pharmacological treatments. All participants will undergo 30 min of acupuncture three times a week for 8 weeks and will be followed up for 12 months. The primary outcome will be the severity of dyspnea, as measured using the Borg Dyspnea Scale and a visual analog scale at rest and after exercise. The secondary outcomes will include the multidimensional profile of dyspnea using Dyspnea-12, the modified Medical Research Council Dyspnea Scale, and the COPD assessment test; quality of life assessments using St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale; and additional measurements of exacerbation frequency, pulmonary function, and the 6-min walking distance. Magnetic resonance imaging (MRI) will be performed before and after exercise to explore the potential neurobiological mechanisms of exertional dyspnea. Anxiety and depression will be measured and analyzed for their correlation with the activation of specific brain areas involved in dyspnea. Discussion: This randomized controlled trial aims to use a multidimensional evaluation of the efficacy of acupuncture in relieving dyspnea in patients with COPD in terms of emotion and quality of life and explore the neurobiological mechanisms underlying the effects of acupuncture on dyspnea from an imaging perspective. It is expected to provide strong evidence to support the use of acupuncture in relieving dyspnea in patients with COPD and those with aother diseases involving dyspnea. Additionally, it provides novel insights into the central mechanisms of acupuncture intervention and dyspnea. Trial registration: Chinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2300071725.

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