Aucubin Alleviates Chronic Obstructive Pulmonary Disease by Activating Nrf2/HO-1 Signaling Pathway.

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.

Determination of predisposing factors for prolonged intensive care in patients with exacerbation of chronic obstructive pulmonary disease.

Objectives: To determine the predisposing factors for lengthy intensive care unit stay of chronic obstructive pulmonary disease patients with acute exacerbation. METHODS: The retrospective study was conducted after approval from the ethics review committee of Atatürk Sanatorium Training and Research Hospital, Turkey, and comprised data from January 1, 2017, to August 31, 2022, related to acute exacerbation chronic obstructive pulmonary disease patients receiving intensive care unit treatment. Demographics, comorbidities, treatment, length of stay in hospital and in intensive care unit, and nutritional status were evaluated. Data of patients who spent <10 days in intensive care unit formed Group 1, while those having spent 10 days or more formed Group 2 for comparison purposes. Data was analysed using SPSS 22. RESULTS: Of the 460 patients, 366(79.6%) were in Group 1; 224(61.2%) males and 64(38.8%) females with mean age 70.81±11.57 years. There were 94(20.4%) patients in Group 2; 62(66%) males and 32(34%) females with mean age 72.38±10.88 years (p>0.05). Inotropic agent support, need for haemodialysis, timeframe of invasive mechanical ventilation, length of stay in hospital, 1-month mortality, antibiotic use, use of diuretic agent, acute physiology and chronic health evaluation-ii score, nutrition risk in the critically ill score, history of lung malignancy, and pneumonic infiltration on chest radiograph were significantly more frequenttly observed in Group 2 patients (p<0.05). Age, timeframe of invasive mechanical ventilation, and length of stay in hospital were the factors prolonging intensive care unit stay (p<0.05). CONCLUSIONS: Higher age, longer invasive mechanical ventilation timeframe and hospital stay with acute exacerbation chronic obstructive pulmonary disease caused a prolonged stay in intensive care unit.

Effects of whole-body vibration exercise on functional capacity, muscle strength, and quality of life in individuals with severe chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Whole body vibration (WBV) exercise is a therapy used for individuals with low tolerance to conventional exercises, such as patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the impact of WBV exercise on the functional capacity, muscle strength, and health-related quality of life (HRQoL) in severe COPD patients. METHODS: Studies published until March 2024 were reviewed, encompassing randomized clinical trials (RCTs) without temporal or linguistic constraints, comparing WBV exercise with other interventions. The PubMed/MEDLINE, Scopus, Cochrane Airways Trials Register, and CINAHL databases were queried. The Revised Cochrane risk-of-bias tool for randomized trials 2.0A was employed for quality assessment. RESULTS: Among 351 screened studies, 7 met the criteria, totaling 356 participants (WBV group, n = 182; control group, n = 174). Meta-analysis revealed a significant mean difference of 41.36 m [95%CI (13.28-69.44); p = .004] in the 6-minute walk test distance favoring the WBV group for functional capacity. Lower limb muscle strength improved in 57.14% of included studies. HRQoL meta-analysis demonstrated a 1.13-point difference [95%CI -1.24-3.51; p = .35] favoring WBV, although group differences were not significant. A mean difference of 2.31 points favored the control group in health condition [95%CI (-1.32-5.94); p = .021]. CONCLUSION: WBV exercise is recognized as a promising therapeutic modality for severe COPD patients, notably enhancing functional capacity. Although heterogeneous study protocols weaken the evidence for clinically relevant outcomes, improvements in lower limb muscle strength and HRQoL were also observed, differences between groups were not significant.

Optimizing discharge antimicrobial therapy: Evaluation of a transitions of care process and electronic scoring system for patients with community-acquired pneumonia or chronic obstructive pulmonary disease.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Prescribing excess antibiotic duration at hospital discharge is common. A pharmacist-led Antimicrobial Stewardship Program Transition of Care (ASP TOC) intervention was associated with improved discharge prescribing. To improve the sustainability of this service, an electronic scoring system (ESS), which included the ASP TOC electronic variable, was implemented in the electronic medical record to prioritize pharmacist workload. The purpose of this study was to evaluate the implementation of the ASP TOC variable in the ESS in patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary disease (COPD). METHODS: This institutional review board-approved, retrospective quasi-experiment included patients discharged on oral antibiotics for CAP or COPD exacerbation (lower respiratory tract infection) from November 1, 2021, to March 1, 2022 (the preintervention period) and November 1, 2022, to March 1, 2023 (the postintervention period). The primary endpoint was optimized discharge antimicrobial regimen. A sample of at least 194 patients was required to achieve 80% power to detect a 20% difference in the frequency of optimized therapy. Multivariable logistic regression was used to identify factors associated with optimized regimens. RESULTS: Similar baseline characteristics were observed in both study groups (n = 100 for both groups). The frequency of optimized discharge regimens improved from 69% to 82% (P = 0.033). The percentage of ASP TOC interventions documented as completed by a pharmacist increased from 4% to 25% (P < 0.001). ASP TOC intervention, female gender, and COPD were independently associated with an optimized discharge regimen (adjusted odds ratios, 6.57, 1.61, and 3.89, respectively; 95% CI, 1.51-28.63, 0.81-3.17, and 1.85-8.20, respectively). CONCLUSION: After the launch of the ASP TOC variable, there was an increase in optimized discharge regimens and ASP TOC interventions completed. Pharmacists' use of the ASP TOC variable through an ESS can aid in improving discharge prescribing.

Pyroptosis-Related Genes as Diagnostic Markers in Chronic Obstructive Pulmonary Disease and Its Correlation with Immune Infiltration.

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.

Prevalence, Incidence, and Risk of Chronic Obstructive Pulmonary Disease Among Psoriasis Patients.

BACKGROUND: Understanding the relationship between psoriasis and chronic obstructive pulmonary disease (COPD) may enhance disease management. OBJECTIVES: We aimed to determine the (1) prevalence and (2) incidence and risk of COPD in psoriasis patients. RESULTS: The COPD prevalence was 9.64% in psoriasis patients and 6.94% in psoriasis-free patients. The COPD incidence was 10.74 per 1000 person-years in psoriasis patients and 6.36 per 1000 person-years in psoriasis-free patients. Multivariable Cox regression showed no association between psoriasis and COPD development (HR 0.99, p = 0.271). CONCLUSIONS: Our findings suggest that psoriasis is not an independent risk factor for COPD development.

Peroxiredoxin 6 Protects Pulmonary Epithelial Cells From Cigarette-related Ferroptosis in Chronic Obstructive Pulmonary Disease.

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.

Development and Validation of Machine Learning-Based Models for Prediction of Intensive Care Unit Admission and In-Hospital Mortality in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

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.

Examining the Impact of Social Support on Psychological Well-Being Among Canadian Individuals With COPD: Implications for Government Policies.

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.

A Case Report of an Elderly Patient With Cushing's Disease and Multiple Chronic Conditions.

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.

Inhalation of nicotine-containing electronic cigarette vapor exacerbates the features of COPD by inducing ferroptosis in ßENaC-overexpressing mice.

Introduction: Chronic obstructive pulmonary disease (COPD) is currently listed as the 3rd leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood. Methods: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics. Results: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells. Discussion: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.

Association Between Urinary Phthalate Metabolites and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

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.

COPD Exacerbations Before and During COVID-19 in France, Germany, Italy, the UK and the US.

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.

Risk of Cardiovascular Events Associated with Chronic Obstructive Pulmonary Disease and/or Metabolic Syndrome: A Large-Scale Nationwide Population-Based Cohort Study.

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.

RNA-binding protein AZGP1 inhibits epithelial cell proliferation by regulating the genes of alternative splicing in COPD.

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.

Impacts of a Dysphagia Screening Questionnaire on Speech Pathology Input Using a Transdisciplinary Approach for Patients with Chronic Obstructive Pulmonary Disease in a Pulmonary Rehabilitation Program.

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.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

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.

SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation.

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.

Impact of the COVID-19 Pandemic on Hospital Admission Rate, Length of Stay, and Mortality Rate for Patients with Chronic Obstructive Pulmonary Disease Exacerbation: A Retrospective Study.

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.