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.

Unilateral Alveolar Hemorrhage: A Rare Pulmonary Complication in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that presents a broad spectrum of clinical manifestations. Alveolar hemorrhage in SLE is rare and has a poor prognosis. We present the case of a patient with a diagnosis of SLE and lupus nephropathy on hemodialysis who presented criteria for alveolar hemorrhage with unilateral involvement, with clinical improvement after the administration of steroid boluses. The uncommon presentation of unilateral pulmonary involvement and the importance of making an adequate protocol for ruling out differential diagnoses are highlighted.

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.

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.

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.

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.

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.

The impact of traditional mind-body exercises on pulmonary function, exercise capacity, and quality of life in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.

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].

Influence of heart failure (HF) comorbidity in chronic obstructive pulmonary disease (COPD) and isolated forms of HF and COPD on cardiovascular function during hospitalization.

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 hours 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- -0.62); -2.33(-2.60- -2.12); -1.32(-1.42- -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).

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.

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.

A systematic review of the impact of pulmonary thromboendarterectomy on health-related quality of life.

Pulmonary thromboendarterectomy (PTE) is the current gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH) and is a viable treatment option for chronic thromboembolic pulmonary disease (CTEPD). The progressive nature of both diseases severely impacts health-related quality of life (HRQoL) across a variety of domains. This systematic review was performed to evaluate the impact of PTE on short- and long-term HRQoL. A literature search was conducted on PubMed for studies matching the eligibility criteria between January 2000 and September 2022. OVID (MEDLINE), Google Scholar, EBSCOhost (EMBASE), and bibliographies of included studies were reviewed. Inclusion of studies was based on predetermined eligibility criteria. Quality appraisal and data tabulation were performed using predetermined forms. Results were synthesized by narrative review. The structure of this systematic review follows the PRISMA guidelines. This systematic review was prospectively registered in the PROSPERO register (CRD42022342144). Thirteen studies (2184 patients) were included. Within 3 months post-PTE, HRQoL improved in both CTEPD and CTEPH as measured by disease-specific and generic questionnaires. HRQoL improvements were sustained up to 5 years postoperatively in patients with CTEPH post-PTE. PTE remains the gold standard for treating CTEPH and improving HRQoL. Residual pulmonary hypertension and comorbidities such as COPD and coronary artery disease decrement HRQoL over time. The impact of mPAP and PVR on HRQoL outcomes postoperatively remain ambiguous. Pulmonary thromboendarterectomy remains the gold standard for treating CTEPH and has shown to improve HRQoL outcomes at 3-month sustaining improvements up to 5-year postoperatively. Residual pulmonary hypertension and comorbidities hinder HRQoL outcomes post-PTE.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary disease without pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.

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.

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.

Overexpression of USP8 inhibits inflammation and ferroptosis in chronic obstructive pulmonary disease by regulating the OTUB1/SLC7A11 signaling pathway.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a familiar disease, and owns high morbidity and mortality, which critically damages the health of patients. Ubiquitin-specific peptidase 8 (USP8) is a pivotal protein to join in the regulation of some diseases. In a previous report, it was determined that USP8 expression is down-regulated in LPS-treated BEAS-2B cells, and USP8 restrains inflammatory response and accelerates cell viability. However, the regulatory roles of USP8 on ferroptosis in COPD are rarely reported, and the associated molecular mechanisms keep vague. OBJECTIVE: To investigate the regulatory functions of USP8 in COPD progression. MATERIAL AND METHODS: The lung functions were measured through the Buxco Fine Pointe Series Whole Body Plethysmography (WBP). The Fe level was tested through the Fe assay kit. The protein expressions were assessed through western blot. The levels of tumor necrosis -factor-α, interleukin 6, and interleukin 8 were evaluated through enzyme-linked immunosorbent serologic assay. Cell viability was tested through CCK-8 assay. RESULTS: In this work, it was discovered that overexpression of USP8 improved lung function in COPD mice. In addition, overexpression of USP8 repressed ferroptosis by regulating glutathione peroxidase 4 and acyl-CoA synthetase long-chain family 4 expressions in COPD mice. Overexpression of USP8 suppressed inflammation in COPD mice. Furthermore, overexpression of USP8 suppressed ferroptosis in COPD cell model. At last, it was verified that overexpression of USP8 accelerated ubiquitin aldehyde-binding protein 1 (OTUB1)/solute carrier family 7 member 11 (SLC7A11) pathway. CONCLUSION: This study manifested that overexpression of USP8 restrained inflammation and ferroptosis in COPD by regulating the OTUB1/SLC7A11 signaling pathway. This discovery hinted that USP8 could be a potential target for COPD treatment.

Increased Risk of Severe Cardiovascular Events Following Exacerbations of Chronic Obstructive Pulmonary Disease: Results of the EXACOS-CV Study in Japan.

INTRODUCTION: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are known to increase the risk of cardiovascular events. However, this association has not been investigated specifically in patients with COPD in Japan, whose characteristics may differ from those of Western patients (i.e., western Europe, the US, and Canada). METHODS: This longitudinal retrospective cohort study analyzed secondary claims data and included patients aged ≥ 40 years with COPD (International Classification of Diseases-10 codes J41-J44). All exacerbations occurring during follow-up were measured. Time-dependent Cox models were used to estimate hazard ratios (HRs) for the association between time periods following an exacerbation of COPD (vs. time prior to a first exacerbation) and occurrence of a first hospitalization for a severe fatal or non-fatal cardiovascular event. RESULTS: The analysis included 152,712 patients with COPD with a mean age of 73.8 years and 37.6% of whom were female. During a median follow-up of 37 months, 63,182 (41.4%) patients experienced ≥ 1 exacerbation and 13,314 (8.7%) patients experienced ≥ 1 severe cardiovascular event. Following an exacerbation of COPD, the risk of a severe cardiovascular event was increased in the first 30 days [adjusted HR (aHR) 1.44, 95% confidence interval (CI) 1.33-1.55] and remained elevated for 365 days post-exacerbation (aHR 1.13, 95% CI 1.04-1.23). Specifically, the risks of acute coronary syndrome or arrhythmias remained significantly increased for up to 180 days, and the risk of decompensated heart failure for 1 year. CONCLUSION: Among Japanese patients with COPD, the risk of experiencing a severe cardiovascular event increased following a COPD exacerbation and remained elevated for 365 days, emphasizing the need to prevent exacerbations.