Chronic Obstructive Pulmonary Disease Research Articles

Pharmacokinetics of pulmonary indacaterol in rat lung using molecular imprinting solid-phase extraction coupled with RP-UPLC

Indacaterol, a β2 agonist prescribed for long-term management of patients with chronic obstructive pulmonary disease and asthma. In this study the first MISPE cartridges was developed using indacaterol as a template for its selective extraction from rat lung tissues, enabling precise pharmacokinetic evaluation at the drug’s site of action. A molecular imprinting polymer was synthesized using indacaterol as a template, methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a cross-linker with a molar ratio (1: 4: 20). The polymer was characterized by a high binding capacity of 9840 ± 0.86 and high selectivity with an imprinting factor of 4.53 ± 0.12. The synthesized polymer was utilized as a sorbent in solid-phase extraction to purify and extract indacaterol from lung tissue matrix. The optimum molecularly imprinted solid-phase extraction (MISPE) conditions were 20.0 mg of molecular imprinting polymer and non-imprinting polymer, acetonitrile as the loading solvent, acetonitrile: water (20: 80; by volume) as the washing solvent, and methanol: acetic acid (90: 10; by volume) as the eluting solvent. A pharmacokinetic study was performed for indacaterol in rat lungs using the synthesized and optimized MISPE cartridge as a tool for sample purification. These parameters were determined in the lung tissues of rats emphasizing the local exposure of indacaterol to its target organ. The Cmax and Tmax were 51.020 ± 2.810 µg mL− 1 and 0.083 ± 0.001 h, respectively. The AUC 0−24 and AUC0 − inf were 175.920 ± 1.053 and 542.000 ± 5.245 µg h mL− 1, respectively. The elimination rate constant was 0.014 ± 0.00012 h− 1 and the half-life time was 48.510 ± 0.012 h. This study successfully developed and optimized MISPE cartridges using indacaterol as a template, enabling precise pharmacokinetic evaluation in rat lung tissues. The cartridges demonstrated high binding capacity and selectivity, providing crucial insights into the local exposure of indacaterol at its site of action.

Biofilm infections of endobronchial valves in COPD patients after endoscopic lung volume reduction: a pilot study with FISHseq

Endoscopic lung volume reduction (ELVR) using endobronchial valves (EBV) is a treatment option for a subset of patients with severe chronic obstructive pulmonary disease (COPD), suffering from emphysema and hyperinflation. In this pilot study, we aimed to determine the presence of bacterial biofilm infections on EBV and investigate their involvement in lack of clinical benefits, worsening symptomatology, and increased exacerbations that lead to the decision to remove EBVs. We analyzed ten COPD patients with ELVR who underwent EBV removal. Clinical data were compared to the microbiological findings from conventional EBV culture. In addition, EBV were analyzed by FISHseq, a combination of Fluorescence in situ hybridization (FISH) with PCR and sequencing, for visualization and identification of microorganisms and biofilms. All ten patients presented with clinical symptoms, including pneumonia and recurrent exacerbations. Microbiological cultures from EBV detected several microorganisms in all ten patients. FISHseq showed either mixed or monospecies colonization on the EBV, including oropharyngeal bacterial flora, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus spp., and Fusobacterium sp. On 5/10 EBV, FISHseq visualized biofilms, on 1/10 microbial microcolonies, on 3/10 single microorganisms, and on 1/10 no microorganisms. The results of the study demonstrate the presence of biofilms on EBV for the first time and its potential involvement in increased exacerbations and clinical worsening in patients with ELVR. However, further prospective studies are needed to evaluate the clinical relevance of biofilm formation on EBV and appropriate treatment options to avoid infections in patients with ELVR.

Early diagnosis and treatment of chronic obstructive pulmonary disease and bronchial asthma

Early diagnosis and treatment of chronic obstructive pulmonary disease and bronchial asthma

Fractional Exhaled Nitric Oxide (FeNO) in Biomass Smoke-Associated Chronic Obstructive Pulmonary Disease.

To measure FeNO levels in patients with COPD-BS and to compare these with those of patients with stable COPD-TS and in healthy controls. Transversal, observational, descriptive, comparative, and analytical study. A total of 57 patients, including 23 with COPD-BS, 17 with COPD-TS, and 17 healthy control subjects. The measurement of FeNO was carried out on all of these by means of the on-line chemiluminescence technique; the values were expressed in parts per billion (ppb) for their analysis. It was observed that the FeNO values were similar between COPD-BS and COPD-TS and were significantly different between the healthy and stable COPD (both groups). No correlation was found between pulmonary function and symptoms with FeNO in any of the groups. The level of FeNO in stable COPD is found to be increased in a similar manner in COPD-BS and COPD-TS, with a significant difference on comparing it with that of the healthy subjects.

Comprehensive comorbidity assessment for the ECOPD: a long-term multi-centre retrospective study

BackgroundExacerbation of chronic obstructive pulmonary disease (ECOPD) results in severe adverse outcomes and mortality. It is often associated with increased local and systemic inflammation. However, individual susceptibility to exacerbations remains largely unknown. Our study aimed to investigate the association between comorbidities and exacerbation outcomes.MethodsWe included patients with the primary discharge diagnosis of exacerbation for more 10 years in China. Data on all comorbidities were collected and analysed to determine the impact of the comorbidities on 1-year exacerbation readmission, length of hospital stay, and hospital cost. Univariable and multivariable logistic regression analyses were performed, and predictive models were developed.ResultsThis extensive investigation evaluated a total of 15,708 individuals from five prominent locations in China, revealing notable variations in the prevalence of comorbidities and healthcare expenses among different regions. The study shows that there is a high rate of readmission within one year, namely 15.8%. The most common conditions among readmitted patients are hypertension (38.6%), ischemic heart disease (16.9%), and diabetes mellitus (16.6%). An extensive multivariable study revealed that age, gender, and particular comorbidities such as malnutrition and hyperlipidemia are important factors that can significantly predict greater readmission rates, longer hospital stays or increased healthcare costs. The multivariable models show a moderate to good ability to predict patient outcomes, with concordance index ranging from 0.701 to 0.752. This suggests that targeted interventions in these areas could improve patient outcomes and make better use of healthcare resources.ConclusionsThe results regarding the association between severe exacerbations and systemic disease status support the integration of systematic evaluation of comorbidities into the management of exacerbations and the intensification of treatment of important comorbidities as a appropriate measure for prevention of further exacerbations. Our models also provide a novel tool for clinicians to determine the risk of the 1-year recurrence of severe ECOPD in hospitalised patients.

A Multimodal Intervention to Improve Guideline-Based Screening for Alpha-1 Antitrypsin Deficiency in a Community Health Setting.

Evidence-based guidelines recommend screening all individuals with chronic obstructive pulmonary disease (COPD) for the genetic disorder alpha-1 antitrypsin deficiency (AATD). However, it is estimated that only 5% of people with COPD have been tested for AATD, and a large fraction of the estimated 70,000 to 100,000 Americans with AATD have not yet been diagnosed. Low familiarity with AATD and limited knowledge about diagnostic tests and available treatments contribute to suboptimal screening rates. To address barriers to and improve rates of guideline-based AATD diagnostic testing among racially and ethnically diverse patients with COPD at a large community health center. A quality improvement initiative consisting of educational sessions and electronic health record (EHR) system interventions was implemented to improve the adoption of guideline-based screening for AATD in patients with COPD. An analysis of EHR data demonstrated that of patients with a COPD diagnosis (N = 1,030), 22.2% (n = 229) were screened for AATD in the 12 months following the start of the quality improvement initiative compared with 1.3% (n = 13) of patients with a COPD diagnosis (N = 972) seen in the 12 months prior to the start of the quality improvement initiative (P < 0.001). A quality improvement initiative consisting of educational sessions and EHR system modifications was successful in increasing clinicians' knowledge and diagnostic screening rates for AATD in patients with COPD at a large community health center.

Lipid peroxidation triggered by the degradation of xCT contributes to gasdermin D-mediated pyroptosis in COPD

BackgroundPyroptosis is an inflammatory form of regulated necrosis that has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the role of lipid peroxidation in pyroptosis and its underlying mechanisms in COPD remain unclear. MethodsIn vitro, human bronchial epithelial cells (Beas-2b cells) were exposed to cigarette smoke extract (CSE) for 24 h. In vivo, mice were exposed to cigarette smoke (CS) for 4 weeks. To investigate the role of xCT, we used siRNA and AAV6 to conditionally knock down xCT in vitro and in vivo, respectively. ResultsThe administration of ferrostatin-1 (Fer-1), a ferroptosis inhibitor that inhibits lipid peroxidation, significantly reduced the cytotoxicity of CSE to Beas-2b cells and mitigated inflammatory exudation, lung injury and mucus hypersecretion in mice with CS-induced COPD. Fer-1 suppressed gasdermin D (GSDMD)-mediated pyroptosis caused by CS in vitro and in vivo. However, in Beas-2b cells and the lung epithelial cells of mice, conditional knockdown of xCT (a negative regulatory factor of lipid peroxidation) inhibited the xCT/GPx4 axis, leading to more severe lipid peroxidation and GSDMD-mediated pyroptosis during cigarette smoke exposure. Moreover, we found that CS promoted the degradation of xCT through the ubiquitin proteasome system (UPS) and that treatment with MG132 significantly inhibited the degradation of xCT and downregulated the expression of pyroptosis-related proteins. ConclusionThe results of this study suggested that the ubiquitination-mediated degradation of xCT drives GSDMD-mediated pyroptosis in COPD and is a potential therapeutic target for COPD.

Residential exposure to Aspergillus spp. is associated with exacerbations in COPD.

Sensitisation to Aspergillus fumigatus is linked to worse outcomes in patients with chronic obstructive pulmonary disease (COPD), however, its prevalence and clinical implications in domestic (residential) settings remains unknown. Individuals with COPD (n=43) recruited in Singapore had their residences prospectively sampled and assessed by shotgun metagenomic sequencing including indoor air, outdoor air, and touch surfaces (total: 126 specimens). The abundance of environmental A. fumigatus and the occurrence of A. fumigatus (Asp f) allergens in the environment were determined and immunological responses to A. fumigatus allergens determined in association with clinical outcomes including exacerbation frequency. Findings were validated in 12 individuals (31 specimens) with COPD in Vancouver, Canada, a climatically different region. 157 metagenomes from 43 homes were assessed. Eleven and nine separate Aspergillus spp. were identified in Singapore and Vancouver respectively. Despite climatic, temperature, and humidity variation, A. fumigatus was detectable in the environment from both locations. The relative abundance of environmental A. fumigatus was significantly associated with exacerbation frequency in both Singapore (r=0.27, p=0.003) and Vancouver (r=0.49, p=0.01) and individuals with higher Asp f 3 sensitisation responses lived in homes with a greater abundance of environmental Asp f 3 allergens (p=0.037). Patients exposed and sensitised to Asp f 3 allergens demonstrated a higher rate of COPD exacerbations at 1-year follow-up (p=0.021). Environmental A. fumigatus exposure in the home environment including air and surfaces with resulting sensitisation carries pathogenic potential in individuals with COPD. Targeting domestic A. fumigatus abundance may reduce COPD exacerbations.

New insight into the molecular mechanism of TCM Bufei Huoxue formula for chronic obstructive pulmonary disease based on network pharmacology and experimental verification.

To unveil the mechanism of the Bufei Huoxue formula (BHF) for chronic obstructive pulmonary disease (COPD) through integrated network pharmacology (NP) and experimental verification. LC-MS was first applied to the analysis of both in vitro and in vivo samples from BHF for chemical profiling. Then a ligand library was prepared for NP to reveal the mechanism of BHF against COPD. Finally, verification was performed using an animal model related to the results from the NP. A ligand library containing 170 compounds from BHF was obtained, while 357 targets related to COPD were filtered to construct a PPI network. GO and KEGG analysis demonstrated that bavachin, paeoniflorin, and demethylation of formononetin were the major compounds for BHF against COPD, which mainly by regulating the PI3K/Akt pathway. The experiments proved that BHF could alleviate lung injury and attenuate the release of TNF-α and IL-6 in the lung and BALF in a dose-dependent manner. Western blot further demonstrated the down-regulated effect of BHF on p-PI3K. BHF provides a potent alternative for the treatment of COPD, and the mechanism is probably associated with regulating the PI3K/AKT pathway to alleviate inflammatory injury by bavachin, paeoniflorin, and demethylation of formononetin.

Admission and outcomes of COVID-19 among chronic obstructive pulmonary diseases patients in Africa: protocol for a systematic review and meta-analysis.

When the coronavirus case was originally reported in Wuhan, China, in December 2019, it quickly spread throughout the world and became a global public health problem. Evidence of the admission and outcomes of coronavirus disease among patients with chronic obstructive pulmonary disease (COPD) has not been reported in Africa. Consequently, this research protocol uses a systematic review and meta-analysis of the admission and outcomes of COVID-19 in patients with COPD in Africa. All observational studies published in the English language and reporting on the prevalence, admission and outcomes of COVID-19 among patients with COPD in Africa will be included. A search strategy will be implemented using electronic databases and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol recommendations. The findings of this review will be reported to health program designers, decision-makers and healthcare providers.

Lung Structure and Longitudinal Change in Cardiac Structure and Function: The MESA COPD Study.

Lung structure and cardiac structure and function are associated cross-sectionally. The classic literature suggests relationships of airways disease to cor pulmonale and emphysema to reduced cardiac output (CO) but longitudinal data are lacking. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease (COPD) Study was a multi-center longitudinal COPD case-control study of participants 50-79 years with ≥10 pack-years smoking without clinical cardiovascular disease. Segmental airway wall area (WA) and percent emphysema were measured on computed tomography. Right and left ventricle (RV, LV) parameters were assessed on magnetic resonance imaging (MRI) in exams six years apart. Longitudinal and period cross-sectional associations were evaluated with mixed models adjusted for demographics, body size, and smoking. The 187 participants with repeated MRI were 67±7 years old; 42% had COPD; 22% currently smoked; and the race/ethnicity distribution was 54% white, 30% Black, 14% Hispanic, and 3% Asian. Greater WA at enrollment was associated with longitudinal increase in RV mass (3.5 g per 10mm2 WA, 95% CI: 1.1, 5.9). Greater percent emphysema was associated with stably lower LV end diastolic volume (-7.8 mL per 5% emphysema, 95% CI: -10.3, -3.0) and CO (-0.2 L·min-1 per 5% emphysema, 95% CI: -0.4, -0.1). Cardiac associations varied by lung structure over six years in this multi-ethnic study. Greater WA at enrollment was associated with longitudinal increases in RV mass; whereas greater percent emphysema was associated with stable decrements in LV filling and CO.

Expiratory flow limitation development index (ELDI): a novel method of assessing respiratory mechanics in COPD

BackgroundExpiratory flow limitation (EFL) can be detected using oscillometric reactance and is associated with a worse clinical presentation in chronic obstructive pulmonary disease (COPD). Reactance can show negative swings upon exhalation, which may develop at different rates between patients. We propose a new method to quantify the rate of EFL development; the EFL Development Index (ELDI).MethodsA retrospective analysis of data from 124 COPD patients was performed. Data included lung function tests, Impulse Oscillometry (IOS), St Georges Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT) score. Fifty four patients had repeat data after 6 months. Twenty two patients had data recorded after 5 days of treatment with long acting bronchodilator therapy. EDLI was calculated as the mean expiratory reactance divided by the minimum expiratory reactance.ResultsThe mean ELDI was used to categorise patients with rapid onset of EFL (> 0.63; n = 29) or gradual onset (≤ 0.63; n = 34). Those with rapid development had worse airflow obstruction, lower quality of life scores, and greater resting hyperinflation, compared to those with gradual development. In patients with EFL, ELDI correlated with symptoms scores, airflow obstruction, lung volumes and gas diffusion. Both EFL and ELDI were stable over 6 months. EFL and EDLI improved with bronchodilator treatment.ConclusionsCOPD patients with rapid EFL development (determined by ELDI) had worse clinical characteristics than those with gradual EFL development. The rate of EFL development appears to be associated with clinical and physiological characteristics.

Estimating rate of lung function change using clinical spirometry data

RationaleIn chronic obstructive pulmonary disease (COPD), accurately estimating lung function from electronic health record (EHR) data would be beneficial but requires addressing complexities in clinically obtained testing. This study compared...

A quantitative proteomic approach to evaluate the efficacy of carnosine in a murine model of chronic obstructive pulmonary disease (COPD)

The aim of the work was to study a dose-dependent effect of inhaled carnosine (10, 50 or 100 mg/kg/day) in mice exposed to cigarette smoke as a model of chronic obstructive pulmonary disease (COPD). A dose-dependent loading of the dipeptide in lung tissue and bronchoalveolar lavage (BAL) was firstly demonstrated by LC-ESI-MS analysis. Cigarette smoke exposure induced a significant lung inflammation and oxidative stress in mice which was dose-dependently reduced by carnosine. Inflammation was firstly evaluated by measuring the cytokines content in the BAL. All the measured cytokines were found significantly higher in the smoke group in respect to control, although the data are affected by a significant variability. Carnosine was found effective only at the highest dose tested and significantly only for keratinocyte-derived cytokine (KC). Due to the high variability of cytokines, a quantitative proteomic approach to better understand the functional effect of carnosine and its molecular mechanisms was used. Proteomic data clearly indicate that smoke exposure had a great impact on lung tissue with 692 proteins differentially expressed above a threshold of 1.5-fold. Protein network analysis identified the activation of some pathways characteristic of COPD, including inflammatory response, fibrosis, induction of immune system by infiltration and migration of leukocyte pathways, altered pathway of calcium metabolism and oxidative stress. Carnosine at the tested dose of 100 mg/kg was found effective in reverting all the pathways evoked by smoke. Only a partial reverse of the dysregulated proteins was evident at low- and mid-tested doses, although, for some specific proteins, indicating an overall dose-dependent effect. Regarding the molecular mechanisms involved, we found that carnosine upregulated some key enzymes related to Nrf2 activation and in particular glutathione peroxidase, reductase, transferase, SOD, thioredoxins, and carbonyl reductase. Such mechanism would explain the antioxidant and anti-inflammatory effects of the dipeptide.

Multicenter study of the performance of NTM Elite agar for the detection of nontuberculous mycobacteria from patients with cystic fibrosis.

The performance of a novel selective agar was evaluated against the performance of conventional mycobacterial cultures, i.e., a combination of the mycobacterial growth indicator tube (MGIT) with Löwenstein-Jensen (LJ), for the detection of nontuberculous mycobacteria (NTM) in sputum samples from people with cystic fibrosis (pwCF). Two hundred eighty-three sputum samples (231 fresh sputum and 52 spiked sputum) from 143 pwCF were collected. They were inoculated without prior decontamination on NTM Elite agar (30°C ± 2°C for 28 days) and inoculated on both MGIT and LJ (35°C-37°C for 6-8 weeks) after N-acetyl-L-cysteine-2% sodium hydroxide decontamination. NTM were identified by Matrix-Assisted Laser Desorption Ionization/Time of Flight Mass Spectrometry and/or PCR, and whole-genome sequencing. A total of 67 NTM were recovered overall by the combination of all culture media. NTM Elite agar allowed the recovery of 65 NTM (97%), compared to 22 for the conventional MGIT and LJ media combination (32.8%), including 22 NTM for MGIT (32.8%) and 3 NTM with the LJ medium (4.5%). For Mycobacterium abscessus complex, the sensitivity of NTM Elite agar was 95% compared with a sensitivity of 30% for the conventional MGIT and LJ media combination. Overall, 17.3% of cultures on NTM Elite agar were contaminated with other micro-organisms vs 46.3% on MGIT and 77% on LJ. This study shows that the novel selective agar (NTM Elite agar) significantly outperforms the conventional MGIT and LJ media combination in terms of sensitivity, selectivity, and ease of culture, without the requirement of an L3 laboratory.IMPORTANCENontuberculous mycobacteria (NTM) are significant pulmonary pathogens in patients with pre-existing structural lung conditions such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease. Mycobacterium avium complex and Mycobacterium abscessus complex (MABSC) are the most frequently isolated organisms. Compared to the recommended culture method for NTM, which combines solid and liquid culture media, NTM Elite agar enables a faster/easier diagnosis and speeds up identification and susceptibility testing as the final reading is at 28 days instead of 6-8 weeks for the conventional mycobacterial cultures. In addition, for the NTM Elite agar, no decontamination stage before inoculation is necessary, unlike the conventional mycobacterial cultures. NTM Elite agar is derived from a formulation of medium adapted to rapidly growing mycobacteria (RGM). The medium enables the growth of RGM while suppressing other flora. It is supported with published clinical data showing the benefits of this medium.

Reducing Readmissions Using Collaborative Care.

After noting an elevated chronic obstructive pulmonary disease readmission rate for 2022, the inpatient Nurse Navigator at a rural nonprofit, 116-bed acute care facility in the State of Virginia met with interdisciplinary team (IDT) members to identify improvement efforts to decrease 30-day readmission rates. A 116-bed health care facility in Southside Virginia. Quality improvement initiative aimed to decrease 30-day penalty readmission rates using a collaborative IDT approach, focusing on patients 65years or older who are discharged home or to an assisted living facility with a diagnosis of acute myocardial infarction, heart failure, chronic obstructive pulmonary disease, and pneumonia. Compared to the readmission rates obtained in 2022, the 2023 readmission rates among the four diagnoses groups met or were under the disease-specific targets for 2023, supporting the efforts of the collaborative interdisciplinary approach to decrease 30-day readmission rates. Addressing community barriers and social determinants of health at the index admission. Collaborating with IDT members for a safe transition of care. Using the community paramedic program to provide additional resources to a rural community.

Severe Clinical Outcomes Due to Human Adenoviral Respiratory Infections in Hospitalized Immunocompetent Adults

Background Human adenoviral infections typically result in upper respiratory tract infections, conjunctivitis, and gastroenteritis that is classically self-limiting but can be life-threatening in immunocompromised individuals. In relatively rare cases, adenovirus infections in immunocompetent patients can result in hospitalizations and severe outcomes that include need for critical care or death. The risk factors that are associated with severe adenoviral infections in immunocompetent hosts have not been thoroughly investigated and are currently poorly understood. Methods Retrospective cohort of 78 patients with ages ranging from 18–85 years who were admitted to Yale New Haven-affiliated hospitals over a period of 2 years with positive adenovirus tests on a nasopharyngeal respiratory viral panel. Immunocompromised patients were excluded from the study. Patient charts were reviewed to obtain demographic information, comorbid conditions, smoking history, and clinical outcomes. Results Of the 78 patients admitted, 15 (19.2%) were admitted as observation, 44 (56.4%) were admitted to the hospital for over 48 hours, 15 (19.2%) required critical care, and 4 (5.1%) expired during hospitalization. Pulmonary disease as a comorbidity in the form of asthma (33.3%) or chronic obstructive pulmonary disease (12.8%), and smoking history (59.0%) were more common in those with severe adenoviral infections. With severe disease, 13 (16.7%) required mechanical ventilation, 10 (12.8%) required pressor support, and 2 (2.6%) required extracorporeal membrane oxygenation. Conclusions This retrospective study characterizes severity of adenoviral infections in adult immunocompetent patients, highlights the lack of treatment available, and identifies potential risk factors for severe disease, including asthma, smoking, absence of fever, and presence of coinfection.

Targeting Immunoproteasome in Polarized Macrophages Ameliorates Experimental Emphysema Via Activating NRF1/2-P62 Axis and Suppressing IRF4 Transcription.

Chronic obstructive pulmonary disease (COPD) stands as the prevailing chronic airway ailment, characterized by chronic bronchitis and emphysema. Current medications fall short in treatment of these diseases, underscoring the urgent need for effective therapy. Prior research indicated immunoproteasome inhibition alleviated various inflammatory diseases by modulating immune cell functions. However, its therapeutic potential in COPD remains largely unexplored. Here, an elevated expression of immunoproteasome subunits LMP2 and LMP7 in the macrophages isolated from mouse with LPS/Elastase-induced emphysema and polarized macrophages in vitro is observed. Subsequently, intranasal administration of the immunoproteasome-specific inhibitor ONX-0914 significantly mitigated COPD-associated airway inflammation and improved lung function in mice by suppressing macrophage polarization. Additionally, ONX-0914 capsulated in PLGA nanoparticles exhibited more pronounced therapeutic effect on COPD than naked ONX-0914 by targeting immunoproteasome in polarized macrophages. Mechanistically, ONX-0914 activated autophagy and endoplasmic reticulum (ER) stress are not attribute to the ONX-0914 mediated suppression of macrophage polarization. Intriguingly, ONX-0914 inhibited M1 polarization through the nuclear factor erythroid 2-related factor-1 (NRF1) and NRF2-P62 axis, while the suppression of M2 polarization is regulated by inhibiting the transcription of interferon regulatory factor 4 (IRF4). In summary, the findings suggest that targeting immunoproteasome in macrophages holds promise as a therapeutic strategy for COPD.

Percutaneous coronary intervention for left main coronary artery. Temporal trends and long-term outcomes from the all-comers BIA-LM registry.

Percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) was endorsed by trials. Aim was to assess prognosis and temporal trends in real-world registry. 998 patients undergoing LMCA PCI were hospitalized from 12.27.2007 to 02.21.2022. Analysis included mortality predictors, annual and periodic trends (2007-2015 compared to 2015-2022). Median age was 71 years (IQR 16), 736 (73.8%) were male and 448 (51.9%) had multimorbidity (≥3 chronic diseases). Worse prognosis was associated with age ≥75 years (HR 1.61, 95% CI 1.17-2.20, P=0.003), myocardial infarction (HR 1.47, 95% 1.06-2.04, P=0.02), previous myocardial infarction (HR 1.43, 95% CI 1.07-1.91, P=0.02), diabetes (HR 1.38, 95% CI 1.03-1.84, P=0.03), atrial fibrillation (HR 1.74, 95% CI 1.26-2.39, P=0.001), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.27-3.20, P=0.003) and previous stroke (HR 1.78, 95% CI 1.17-2.70, P=0.007). Higher ejection fraction (HR 0.98, 95% CI 0.96-0.99, P<0.001 for 1% increase) and intravascular imaging (HR 0.70, 95% CI 0.49-1.00, P=0.047) yielded better outcomes. Rate of LMCA PCI emerged from 2.2% in 2008 to 6.9% in 2021 (P<0.001). There were increases in annual and periodic rates of multimorbidity (P<0.001), intravascular imaging (P<0.001) and decreases in 30-, 90-day (log-rank P<0.001) and 1-year mortality (log-rank P=0.007). Six-year landmark mortality analysis at 30-days showed trend toward worse prognosis in patients hospitalized in late period (log-rank P=0.051). PCI and multimorbidity rates increased. Short-term mortality decreased, while prognosis beyond 30-days worsened. Advancements in PCI technology may improve early outcomes; however, efforts should be made to reduce burden of multimorbidity.

Effects of Hyperbaric Oxygen Therapy on Lungs Histopathology of Animal Models with Chronic Obstructive Pulmonary Disease

Effects of Hyperbaric Oxygen Therapy on Lungs Histopathology of Animal Models with Chronic Obstructive Pulmonary Disease