Progression Of Chronic Obstructive Pulmonary Disease Research Articles

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates pro-cellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: Unraveling the Molecular Nexus.

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory disorder characterized by persistent airflow limitation and chronic inflammation. In recent years, the role of mitochondrial dysfunction in COPD pathogenesis has emerged as a focal point of investigation. This review endeavors to unravel the molecular nexus between mitochondrial dysfunction and COPD, delving into the intricate interplay of oxidative stress, bioenergetic impairment, mitochondrial genetics, and downstream cellular consequences. Oxidative stress, a consequence of mitochondrial dysfunction, is explored as a driving force behind inflammation, exacerbating the intricate cascade of events leading to COPD progression. Bioenergetic impairment sheds light on the systemic consequences of mitochondrial dysfunction, impacting cellular functions and contributing to the overall energy imbalance observed in COPD patients. This review navigates through the genetic landscape, elucidating the role of mitochondrial DNA mutations, variations, and haplogroups in COPD susceptibility and severity. Cellular consequences, including apoptosis, autophagy, and cellular senescence, are examined, providing insights into the intricate mechanisms by which mitochondrial dysfunction influences COPD pathology. Therapeutic implications, spanning antioxidant strategies, mitochondria-targeted compounds, and lifestyle modifications, are discussed in the context of translational research. Important future directions include identifying novel biomarkers, advancing mitochondria-targeted therapies, and embracing patient-centric approaches to redefine COPD management. This abstract provides a comprehensive overview of our review, offering a roadmap for understanding and addressing the molecular nexus between mitochondrial dysfunction and COPD, with potential implications for precision medicine and improved patient outcomes.

Analysis of network expression and immune infiltration of disulfidptosis-related genes in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays a pivotal role in the development of COPD. Disulfidptosis is a newly discovered type of cell death that may be associated with the progression of COPD. However, the expression and role of disulfidptosis-related genes (DRGs) in COPD remain unclear. The expression of DRGs was identified by analyzing RNA sequencing (RNA-seq) data in COPD. Further, COPD patients were classified into two subtypes by unsupervised cluster analysis to reveal their differences in gene expression and immune infiltration. Meanwhile, hub genes associated with disulfidptosis were screened by weighted gene co-expression network analysis. Subsequently, the hub genes were validated experimentally in cells and animals. In addition, we screened potential therapeutic drugs through the hub genes. We identified two distinct molecular clusters and observed significant differences in immune cell populations between them. In addition, we screened nine hub genes, and experimental validation showed that CDC71, DOHH, PDAP1, and SLC25A39 were significantly upregulated in cigarette smoke-induced COPD mouse lung tissues and bronchial epithelial cells (BEAS-2B) treated with cigarette smoke extract. Finally, we predicted 10 potential small molecule drugs such as Atovaquone, Taurocholic acid, Latamoxef, and Methotrexate. We highlighted the strong association between COPD and disulfidptosis, with DRGs demonstrating a discriminative capacity for COPD. Additionally, the expression of certain novel genes, including CDC71, DOHH, PDAP1, and SLC25A39, is linked to COPD and may aid in the diagnosis and assessment of this condition.

Correlation between Volatile Organic Compounds (VOC) with Leukotriene B4 and Eosinophil Counts in Chronic Obstructive Pulmonary Disease Patients

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by increasing Leukotriene B4 (LTB4) and eosinophil counts. Volatile organic compounds (VOCs) have shown promise as non-invasive biomarkers, reflecting COPD pathophysiology. Identifying specific VOCs associated with increased LTB4 and eosinophil counts could lead to the discovery of potential biomarkers for COPD severity or progression. AIMS: This study aims to investigate the correlation between VOCs and leukotriene B4 (LTB4) levels, as well as eosinophil counts counts in COPD patients. METHOD: Using an observational-analytic method with a case-control approach, 20 COPD patients and 20 controls were enrolled from the respiratory outpatient department of Dr. Saiful Anwar General Hospital, Malang. VOC levels were measured using a breath analyzer, while LTB4 levels were determined through enzyme-linked immunosorbent assays. Spearman’s correlation tests examined associations between VOCs, LTB4, eosinophil counts, and comorbidity, with Mann-Whitney tests comparing results against the control group. Data significance was set at p < 0.05. RESULT: There were 40 COPD patients and 40 controls in this study. There were significant differences between VOCs in the COPD group and the control group (p < 0.05). LTB4 level significantly increased in the COPD group than in the control group (p < 0.001), and there was no difference in the eosinophil level. There was a correlation between LTB4 and VOC level of C2H5OH in COPD patients (p = 0.009; r = 0.410). There was no correlation between eosinophil counts and VOCs (p = 0.939). The level of VOCs was significantly different between patients with only COPD and patients with COPD and comorbid lung cancer (p < 0.05). CONCLUSION: There is a correlation between VOC and LTB4 in COPD patients.

P. gingivalis alters lung microbiota and aggravates disease severity of COPD rats by up-regulating Hsp90α/MLKL

ABSTRACT Background Epidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear. Methods and Results A COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90α/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90α and MLKL in serum and lung tissue verified that Hsp90α/MLKL was up-regulated. Conclusion These results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90α/MLKL might participate in.

Chronic obstructive pulmonary disease: Signs and symptoms, diagnosis, treatments, lifestyle risk factors and management

Chronic Obstructive Pulmonary Disease (COPD) is associated with increased health complications, leading to a rise in mortality rates. COPD remains a significant global health issue, underscoring the importance of recognizing symptoms, facilitating diagnosis, and implementing effective treatment strategies. However, information on lifestyle risk factors and the management of COPD remains fragmented. This review paper aims to understand the clinical pathophysiologic changes triggered by lifestyle practices and their management strategies. It is important to understand its symptoms, diagnostics criteria, and treatment to correlate with lifestyle risk factors and to identify effective lifestyle interventions. Lifestyle practices as defined by dietary practices such being anorexia and low fruit and vegetable intake, smoking habits, alcohol consumption, and physical inactivity have increased the risk of COPD. This review suggested lifestyle approaches for COPD treatment such as regular exercise, a healthy diet, and avoiding smoking. In this case, the development of the guided improved intervention is important for a better understanding of the mechanisms between COPD and its associated lifestyle practices. This information may help clinicians, health practitioners, and dietitians to guide patients to implement improved dietary interventions. To avoid the progression of COPD, lifestyle practice therapy could be the most effective strategies that aid with medications as prescribed by the physicians.

Combined analysis of bulk RNA and single-cell RNA sequencing to identify pyroptosis-related markers and the role of dendritic cells in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea caused by airflow limitation. Further development may lead to decreased lung function and other lung diseases. Pyroptosis is a type of programmed cell death that involves multiple pathways. For example, the pathway induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with COPD exacerbation. Therefore, in this study, various machine learning algorithms were applied to screen for diagnostically relevant pyroptosis-related genes from the GEO dataset, and the results were verified using external datasets. The results showed that deep neural networks and logistic regression algorithms had the highest AUC of 0.91 and 0.74 in the internal and external test sets, respectively. Here, we explored the immune landscape of COPD using diagnosis-related genes. We found that the infiltrating abundance of dendritic cells significantly differed between the COPD and control groups. Finally, the communication patterns of each cell type were explored based on scRNA-seq data. The critical role of significant pathways involved in communication between DCS and other cell populations in the occurrence and progression of COPD was identified.

Bidirectional relationship between chronic obstructive pulmonary disease and oral disease

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that has various comorbid conditions and systemic complications. One of the complications is dental and oral disease, which can occur through systemic inflammatory mechanisms and the long-term side effects of inhaled drugs. Dental and oral diseases can also cause COPD progression, increase the risk of exacerbations, and affect the patient's quality of life. Some mechanisms that may play a role include aspiration of oral pathogens, aspiration of inflammatory proteins, and systemic inflammation. Dysbiosis of the lung microbiome can result from dental and oral conditions, increasing the risk of COPD and pulmonary infections. The association between COPD and oral disease includes the presence of systemic inflammatory conditions, the risk factor of smoking, and the indirect effects of inhaled medication use. Comprehensive management of COPD patients regarding dental and oral health is needed, which includes prevention of dental and oral disease, routine assessment of dental and oral health, provision of specific dental therapy, and personalized treatment in selecting COPD therapy.

Inflammation as the nexus: exploring the link between acute myocardial infarction and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), particularly following acute exacerbations (AE-COPD), significantly heightens the risks and mortality associated with acute myocardial infarction (AMI). The intersection of COPD and AMI is characterised by a considerable overlap in inflammatory mechanisms, which play a crucial role in the development of both conditions. Although extensive research has been conducted on individual inflammatory pathways in AMI and COPD, the understanding of thrombo-inflammatory crosstalk in comorbid settings remains limited. The effectiveness of various inflammatory components in reducing AMI infarct size or slowing COPD progression has shown promise, yet their efficacy in the context of comorbidity with COPD and AMI is not established. This review focuses on the critical importance of both local and systemic inflammation, highlighting it as a key pathophysiological connection between AMI and COPD/AE-COPD.

Association of blood cadmium concentration with chronic obstructive pulmonary disease progression: a prospective cohort study

BackgroundPrior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation.MethodsStable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records.ResultsEach additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration.ConclusionPatients with COPD who have higher blood Cd concentration are susceptible to worse disease progression.Graphical

Natural Killer Cells as a Further Insight into the Course of Chronic Obstructive Pulmonary Disease.

The role of natural killer (NK) cells in chronic obstructive pulmonary disease (COPD) pathogenesis has been discussed but is not yet clearly understood. This current study aimed to evaluate the associations between immunophenotypes, degrees of maturity, and the expression level of functional receptors of NK cells in the lung environment present in bronchoalveolar lavage fluid (BALF), and an attempt was made to determine their relationship in the course and progression of COPD. A total of 15 COPD patients and 14 healthy smokers were included. The clinical parameters of COPD were evaluated. In both groups, NK cells using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry were assessed in the peripheral blood. Additionally, NK cells using the same method were assessed in BALF in the COPD subgroup. The blood's NK cells differed from the estimated group's maturity and receptor expression. Functional receptors CD158b+, CD314+, and CD336+ expressed by NK cells were significantly interlinked with age, RV, TLC, 6MWT, smoking, and the number of exacerbations. These results confirm the essential role of NK cells in COPD pathogenesis. Additionally, the relationship between clinical parameters and NK cell expression may indicate its participation in the disease progression and exacerbation and allow for a better understanding of NK cell biology in COPD.

MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.

GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism. Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD. The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05). In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.

Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: enhancing gut probiotics abundance and the tryptophan-melatonin pathway.

Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.

The Association Between Dietary Magnesium Intake with Chronic Obstructive Pulmonary Disease and Lung Function in US Population: a Cross-sectional Study.

Chronic obstructive pulmonary disease (COPD) is now considered among the top three contributors to mortality globally. There is limited understanding surrounding the contribution of magnesium to the progression of COPD. This survey aims to evaluate the connection between dietary magnesium intake and both lung function and COPD prevalence among the US population. The research comprised 4865 participants in the National Health and Nutrition Examination Survey (NHANES) program conducted from 2007 to 2012. To evaluate the association between dietary magnesium intake and lung function as well as COPD, the study conducted multiple regression analyses, stratified analyses, and smoothed curves. In this study, we explored the relationship between higher magnesium intake and higher FEV1 [β = 0.21 (95% CI 0.12, 0.30)] and FVC [β = 0.25 (95% CI 0.14, 0.36)] after accounting for all potential confounding factors. We demonstrated a relationship between increased magnesium intake and reduced odds of developing COPD [OR = 0.9993 (95% CI 0.9987, 1.0000)]. The results of stratified analyses further indicated that the relationship between magnesium intake and the risk of COPD is more pronounced in the 40-60 age group and males. The study demonstrated positive associations between the intake of dietary magnesium and both FEV1 and FVC. Additionally, an adverse relationship between magnesium intake and the prevalence of COPD was also observed, suggesting that supplementation with magnesium may be a practical approach to preventing and managing COPD.

Cell-free DNA levels associate with COPD exacerbations and mortality

The question addressed by the studyGood biological indicators capable of predicting chronic obstructive pulmonary disease (COPD) phenotypes and clinical trajectories are lacking. Because nuclear and mitochondrial genomes are damaged and released by cigarette smoke exposure, plasma cell-free mitochondrial and nuclear DNA (cf-mtDNA and cf-nDNA) levels could potentially integrate disease physiology and clinical phenotypes in COPD. This study aimed to determine whether plasma cf-mtDNA and cf-nDNA levels are associated with COPD disease severity, exacerbations, and mortality risk.Materials and methodsWe quantified mtDNA and nDNA copy numbers in plasma from participants enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE, n = 2,702) study and determined associations with relevant clinical parameters.ResultsOf the 2,128 participants with COPD, 65% were male and the median age was 64 (interquartile range, 59–69) years. During the baseline visit, cf-mtDNA levels positively correlated with future exacerbation rates in subjects with mild/moderate and severe disease (Global Initiative for Obstructive Lung Disease [GOLD] I/II and III, respectively) or with high eosinophil count (≥ 300). cf-nDNA positively associated with an increased mortality risk (hazard ratio, 1.33 [95% confidence interval, 1.01–1.74] per each natural log of cf-nDNA copy number). Additional analysis revealed that individuals with low cf-mtDNA and high cf-nDNA abundance further increased the mortality risk (hazard ratio, 1.62 [95% confidence interval, 1.16–2.25] per each natural log of cf-nDNA copy number).Answer to the questionPlasma cf-mtDNA and cf-nDNA, when integrated into quantitative clinical measurements, may aid in improving COPD severity and progression assessment.

Hsa_circ_0008833 promotes COPD progression via inducing pyroptosis in bronchial epithelial cells

Purpose: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder. Pyroptosis represents a distinctive form of inflammatory cell death that is mediated through the activation of Caspase-1 and inflammasomes. CircRNAs have emerged as a novel class of biomolecules with implications in various human diseases. This study aims to investigate the circRNAs profile of in COPD progression and identify pivotal circRNAs associated with the development of this disease. Methods: he expression profiles of circRNAs in peripheral blood mononuclear cells of COPD patients were assessed by circRNA microarray. Furthermore, flag-labeled vectors were constructed to assess the potential protein-coding capacity of has-circ-0008833. 16HBE cells were stably transfected with lentivirus approach, and cell proliferation and death were assessed to clarify the functional roles of has-circ-0008833 and its encoded protein circ-0008833aa. Additionally, western blot analysis was furthered performed to determine the level of Caspase-1, IL-18, IL-1β, NLRP3, ASC, and cleaved GSDMD regulated by has-circ-0008833 and circ-0008833-57aa. Results: Initially, we screened the expression profiles of human circRNAs in peripheral blood mononuclear cells of COPD patients, and found that has-circ-0008833 exhibited a significant increase in COPD mononuclear cells. Subsequently, we demonstrated that has-circ-0008833 carried an open reading frame (ORF), which encoded a functional protein, referred to as circ-0008833-57aa. By employing gain-of-function approaches, our results suggested that both circ-0008833 and circ-0008833-57aa inhibited proliferation, but accelerated the rate of 16HBE cell death. Finally, we discovered that circ-0008833 and circ-0008833-57aa promoted the expression of Caspase-1, IL-18, IL-1β, NLRP3, ASC, and cleaved GSDMD in 16HBE cells. Conclusions: Upregulation of circ-0008833 might promote COPD progression by inducing pyroptosis of bronchial epithelial cells through the encoding of a 57-amino acid peptide.

Periodontitis aggravates COPD through the activation of γδ T cell and M2 macrophage.

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease with high morbidity and mortality. Periodontitis exacerbates COPD progression; however, the immune mechanisms by which periodontitis affects COPD remain unclear. Here, by constructing periodontitis and COPD mouse models, we demonstrated that periodontitis and COPD could mutually aggravate disease progression. For the first time, we found that the progression was associated with the activation of γδ T cells and M2 macrophages, and M2 polarization of macrophages was affected by γδ T cells activation. In the lung tissues of COPD with periodontitis, the activation of γδ T cells finally led to the increase of IL 17 and IFN γ expression and M2 macrophage polarization. Furthermore, we found that the periodontitis-associated bacteria Porphyromonas gingivalis (P. gingivalis) promoted the activation of γδ T cells and M2 macrophages ex vivo. The data from clinical bronchoalveolar lavage fluid (BALF) samples were consistent with the in vivo and ex vivo experiments. For the first time, our results identified the crucial role of γδ T-M2 immune mechanism in mediating periodontitis-promoted COPD progression. Therefore, targeting at periodontitis treatment and the γδ T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control.IMPORTANCEPeriodontitis exacerbates chronic obstructive pulmonary disease (COPD) progression. For the first time, the current study identified that the impact of periodontitis on COPD progression was associated with the activation of γδ T cells and M2 macrophages and that M2 polarization of macrophages was affected by γδ T cells activation. The results indicated that targeting at periodontitis treatment and the γδ T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control.

Плейотропные эффекты ацетилсалициловой кислоты

Currently, researchers are investigating new mechanisms of action and potential applications of acetylsalicylic acid (ASA). This article summarizes recent studies on the use of ASA for primary prevention of cardiovascular complications (CVC), cancer, and chronic obstructive pulmonary disease (COPD) in progressive chronic kidney disease (CKD). The article discusses the efficacy and safety of ASA in patients with diabetes, COPD, CKD, and subclinical atherosclerosis of brachiocephalic arteries. ASA is a promising tool for primary prevention of CVC and progression of COPD and its complications, as well as malignant diseases. The safety profile of ASA is also addressed. The optimal dosage form of ASA that is both effective and safe is an important factor that should be considered when prescribing ASA for long-term use. Enteric-coated ASA is now widely used due to its diminished negative effect on gastrointestinal mucosa and improved safety. KEYWORDS: primary prevention, acetylsalicylic acid, antiplatelet therapy, cardiovascular complications, chronic kidney disease, chronic obstructive pulmonary disease, diabetes FOR CITATION: Smirnova M.D. Pleiotropic effects of acetylsalicylic acid. Russian Medical Inquiry. 2024;8(1):31–36 (in Russ.). DOI: 10.32364/2587-6821-2024-8-1-5.

Identification of novel biomarkers related to neutrophilic inflammation in COPD.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic respiratory diseases and the fourth cause of mortality globally. Neutrophilic inflammation has a vital role in the occurrence and progression of COPD. This study aimed to identify the novel hub genes involved in neutrophilic inflammation in COPD through bioinformatic prediction and experimental validation. Both the single-cell RNA sequencing (scRNA-seq) dataset (GSE173896) and the RNA sequencing (RNA-seq) dataset (GSE57148) were downloaded from the Gene Expression Omnibus (GEO) database. The Seurat package was used for quality control, dimensions reduction, and cell identification of scRNA-seq. The irGSEA package was used for scoring individual cells. The Monocle2 package was used for the trajectory analysis of neutrophils. The CIBERSORT algorithm was used for analysis of immune cell infiltration in the lungs of COPD patients and controls in RNA-seq dataset, and weighted gene co-expression network analysis (WGCNA) correlated gene modules with neutrophil infiltration. The Mendelian randomization (MR) analysis explored the causal relationship between feature DEGs and COPD. The protein-protein interaction (PPI) network of novel hub genes was constructed, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate novel hub genes in clinical specimens. In scRNA-seq, the gene sets upregulated in COPD samples were related to the neutrophilic inflammatory response and TNF-α activation of the NF-κB signaling pathway. In RNA-seq, immune infiltration analysis showed neutrophils were upregulated in COPD lung tissue. We combined data from differential and modular genes and identified 51 differential genes associated with neutrophilic inflammation. Using MR analysis, 6 genes were explored to be causally associated with COPD. Meanwhile, 11 hub genes were identified by PPI network analysis, and all of them were upregulated. qRT-PCR experiments validated 9 out of 11 genes in peripheral blood leukocytes of COPD patients. Furthermore, 5 genes negatively correlated with lung function in COPD patients. Finally, a network of transcription factors for NAMPT and PTGS2 was constructed. This study identified nine novel hub genes related to the neutrophilic inflammation in COPD, and two genes were risk factors of COPD, which may serve as potential biomarkers for the clinical severity of COPD.