Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) are two age-related diseases commonly found in the elderly population, and they are associated with severe health consequences. However, it is currently unclear how patients with either one of these diseases or both diseases simultaneously compare to patients without COPD and CVD in terms of the additive impact on overall mortality, CVD-related mortality, and respiratory system disease-related mortality.

The study included 42,317 participants from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. The main objective of the study was to assess the outcomes of all-cause mortality, CVD mortality, and respiratory system disease mortality. We utilized the National Death Index(NDI) Public Access File, up until December 31, 2019, to determine the participants' mortality status and causes of death, with a mean follow-up period of 9.25 years. To ensure the reliability of the results, we employed Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for mortality rates, along with conducting sensitivity analyses.

Among the 42,317 participants, 36,251 individuals (85.7%) had neither COPD nor CVD (COPD-/CVD-). Additionally, 4,252 people (10.0%) had only CVD (COPD-/CVD+), 1,237 people (2.9%) had only COPD (COPD+/CVD-), and 577 people (1.4%) had both COPD and CVD (COPD+/CVD+). Compared to the COPD-/CVD- group, the all-cause mortality rates increased by 1.58-fold (95% CI: 1.46, 1.70), 1.56-fold (95% CI: 1.38, 1.76), and 2.02-fold (95% CI: 1.72, 2.37) in the COPD-/CVD + group, COPD+/CVD- group, and COPD+/CVD + group, respectively, with the COPD+/CVD + group having the highest all-cause mortality risk. Compared to the COPD-/CVD- group, the other three groups showed increased CVD mortality rates, with a HR of 2.35 for the COPD-/CVD + group and COPD+/CVD + group, respectively. Compared to the COPD-/CVD- group, the other three groups had increased respiratory system disease mortality rates, with a HR of 5.00 (95% CI: 3.70, 6.75) for the COPD+/CVD- group and 6.62 (95% CI: 4.56, 9.61) for the COPD+/CVD + group (All trend p-values < 0.0001).

Patients with COPD or CVD, or those who have both conditions, are at an increased risk of all-cause mortality, CVD-related mortality, and respiratory system disease-related mortality. Individuals with either of these diseases require more stringent management to prevent the progression of the other disease and reduce mortality rates.

Chemoradiotherapy (CRT) followed by adjuvant durvalumab is the standard of care for fit patients with unresectable stage III non-small cell lung cancer (NSCLC). However, 20-25 % of the patients do not survive longer than 1 year after treatment initiation, i.e. receive futile treatment. We aimed to develop a prognostic model that can identify patients at high risk of early mortality during and after CRT.

Patients with stage III NSCLC treated with CRT were included in the development- (N = 328; MAASTRO Biobank, 2004-2020, NCT01084785) and validation cohorts (N = 39; NCT02921854, NCT04432142). Both clinical parameters (age, sex, body mass index, performance status (PS), tumor stage (UICC 8), and sequence of chemotherapy administration) and peripheral immune-related biomarkers were included in the model development. Futile treatment was defined as death within one year after the first fraction of RT.

In the multivariable logistic regression analysis, PS ≥ 2 (OR = 2.89, 95 % CI 1.25-6.66, p = 0.013), stage IIIC (OR = 3.07, 95 % CI 3.07-6.9, p = 0.007), sequential chemotherapy (OR = 2.07, 95 % CI 1.19-3.62, p = 0.010), IL-6 (OR = 2.17, 95 % CI 1.27-3.70, p = 0.005), IP-10 (OR = 1.58, 95 % CI 0.92-2.73, p = 0.099), and soluble programmed death-ligand 1 (sPD-L1) (OR = 3.24, 95 % CI 1.90-5.54, p < 0.001) were identified as independent risk factors of early mortality. A nomogram was developed to calculate the risk of receiving futile treatment for each patient. The AUC of the development and validation cohort was 0.774 (95 % CI 0.716-0.832) and 0.734 (95 % CI 0.568-0.902), respectively. Patients classified as intermediate or high risk to receive futile treatment presented 23.7 % of the total cohort.

A prognostic model was developed that can identify patients who are at high risk of early mortality during and after CRT. These patients may be included in clinical trials aiming to improve their outcome.

Chronic obstructive pulmonary disease (COPD), a chronic respiratory condition with airflow limitation, is the fourth leading global cause of death. Biomarkers are key for classifying COPD, detecting exacerbations, guiding treatment, and prognosis. This article uses bibliometrics and visualization to analyze COPD biomarker research trends, providing insights for future studies.

This study adopts a range of literature analysis tools, including HistCite, VOSviewer, and CiteSpace, to systematically analyze literature on COPD biomarkers within the Web of Science Core Collection database from 2005 to 2024.

A total of 1835 papers or reviews related to COPD biomarkers are included in this study. Since 2003, the number of publications in this field has been on an upward trajectory. The United States being most influential in this field (n = 415, TLCS = 2319). Prominent institutions such as the University of British Columbia consistently deliver high-quality research results. Tal-Singer R, Sin DD, and Vestbo J have made significant contributions to COPD biomarker research. The journal American Journal of Respiratory and Critical Care Medicine is the most authoritative choice for researchers in the field.This research has long focused on biomarkers associated with the inflammatory response (C-reactive protein, eosinophils, etc.), pulmonary function, induced sputum, and computed tomography. Looking ahead, biomarkers such as microRNA, exosomes, DNA methylation, and microbiomics are likely to become popular topics, particularly regarding their roles in the prognosis and mechanisms of COPD.

Bibliometric analysis suggests that future research on COPD biomarkers will focus on advanced fields, such as microRNA, exosomes, DNA methylation, and microbiomics.

Evaluating the role of IL-6 and CD4+/CD8+ in predicting the prognosis of elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).

This study retrospectively enrolled 413 elderly patients who were hospitalized for AECOPD between January 2019 and December 2021. Patients were divided into event and non-event groups based on whether they were readmitted or died due to AECOPD during 18 months of follow-up. The associations between IL-6 and CD4+/CD8+ with adverse events were assessed using Cox proportional hazards regression models, Kaplan-Meier survival analysis, and restricted cubic spline (RCS) models. Additionally, subgroup analyses were conducted to evaluate the stability of these associations, and ROC curves were used to assess the predictive ability of IL-6 combined with CD4+/CD8+ for adverse events.

A total of 413 patients were included in the study, with 218 experiencing adverse events. Patients with high levels of IL-6 and low levels of CD4+/CD8+ had a higher risk of adverse events. There was a non-linear relationship between IL-6 and CD4+/CD8+ with adverse events (p<0.05). Subgroup analyses further confirmed the robustness of this association. ROC curve analysis indicated that combining IL-6 with CD4+/CD8+ significantly improved the predictive value for adverse events.

There is a non-linear relationship between IL-6 and CD4+/CD8+ and adverse events in elderly patients with AECOPD. Combining IL-6 with CD4+/CD8+ ratios significantly enhances the predictive value for adverse events.

Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV1, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18-month measures of disease progression associated with 18-54-month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort.

Analysing data of 1364 patients from the German observational COSYCONET-cohort, disease progression and improvement patterns were assessed for their impact on mortality via Cox hazard regression models. Association of biomarkers and COPD Assessment test items with phenotypes of disease progression or improvement were evaluated using logistic regression and random forest models.

Increased risk of 18-54-month mortality was linked to decrease in KCO % predicted (7.5% increments) and FEV1 (20 mL increments), increase in RV/TLC (2% increments) and SGRQ (≥6 points), and an exacerbation grade of 2 at 18 months. Decrease in KCO % predicted ≥7.5% and an increase of RV/TLC ≥2% were the most frequent measures of 18-month disease progression occurring in ~52% and ~46% of patients, respectively. IL-6 and CRP thresholds exhibited significant associations with medium- and long-term disease measures.

In a multicentric cohort of COPD, new markers of current disease activity predicted mid-term mortality and could not be anticipated by baseline biomarkers.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease, and inflammation plays a key role in the pathogenesis of COPD. The aim of this study is to investigate the association between systemic immune inflammation index (SII), systemic inflammatory response index (SIRI),pan-immune inflammation value (PIV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD), and to evaluate the effect of composite inflammatory markers on the prognosis of COPD patients. We obtained data on COPD patients from the Medical Information Mart for Intensive Care (MIMIC) -IV database and divided patients into four groups based on quartiles of baseline levels of inflammatory markers, The primary outcomes were in-hospital and ICU mortality. We comprehensively explored the association between composite inflammatory markers and mortality in patients with COPD using restricted cubic splints (RCS), COX proportional hazards regression models, Kaplan-Meier curves, receiver operating characteristic (ROC), and subgroup analyses. A total of 1234 COPD patients were included in this study. RCS results showed that SII, SIRI, PLR, PIV and NLR were positively and non-linearly correlated with the increased risk of in-hospital mortality in COPD patients. Multivariate COX regression analysis showed that compound inflammatory markers were independent risk factors for in-hospital mortality in COPD patients. The KM curve results showed that COPD patients with higher SII, SIRI, PLR and PIV had a significantly lower survival probability. 5 kinds of compound between inflammatory markers and mortality in patients with COPD is related to nonlinear correlation, can increase the risk of mortality in patients with COPD is a risk factor for the prognosis of patients with COPD, and may serve as potential biomarkers for clinical COPD risk stratification and treatment management in critical patients.

Few studies have investigated the effects of both dietary inflammatory index (DII) and composite dietary antioxidant index (CDAI) on mortality in patients with Chronic Obstructive Pulmonary Disease (COPD). Our research aimed to explore the associations between the two indicators with all-cause mortality in COPD patients.

We conducted a prospective cohort analysis based on data from the six cycles of the National Health and Nutrition Examination Survey (NHANES) dataset from 2007 to 2018. Multivariate Cox proportional hazard models were used to analyze the effects of DII and CDAI on all-cause mortality in COPD. We employed restricted cubic spline (RCS) analysis to examine the dose-response relationship between two indicators and all-cause mortality, used threshold effect analysis to determine the inflection point, and conducted subgroup analysis and interaction tests to verify the stability of the results.

A total of 1,457 COPD patients aged over 40 were enrolled in the study. The median follow-up time was 76.8 months. The multivariate Cox proportional hazards model showed that increased DII was associated with an increase in all-cause mortality (HR (95% CI): 1.11(1.04, 1.18), p = 0.002). In contrast, CDAI was negatively correlated with all-cause mortality (HR (95% CI): 0.95(0.91, 0.99), p = 0.01). The RCS analysis showed a nonlinear correlation between DII or CDAI and all-cause mortality. The maximum pro-inflammatory inflection point of DII was 2.32, while the antioxidant threshold of CDAI is -0.12. Subgroup analyses indicated that the relationship between exposure variables and all-cause mortality was stable in most populations.

Reducing the pro-inflammatory diet or increasing the antioxidant diet can reduce all-cause mortality in COPD patients.

The prevalence of chronic obstructive pulmonary disease (COPD) is increasing in Saudi Arabia, yet there is a lack of studies on the usefulness of routine hematological parameters in predicting mortality.

To determine hematological parameters that can predict mortality in patients with COPD exacerbation admitted to intensive care units.

This multicenter retrospective study included patients with COPD admitted at intensive care units of Ministry of National Guard Health Affairs hospitals in Saudi Arabia between 2016 to 2021. Hematological parameters were used to predict mortality. ROC curve analysis was used to establish the threshold value of variables linked to risk of mortality and optimal cut-off points, and its sensitivity and specificity were determined.

The study included 323 patients with COPD, of which 61% were females and the mean age was 72.7 (±12.7) years. The median length of hospital stay was 14 days (range: 6-26 days), and the overall mortality rate was 37.2%. After adjusting for gender and length of hospital stay in the multivariate analysis, independent predictors of mortality were age (OR: 1.029, 95% CI: 1.008-1.051; P = 0.007) and low mean corpuscular hemoglobin concentration (MCHC) (OR: 0.985, 95% CI: 0.970-1.000; P = 0.047). The ROC curve analysis revealed a cut-off value of 320.5 g/L for MCHC, with an AUC of 0.576.

This study found that in patients with COPD exacerbation admitted to ICU, older age likely increases the risk of mortality, whereas low MCHC likely decreases the risk of mortality. Further large-scale studies are required to validate these findings.

Eosinophils are central inflammatory cells in asthma; however, a portion of patients with chronic obstructive pulmonary disease (COPD) have blood or sputum eosinophilia, a condition termed eosinophilic COPD (eCOPD), which may contribute to the progression of the disease. We hypothesize that eosinophilic inflammation in eCOPD patients is related to Type 2 (T2)-high inflammation seen in asthma and that serum mediators might help us to identify T2-high inflammation in patients and choose an appropriate personalized treatment strategy. Thus, we aimed to investigate ten serum levels of T2-high inflammation mediators in eCOPD patients and compare them to severe non-allergic eosinophilic asthma (SNEA) patients. We included 8 subjects with eCOPD, 10 with SNEA, and 11 healthy subjects (HS) as a control group. The concentrations of biomarkers in serum samples were analyzed using an enzyme-linked immunosorbent assay (ELISA). In this study, we found that eCOPD patients were distinguished from SNEA patients by elevated serum levels of sIL-5Rα, MET, TRX1, ICTP, and IL-4, as well as decreased serum levels of eotaxin-1 and sFcεRI. Moreover, MET, ICTP, eotaxin-1, and sFcεRI demonstrated high sensitivity and specificity as potential biomarkers for eCOPD patients. Furthermore, serum levels of IL-5 and IL-25 in combination with sIL-5Rα, MET, and IL-4 demonstrated a high value in identifying T2-high inflammation in eCOPD patients. In conclusion, this study highlights that while T2-high inflammation drives eosinophilic inflammation in both eCOPD and SNEA through similar mechanisms, the distinct expression of its mediators reflects an imbalance between T1 and T2 inflammation pathways in eCOPD patients. A combined analysis of serum mediators may aid in identifying T2-high inflammation in eCOPD patients and in selecting an appropriate personalized treatment strategy.

Septic lung injury (SLI) is a severe condition with high mortality, and ferroptosis, a form of programmed cell death, is implicated in its pathogenesis. However, the explicit mechanisms underlying this condition remain unclear. This study aimed to elucidate and validate key ferroptosis-related genes involved in the pathogenesis of SLI through bioinformatics analysis and experimental validation.

Microarray data related to SLI from the GSE130936 dataset were downloaded from the Gene Expression Omnibus (GEO) database. These data were then intersected with the FerrDb database to obtain ferroptosis-related differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks and functional enrichment analysis were employed to identify key ferroptosis-related DEGs. The Connectivity Map (c-MAP) tool was used to search for potential compounds or drugs that may inhibit ferroptosis-related DEGs. The transcriptional levels of the key genes and potential therapeutic compounds were verified in an LPS-induced mouse model of lung injury. The expression of these key genes was further verified using the GSE60088 and GSE137342 datasets.

38 ferroptosis-related DEGs were identified between the septic and control mice. PPI network analysis revealed four modules, the most significant of which included eight ferroptosis-related DEGs. Functional enrichment analysis showed that these genes were enriched in the HIF-1 signaling pathway, including IL-6 (Interleukin-6), TIMP1 (Tissue Inhibitor of Metalloproteinase 1), HIF-1α (Hypoxia-Inducible Factor-1α), and HMOX1 (Heme Oxygenase-1). Phloretin, a natural compound, was identified as a potential inhibitor of these genes. Treatment with phloretin significantly reduced the expression of these genes (p < 0.05), mitigated lung injury, improved inflammatory profiles by approximately 50%, and ferroptosis profiles by nearly 30% in the SLI models.

This study elucidates the significant role of ferroptosis in SLI and identifies phloretin as a potential therapeutic agent. However, further research, particularly involving human clinical trials, is necessary to validate these findings for clinical use.

Bovine respiratory disease (BRD) is a leading cause of mortality and compromised welfare in bovines. It is a polymicrobial syndrome resulting from a complex interplay of viral and bacterial pathogens with environmental factors. Despite the availability of vaccines, incidence and severity in young calves remains unabated. A more precise analysis of host innate immune responses during infection will identify improved diagnostic and prognostic biomarkers for early intervention and targeted treatments to prevent severe disease and loss of production efficiency. Here, we investigate hematological and innate immune responses using standardized ex-vivo whole blood assays in calves diagnosed with BRD. A total of 65 calves were recruited for this study, all between 2-8 weeks of age with 28 diagnosed with BRD by a thoracic ultrasonography score (TUS) and 19 by Wisconsin health score (WHS) and all data compared to 22 healthy controls from the same 9 study farms. Haematology revealed circulating immune cell populations were similar in both TUS positive and WHS positive calves compared to healthy controls. Gene expression analysis of 48 innate immune signalling genes in whole blood stimulated with TLR ligands was completed in a subset of calves. TLR1/2 stimulation with Pam3CSK4 showed a decreased pattern of expression in IL-1 and inflammasome related genes in addition to chemokine genes in calves with BRD. In response to TLR ligands LPS, Pam3CSK4 and R848, protein analysis of supernatant collected from all calves with BRD revealed significantly increased IL-6, but not IL-1β or IL-8, compared to healthy controls. This hyper-induction of IL-6 was observed most significantly in response to TLR1/2 stimulation in TUS positive calves. ROC analysis identified this induced IL-6 response to TLR1/2 stimulation as a potential diagnostic for BRD with a 74% true positive and 5% false positive detection rate for an IL-6 concentration >1780pg/mL. Overall, these results show altered immune responses specifically upon TLR1/2 activation is associated with BRD pathology which may contribute to disease progression. We have also identified induced IL-6 as a potentially informative biomarker for improved early intervention strategies for BRD.

With a growing global population affected by Chronic Obstructive Pulmonary Disease (COPD), the traditional Chinese herbal formula Houpo Mahuang Decoction (HPMHD) has been used for centuries to address respiratory ailments. While studies have demonstrated the therapeutic benefits of HPMHD in COPD, the effective active ingredients, potential targets, and molecular mechanisms underlying its effectiveness remained unclear.

The mechanisms of action of certain HPMHD components, targets, and pathways for the treatment of COPD were predicted using a network pharmacology method. We induced a COPD mouse model using porcine pancreatic elastase and evaluated the pathological changes and healing processes through HE and Masson staining. Immunofluorescence was used to assess the levels of IL-6 and TNF-ɑ. RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) in the lungs of normal, control, and treated mice, revealing the biological pathways enriched by HPMHD in COPD treatment. Finally, the expression of DEGs was verified using Western blotting and RT-qPCR.

HPMHD effectively alleviated pathological symptoms and improved COPD in mice by modulating the IL-17 signaling pathway. Treatment with HPMHD improved lung morphology and structure, reduced inflammatory cell infiltration, and inhibited IL-6 and TNF-ɑ levels. Network pharmacology and transcriptomics further revealed the mechanism, indicating that the IL-17 signaling pathway might been instrumental in the inhibitory effect of HPMHD on mouse model of COPD. Subsequent experiments, including protein blotting and RT-qPCR analysis, confirmed the activation of the IL-17 signaling pathway by HPMHD in the COPD mouse model, further supporting the initial findings.

HPMHD was shown to alleviate COPD and reduce lung inflammation in mice, potentially through the activation of the IL-17 signaling pathway. This study provides a novel direction for the development of COPD drugs.

Chronic Obstructive Pulmonary Disease (COPD) significantly impacts patients' quality of life and burdens healthcare systems. Magnesium is crucial for lung function and reducing respiratory disease risk. This study investigates the association between Magnesium Depletion Score (MDS) and COPD and explores whether inflammatory markers mediate this relationship. A cross-sectional analysis was conducted using data from 30,490 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. MDS was calculated based on diuretic use, proton pump inhibitors, renal function, and alcohol consumption. Univariable and multivariable logistic regression analyses were performed to assess the association between MDS and COPD, adjusting for potential confounders. Mediation analysis was used to examine the roles of neutrophils, serum albumin, and the Systemic Immune-Inflammation Index (SII). In the univariable logistic model, higher MDS was significantly associated with increased COPD risk. Specifically, compared to MDS = 0, the odds ratios (OR) for COPD were 2.50, 4.12, 6.13, 8.53, and 7.81 for MDS = 1, 2, 3, 4, and 5, respectively (all P < 0.001). In the multivariable model, the ORs were 1.79, 2.25, 2.71, and 3.44 for MDS = 1, 2, 3, and 4, respectively (all P < 0.001). Higher neutrophil levels and SII were positively associated with increased COPD risk, while higher serum albumin levels were inversely associated. Mediation analysis indicated that neutrophils, serum albumin, and SII significantly mediated the MDS-COPD relationship. Higher MDS is significantly associated with increased COPD risk, mediated by systemic inflammation markers. Improving magnesium levels could potentially reduce COPD risk, warranting further research on magnesium supplementation in COPD prevention and management.

The status of cognitive frailty in elderly patients with chronic obstructive pulmonary disease (COPD) and its influencing factors in China remains unclear. This study aimed to investigate the prevalence of and factors associated with cognitive frailty in elderly patients with COPD. This cross-sectional study enrolled elderly patients with stable COPD between May and November 2022 from the Respiratory Department of the First Affiliated Hospital of Zhengzhou University and the Fifth Affiliated Hospital of Zhengzhou University. Convenience sampling method was adopted. Frailty Phenotype scale, Montreal Cognitive Assessment scale, Geriatric Depression Scale, and Clinical Dementia Rating scale were used to assess the prevalence of cognitive frailty in elderly patients with COPD. Multivariable logistic regression analysis was used to explore the associated factors. A total of 406 valid questionnaires were collected, and 173 patients (35.6%) had cognitive frailty. Binary logistic regression analysis showed that sex (odds ratio [OR] = 0.009; 95%CI: 0.001-0.770; P = .038), depression (OR = 17.780; 95%CI: 1.092-289.478; P = .043), modified Medical Research Council grade 1-3 (OR = 28.394-4095.683; 95%CI: 1.086-4,592,652.211; P < .05), global initiative for chronic obstructive lung disease grade 2 and 3 (OR = 32.508-282.072; 95%CI: 1.101-12,516.874; P < .05), and frequencies of acute exacerbations of COPD and hospitalizations within 1 year of 2 times (OR = 21.907; 95%CI: 4.587-104.622; P < .001) were independently associated with cognitive frailty. The prevalence of cognitive frailty in elderly patients with stable COPD was high. Female, depression, modified Medical Research Council grade, global initiative for chronic obstructive lung disease grade, and frequencies of acute exacerbations of COPD and hospitalizations within 1 year might be the factors independently associated with cognitive frailty, educational level might be a protective associated factor for cognitive frailty.

Monocytes play a crucial role in innate immune responses for host defense, however, their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6Rhi monocytes in the lungs of COPD patients.

Using flow cytometry, we assessed the abundance of pulmonary CD14+IL-6Rhi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14+ monocytes isolated from the peripheral blood of patients with COPD was also examined. CD45+CD206-CD14+IL-6Rhi and CD45+CD206-CD14+IL-6R-/lo cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate the IL-6 responsiveness of IL-6R+ monocytes.

The number of pulmonary CD14+IL-6Rhi monocytes was elevated in COPD patients compared to CNS, whereas CD14+ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14+IL-6Rhi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced changes in the expression of genes linked to chemotaxis and organism development.

In patients with COPD, CD14+IL-6Rhi monocytes are increased in lung tissues compared to those in CNS. They exhibit a transcriptome profile different from that of CD14+IL-6R-/lo monocytes.

Chronic obstructive pulmonary disease(COPD) is a gradually worsening and fatal heterogeneous lung disease characterized by airflow limitation and increasingly decline in lung function. Currently, it is one of the leading causes of death worldwide. The consistent feature of COPD is airway inflammation. Several inflammatory factors are known to be involved in COPD pathogenesis; however, anti-inflammatory therapy is not the first-line treatment for COPD. Although bronchodilators, corticosteroids and roflumilast could improve airflow and control symptoms, they could not reverse the disease. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway plays an important novel role in the immune system and has been confirmed to be a key mediator of inflammation during infection, cellular stress, and tissue damage. Recent studies have emphasized that abnormal activation of cGAS-STING contributes to COPD, providing a direction for new treatments that we urgently need to develop. Here, we focused on the cGAS-STING pathway, providing insight into its molecular mechanism and summarizing the current knowledge on the role of the cGAS-STING pathway in COPD. Moreover, we explored antagonists of cGAS and STING to identify potential therapeutic strategies for COPD that target the cGAS-STING pathway.

To explore the correlation between serum bilirubin, blood uric acid, and C-reactive protein (CRP) and the severity of chronic obstructive pulmonary disease (COPD).

Patients with COPD who were admitted to our hospital between March 2020 and March 2023 were retrospectively studied. Based on whether their condition progressed to the acute exacerbation stage, they were divided into an exacerbation group (100 cases) and a stability group (100 cases). The clinical data from both groups were analysed to assess the correlations between serum bilirubin, blood uric acid, CRP, and the severity of COPD.

Univariate analysis indicated significant differences in the neutrophil-to-lymphocyte ratio (t = 5.678, P < 0.05), α-hydroxybutyrate dehydrogenase (t = 5.862, P < 0.05), total bilirubin (t = 4.341, P < 0.05), direct bilirubin (t = 5.342, P < 0.05), indirect bilirubin (t = 5.452, P < 0.05), blood uric acid (t = 4.698, P < 0.05), and CRP (t = 4.892, P < 0.05) between the two groups. Multivariate analysis revealed that total bilirubin, blood uric acid, and CRP were positively correlated with exacerbations of COPD (regression coefficients were 0.413, 0.354, and 0.356, respectively; P < 0.05). The evaluation of predictive value showed that the combined predictive value of these three indicators was the highest, with an AUC of 0.823 (95% CI: 0.754-0.911).

Serum bilirubin, blood uric acid, and CRP levels are elevated in patients with acute exacerbations of COPD (AECOPD), showing good consistency in predicting the occurrence of AECOPD. The combined diagnostic value of these three indicators is greater than that of any single indicator, providing a reference for the early clinical prediction of AECOPD.

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005-2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (β = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

Chronic obstructive pulmonary disease (COPD), a global healthcare and socioeconomic burden, is a multifaceted respiratory disorder that results in substantial decline in health status and life quality. Acute exacerbations of the disease contribute significantly to increased morbidity and mortality. Consequently, the identification of reliable and effective biomarkers for rapid diagnosis, prediction, and prognosis of exacerbations is imperative. In addition, biomarkers play a crucial role in monitoring responses to therapeutic interventions and exploring innovative treatment strategies. Although established markers such as CRP, fibrinogen and neutrophil count are routinely used, a universal marker is lacking. Fortunately, an increasing number of studies based on next generation analytics have explored potential biomarkers in COPD. Here we review those advances and the need for standardized validation studies in the appropriate clinical setting.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways characterized by impaired lung function induced by cigarette smoke (CS). Reduced DACH1 (dachshund homolog 1) expression has a detrimental role in numerous disorders, but its role in COPD remains understudied. This study aimed to elucidate the role and underlying mechanism of DACH1 in airway inflammation in COPD by measuring DACH1 expression in lung tissues of patients with COPD. Airway epithelium-specific DACH1-knockdown mice and adenoassociated virus-transfected DACH1-overexpressing mice were used to investigate the role of DACH1 and the potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by CS extract stimulation in vitro. Compared with nonsmokers and smokers without COPD, patients with COPD had reduced DACH1 expression, especially in the airway epithelium. Airway epithelium-specific DACH1 knockdown aggravated airway inflammation and lung function decline caused by CS in mice, whereas DACH1 overexpression protected mice from airway inflammation and lung function decline. DACH1 knockdown and overexpression promoted and inhibited IL-6 and IL-8 secretion, respectively, in 16HBE human bronchial epidermal cells after CS extract stimulation. NRF2 (nuclear factor erythroid 2-related factor 2) was discovered to be a novel downstream target of DACH1, which binds directly to its promoter. By activating NRF2 signaling, DACH1 induction reduced inflammation. DACH1 levels are lower in smokers and nonsmoking patients with COPD than in nonsmokers. DACH1 has protective effects against inflammation induced by CS by activating the NRF2 signaling pathway. Targeting DACH1 is a potentially viable therapeutic approach for COPD treatment.

Damage-associated molecular patterns (DAMPs) are endogenous danger signals that alert and activate the immune system upon cellular damage or death. It has previously been shown that DAMP release is increased in patients with COPD, leading to higher levels in extracellular fluids such as serum. In the current study we investigated whether the serum levels of DAMPs were associated with survival rates in COPD patients.

A panel of seven DAMPs, consisting of HMGB1, fibrinogen, α-defensin, heat shock protein 70, S100A8, galectin-9 and double-stranded DNA (dsDNA), was measured in serum of 949 severe COPD patients. Maximally selected rank statistics was used to define cut-off values and a Cox proportional hazards model was used to evaluate the effect of high or low DAMP levels on 4-year survival. For DAMPs that were found to affect survival significantly, baseline characteristics were compared between the two DAMP groups.

Out of the seven DAMPs, only dsDNA was significantly associated with 4-year survival. Patients with elevated serum level of dsDNA had higher 4-year mortality rates, lower FEV1 % predicted values and higher emphysema scores.

In conclusion, in a clinical cohort of 949 patients with moderate-to-severe COPD, elevated serum levels of dsDNA were associated with a higher risk of death. This study further illustrates the potential role of circulating DAMPs, such as dsDNA, in the progression of COPD. Together, the results of this study suggest that levels of circulating dsDNA might serve as an additional prognostic biomarker for survival in COPD patients.

Airflow limitation is a hallmark of chronic obstructive pulmonary disease, which can develop through different lung function trajectories across the life span. There is a need for longitudinal studies aimed at identifying circulating biomarkers of airflow limitation across different stages of life.

This study sought to identify a signature of serum proteins associated with airflow limitation and evaluate their relation to lung function longitudinally in adults and children.

This study used data from 3 adult cohorts (TESAOD [Tucson Epidemiological Study of Airway Obstructive Disease], SAPALDIA [Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults], LSC [Lovelace Smoker Cohort]) and 1 birth cohort (TCRS [Tucson Children's Respiratory Study]) (N = 1940). In TESAOD, among 46 circulating proteins, we identified those associated with FEV1/forced vital capacity (FVC) percent (%) predicted levels and generated a score based on the sum of their z-scores. Cross-sectional analyses were used to test the score for association with concomitant lung function. Longitudinal analyses were used to test the score for association with subsequent lung function growth in childhood and decline in adult life.

After false discovery rate adjustment, serum levels of 5 proteins (HP, carcinoembryonic antigen, ICAM1, CRP, TIMP1) were associated with percent predicted levels of FEV1/FVC and FEV1 in TESAOD. In cross-sectional multivariate analyses the 5-biomarker score was associated with FEV1 % predicted in all adult cohorts (meta-analyzed FEV1 decrease for 1-SD score increase: -2.9%; 95% CI: -3.9%, -1.9%; P = 2.4 × 10-16). In multivariate longitudinal analyses, the biomarker score at 6 years of age was inversely associated with FEV1 and FEV1/FVC levels attained by young adult life (P = .02 and .005, respectively). In adults, persistently high levels of the biomarker score were associated with subsequent accelerated decline of FEV1 and FEV1/FVC (P = .01 and .001).

A signature of 5 circulating biomarkers of airflow limitation was associated with both impaired lung function growth in childhood and accelerated lung function decline in adult life, indicating that these proteins may be involved in multiple lung function trajectories leading to chronic obstructive pulmonary disease.

Investigate the efficacy of blood microRNAs (miRNAs) as diagnostic biomarkers for Chronic Obstructive Pulmonary Disease (COPD).

We conducted a comprehensive search in English and Chinese databases, selecting studies based on predetermined criteria. Diagnostic parameters like summarized sensitivity (SSEN), summarized specificity (SSPE), summarized positive likelihood ratio (SPLR), summarized negative likelihood ratio (SNLR), and diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curves were analyzed using a bivariate model. Each parameter was accompanied by a 95% confidence interval (CI).

Eighteen high-quality studies were included. For diagnosing COPD with blood miRNAs, the SSEN was 0.83 (95% CI 0.76-0.89), SSPE 0.76 (95% CI 0.70-0.82), SPLR 3.50 (95% CI 2.66-4.60), SNLR 0.22 (95% CI 0.15-0.33), DOR 15.72 (95% CI 8.58-28.77), and AUC 0.86 (95% CI 0.82-0.88). In acute exacerbations, SSEN was 0.85 (95% CI 0.76-0.91), SSPE 0.80 (95% CI 0.73-0.86), SPLR 4.26 (95% CI 3.05-5.95), SNLR 0.19 (95% CI 0.12-0.30), DOR 22.29 (95% CI 11.47-43.33), and AUC 0.89 (95% CI 0.86-0.91).

Blood miRNAs demonstrate significant accuracy in diagnosing COPD, both in general and during acute exacerbations, suggesting their potential as reliable biomarkers.

Chronic obstructive pulmonary disease (COPD) accounts for 545 million people living with chronic respiratory disorders and is the third leading cause of morbidity and mortality around the world. COPD is a progressive disease, characterized by episodes of acute worsening of symptoms such as cough, dyspnea, and sputum production.

Airway inflammation is a prominent feature of COPD. Chronic airway inflammation results in airway structural remodeling and emphysema. Persistent airway inflammation is a treatable trait of COPD and plays a significant role in disease development and progression. In this review, the authors summarize the current and emerging biomarkers that reveal the heterogeneity of airway inflammation subtypes, clinical outcomes, and therapeutic response in COPD.

Airway inflammation can be broadly categorized as eosinophilic (type 2 inflammation) and non-eosinophilic (non-type 2 inflammation) in COPD. Currently, blood eosinophil counts are incorporated in clinical practice guidelines to identify COPD patients who are at a higher risk of exacerbations and lung function decline, and who are likely to respond to inhaled corticosteroids. As new therapeutics are being developed for the chronic management of COPD, it is essential to identify biomarkers that will predict treatment response.

Compared to normal PiMM, individuals with severe α1-antitrypsin (AAT) PiZZ (Glu342Lys) genotype deficiency are at higher risk of developing early-onset chronic obstructive pulmonary disease (COPD)/emphysema associated with Z-AAT polymers and neutrophilic inflammation. We aimed to investigate putative differences in plasma levels of acute phase proteins (APP) between PiMM and PiZZ subjects and to determine plasma Z-AAT polymer levels in PiZZ subjects.

Nephelometric analysis of seven plasma APPs was performed in 67 PiMM and 44 PiZZ subjects, of whom 43 and 42, respectively, had stable COPD. Of the PiZZ-COPD patients, 21 received and 23 did not receive intravenous therapy with human AAT preparations (IV-AAT). Plasma levels of Z-AAT polymers were determined by Western blotting using specific mouse monoclonal antibodies (2C1 and LG96).

In addition to lower plasma AAT, PiZZ patients had higher α2-macroglobulin (A2MG) levels than PiMM patients. In contrast, PiZZ who received IV-AAT had higher AAT values but lower A2MG values than PiZZ without IV-AAT. Regardless of the AAT genotype, AAT levels were inversely correlated with A2MG, and the AAT/A2MG ratio was correlated with lung diffusion capacity (DCLO%). All PiZZ patients had circulating Z-AAT polymer levels that correlated directly with A2MG. In PiZZ without IV-AAT therapy polymer levels correlated inversely with the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC).

Combined measurement of plasma AAT and A2MG levels may be of clinical value in assessing the progression of COPD and requires further attention.

Chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity, presents significant challenges, particularly with exacerbations, which drastically impact patients' health and healthcare costs. The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend comprehensive assessments beyond spirometry, with the COPD assessment test (CAT) emerging as a pivotal tool. Despite its utility, the relationship between CAT scores and specific biomarkers during exacerbations remains unclear. Hence, this study aims to assess the correlation between the CAT score and specific circulating biomarkers. A cross-sectional study from August 2023 to January 2024 included 59 COPD patients with exacerbations who underwent pulmonary function tests and completed the CAT score assessment. The CAT score cut-off point was set at 20, where a CAT score <20 indicated a low impact on health status and a CAT score ≥20 indicated a high impact on health status. On the same day, measurements of neutrophils, leukocytes, eosinophils, C-reactive protein, and procalcitonin were conducted. Patients with CAT scores ≥20 had significantly higher levels of neutrophils (p=0.001), leukocytes (p=0.006), procalcitonin (p=0.010), and forced expiratory volume in the first second/forced vital capacity (p=0.002), but lower eosinophil levels (p=0.025). A positive correlation existed between total CAT score and neutrophils (p=0.001), leukocytes (p=0.000), and procalcitonin (p=0.010), while eosinophil levels showed a negative correlation (p=0.025). The spirometry parameters showed no correlation with the total CAT score. This study highlights the link between CAT and key inflammatory biomarkers, supporting the use of blood biomarkers to identify COPD patients at risk of exacerbations.

Chronic Obstructive Pulmonary Disease (COPD) is a pathological condition of the respiratory system characterized by chronic airflow obstruction, associated with changes in the lung parenchyma (pulmonary emphysema), bronchi (chronic bronchitis) and bronchioles (small airways disease). In the last years, the importance of phenotyping and endotyping COPD patients has strongly emerged. Metabolomics refers to the study of metabolites (both intermediate or final products) and their biological processes in biomatrices. The application of metabolomics to respiratory diseases and, particularly, to COPD started more than one decade ago and since then the number of scientific publications on the topic has constantly grown. In respiratory diseases, metabolomic studies have focused on the detection of metabolites derived from biomatrices such as exhaled breath condensate, bronchoalveolar lavage, and also plasma, serum and urine. Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy are powerful tools in the precise identification of potentially prognostic and treatment response biomarkers. The aim of this article was to comprehensively review the relevant literature regarding the applications of metabolomics in COPD, clarifying the potential clinical utility of the metabolomic profile from several biologic matrices in detecting biomarkers of disease and prognosis for COPD. Meanwhile, a complete description of the technological instruments and techniques currently adopted in the metabolomics research will be described.

Good 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.

We 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.

Of 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).

Plasma cf-mtDNA and cf-nDNA, when integrated into quantitative clinical measurements, may aid in improving COPD severity and progression assessment.

Real-life effectiveness data on once-daily single-inhaler triple therapy (odSITT) with the inhaled corticosteroid fluticasone furoate (FF), the long-acting muscarinic antagonist umeclidinium (UMEC), and the long-acting β2-agonist vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) are important to complement evidence from well-controlled randomized clinical trials. Effectiveness of odSITT was quantified by assessing health status and symptoms in usual care.

ELLITHE was a single-country (Germany), multicenter, open-label, non-interventional effectiveness study between 2020 and 2022, evaluating the effect of treatment initiation with FF/UMEC/VI 100/62.5/25 µg once-daily via the ELLIPTA inhaler on improvements in clinical outcomes versus baseline in COPD patients. The primary endpoint was the change in the total COPD Assessment Test (CAT) score between baseline and month 12. Key secondary endpoints included change in CAT score over time, occurrence of exacerbations until month 12, changes in forced expiratory volume in one second (FEV1), inhaler adherence, and safety.

Nine hundred and six patients were included (age 66.6 years, 55.6% male, mean FEV1 52.6% of predicted, mean CAT 21.5 units, 1.4 exacerbations/year pre-study). About 63.9% of patients were escalated from dual therapies, and 18% were switched from multiple-inhaler triple therapies. Reductions in CAT score at month 12 were statistically significant and above the threshold of clinical importance (-2.6 units; p < 0.0001). CAT score also improved at interim visits. CAT improvements were more pronounced in patients with high baseline scores and better inhaler adherence. Exacerbations during follow-up were rare (0.2 events/year) compared to pre-study (1.4 events/year). FEV1 was improved by 93 mL (p < 0.0001). No new safety effects were observed.

In usual care, treatment with odSITT resulted in significant and clinically relevant improvements of CAT score and FEV1 in COPD patients, regardless of the occurrence of exacerbations. These findings challenge the current guideline recommendations for SITT only in patients experiencing exacerbations.

Research has shown a connection between inflammation and chronic obstructive pulmonary disease (COPD), however the relationship between inflammation mediators and COPD causation remains unknown. To investigate the causal relationship of mediators of inflammation and COPD, we conducted a two-sample Mendelian randomization (MR) study. In our study, we incorporated 41 regulators of inflammation from 8293 Finnish individuals from genome-wide association studies (GWASs) of COPD corresponding to GWAS summary data for 2115 cases and 454,233 healthy individuals in Europe. Our research validated that higher levels of interleukin 8 (IL-8) are related with a decrease occurrence of COPD (OR = 0.795, 95 % CI = 0.642-0.984, p = 0.035) but that elevated levels of interleukin 18(IL-18) and interleukin 2 (IL-2) may be connected to an amplified risk of COPD (OR = 1.247, 95 % CI = 1.011-1.538; p = 0.039; OR = 1.257, 95 % CI = 1.037-1.523, p = 0.020, respectively). According to our research, cytokines play a crucial role in the development of COPD, and further investigation is necessary to explore the potential of utilizing these cytokines as targets for treatment and prevention of COPD.

The global prevalence of chronic obstructive pulmonary disease (COPD) has increased over the last decade and has emerged as the third leading cause of death worldwide. It is characterized by emphysema with prolonged airflow limitation. COPD patients are more susceptible to COVID-19 and increase the disease severity about four times. The most used drugs to treat it show numerous side effects, including immune suppression and infection. This review discusses a narrative opinion and critical review of COPD. We present different aspects of the disease, from cellular and inflammatory responses to cigarette smoking in COPD and signaling pathways. In addition, we highlighted various risk factors for developing COPD apart from smoking, like occupational exposure, pollutants, genetic factors, gender, etc. After the recent elucidation of the underlying inflammatory signaling pathways in COPD, new molecular targeted drug candidates for COPD are signal-transmitting substances. We further summarize recent developments in biomarker discovery for COPD and its implications for disease diagnosis. In addition, we discuss novel drug targets for COPD that could be explored for drug development and subsequent clinical management of cardiovascular disease and COVID-19, commonly associated with COPD. Our extensive analysis of COPD cause, etiology, diagnosis, and therapeutic will provide a better understanding of the disease and the development of effective therapeutic options. In-depth knowledge of the underlying mechanism will offer deeper insights into identifying novel molecular targets for developing potent therapeutics and biomarkers of disease diagnosis.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is the exacerbation of a range of respiratory symptoms during the stable phase of chronic obstructive pulmonary disease (COPD). AECOPD is thus a dangerous stage and key event in the course of COPD, as its deterioration and frequency seriously affects the quality of life of patients and shortens their survival. Acute exacerbations occur and develop due to many factors such as infection, tobacco smoke inhalation, air pollution, comorbidities, airflow limitation, various biomarkers, history of previous deterioration, natural killer cell abnormalities, immunoglobulin G deficiency, genetics, abnormal muscle and nutritional status, negative psychology, and seasonal temperature changes. There is relatively limited research on the impact of the role of standardized management on the alleviation of AECOPD. However, with the establishment of relevant prevention and management systems and the promotion of artificial intelligence technology and Internet medical approaches, long-term effective and standardized management of COPD patients may help to achieve the quality of life and disease prognosis in COPD patients and reduce the risk of AE.

COPD is a heterogeneous disorder that shows diverse clinical presentations (phenotypes and "treatable traits") and biological mechanisms (endotypes). This heterogeneity implies that to carry out a more personalised clinical management, it is necessary to classify each patient accurately. With this objective, and in addition to clinical features, it would be very useful to have well-defined biological markers. The search for these markers may either be done through more conventional laboratory and hypothesis-driven techniques or relatively blind high-throughput methods, with the omics approaches being suitable for the latter. Metabolomics is the science that studies biological processes through their metabolites, using various techniques such as gas and liquid chromatography, mass spectrometry and nuclear magnetic resonance. The most relevant metabolomics studies carried out in COPD highlight the importance of metabolites involved in pathways directly related to proteins (peptides and amino acids), nucleic acids (nitrogenous bases and nucleosides), and lipids and their derivatives (especially fatty acids, phospholipids, ceramides and eicosanoids). These findings indicate the relevance of inflammatory-immune processes, oxidative stress, increased catabolism and alterations in the energy production. However, some specific findings have also been reported for different COPD phenotypes, demographic characteristics of the patients, disease progression profiles, exacerbations, systemic manifestations and even diverse treatments. Unfortunately, the studies carried out to date have some limitations and shortcomings and there is still a need to define clear metabolomic profiles with clinical utility for the management of COPD and its implicit heterogeneity.

Ivy leaf dry extract EA 575® is used to improve complaints of chronic inflammatory bronchial diseases and acute inflammation of the respiratory tract accompanied by coughing. Its mechanism of action has so far been explained by influencing β2-adrenergic signal transduction. In the present study, we investigated a possible influence on adenosine receptor A2B (A2BAR) signalling, as it has been described to play a significant and detrimental role in chronic inflammatory airway diseases. The influence of EA 575® on A2BAR signalling was assessed with measurements of dynamic mass redistribution. Subsequently, the effects on A2BAR-mediated second messenger cAMP levels, β-arrestin 2 recruitment, and cAMP response element (CRE) activation were examined using luciferase-based HEK293 reporter cell lines. Lastly, the impact on A2BAR-mediated IL-6 release in Calu-3 epithelial lung cells was investigated via the Lumit™ Immunoassay. Additionally, the adenosine receptor subtype mediating these effects was specified, and A2BAR was found to be responsible. The present study demonstrates an inhibitory influence of EA 575® on A2BAR-mediated general cellular response, cAMP levels, β-arrestin 2 recruitment, CRE activation, and IL-6 release. Since these EA 575®-mediated effects occur within a time frame of several hours of incubation, its mode of action can be described as indirect. The present data are the first to describe an inhibitory effect of EA 575® on A2BAR signalling. This may offer an explanation for the beneficial clinical effects of the extract in adjuvant asthma therapy.

The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in a single individual, also known as overlap syndrome (OVS), is associated with higher cardiovascular risk and mortality than either OSA or COPD alone. However, the underlying mechanisms remain unclear. We hypothesized that patients with OVS have elevated systemic inflammatory biomarkers relative to patients with either disease alone, which could explain greater cardiovascular risk observed in OVS.

We included 255 participants in the study, 55 with COPD alone, 100 with OSA alone, 50 with OVS, and 50 healthy controls. All participants underwent a home sleep study, spirometry, and a blood draw for high-sensitivity C-reactive protein and total blood count analysis. In a randomly selected subset of 186 participants, inflammatory protein profiling was performed using Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assays. Biomarker level differences across groups were identified using a mixed linear model.

Levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and granulocyte colony stimulating factor (G-CSF) were higher in participants with OVS and COPD compared with healthy controls and participants with OSA. Furthermore, participants with OVS had higher circulating levels of leukocytes and neutrophils than those with COPD, OSA, and controls.

COPD and OVS are associated with higher systemic inflammation relative to OSA and healthy controls. This work proposes the potential utilization of interleukin 6, granulocyte colony stimulating factor, and high-sensitivity C-reactive protein as screening biomarkers for COPD in patients with OSA. Inflammatory pathways may not fully explain the higher cardiovascular risk observed in OVS, indicating the need for further investigation.

Sanchez-Azofra A, Gu W, Masso-Silva JA, et al. Inflammation biomarkers in OSA, chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease/OSA overlap syndrome. J Clin Sleep Med. 2023;19(8):1447-1456.

Acute lung injury leads to the development of chronic conditions such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma as well as alveolar sarcoma. Various investigations are being performed worldwide to understand the pathophysiology of these diseases, develop novel bioactive compounds and inhibitors to target the ailment. Generally, in vivo models are used to understand the disease outcome and therapeutic suppressing effects for which the animals are chemically or physically induced to mimic the onset of definite disease conditions. Amongst the chemical inducing agents, Bleomycin (BLM) is the most successful inducer. It is reported to target various receptors and activate inflammatory pathways, cellular apoptosis, epithelial mesenchymal transition leading to the release of inflammatory cytokines, and proteases. Mice is one of the most widely used animal model for BLM induced pulmonary associated studies apart from rat, rabbit, sheep, pig, and monkey. Although, there is considerable variation amongst in vivo studies for BLM induction which suggests a detailed study on the same to understand the mechanism of action of BLM at molecular level. Hence, herein we have reviewed various chemical inducers, mechanism of action of BLM in inducing lung injury in vivo, its advantages and disadvantages. Further, we have also discussed the rationale behind various in vivo models and recent development in BLM induction for various animals.

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a p-value < 3.3 × 10^-5 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1) to be associated with the COPD risk and two with the LC risk (HLA-C, HLA-B), with statistical significance. We also identified two SNPs located in the IL2RA gene associated with LC (rs2386841; p = 1.86 × 10^-4) and COPD (rs11256442; p = 9.79 × 10^-3) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.