Prophylactic antibiotics for preventing ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis.

BACKGROUND: The role of prophylactic antibiotics in preventing ventilator-associated pneumonia (VAP) in patients undergoing invasive mechanical ventilation (IMV) remains unclear. This network meta-analysis compared the efficacy and safety of antibiotic prophylaxis in preventing VAP in an IMV population in intensive-care units (ICUs). METHODS: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases from inception to December 2021, to identify relevant studies assessing the impact of prophylactic antibiotics on the incidence of VAP, the mortality, and the duration of ICU stays and hospitalization to perform a meta-analysis. RESULTS: Thirteen studies (2144 patients) were included, 12 of which were selected for the primary analysis, which revealed that treatment with prophylactic antibiotics resulted in a lower VAP rate compared with control groups [risk ratio (RR) = 0.62]. Bayesian network meta-analysis indicated that aerosolized tobramycin and intravenous ampicillin-sulbactam presented the greatest likelihood being the most efficient regimen for reducing VAP. CONCLUSIONS: Antibiotic prophylaxis may reduce the incidence of VAP, but not the mortality, for adult patients undergoing IMV in ICUs. Tobramycin via nebulization and ampicillin-sulbactam via intravenous administration presented the greatest likelihood of being the most efficient regimen for preventing VAP. However, well-designed randomized studies are warranted before definite recommendations can be made.

Efficacy of positive airway pressure therapy and high flow nasal cannula oxygen in acute cardiogenic pulmonary oedema: A protocol for systematic review and network meta-analysis.

Introduction: Positive airway pressure (PAP) therapy is currently the first-line respiratory support technique for acute respiratory failure (ARF) due to acute cardiogenic pulmonary edema (ACPE), but the accompanied adverse events and patient's intolerance with treatment in some cases limited its use in clinical practice. Some recent trials indicated that high-flow nasal cannula oxygen (HFNO) is a promising alternative to PAP therapy. In order to choose the optimum treatment for patients with ACPE, this network meta-analysis will firstly compares the efficacy of HFNO, PAP, and conventional oxygen therapy (COT). Methods and analysis: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement and its extension for network meta-analysis will be followed in the conduct of this investigation. We will examine these databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. The ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform Search Portal will be used to search ongoing trials. Only randomized controlled trials meeting the eligibility criteria will be included. Through the Cochrane Collaboration's tool, the included studies' risk of bias will be assessed. The pairwise meta-analysis will be performed with RevMan 5.4.1 software. A Bayesian network meta-analysis will use random-effects models to derive odds ratios for the treatment effects of all interventions compared to each other using R software (version 3.6.1), and the rjags and gemtc packages. The Q statistic and I2 index will be used for investigating the heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence.

Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis.

Background: JAK (Janus kinases) inhibitors have been proposed as a promising treatment option for the coronavirus disease-2019 (COVID-19). However, the benefits of JAK inhibitors and the optimum thereof for COVID-19 have not been adequately defined. Methods: Databases were searched from their inception dates to 17 June 2022. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. The primary outcome was the coefficient of mortality. Results: Twenty-eight studies of 8,206 patients were included and assessed qualitatively (modified Jadad and Newcastle-Ottawa Scale scores). A pairwise meta-analysis revealed that JAK inhibitors effectively reduced the mortality (OR = 0.54; 95% CI: 0.46-0.63; P < 0.00001; I 2 = 32%) without increasing the risk of adverse events (OR = 1.02; 95% CI: 0.88-1.18; P = 0.79; I 2 = 12%). In a network meta-analysis, clinical efficacy benefits were seen among different types of JAK inhibitors (baricitinib, ruxolitinib, and tofacitinib) without the observation of a declined incidence of adverse events. The assessment of rank probabilities indicated that ruxolitinib presented the greatest likelihood of benefits regarding mortality and adverse events. Conclusion: JAK inhibitors appear to be a promising treatment for COVID-19 concerning reducing mortality, and they do not increase the risk of adverse events vs. standard of care. A network meta-analysis suggests that mortality benefits are associated with specific JAK inhibitors, and among these, ruxolitinib presents the greatest likelihood of having benefits for mortality and adverse events. Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42022343338].

The link between ferroptosis and airway inflammatory diseases: A novel target for treatment.

Ferroptosis is an iron-dependent mode of cell death characterized by intracellular lipid peroxide accumulation and a redox reaction imbalance. Compared with other modes of cell death, ferroptosis has specific biological and morphological features. The iron-dependent lipid peroxidation accumulation is manifested explicitly in the abnormal metabolism of intracellular lipid oxides catalyzed by excessive iron ions with the production of many reactive oxygen species and over-oxidization of polyunsaturated fatty acids. Recent studies have shown that various diseases, which include intestinal diseases and cancer, are associated with ferroptosis, but few studies are related to airway inflammatory diseases. This review provides a comprehensive analysis of the primary damage mechanisms of ferroptosis and summarizes the relationship between ferroptosis and airway inflammatory diseases. In addition to common acute and chronic airway inflammatory diseases, we also focus on the progress of research on COVID-19 in relation to ferroptosis. New therapeutic approaches and current issues to be addressed in the treatment of inflammatory airway diseases using ferroptosis are further proposed.

Seven ferroptosis-specific expressed genes are considered as potential biomarkers for the diagnosis and treatment of cigarette smoke-induced chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incomplete reversible airway obstruction, with high mortality and disability rates, and smoking is the primary risk factor for COPD. Studies performed to date have confirmed that iron and ferroptosis play crucial roles in the development of cigarette smoke-induced COPD, but the exact mechanisms have not been fully elucidated. Methods: The microarray datasets GSE10006, GSE11784, and GSE20257 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between COPD smokers and non-smokers airway epithelial. Protein-protein interaction (PPI) and hub gene networks were constructed using the STRING database and Cytoscape software. At the same time, the 3 datasets were screened for ferroptosis-related genes that were co-differentially expressed. The ferroptosis-related hub genes (FRHGs) that overlapped with the ferroptosis-related genes and hub genes were then identified. Next, the mRNA-miRNA network was constructed, and Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were performed. Finally, GSE19407, GSE994, and GSE27973 were used to evaluate the expression of hub genes. Results: We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties. The molecular functions (MFs) of FRHGs mainly influence biological processes (BPs) responding to oxidative stress. Nrf2 pathways may be the key pathways regulating ferroptosis in cigarette smoke-induced COPD. Meanwhile, co-expressed mRNAs and miRNAs were selected to construct mRNA-miRNA interaction networks. Furthermore, based on the 7 FRHGs mentioned above, we found that benzoic acid showed high drug targeting relevance. Conclusions: This work identified 7 FRHGs as potential biomarkers for the diagnosis and treatment of COPD and provided insights into the mechanisms of disease development in cigarette smoke-induced COPD at the transcriptome level.

Isorhamnetin Alleviates Airway Inflammation by Regulating the Nrf2/Keap1 Pathway in a Mouse Model of COPD.

Chronic obstructive pulmonary disease (COPD) is a severely disabling chronic lung disease characterized by persistent airway inflammation, which leads to limited expiratory airflow that deteriorates over time. Isorhamnetin (Iso) is one of the most important active components in the fruit of Hippophae rhamnoides L. and leaves of Ginkgo biloba L, which is widely used in many pulmonary disease studies because of its anti-inflammatory effects. Here, we investigated the pharmacological action of Iso in CS-induced airway inflammation and dissected the anti-inflammation mechanisms of Iso in COPD mice. A mouse model of COPD was established by exposure to cigarette smoke (CS) and intratracheal inhalation of lipopolysaccharide (LPS). Our results illustrated that Iso treatment significantly reduced leukocyte recruitment and excessive secretion of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation, normal T-cell expressed and secreted (RANTES) in BALF of CS-induced COPD mice in a dose-dependent manner. This improved airway collagen deposition and emphysema, and further alleviated the decline in lung functions and systemic symptoms of hypoxia and weight loss. Additionally, Iso treatment obviously improves the T lymphocyte dysregualtion in peripheral blood of COPD mice. Mechanistically, Iso may degrade Keap1 through ubiquitination of p62, thereby activating the nuclear factor erythroid 2-related factor (Nrf2) pathway to increase the expression of protective factors, such as heme oxygenase-1 (HO-1), superoxide dismutase (SOD) 1, and SOD2, in lungs of CS-exposed mice, which plays an anti-inflammatory role in COPD. In conclusion, our study indicates that Iso significantly alleviates the inflammatory response in CS-induced COPD mice mainly by affecting the Nrf2/Keap1 pathway. More importantly, Iso exhibited anti-inflammatory effects comparable with Dex in COPD and we did not observe discernible side effects of Iso. The high safety profile of Iso may make it a potential drug candidate for COPD.

Clinical efficacy and adverse events of baricitinib treatment for coronavirus disease-2019 (COVID-19): A systematic review and meta-analysis.

The benefits of baricitinib in coronavirus disease-2019 are inadequately defined. We performed a systematic review and meta-analysis of studies of baricitinib to determine its clinical efficacy and adverse events in patients with COVID-19. Databases were searched from their inception to September 5, 2021. The primary outcome was the coefficient of mortality. We also compared secondary indicators and adverse events between baricitinib treatment and placebo or other treatments. Twelve studies of 3564 patients were included and assessed qualitatively (modified Jadad and Newcastle-Ottawa Scale scores). Baricitinib effectively improved the mortality rate (relative risk of mortality = 0.56; 95% confidence interval: 0.46-0.69; p < 0.001; I2 = 2%), and this result was unchanged by subgroup analysis. Baricitinib improved intensive care unit admission, the requirement for invasive mechanical ventilation, and improved the oxygenation index. Data from these studies also showed that baricitinib slightly reduced the risk of adverse events. Regarding the choice of the drug dosage of baricitinib, the high-dose group appeared to have additional benefits for clinical efficacy. Our study shows that baricitinib may be a promising, safe, and effective anti-severe acute respiratory syndrome-coronavirus-2 drug candidate, with the advantages of low cost, easy production, and convenient storage.

Isorhamnetin inhibits amplification of influenza A H1N1 virus inflammation mediated by interferon via the RIG-I/JNK pathway.

BACKGROUND: Interferon (IFN) amplifies the influenza virus-mediated inflammatory response by forming a paracrine signal feedback loop, which is considered an important cause of excessive inflammatory damage. Isorhamnetin has a wide spectrum of beneficial pharmacological properties, including anti-inflammatory and antiviral effects. The regulatory effect and mechanism of isorhamnetin on influenza virus-mediated inflammation have not yet been reported. METHODS: We pre-treated A549 cells with IFN-ß (50 ng/mL) for 4 h followed by IAV (H1N1) infection to simulate the inflammation amplification effect caused by the paracrine effect of IFN-ß. The anti-inflammation activity of isorhamnetin against amplification inflammation of interferon mediated by IAV (H1N1) was assessed by performing quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) in A549 cells. RESULTS: Compared with the virus infection group, the IFN-ß pretreatment virus infection group had an upregulated level of pro-inflammatory cytokine expression, which was inhibited by isorhamnetin significantly via the retinoic acid-induced gene I (RIG-I)/c-Jun N-terminal kinase (JNK) signaling pathway. Molecular docking studies further verified that isorhamnetin can interact with JNK. CONCLUSIONS: Our work was the first to demonstrate the anti-inflammatory activity and mechanism of isorhamnetin during influenza virus infection. Isorhamnetin significantly improves the excessive inflammatory response mediated by IAV (H1N1) infection mainly via the RIG-I/JNK pathway. Additionally, isorhamnetin exhibited an apparent antiviral effect of H1N1 in vitro.

Impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation.

Chronic obstructive pulmonary disease (COPD) often tends to respond poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2 (HDAC-2) activity is an important mechanism behind this GC insensitivity. In this study, we investigated the effects of three phosphodiesterase inhibitors (PDEIs), with an anti-inflammatory propensity, on cigarette smoke (CS)-induced pulmonary inflammation and HDAC-2 activity. Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course of 30 weeks. Administration of the PDEIs commenced from the 29th week and followed a schedule of once daily treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was administered intragastrically (5 mg·kg-1 ), while pentoxifylline (PTX) (10 mg·kg-1 ) and theophylline (THEO) (10 mg·kg-1 ) were administered intraperitoneally, either alone or in combination with a GC (triamcinolone acetonide or TRI, 5 mg·kg-1 , i.m., single injection). Lung morphometry, as well as the activity of HDAC-2, pro-inflammatory cytokines and reactive oxygen species (ROS) were assessed at the end of the 30-week course. CS exposure was associated with a reduction in HDAC-2 activity and the up-regulation of ROS expression. PTX, ROF, and THEO administration led to the partial restoration of HDAC-2 activity, which was favorably associated with the reduction of ROS expression. However, combining TRI to any of these PDEIs did not synergistically augment HDAC-2 activity. Inactivation of HDAC-2 due to long-term CS exposure is closely related to exaggerated oxidative stress, and this reduced HDAC-2 activity could partially be restored through the use of PDEIs. This finding provides a potential novel approach for further clinical research.

Metabolomic profiling of anaerobic and aerobic energy metabolic pathways in chronic obstructive pulmonary disease.

While there is no cure for chronic obstructive pulmonary disease (COPD), its progressive nature and the formidable challenge to manage its symptoms warrant a more extensive study of the pathogenesis and related mechanisms. A new emphasis on COPD study is the change of energy metabolism. For the first time, this study investigated the anaerobic and aerobic energy metabolic pathways in COPD using the metabolomic approach. Metabolomic analysis was used to investigate energy metabolites in 140 COPD patients. The significance of energy metabolism in COPD was comprehensively explored by the Global Initiative for Chronic Obstructive Lung Disease-GOLD grading, acute exacerbation vs. stable phase (either clinical stability or four-week stable phase), age group, smoking index, lung function, and COPD Assessment Test (CAT) score. Through comprehensive evaluation, we found that COPD patients have a significant imbalance in the aerobic and anaerobic energy metabolisms in resting state, and a high tendency of anaerobic energy supply mechanism that correlates positively with disease progression. This study highlighted the significance of anaerobic and low-efficiency energy supply pathways in lung injury and linked it to the energy-inflammation-lung ventilatory function and the motion limitation mechanism in COPD patients, which implies a novel therapeutic direction for this devastating disease.

Krebs Von den Lungen-6 as a predictive indicator for the risk of secondary pulmonary fibrosis and its reversibility in COVID-19 patients.

Dysregulated immune response and abnormal repairment could cause secondary pulmonary fibrosis of varying severity in COVID-19, especially for the elders. The Krebs Von den Lungen-6 (KL-6) as a sensitive marker reflects the degree of fibrosis and this study will focus on analyzing the evaluative efficacy and predictive role of KL-6 in COVID-19 secondary pulmonary fibrosis. The study lasted more than three months and included total 289 COVID-19 patients who were divided into moderate (n=226) and severe groups (n=63) according to the severity of illness. Clinical information such as inflammation indicators, radiological results and lung function tests were collected. The time points of nucleic acid test were also recorded. Furthermore, based on Chest radiology detection, it was identified that 80 (27.7%) patients developed reversible pulmonary fibrosis and 34 (11.8%) patients developed irreversible pulmonary fibrosis. Receiver operating characteristic (ROC) curve analysis shows that KL-6 could diagnose the severity of COVID-19 (AUC=0.862) and predict the occurrence of pulmonary fibrosis (AUC = 0.741) and irreversible pulmonary fibrosis (AUC=0.872). Importantly, the cross-correlation analysis demonstrates that KL-6 rises earlier than the development of lung radiology fibrosis, thus also illuminating the predictive function of KL-6. We set specific values (505U/mL and 674U/mL) for KL-6 in order to assess the risk of pulmonary fibrosis after SARS-CoV-2 infection. The survival curves for days in hospital show that the higher the KL-6 levels, the longer the hospital stay (P<0.0001). In conclusion, KL-6 could be used as an important predictor to evaluate the secondary pulmonary fibrosis degree for COVID-19.

Krebs von den Lungen-6 and surfactant protein-A in interstitial pneumonia with autoimmune features.

ABSTRACT: Interstitial pneumonia with autoimmune features (IPAF) is a special subtype of interstitial lung disease that has received worldwide attention. Krebs von den Lungen-6 (KL-6) and surfactant protein-A (SP-A) can be used as an important biomarker of interstitial lung disease, but its exact relationship with IPAF is poorly understood.A total of 65 IPAF patients were included in the study and were followed up for 52 weeks. The KL-6 and SP-A were evaluated by chemiluminescence enzyme immunoassay. The above indicators were tested at 2 time points, baseline (the first admission of patients) and 52 weeks. We also collected the indicators of antinuclear antibodies and rheumatoid factor. Based on high-resolution computed tomography evaluations, patients were divided into: aggravation, stable, and improvement group. At same time, 30 age-matched normal people as normal control were recruited, the same information was collected. Correlations among the groups were compared and analyzed.The KL-6 and SP-A level in IPAF patients were significantly higher than normal controls (fold increase = 11.35 and 1.39, both P < .001) and differed significantly at baseline and 52 weeks in IPAF (difference ratio = 37.7% and 21.3%, P < .05, both). There were significant differences at baseline and 52 weeks (r values of aggravation, improvement, and stable groups for KL-6 were 0.705, 0.770, and 0.344, P = .001, .001, and .163, and for SP-A the r value were 0.672, 0.375, and 0.316, P = .001, .126, and .152). In aggravation group, KL-6 and SP-A were correlated with CT scores (both P < .05). Diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC), % predicted showed a progressive downward trend, with a significant difference at baseline and 52 weeks in IPAF patients (difference ratio = 23.8% and 20.6%, both P < .05). There was a significant correlation between KL-6 and FVC % predicted and DLCO (both P < .05), SP-A showed negatively correlated with DLCO, but not significantly correlated with FVC % predicted (P < .05 and .47).This study demonstrated that KL-6 and SP-A can reflect disease progression, and both 2 play a key role at reflection of lung epithelial cell injury and fibrosis degree in IPAF.

Heparin-binding protein levels correlate with aggravation and multiorgan damage in severe COVID-19.

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients may suffer persistent systemic inflammation and multiple organ failure, leading to a poor prognosis. RESEARCH QUESTION: To examine the relevance of the novel inflammatory factor heparin-binding protein (HBP) in critically ill COVID-19 patients, and evaluate the correlation of the biomarker with disease progression. STUDY DESIGN AND METHODS: 18 critically ill COVID-19 patients who suffered from respiratory failure and sepsis, including 12 cases who experienced a rapidly deteriorating clinical condition and six cases without deterioration, were investigated. They were compared with 15 age- and sex- matched COVID-19-negative patients with respiratory failure. Clinical data were collected and HBP levels were investigated. RESULTS: HBP was significantly increased in critically ill COVID-19 patients following disease aggravation and tracked with disease progression. HBP elevation preceded the clinical manifestations for up to 5 days and was closely correlated with patients' pulmonary ventilation and perfusion status. INTERPRETATION: HBP levels are associated with COVID-19 disease progression in critically ill patients. As a potential mediator of disease aggravation and multiple organ injuries that are triggered by continuing inflammation and oxygen deficits, HBP warrants further study as a disease biomarker and potential therapeutic target.

Predictive effects of IgA and IgG combination to assess pulmonary exudation progression in COVID-19 patients.

Our study intended to longitudinally explore the prediction effect of immunoglobulin A (IgA) on pulmonary exudation progression in COVID-19 patients. The serum IgA was tested with chemiluminescence method. Autoregressive moving average model was used to extrapolate the IgA levels before hospital admission. The positive rate of IgA and IgG in our cohort was 97% and 79.0%, respectively. In this study, the IgA levels peaks within 10-15 days after admission, while the IgG levels peaks at admission. We found that the time difference between their peaks was about 10 days. Viral RNA detection results showed that the positive rate in sputum and feces were the highest. Blood gas analysis showed that deterioration of hypoxia with the enlargement of pulmonary exudation area. And alveolar-arterial oxygen difference and oxygenation index were correlated with IgA and IgG. The results of biopsy showed that the epithelium of lung was exfoliated and the mucosa was edematous. In severe COVID-19 patients, the combination of IgA and IgG can predict the progress of pulmonary lesions and is closely related to hypoxemia and both also play an important defense role in invasion and destruction of bronchial and alveolar epithelium by SARS-CoV-2.

Exploration of n-6 and n-3 Polyunsaturated Fatty Acids Metabolites Associated with Nutritional Levels in Patients with Severe Stable Chronic Obstructive Pulmonary Disease.

Background and Objective: Severe chronic obstructive pulmonary disease (COPD) is the terminal stage of the disease characterized by declined lung function, malnutrition, and poor prognosis. Such patients cannot tolerate long-time sports rehabilitation owing to dyspnea and fail to achieve the desired therapeutic effect; therefore, increasing nutritional support will be an important strategy for them. The present study applied metabolomics technology to evaluate the correlation between serum concentrations of polyunsaturated fatty acid (PUFA) metabolites, nutritional status, and lung function in patients with COPD to provide a theoretical basis for accurate nutritional support. Materials and Methods: We enrolled 82 patients with stable severe COPD in our hospital. The general characteristics including height, weight, and lung function were recorded. Metabolomics was used to detect the concentrations of serum metabolites of n-3 and n-6 at baseline and at 24 and 52 weeks after enrollment. The correlations between nutrition level and pulmonary function and clinical indicators were evaluated. Results: The concentrations of n-3 and n-6 increased over time along with the progression of COPD. Body mass index (BMI) and percent of ideal body weight (IBW%) decreased with disease development, and BMI was found to be significantly correlated with FEV1% predicted and FEV1/FVC. Serum levels of n-6 metabolites such as linoleic acid (LA), γ-linoleic acid (GLA), and arachidonic acid (ARA) (all P < 0.01) and the n-3 metabolites such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (all P < 0.05) showed significant correlations with BMI and were closely correlated with FEV1% predicted and FEV1/FVC of lung function (all P< 0.05). Conclusion: This study demonstrates that malnutrition in patients with severe COPD is progressive and is positively correlated with n-3 and n-6 polyunsaturated fatty acids and lung function.

Sputum and serum autoantibody profiles and their clinical correlation patterns in COPD patients with and without eosinophilic airway inflammation.

BACKGROUND: Autoimmunity plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the autoantibody responses and their clinical correlation patterns in COPD patients with and without airway eosinophilic inflammation are unknown. The aim of this study was to compare the autoantibody profiles and their clinical associations in stable COPD patients, stratified by airway inflammatory phenotypes. METHODS: Matched sputum and serum, obtained from 62 stable COPD patients and 14 age-matched controls, were assayed for the presence of IgG and IgM antibodies against 13 autoantigens using protein array. A sputum eosinophil count ≥3% was used as cut-off value to stratify COPD patients into eosinophilic and non-eosinophilic groups. Correlation network analysis was used to evaluate the correlation patterns among autoantibody and clinical variables in each group. RESULTS: There were no significant differences of clinical parameters and autoantibody levels between the two COPD groups. In non-eosinophilic COPD, sputum anti-CytochromeC_IgG and anti-Aggrecan_IgM were significantly higher than those in healthy controls, and prior exacerbation was positively associated with lung function and sputum anti-Collagen-IV_IgG. While in eosinophilic COPD, sputum/serum anti-heat shock protein (HSP)47_IgG, serum anti-HSP70_IgG and serum anti-Amyloid-beta_IgG were significantly lower than those in healthy controls, and no significant correlation between prior exacerbations and lung function was found. Differences were also observed in network hubs, with the network for non-eosinophilic COPD possessing 9 hubs comprising two lung function parameters and seven autoantibodies, compared with eosinophilic COPD possessing 12 hubs all comprising autoantibodies. CONCLUSIONS: Autoantibody responses were heterogeneous and differentially correlated with the exacerbation risk and other clinical parameters in COPD patients of different inflammatory phenotypes. These findings provide useful insight into the need for personalized management for preventing COPD exacerbations.

Exploration and correlation analysis of changes in Krebs von den Lungen-6 levels in COVID-19 patients with different types in China.

This study aimed to determine the clinical significance of Krebs von den Lungen-6 (KL-6) in patients with COVID-19, so as to find a marker with high sensitivity, specificity and easy detection to evaluate the lung injury and inflammation of COVID-19. Sixty-three COVID-19 patients and 43 non-COVID-19 patients with similar clinical phenotypes and/or imaging findings were enrolled to test the levels of KL-6 using chemiluminescent immunoassay. In addition, the blood gas, imaging and lymphocyte factors tests were collected from all participants. The data was finally analyzed using multivariate statistical analysis. The results showed KL-6 levels in COVID-19 patients were higher than those in non-COVID-19 patients (P < 0.001). Moreover, the KL-6 levels in severe and critically severe patients were significantly upregulated compared with patients with mild and common type (P < 0.05). Meanwhile, the imaging evaluation showed a significant correlation between KL-6 and pulmonary lesion area (P < 0.05). KL-6 was also found to be significantly correlated with oxygenation index and oxygen partial pressure difference of alveolar artery (PA-aDO2) (Both P < 0.01). In conclusion, KL-6 could be an indicator to evaluate the progression of COVID-19, which is parallel to the level of lung injury and inflammation in patients. Moreover, it can also reflect the pulmonary ventilation function.