Objective To explore the correlation and diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in peripheral blood of patients with exacerbation of chronic obstructive pulmonary disease (COPD). Methods One hundred patients with acute exacerbation of COPD who were hospitalized in the hospital between January 2019 and October 2020 were selected as exacerbation group, and another 100 patients with stable COPD who received treatment during the same time period were enrolled as stable group. The general data of patients were collected, and blood samples were collected to detect hemoglobin (Hb), platelet count (PLT), white blood cell count (WBC), neutrophil count, lymphocyte count and RDW, and the NLR was calculated. The correlation between the detection indicators was analyzed and receiver operating characteristic (ROC) curve was drawn to analyze the detection significance of related indicators. Results There were no statistical differences in the levels of Hb and PLT between the exacerbation group and the stable group (P>0.05). The levels of WBC, NLR, RDW and high-sensitivity C-reactive protein (hs-CRP) in the exacerbation group were significantly higher than those in the stable group (all P<0.05). NLR in the patients with acute exacerbation of COPD was positively correlated with serological indicators of WBC and hs-CRP (all P<0.05). ROC curve showed that the sensitivity and specificity of NLR in the diagnosis of acute exacerbation of COPD were 92.0% and 68.0% respectively, those of RDW were 91.0% and 58.0% respectively, those of hs-CRP were 77.0% and 71.0% respectively, and those of NLR+RDW were 90.0% and 73.0% respectively. NLR had the highest diagnostic specificity, RDW had the highest diagnostic sensitivity, and NLR+RDW had the best diagnostic efficiency. Conclusions Serological indicators of WBC, hs-CRP, NLR and RDW in patients with acute exacerbation of COPD will be abnormally increased, and NLR has a positive correlation with WBC and hs-CRP. NLR and RDW have high specificity and high sensitivity respectively in the diagnosis of patients with exacerbation of COPD, and their detection can strengthen the diagnosis and mastery of disease in patients.
ObjectiveTo evaluate the value of serum procalcitonin (PCT) level after conventional intravenous antibiotic treatment to predict the risk of re-exacerbation, and vertify the feasiblity of an additional course of oral antibiotics after discharge to reduce the risk of re-exacerbation. MethodsThe patients who hospitalized in West China Hospital from October 2012 to October 2013 because of infectious acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were recruited. The concentrations of PCT and C-reactive protein (CRP), the number of white blood cell (WBC) and neutrophil percentage at the end of intravenous antibiotic therapy were recorded. The information about additional course of antibiotics was collected according to the medical instruction and visit. The subjects were followed up for 1 year.The time to the first re-exacerbation and frequencies of exacerbations were recorded. The Cox regression model was used to estimate the hazard rations (HR). ResultsOne hundred and thirty-eight eligible patients were included totally. The HRs in PCT≥0.11μg/L and neutrophil percentage≥70% were 1.462 (P=0.035) and 1.673 (P=0.005) respectively, suggesting higher risk of re-exacerbation. There was no relationship of CRP (P=0.330) or WBC (P=0.432) with the risk of re-exacerbation. Generally an additional course of antibiotics had no effects on re-exacerbation (P=0.231) but this therapy could reduce the risk of re-exacerbation in high PCT level group (HR=2.29, P=0.004). ConclusionsSerum PCT concentrations and neutrophil percentage after conventional intravenous antibiotic treatment can predict the risk of re-exacerbations in the future. An additional course of antibiotics in the patients with high PCT level can reduce the risk of re-exacerbation.
ObjectiveTo determine whether there is an imbalance of KLF2/RelA in peripheral blood neutrophils in patients with bronchial asthma, and explore the relationship between KLF2/RelA imbalance and neutrophil apoptosis.MethodsFrom April 2011 to April 2012, a total of 39 patients with acute attack of asthma in Hunan People's Hospital and Third People's Hospital of Changsha were enrolled, with 13 cases in mild asthma group, 17 cases in moderate asthma group, and 9 cases in severe asthma group. Fifteen healthy subjects were recruited as control group. Peripheral blood were collected from all subjects followed by separation of neutrophils. The apoptosis of neutrophils were measured by flow cytometry. The expression of KLF2 and RelA were detected by Western blot. The relationship between the ratio of KLF2/RelA and neutrophil apoptosis rate was analyzed by Pearson correlation test.ResultsNeutrophil apoptosis rates in the mild, moderate and severe asthma groups [(4.45±0.76)%, (2.10±0.25)%, (1.81±0.67)%, repectively] were lower than that in the healthy control group [(5.36±0.57)%, all P<0.01]. The apoptosis rates of neutrophils in the moderate and severe asthma groups were lower than that in the mild asthma group (bothP<0.01), but there was no significant difference between the moderate asthma group and the severe asthma group (P>0.05). The ratios of neutrophil KLF2/RelA in the mild, moderate and severe asthma groups were lower than that in the normal control group (0.667±0.351, 0.384±0.203, 0.536±0.293vs. 4.038±2.011, all P<0.01). There was no significant difference between the groups of mild, moderate and severe asthma (P>0.05). The neutrophil apoptosis rate was positively correlated with the percentage of neutrophil KLF2/RelA (r=0.592 0, P<0.000 1).ConclusionThere is an imbalance of KLF2/RelA in peripheral blood neutrophils in patients with bronchial asthma, and the imbalance of KLF2/RelA may be the mechanism of apoptosis of peripheral blood neutrophils.
ObjectiveTo observe the correlation between blood cell-related inflammatory markers and diabetic retinopathy (DR). MethodsA cross-sectional study. From June 2020 to February 2022, the phase Ⅰ data of Beichen Eye Study in Tianjin Medical University Eye Hospital were included in the study. The research contents included questionnaires, routine systemic and ocular examinations, and laboratory blood cell-related indicators including mean platelet volume (MPV), platelet distribution width (PDW), neutrophils, and lymphocytes were performed. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The diagnosis and classification of DR referred to the international clinical classification standard of DR. Monocular or binocular DR was defined as DR patients. Participants were categorized into different groups based on whether they had diabetes and whether they had DR. The groups included the no-diabetes group, the diabetes without DR group, and the DR group. The Kruskal-Wallis H test was used for the comparison of quantitative data among multiple groups. Wilcoxon test was used for comparison between the two groups. The χ2 test was used to compare the categorical variables between groups. The variables was adjusted step by step, an unadjusted univariate model was built and the different parameters of the model Ⅰ, Ⅱ, Ⅲ were adjusted. The correlation between MPV, PDW, NLR, PLR, and DR in different models was analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different NLR models for DR. ResultsA total of 3 328 subjects were recruited. Among them, 1 121 (33.68 %, 1 121/3 328) were males and 2 207 (66.32 %, 2 207/3 328) were females. The median age of the included participants was 61.84 (6.05) years. The no-diabetes group, the diabetes without DR group, and the DR group were 2 679, 476, and 173, respectively. There was no significant difference in MPV and PLR among the three groups (H=5.98, 1.94; P=0.051, 0.379). However, compared with no-diabetes group and the diabetes without DR group, PDW and NLR in the DR group showed an upward trend. In model Ⅲ with completely adjusted related factors, NLR was an independent risk factor for DR in no-diabetes group and DR group [odds ratio (OR)=1.440, 95% confidence interval (CI) 1.087-1.920, P=0.041], diabetes without DR group and DR group [OR=1.990, 95% CI 1.440-2.749, P＜0.001]. The results of ROC curve analysis showed that the diagnostic efficiency of NLR model Ⅲ was the highest, the area under the curve was 0.751 (95%CI 0.706-0.796, P＜0.001), the optimal cutoff value was 0.390, and the sensitivity and specificity were 74.3% and 64.8%, respectively. ConclusionsThe NLR of the DR group is significantly higher than that of the no-diabetes group and diabetes without DR group. NLR is an independent risk factor for DR.
Objective To systematically review the relationship between the neutrophil to lymphocyte ratio (NLR) and the short-term prognosis of patients with acute aortic dissection. MethodDatabases including PubMed, Web of Science, CNKI, CBM, and WanFang Data were electronically searched to collect studies on the prognosis associated with neutrophil/lymphocyte ratio and acute aortic dissection from inception to July 2021. Two reviewers independently screened literature, extracted data, and evaluated the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software. Results A total of 10 case-control studies involving 1 638 patients were included. The results of meta-analysis revealed that the in-hospital mortality group of patients with acute aortic dissection had higher NLR levels than the survival group (MD=4.94, 95%CI 2.67 to 7.61, P<0.0001). In patients with acute aortic dissection, there was no statistical difference in in-hospital mortality between the low NLR group and the high NLR group (OR=3.03, 95%CI 1.00 to 9.15, P=0.05). Conclusion Patients with acute aortic dissection who died in hospital shows higher NLR levels than those who survived. However, due to the quantity and quality of included studies, the above conclusions are needed to be verified by more high-quality studies.
Neutrophil extracellular traps (NETs), composed of deoxyribonucleic acid (DNA), histones, and granule enzymes, exhibit a “double-edged sword” effect in retinal neovascularization (RNV) diseases. The formation of NETs involves classical lytic and non-lytic pathways, as well as peptidylarginine deiminase 4 (PAD4)-dependent and reactive oxygen species-dependent molecular mechanisms. Across different types of RNV, the roles of NETs vary markedly. In diabetic retinopathy, NETs accelerate disease progression by amplifying inflammatory responses, disrupting the blood-retinal barrier, and increasing vascular permeability. During specific stages of retinopathy of prematurity, NETs participate in the clearance of senescent vessels and promote beneficial vascular remodeling. In retinal vein occlusion, their pro-coagulant and pro-inflammatory properties may exacerbate thrombosis and ischemia. The functions of NETs are dynamically regulated by disease stage, microenvironmental factors, and interactions with immune cells. Therefore, therapeutic strategies aimed at clearing NETs (e.g., deoxyribonuclease I) or inhibiting NET formation (e.g., PAD4 inhibitors) may serve as complementary approaches to current anti-vascular endothelial growth factor therapies, although further studies are needed to elucidate optimal intervention timing, safety, and combination treatment strategies for clinical translation.
Objective To investigate the clinical value of peripheral serum cell-free DNA/neutrophil extracellular traps (cf-DNA/NETs) level in diagnosis and severity assessment of sepsis patients. Methods Forty patients with sepsis and 40 patients with non-infectious systemic inflammatory response syndrome (nf-SIRS) were enrolled in this study. The cf-DNA/NETs level in serum of all subjects were measured. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of the cf-DNA/NETs, white blood cell count (WBC), procalcitonin (PCT) and interleukin-6 (IL-6). The sepsis patients were stratified into a survival group and a death group according to the prognosis. Sequential organ failure (SOFA) score were recorded in the sepsis patients, and the correlations between SOFA and cf-DNA/NETs, PCT, WBC, IL-6 were analyzed. Results Compared with the nf-SIRS group, cf-DNA/NETs and PCT levels were significantly higher in the sepsis group (both P<0.05). WBC and IL-6 showed no significant differences between the two groups (bothP>0.05). The area under the ROC curve (AUC) of cf-DNA/NETs was 0.884 for diagnosis of sepsis, and it was higher than the AUC of PCT (0.803). The cf-DNA/NETs showed better sensitivity (81.2% and 79.2%) and specificity (81.0% and 82.4%) than PCT. cf-DNA/NETs and PCT were significantly higher in the death group than those in the survival group. Bivariate collection analysis revealed positive correlations between SOFA score and the two biomarkers of cf-DNA/NETs and PCT (r1=0.573, r2=0.518; both P<0.01). Conclusions cf-DNA/NETs and PCT have certain value in early diagnosis of sepsis, and cf-DNA/NETs shows better diagnostic value in distinguishing sepsis from nf-SIRS than PCT. cf-DNA/NETs can be used as a routine monitoring index to help assess disease severity in sepsis.
ObjectiveTo explore the clinical characteristics and long term mortality of patients with eosinophilic and neutrophilic chronic obstructive pulmonary disease (COPD) exacerbations requiring hospital admission.MethodsA retrospective review of the clinical data and long-term follow up was performed for 510 patients with first diagnosis of acute exacerbation of COPD (AECOPD) requiring hospital admission between January 2015 and December 2016. The follow-up was completed in January 1, 2020. These patients were divided into three groups according to routine blood test: an eosinophilic exacerbation group, with peripheral blood eosinophils >2%; a neutrophilic exacerbation group, with peripheral blood neutrophils >65% or leukocytes >11×109/L; a paucigranulocytic exacerbation group, any case did not belong to the above two groups. The differences of clinical characteristics were compared among three groups. Cox regression model was used for analysis of independent risk factors of all-cause mortality of AECOPD patients.ResultsA total of 510 AECOPD patients were enrolled (180 eosinophilic, 273 neutrophilic and 57 paucigranulocytic, respectively). Compared with the neutrophilic exacerbation group, the eosinophilic exacerbation group had shorter time since onset of symptoms, the lower proportion of comorbid heart failure, the lower proportion of mechanical ventilation, dual antibiotics and systematic corticosteroid treatment, the shorter length of hospitalization and lower hospital mortality (all P<0.05). The average follow-up duration was 41 months for 485 AECOPD patients who completed long term follow-up. Compared with the eosinophilic exacerbation group, the neutrophilic exacerbation group was associated with a higher long-term mortality of AECOPD (HR=1.691, 95%CI 1.205 - 2.373, P=0.002).ConclusionCOPD patients with neutrophilic exacerbations have more serious clinical features and higher mortality than those with eosinophilic exacerbations.
ObjectiveTo investigate the expression and pathological significance of neutrophil elastase (NE) and mucin 5AC (MUC5AC) in chronic obstructive pulmonary disease (COPD) rats. MethodsA total of 60 male specific pathogens free Sprague-Dawley rats were randomly divided into model group and blank group, each with 30 rats. The number of goblet cells and the positive expression of NE and MUC5AC were compared between the two groups by hematoxylin-eosin staining, alcianblue-periodic acid Schiff staining and immunohistochemical staining. ResultsNo rats died accidentally during the experiment. The number of goblet cells was 57.93±7.79 in the model group and 6.80±3.19 in the blank group, and the difference between the two groups was statistically significant (t=?44.267, P<0.05). The median (lower quartile, upper quartile) of the positive expression score of NE was 0 (0, 0) in the blank group and 2 (2, 3) in the model group, the median (lower quartile, upper quartile) of the positive expression score of MUC5AC was 0 (0, 1) in the blank group and 2 (2, 2) in the model group, and the differences between the two groups were statistically significant (P<0.05).ConclusionsThe positive expression of NE, goblet cells, MUC5AC and mucus secretion in COPD model rats increases significantly. Perhaps NE and MUC5AC can be used as target interventions to inhibit mucus hypersecretion.
The effect of neutrophil extracellular traps (NETs) on promoting intravascular microthrombi formation and exacerbating the severity of sepsis in patients has gained extensive attention. However, in sepsis, the mechanisms and key signaling molecules mediating NET formation during direct interactions of endothelial cells and neutrophils still need further explored. Herein, we utilized lipoteichoic acid (LTA), a component shared by Gram-positive bacteria, to induce NET extrusion from neutrophils firmly adhered to the glass slides coated with intercellular adhesion molecule-1(ICAM-1). We also used Sytox green to label NET-DNA and Flou-4 AM as the intracellular Ca2+ signaling indicator to observe the NET formation and fluctuation of Ca2+ signaling. Our results illustrated that LTA was able to induce NET release from neutrophils firmly attached to ICAM-1-coated glass slides, and the process was time-dependent. In addition, our study indicated that LTA-induced NET release by neutrophils stably adhered to ICAM-1 depended on Ca2+ signaling but not intracellular reactive oxygen species (ROS). This study reveals NET formation mediated by direct interactions between endothelial ICAM-1 and neutrophils under LTA stimulation and key signaling molecules involved, providing the theoretical basis for medicine development and clinical treatment for related diseases.