| Objective:The levels of TNF-α,sTNFR-55,sTNFR-75 in serum and induced sputum,and the expression of sputum inflammatory cells in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)were measured,and the correlation analysis was carried out with clinical parameters to clarify whether TNF-α,sTNFR-55,sTNFR-75 and sputum inflammatory cells can be used as biomarkers for evaluating the condition and curative effect of AECOPD patients.In order to provide a theoretical basis for the research of TNF-α system related biological agents.Methods:According to the guidelines of the Global Initiative for Chronic Obstructive Pulmonary Disease(GOLD)in 2018,40 patients with moderate and severe AECOPD(GOLD guidelines group C and group D)hospitalized in the Department of Respiratory and Critical Medicine of the First Affiliated Hospital of Kunming Medical University from December 1,2019 to December 31,2020 were enrolled.Clinical data(gender,age,smoking index,Body Mass Index,BMI),annual acute exacerbation times,past medical history,CAT score(cough,expectoration),mMRC score)were collected.Before and after treatment,all subjects were examined for lung function(forced expiratory volume in 1 second(FEV1),the percentage of forced expiratory volume in 1 second(FEV1%pred),FEV1/Forced Vital Capacity,FVC)),combined with laboratory indicators(blood routine,blood biochemistry,blood gas analysis,urine volume)and previous medical history,Acute Physiology And Chronic Health Evaluation(APACHEIII)was performed,sputum induction operation and sputum cytological classification were performed,and fasting venous blood was collected;At the same time,the levels of TNF-α,sTNFR-55 and sTNFR-75 in serum and induced sputum were measured by enzyme-linked immunosorbent assay.The APACHEⅢ score,lung function index,the proportion of inflammatory cells in induced sputum,the levels of inflammatory mediators(TNF-α,sTNFR-55,sTNFR-75)in induced sputum and serum were compared between the two groups before treatment(group Ⅰ)and after treatment(group Ⅱ).According to the percentage of eosinophils in induced sputum(2.5%),the patients were divided into eosinophil-dominated group(group Ⅲ,eosinophil percentage of induced sputum≥2.5%)and non-eosinophil-dominated group(group Ⅳ,eosinophil percentage of induced sputum<2.5%).The differences of clinical symptoms(mMRC score,cough and expectoration score in CAT)between the two groups were compared,and the correlation between clinical manifestations and airway inflammation was analyzed.Results:① After treatment,pulmonary function indexes FEV1,FEV1%pred and FEVi/FVC in patients with AECOPD increased compared with those before treatment(t=2.713,2.997,3.166,P<0.05),while APACHEⅢ score decreased(t=7.727,P<0.001).②After treatment,the levels of TNF-α in sputum and serum decreased significantly(P<0.05),and the levels of sTNFR-55 in sputum increased(t=3.044,P=0.004),while the levels of sTNFR-55 and sTNFR-75 in serum had no significant difference(P>0.05).③After treatment,the proportion of neutrophils(t=2.612,P=0.013)and eosinophils(P>0.05)in sputum decreased,while the proportion of macrophages(t=2.699,P=0.010)and lymphocytes(P>0.05)increased.④FEV1,FEV1%pred,FEV1/FVC were negatively correlated with the level of TNF-αin sputum(r was-0.827,-0.865,-0.868,respectively,P<0.001),and positively correlated with the level of sTNFR in sputum(rsTNFR-55 was 0.415,0.330 and 0.305,respectively,P<0.05;rsTNFR-75 was 0.903,0.969 and 0.965,respectively,P<0.001),which was negatively correlated with the proportion of sputum neutrophils(r was-0.762,-0.757 and-0.776,respectively,P<0.001).⑤APACHEⅢ score was positively correlated with the level of TNF-α in sputum(r=0.374,P=0.001),and negatively correlated with the level of sTNFR level(r was-0.227,-0.341,respectively,P<0.05),and positively correlated with neutrophil ratio in sputum(r=0.393,P<0.001)⑥There was no correlation between TNF-α/sTNFR levels in induced sputum and serum(P>0.05),and its level in serum has no correlation with lung function index and APACHEⅢ score(P>0.05).⑦CAT(cough and expectoration)score in group Ⅳwas significantly higher than that in group Ⅲ(t=-2.777,P=0.008).There was no significant difference in mMRC score between the two groups(P>0.05),and CAT(cough and expectoration)score was positively correlated with neutrophil ratio(r=0.355,P=0.024).Conclusion:1.After treatment,the proportion of neutrophils and TNF-α level in induced sputum decreased,and they were negatively correlated with lung function index and positively correlated with APACHEⅢ score;The levels of sTNFR-55 and sTNFR-75 in induced sputum increased after treatment,and they were positively correlated with lung function index and negatively correlated with APACHEⅢ score,suggesting that the reduction of airway inflammation,the decrease of pro-inflammatory mediators and the increase of anti-inflammatory mediators are parallel to the remission of disease and the improvement of lung function.The levels of TNF-α,sTNFR-55,sTNFR-75 and the proportion of neutrophil in induced sputum are expected to be inflammatory markers for evaluating the curative effect and severity of AECOPD.2.NO correlation was found between induced sputum and serum levels of TNF-α/sTNFR in patients with AECOPD,nor between serum TNF-α/sTNFR and lung function and APACHEⅢ score.There may be different regulatory mechanisms between systemic and airway inflammation in COPD,and the relationship between them is still unclear.3.The ratio of neutrophils in sputum of patients with AECOPD is related to CAT(cough and expectoration)score instead of mMRC score,and airway inflammation of neutrophils may be related to clinical manifestations(cough and expectoration).4.Neutrophils were predominant in induced sputum of AECOPD before and after treatment.About 45%of patients had increased eosinophils.There was no significant difference in the proportion of eosinophils in induced sputum after treatment,suggesting that the mechanism of eosinophils in COPD is different from that in asthma,and there may be hormone resistance related mechanism. |
PDF Full Text Request