The Difference And Clinical Significance Of Plasma IL-5 And IL-8 Levels Among Inflammatory Phenotypes In Patients With Asthma Attack

BackgroundBronchial asthma（Asthma for short）is a heterogeneous disease with complex pathogenesis and high prevalence.Acute attack of asthma is the main cause of deterioration,disability and even death of patients.The acute attack of asthma is closely related to airway inflammation,and most of the previous phenotypic studies are in the stable stage of asthma.At present,induced sputum is the gold standard for judging the inflammatory phenotype of asthma.However,due to the limitations of induced sputum operation and the development of biomarkers and targeted therapy,looking for alternative markers of acute inflammatory phenotype is of great value to the diagnosis and prognosis of asthma.ObjectiveTo analyze the differences of different airway inflammatory phenotypes in clinical features,pulmonary function and plasma inflammatory factors（IL-5,IL-8）expression in patients with acute asthma,and to explore the phenotypic risk factors and predictive markers.Methods1.Research object:Prospective study included 120 patients with acute asthma who were not treated in Luoyang Central Hospital from May 2019 to July 2020.Among them,11 patients could not take sputum samples because they could not tolerate induced sputum operation,so the remaining 109 patients were divided into four inflammatory phenotypes according to induced sputum cell count,which were eosinophilic asthma（EA）,neutrophilic asthma（NA）,mixedgranulocytic asthma（MA）and paucigranulocytic asthma（PA）.In the same period,30 healthy persons in the physical examination center of our hospital were randomly selected as the control group.2.Specimen collection:All candidates registered demography,smoking history,allergy history and other information.Fill in the score of asthma control test（ACT）.Fractional exhaled nitric oxide（FeNO）,pulmonary function and induced sputum test were completed.Collected 5 ml of venous blood from the elbow on an empty stomach.After centrifugation（2000 r/min,5 min）,plasma was obtained.Plasma IL-5 and IL-8concentrations were detected with plasma interleukin ELISA kit.3.Statistical method:SPSS25.0 software was used for statistical analysis.According to the data types,different statistical methods were selected to analyze the differences among the four inflammatory phenotypes.According to the analysis of induced sputum cells,airway inflammation was divided into eosinophilic inflammation or neutral inflammation,and then binary Logistic regression was used to analyze the risk factors of airway inflammation phenotype.Multivariate ROC curves were drawn to explore the markers of phenotypic diagnosis.The double-tailed P value is calculated at the significance level of 5%.Results1.There was no significant difference in general condition between asthma group and healthy group（P>0.05）,but the proportion of allergic history,FeNO,plasma IL-5 and IL-8levels were higher,while lung function FEV₁/FVC and FEV₁%were lower in asthma group than those in healthy group（all P<0.05）.2.According to the current international classification of inflammatory phenotypes of asthma,the phenotypic distribution of asthma group were 37 cases of EA（33.9%）,26cases of NA（23.9%）,24 cases of PA（22.0%）and 22 cases of MA（20.2%）.3.With phenotypic difference analysis,compared with NA,the proportion of EA with allergic history and FeNO level was higher,but the proportion of smoking patients was lower（all P<0.05）.The scores of PA pulmonary function（FEV₁%and PEF%）and asthma control test（ACT）were higher than those of the other three groups（all P<0.05）.The pulmonary function（FEV₁/FVC,FEV₁%,PEF%）in NA and MA groups was worse than that in EA and PA groups.The level of plasma IL-5 in eosinophilic inflammatory asthma group（EA and MA）was higher than that in non-eosinophilic group（NA and PA）（all P<0.05）.The level of plasma IL-8 in neutrophilic inflammatory asthma group（NA and MA）was higher than that in non-neutrophilic group（EA and PA）（all P<0.05）.4.Logistic regression analysis showed that the increase of FeNO and plasma IL-5levels and the history of allergy were the risk factors of eosinophilic inflammatory asthma,while the severity of lung function,the increase of plasma IL-8 level and the decrease of ACT score were the risk factors of neutral inflammatory asthma.5.Multi-index ROC curve of eosinophilic inflammatory asthma:In a single indicator,when the cutoff value of FeNO was 35.5 ppd,the AUC was 0.910（95%CI:0.871～1.000,P<0.01）,the maximum of Jordan index was 0.898,the sensitivity was 91.0%,and the specificity was 98.8%.Taking FeNO,plasma IL-5 and allergic history as joint predictors,the AUC was 0.931（95%CI:0.896～1.000,P<0.01）,the maximum of Yoden index was0.901,the sensitivity was 91.9%,and the specificity was 98.2%.6.Multi-index ROC curve of neutral inflammatory asthma:In a single indicator,when the pulmonary function grade≥3,the AUC was 0.818（95%CI:0.756～0.921,P<0.0l）,the maximum of Jordan index was 0.695,the sensitivity was 87.5%,and the specificity was82.0%.Taking plasma IL-8 level,pulmonary function severity grade and ACT score as joint predictors,the AUC was 0.893（95%CI:0.813～1.000,P<0.01）,the maximum Jordan index was 0.762,the sensitivity was 88.3%,and the specificity was 87.9%.ConclusionIn this cohort study,asthma airway inflammation was divided into four types:EA,NA,MA,and PA,of which the EA type was the most common（33.9%）;There were differences between the four phenotypes,suggesting that there may be different pathogenesis and markers.Further analysis shows that combined detection has the highest risk prediction and diagnostic value for asthma phenotype,suggesting that plasma IL-5 and IL-8 may be biomarkers of asthma inflammatory phenotype,and clinical diagnosis and treatment should pay more attention to related indicators.This experiment provides support for accurate diagnosis and treatment of asthma patients and biological targeted therapy.