| Background:Bronchial asthma（asthma for short）is a complex and heterogeneous chronic bronchial inflammatory disease characterized by reversible airway obstruction and airway hyperresponsiveness（AHR）.Asthma is a chronic airway inflammation characterized by the involvement of various types of inflammatory cells（eosinophils,neutrophils,T lymphocytes,etc.）,inflammatory mediators and cytokines.In recent years,with the increasing number of studies on the heterogeneity of asthma,researchers have found that asthma can be divided into different phenotypes based on factors such as pathogenesis,disease severity,age,and pathogenesis.In a large number of past studies,asthma airway inflammation is generally considered to be an immune response driven by T helper 2（Th2）cells and eosinophils.However,there is also a subset of asthmatics who do not exhibit "Th2 asthma" features and respond poorly to inhaled corticosteroids.According to recent research reports,asthma can be divided into the following four different inflammatory subtypes according to the proportion of inflammatory cells in the induced sputum of asthma patients:eosinophilic asthma（EA）,granulocytic Paucigranulocytic asthma（PA）,neutrophilic asthma（NA）and mixed granulocytic asthma（MA）,each phenotype has its own mechanism of action and different treatment response.Interleukin-38（IL-38）is a newly discovered member of the IL-1 family,which is produced by various types of cells such as killer T cells,monocytes,and plasmacytoid dendritic cells.Because IL-38 is highly homologous to the sequence of Interleukin-36 Receptor--or Antagonist（IL-36Ra）,IL-38 is considered to have similar effects with IL-36 Ra,However,the role of IL-38 in the asthma phenotype remains unclear.This study focused on the differences in the expression of IL-38 in the sputum supernatant of patients with different asthma subtypes and the potential role of IL-38 in the pathophysiological mechanism of asthma,providing new clues for the precise treatment and management of asthma.Objective:This study aimed to investigate the clinical characteristics and sputum IL-38 expression levels of patients with different asthma subtypes and healthy controls,and to investigate the relationship between IL-38 and other inflammatory factors,lung function,age,gender,exhaled nitric oxide（Fractional exhaled nitric oxide）nitric oxide,FENO)and smoking history.Methods:Randomly recruited 60 asthmatic patients and 21 healthy control subjects from the stable asthma patients（from January 2021 to December 2021）who were reviewed in the outpatient department of Respiratory and Critical Care Medicine,Bethune Second Hospital of Jilin University.The subjects’ induced sputum samples,and the inflammatory cell count and proportion in the sputum supernatant were evaluated,classified according to Gibson PG’s classification criteria for asthma inflammation subtypes,and the subjects’ clinical data were collected.The expression levels of IL-38 and other related inflammatory factors in the sputum supernatant of all subjects were measured by enzyme-linked immunosorbent assay（ELISA）and multi-factor detection technology,respectively.Results:（1）Clinical characteristics and IL-38 expression analysis of asthma patients and healthy subjects:（1）A total of 60 stable asthma patients（26 females and 34 males）and 21 healthy volunteers（8 females and 13 males）Example)participated in this study.（2）There was no significant difference in gender and smoking history between the asthma group and the healthy control group;the asthma group was older than the healthy control group,and the difference was statistically significant;the body mass index（BMI）of the asthma group was smaller than that of the healthy control group（2）Compared with the healthy control group,the count and proportion of sputum eosinophils and the count and proportion of neutrophils in the asthma group were significantly increased,and the difference was statistically significant;Compared with the control group,the sputum macrophage count and proportion were lower in the asthma group,and the difference was statistically significant.（3）Compared with the healthy control group,the asthma group had worse lung function,and the difference was statistically significant.The FENO value of the asthma group was higher than that of the healthy control group,and the difference was statistically significant.（4）There was no significant difference in the expression of IL-38 between the asthma group and the healthy control group.（2）Analysis of clinical characteristics and IL-38 expression of different asthma inflammatory subtypes:（1）PA patients accounted for 50.0%;EA patients accounted for 36.7%;MA patients accounted for 6.6%;NA patients accounted for 6.6% was6.6%.Among the four asthma inflammatory subtypes,the PA type accounted for the largest proportion,while the MA type and NA type accounted for the least.（2）The FENO value of MA asthma patients was the highest,the FENO value of PA asthma patients was the lowest,and the lung function of NA asthma patients was the worst,and the difference was statistically significant.（3）Among the four asthma subtypes,the expression of IL-38 was the highest in NA asthma,and the difference was statistically significant.（4）The correlation analysis between IL-38 and other inflammatory factors and FENO: IL-38 was positively correlated with IL-17A（r=0.758,P<0.01）,and positively correlated with FENO（r=0.965,P<0.01）.Conclusions:（1）In this study,PA type asthma accounted for the highest proportion,and MA type and NA type accounted for the lowest.（2）The clinical characteristics of different asthma inflammatory subtypes were different: NA patients had the worst lung function,MA patients had the highest FENO value,and PA patients had the lowest FENO value.The inflammatory cells infiltrated in the airways of patients with different asthma inflammatory subtypes are also different,reflecting the heterogeneity of asthma.（3）IL-38 has the highest expression in the sputum of NA asthma patients,and IL-38 has a significant positive correlation with IL-17 factors involved in mobilizing,recruiting and activating neutrophils.It is speculated that IL-38 may be involved in the regulation Inflammatory responses in neutrophilic asthma.More in-depth studies are needed to clarify the role of IL-38 in asthma inflammatory subtypes and to provide new strategies for individualized treatment of asthma. |
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