| Background: Bronchial asthma(abbreviated as asthma)is a chronic airway inflammatory disease affected by environmental and genetic factors,with a high degree of heterogeneity.In recent years,research on its "phenotype" has provided a new direction for individualized treatment of asthma.Eosinophilia represents the main feature of what we call typical atopic asthma,this phenotype usually responds well to corticosteroids.Only a small part of severe asthma,even in the presence of eosinophils,has a weak response to inhaled corticosteroids.The neutrophil phenotype driven by the presence of neutrophils shows insufficient response to corticosteroid treatment even in mild asthma.In recent years,Gibson PG proposed to classify asthma patients according to the proportion of inflammatory cells in induced sputum into inflammatory subtypes,which are divided into paucigranulocytic asthma(PA),mixed granulocytic asthma(MA),eosinophilic asthma(EA)and neutrophilic asthma(NA).Interleukin-36(IL-36)subfamily is an inflammatory factor of the IL-1 family discovered in recent years,divided into IL-36α,IL-36β,IL-36γ and IL-36 Ra.It is involved in the pathogenesis of a variety of inflammatory diseases and allergic diseases.However,the specific mechanism of IL-36 in asthma is still unclear.Our research is to explore the expression of IL-36 in different inflammatory subtypes of asthma,further clarify the role of IL-36 in the pathogenesis of asthma,and provide new ideas for individualized treatment of asthma.Objective: This study used induced sputum technology to classify asthma inflammatory subtypes and detected the expression of IL-36 inflammatory factors in different inflammatory subtypes of asthma to reveal the pathogenesis of IL-36 in different inflammatory subtypes of asthma,and to provide a basis for individualized targeted therapy of asthma.(1)Randomly enrolled 62 patients with stable asthma in the Department of Respiratory Medicine,Second Hospital of Jilin University from September 2018 to December 2020.At the same time,16 healthy volunteers were recruited to perform induced sputum,sputum cell smears and cell counts.And according to the classification of asthma inflammation subtypes proposed by Gibson PG to classify asthma patients.Collect basic information and clinical data of asthma patients.Methods:(2)The expression levels of IL-36α,IL-36β,IL-36γ,IL-36 Ra and interleukin-1β(IL-1β)inflammatory factors in the sputum supernatant of all subjects were detected by the enzymelinked immunosorbent assay(ELISA)method.In addition,multi-factor detection technology was used to detect the expression levels of inflammatory mediators such as interleukin-5(IL-5),interferon-γ(INF-γ),interleukin-2(IL-2),Interleukin-6(IL-6),Interleukin-9(IL-9),Interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),Interleukin-17A(IL-17A),Interleukin-17F(IL-17F),interleukin-4(IL-4)and interleukin-22(IL-22).The general clinical data of asthma patients and healthy people were analyzed by statistical methods,and the differences in the expression levels of inflammatory factors were compared and analyzed.Results:(1)Clinical data and IL-36 cytokine expression analysis of asthma group and healthy control group:(1)This study collected 62 patients with stable asthma,33 males and 29 females;16 healthy controls,including 9 males and 7 females.The clinical data of the two groups were compared,and there was no significant difference in age,gender,body mass index and smoking history(P>0.05).(2)The total count of sputum cells in the asthma group was higher than that in the healthy control group.The sputum cell count and the percentage of eosinophils and neutrophils in the asthma group were significantly higher than the healthy control group,while the macrophage count and the percentage were significantly lower than the control group(P<0.05).(3)The percentage of FEV1,FVC,FEV1 percent predicted and the ratio of FEV1 to FVC after inhaling bronchodilators in the asthma group were lower than those in the control group,and asthma patients had higher fractional exhaled nitric oxide(FENO)compared with the healthy control group,the difference was significant(P<0.05).(4)Among the subtypes of IL-36,IL-36α and IL-36β in the sputum supernatant of asthma patients were significantly higher than those in healthy controls [41.5(38.3,48.6)vs 38.7(36.7,39.6),31.7(30.8,34.0)vs 30.9(30.5,31.5)pg/ml],the difference was statistically significant(P<0.05);while the asthma group IL-36 Ra [30.6(27.2,33.2)pg/ml] compared with the control group [42.3(33.9,47.4)pg/ml] decreased,the difference was statistically significant(P<0.05).The expression level of IL-36γ in the asthma group was higher than that in the control group [280.5(238.3,406.6)vs 263.0(228.9,376.3)pg/ml],the difference was not statistically significant.(2)Comparison of the distribution characteristics of the four asthma subtypes and the expression level of IL-36 factor:(1)24 cases of PA(38.7%),23 cases of EA(37.1%),9 cases of NA(14.5%),and 6 cases of MA(9.7%).Among the four types of asthma,PA is the most,followed by EA and NA,and MA is the least.(2)The FENO in the EA group was higher;the lung function in the NA group was the worst.(3)IL-36α is highly expressed in MA and NA,NA group and MA group [43.2(38.1,998.2)vs 43.8(37.7,77.7)pg/ml],NA group and EA group [43.2(38.1,998.2)vs 41.2(37.5,46.8)pg/ml],the difference between NA group and PA group [43.2(38.1,998.2)vs 40.8(38.6,47.1)pg/ml] was statistically significant(P<0.05).IL-36β expression level in NA group was higher than EA group [41.4(30.5,119.4)vs 31.5(30.6,32.4)pg/ml],NA group was higher than PA group [41.4(30.5,119.4)vs 31.4(30.8,33.1)pg/ ml] were significantly increased,and the difference was statistically significant(P<0.05).The NA group was higher than the MA group [41.4(30.5,119.4)vs 32.4(31.9,112.4)pg/ml],the difference was not statistically significant(P>0.05).(3)Analysis of the correlation between IL-36 and sputum inflammatory cells and other inflammatory factors: IL-36α,IL-36β,IL-1β and sputum neutrophil count are positively correlated;IL-36α is positively correlated with IL-36β,IL-1β,and IL-6;IL-36β is positively correlated with IL-1β,TNF-α.Conclusions:(1)In this investigation,there were more patients with asthma inflammatory phenotypes PA and EA,and NA and MA accounted for a small proportion.Different inflammatory subtypes of asthma have different predominant infiltration of inflammatory cells,so the pathogenesis is also different,and the treatment for the phenotype is also different.Thedifference fully reflects the heterogeneity of asthma.The classification of asthma according to the phenotype provides new ideas for the treatment and management of asthma.(2)IL-36α and IL-36β are significantly higher in neutrophil asthma,IL-36α and IL-36β may participate in the immune inflammatory response of neutrophil asthma by mediating Th1 cells.Further exploration of this factor will facilitate the development of targeted drugs and open up a new path for the individualized treatment of asthma. |
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