| Background and ObjectiveBronchial asthma(asthma) is a serious global health problem with an estimated 300 million affected individuals.People of all ages in countries throughout the world are affected by this chronic airway disorder that,when uncontrolled,can place severe limits on daily life and is sometimes fatal.In our country,the prevalence of asthma is increasing,and the mortality,about 36.7 death/100,000,is ranking the first of the world.Globally,with the increasing burden on the societies and families,asthma has been a very important public health problem.The core of the pathogenesis of asthma is chronic airway inflammation,which is formed complicatedly and perhaps includes the chain-reaction caused by the interaction of various kinds of cytokines, inflammatory mediators and external factors.It is well known that Eosinophils plays a very important role in the pathogenesis and progress of asthma.According to recent researches,Neutrophils is involved as well in several processes of asthma,such as the formation of the airway inflammation,airway hyperresponsiveness,increased gland secretion and airway remolding,etc.This neutrophilic inflammation pattern,which is different from the eosinophilic one,can present in some asthmatic patients,and,along with its effect,may have a close relationship with the inflammatory network formed by IL-17A,IL-8 and MMP-9,of which the mechanism remains unknown.Presently, there are few domestic researches about the correlation among the expressions of IL-17A,IL-8 and MMP-9 in asthmatic airway and their relationships with the neutrophilic inflammation.Airway inflammation is the essence of asthma,therefore,it should be clinically meaningful that those studies targeting on the index which can reflect the airway inflammation mode and severity.This study preliminarily discuss the distribution of inflammatory cells and the role of that three inflammatory mediators in chronic airway inflammation of asthmatics,and provide theory for the researches concerned pathogenesis and clinical treatment of asthma,by counting the differential inflammatory cells in sputum and detecting the concentrations of IL-17A, IL-8 and MMP-9 in supernatants fluid of induced sputum and peripheral blood and monitoring the change of those index after the administration of glucocorticosteroids.Subjects and MethodsAirway cells were obtained by sputum induction from 15 healthy(control group),15 patients(CB group) in exacerbation of chronic bronchitis and 45 asthmatic individuals (30 mild to moderate asthmatics and 15 severe asthma patients are involves in this group) to processed for differential cell count,and the serum from the peripheral blood and the sputum supernatant was assayed for the levels of IL-17A,IL-8,MMP-9 According to the severity of patients,20 mild to moderate asthmatics and 15 severe patients with asthma received corticosteroid therapy for four weeks,and the induces sputum measurements were repeated.ResultsThe induced sputum tests were performed successfully in all subjects,and none of them occurred the adverse reaction of airways spasm.Before the corticosteroid treatment,the percentage of sputum Neutrophils and Eosinophils were significantly elevated in patients with severe asthma[(59.8±15.8)%, (8.7±4.1)%]compared to patients with mild-to-moderate asthma[(42.1±14.6)%, (5.5±3.4)%],healthy controls[(26.3±10.3)%,(1.0±0.8)%],and CB group patients [(48.8±15.2),(1.1±1.2)](P＜0.05).And the percentage of sputum Neutrophils and Eosinophils had significantly differences in patients with mild-to-moderate asthma compared to healthy controls(P＜0.01).The levels of sputum IL-17A,IL-8 and MMP-9 were significantly elevated in patients with severe asthma [(265.5±157.0)pg/ml,(459.3±223.6)pg/ml,(436.7±247.8) ng/ml]compared to healthy controls[(54.7±22.7)pg/ml,(203.2±103.5) pg/ml,(140.8±105.2)ng/ml]and chronic bronchitis patients[(113.0±94.8)pg/ml,(297.2±194.2)pg/ml,(217.0±103.5) ng/ml] (P＜0.01).The levels of IL-17A,IL-8 had significantly differences in patients with mild-to-moderate asthma compared to healthy controls(P＜0.01).The sputum IL-17A levels in chronic bronchitis group had significantly differences compared to the mild to moderate asthmatics.The percentage of sputum Neutrophils and Eosinophils positively correlated with the levels of FEV1%Pred(r=-0.601,P＜0.01;r=-0.699, P＜0.01).The percentage of sputum Neutrophils positively correlated with the levels of sputum IL-17A,IL-8,MMP-9(r=0.240,P＜0.05;r=0.349,P＜0.01;r=0.301,P＜0.01) The level of sputum IL-17A positively correlated with the level of IL-8 and MMP-9(r=0.342,P＜0.01;r=0.241,P＜0.01).The levels of FEV1%Pred negatively correlated with the levels of sputum IL-17A,IL-8,MMP-9(r=-0.552, P＜0.01;r=-0.358,P＜0.01;r=-0.515,P＜0.01).The level of serum IL-17A,IL-8 and MMP-9 in severe asthmatics[(133.7±63.9) pg/ml,(414.7±209.1) pg/ml, (413.8±129.5) ng/ml]were significantly elevated compare with mild to moderate group[(79.7±45.1) pg/ml,(259.1±186.5) pg/ml,(206.1±121.8) ng/ml],healthy control[(39.3±18.6) pg/ml,(175.3±80.2) pg/ml,(155.7±92.8) ng/ml],and CB group[(63.6±43.0) pg/ml,(226.5±149.8) pg/ml,(240.5±180.7) ng/ml](p＜0.01).The percentage of sputum Neutrophils positively correlated with the levels of serum IL-17A,IL-8,MMP-9(r=-0.562,P＜0.01;r=-0.406,P＜0.01;r=-0.584,P＜0.01).The levels of FEV1%Pred negatively correlated with the levels of serum IL-17A,IL-8, MMP-9(r=0.258,P＜0.05;r=0.407,P＜0.01).The levels of serum IL-17A positively correlated with the levels of serum IL-8 and MMP-9(r=0.243,P＜0.05;r=0.378, P＜0.05).There were significant correlations about the levels of IL-17A,IL-8,MMP-9 between in sputum and in serum(r=0.838,P＜0.01;r=0.811,P＜0.01;r=0.506, P＜0.01).After steroid therapy,the percentage of Eosinophils(t=6.227,P＜0.01),the levels of IL-17A(t=3.918,P＜0.01),IL-8(t=6.645,P＜0.01),MMP-9(t=3.904,P＜0.01)decreased significantly in all patients,but the percentage of Neutrophils(t=-1.121,P＞0.05) remained unchanged and still significantly higher in severe asthmatics compared to mild-to-moderate asthmatics(t=-2.716,P＜0.05).Conclusions(1) Sputum induction is safe and reliable and possesses practical value on research and clinical practice of airway inflammatory diseases.(2) Neutrophil infiltration is involved in the chronic airway inflammation and related to the degree of airway obstruction and,to certain extent,reflects the severity of disease and characterizes severe asthma.Neutrophil-mediated airway inflammation may be a significant inflammatory mode of asthmatics.(3) The expression levels of IL-17A,IL-8,MMP-9 are related to the process of airway inflammations and may be involved in the neutrophil-mediated airway inflammation and are capable of being a good tool for evaluating the airway inflammation modes,determining the severity of disease and observing the effect of treatment in patients with asthma. |
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