支气管哮喘气道炎症可能机制的探讨

目的 探讨支气管哮喘(简称哮喘)患者气道炎症特征及其可能机制,并进一步观察吸入糖皮质激素治疗对气道炎性细胞分类计数、炎症介质等的影响.方法 分别选择轻度(轻度组)、中度(中度组)和重度(重度组)持续哮喘患者15例、14例和19例,正常对照组15名,分别行哮喘症状控制评分、肺功能测定、诱导痰炎性细胞分类计数、调节激活正常T细胞表达和分泌细胞因子(RANTES)、嗜酸粒细胞阳离子蛋白(ECP)、白介素8(IL-8)及髓过氧化物酶(MPO)浓度检测,然后规范吸人糖皮质激素治疗4周,随访复查上述指标.结果 诱导痰NEU%、IL-8及MPO重度组明显升高,分别为(62.40±22.05)%、594.53±85.11、39.25±10.67与轻度组(47.23±15.12)%、183.63±120.98、12.47±4.15]、中度组(46.13±19.23)%、352.76±71.72、22.93±7.35]、正常对照组(31.44±13.31)%、103.26±36.33、10.22±4.13]比较差异均有统计学意义(P＜0.01);RANTES、嗜酸粒细胞百分比(EOS%)和ECP浓度在各哮喘组间比较差异无统计学意义(P＞0.05).EOS%与RANTES、ECP水平呈正相关(r=0.557,P＜0.05;r=0.852,P＜0.01);NEU%与IL-8、MPO水平呈正相关(r=0.732,P＜0.05;r=0.806,P＜0.05);经糖皮质激素治疗后,对轻、中、重度哮喘患者合并进行分析表明,治疗后症状评分由(9.8±5.4)分下降至(4.0±3.5)分和肺功能指标第一秒用力呼气容积占预计值百分比由(62.2±23.3)%升高至(75.9±17.5)%显著改善,差异有统计学意义(P＜0.01).在接受糖皮质激素治疗后,RANTES、EOS%和ECP水平均显著降低.另外MPO水平也显著降低(P＜0.01);但治疗后在重度组仍显著高于轻、中度组(P＜0.01).但IL-8、NEU%治疗后无明显降低(P＞0.05),而且治疗后IL-8、NEU%在重度组仍显著高于轻、中度组(P＜0.01).结论 中性粒细胞增多是重度哮喘的气道炎症特征之一,EOS与病情严重程度无关.EOS哮喘的发生可能与RANTES的趋化、EOS的活化、ECP的释放有关,激素可以抑制EOS气道炎症.而中性粒细胞哮喘的发生可能与IL-8的趋化、NEU的活化、MPO的释放有关.

Characteristics of airway inflammation in bronchial asthma

Objective To investigate the characteristics of airway inflammation in asthma and the effect of the airway inflammation after being inhaled eorticorsteroid.Methods Fifteen patients with mild persistent asthma,14 patients with moderate persistent asthma and 19 patients with severe persistentasthma,as well as 15 normal control subjects,were included.At baseline,asthma symptom score was recorded,and lung function was measured.Induced sputum was obtained and processed for cell differentiation and the supernatant was assayed for the concentrations of RANTES,IL-8,ECP and MPO.Then all the asthmatic patients received inhaled corticosteroid(Pulmicort,Astra-Zeneca)therapy for four weeks,and the above measurements were repeated.Results The percentage of sputum neutrophils,IL-8 and MPO were significantly increased in patients with severe asthma(62.40±22.05%,594.53±85.11,39.25±10.67)as compared to patients with mild(47.23±15.12%,183.63±120.98,12.47±4.15)and modcrate(46.13±19.23%,352.76±71.72,22.93±7.35)asthma and normal controls(31.44±13.31%,103.26±36.33.10.22±4.13)(P＜0.01).On the contrary,the percentage of sputum eosinophils and the level of RANTES and ECP had no significant difference among mild,moderate and severe asthma(P＞0.05);EOS% positively correlated with RANTES and ECP(r=0.557,P＜0.05;r=0.852,P＜0.01);NEU% positively correlated with IL-8 and MPO(r=0.732,P＜0.05;r=0.806,P＜0.05);After steroid therapy,the symptom score decreased from(9.8±5.4)marks to(4.0±3.5)marks,pulmonary function (FEV1%)increased from(62.2±23.3)%to(75.9±17.5)%(P＜0.01).The percentage of eosinophils and the levels of RANTES and ECP all decreased significantly(P＜0.01).The levels of MPO also decreased significantly(P＜0.01),but the percentage of neutrophils and IL-8 remained unchanged(P＞0.05).IL-8,NEU%and MPO were still significantly higher in severe asthmatic patients as compared to mild and moderate asthmatic patients after steroid therapy.Conclusions Airway neutrophilia is a feature of severe asthma.EOS has no relationship with the degree of asthma.IL-8 pathway may be involved in the initial neutrophil influx into the airways.RANTES pathway may be involved in the initial eosinophil influx into the airways.Steroid can be used to inhibit the airway inflammation of eosinophils.