支气管哮喘患者痰嗜酸粒细胞相对计数与糖皮质激素治疗反应性的关系

目的观察支气管哮喘（简称哮喘）患者不同气道炎症类型（嗜酸粒细胞炎症与非嗜酸粒细胞炎症）对吸人糖皮质激素（简称激素）治疗的反应性。方法选择近3个月内未接受激素治疗的慢性持续性哮喘患者42例，根据诱导痰嗜酸粒细胞百分比将患者分为嗜酸粒细胞增高组（嗜酸粒细胞〉3％，23例）与非嗜酸粒细胞增高组（嗜酸粒细胞〈3％，19例），进行哮喘症状评分、肺功能检查、诱导痰细胞分类计数。采用酶联免疫荧光法测定痰液嗜酸粒细胞阳离子蛋白（ECP）的浓度。吸人激素治疗1、3个月时进行随访，重复上述哮喘疗效的评价指标。结果嗜酸粒细胞增高组痰嗜酸粒细胞比值、ECP水平基线值分别为0．080（0．063～0．178）、（324±149）μg／L，非嗜酸粒细胞增高组分别为0．017（0．006～0．021）、（152±68）μg／L，两组比较差异有统计学意义（t值分别为4．40、3．33，P均〈0、01）。嗜酸粒细胞增高组第一秒用力呼气容积（FEV1）、FEV1占预计值百分比（FEV1占预计值％）、症状评分的基线值分别为（1．98±0．67）L、（65±20）％、7．0（5．0～10．0）分，非嗜酸粒细胞增高组分别为（2．07±1．05）L、（66±27）％、5．0（2．0～9．0）分，两组比较差异无统计学意义（t值分别为-0．62、-0．09、1．32，P均〉0．05）。吸入激素治疗1、3个月后嗜酸粒细胞增高组的嗜酸粒细胞比值、ECP水平、症状评分、FEV1和FEV1占预计值％分别为0．019（0．010～0．060）、0．036（0．006～0．070）、（173±153）μg／L、（173±122）μg／L、3．0（1．0～6．0）分、3．0（1．0～5．0）分、（2．42±0．64）L、（2．43±0．76）L、（77±13）％、（77±18）％，与基线值比较差异有统计学意义（F值分别为6．73、6．71、5．93、7．38、5．78，P均〈0．05）。非嗜酸粒细胞增高组分别为0．013（0．000～0．025）、0．012（0．004～0．031）、（111±50）μg／L、（117±50）μg／L、3．0（0．0～6．0）分、3．0（1．0～7．3）分、（2．22±0．86）L、（2．21±0．24）L、（71±20）％、（65±21）％，与基线值比较，嗜酸粒细胞比值、FEV1和FEV1占预计值％均无统计学意义（F值分别为1．98、0．80、1．37，P均〉0．05），而ECP水平和症状评分比较差异有统计学意义（F值分别为3．78、3．59，P均〈0．05）。多元线性回归分析显示，病情严重度、基线FEV1和痰嗜酸粒细胞百分比与FEV1改善程度相关（r值分别为-0．27、-0．02、0．03，P均〈0．05）。痰嗜酸粒细胞比值的基线值对激素治疗反应的阴性预测值最高（89．5％）。结论对于痰嗜酸粒细胞增高的哮喘患者，吸人激素治疗能够抑制嗜酸粒细胞炎症，改善肺功能和症状评分。非嗜酸粒细胞增高哮喘患者对激素治疗反应性差，FEV1无改善。痰嗜酸粒细胞比值不高是激素治疗反应性差的最佳预测指标。

The relationship between sputum eosinophils and responses to treatment of inhaled glucocorticoids in patients with persistent asthma

OBJECTIVE: To evaluate the treatment responses of asthmatics with and without sputum eosinophilia to inhaled glucocorticoids, and therefore to verify whether low sputum eosinophils predict poor response to treatment with inhaled glucocorticoids. METHODS: Forty-two symptomatic asthmatic patients, who had not received glucocorticoid therapy in the 3 months preceding the study, were examined before and 1 month and 3 months after treatment with inhaled glucocorticoids. At each visit, all patients underwent spirometry, symptom scoring and sputum induction. The level of eosinophil cationic protein (ECP) in the sputum supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to sputum eosinophil (EOS) percentages, an EOS group (EOS > 3%) and a non-EOS group (EOS < 3%). The response to inhaled glucocorticoid therapy (as measured by symptom scores and FEV(1)% pred) and the changes of sputum measurements were compared between the 2 groups. RESULTS: In the EOS group, the baseline EOS 0.080 (0.063 - 0.178)] and ECP level (324 +/- 149) microg/L] were significantly higher than those of the non-EOS group 0.017 (0.006 - 0.021) and (152 +/- 68) microg/L, respectively, t = 4.40, 3.33, both, all P < 0.01]. Baseline FEV(1), FEV(1)% pred and symptom scores were not different between the 2 groups EOS group: (1.98 +/- 0.67) L, (65 +/- 20)%, 7.0 (5.0 - 10.0), non-EOS group: (2.07 +/- 1.05) L, (66 +/- 27)%, 5.0 (2.0 - 9.0), t = -0.62, -0.09, 1.32, respectively, all P > 0.05]. After 1 month and 3 months inhaled glucocorticoid therapy, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were 0.019 (0.010 - 0.060), 0.036 (0.006 - 0.070); (173 +/- 153) microg/L, (173 +/- 122) microg/L; 3.0 (1.0 - 6.0), 3.0 (1.0 - 5.0); (2.42 +/- 0.64) L, (2.43 +/- 0.76) L; (77 +/- 13)%, (77 +/- 18)%; respectively in the EOS group, which were significantly different as compared to baseline values (F = 6.73, 6.71, 5.93, 7.38, 5.78, respectively, all P < 0.05). But in the non-EOS group, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were 0.013 (0.000 - 0.025), 0.012 (0.004 - 0.031), (111 +/- 50) microg/L, (117 +/- 50) microg/L; 3.0 (0.0 - 6.0), 3.0 (1.0 - 7.3), (2.22 +/- 0.86) L, (2.21 +/- 0.24) L, (71 +/- 20)%, (65 +/- 21)%; respectively at 1 and 3 months, which showed that the sputum EOS, FEV(1) and FEV(1)% pred did not change (F = 1.98, 0.80, 1.37, respectively, all P > 0.05), but the ECP level and the symptom score improved (F = 3.78, 3.59, respectively, both P < 0.05). Multiple stepwise regression showed that baseline FEV(1), severity degree and sputum EOS correlated significantly with changes in FEV(1) after treatment. Among the baseline indexes examined, sputum EOS had the highest negative predictive value (89.5%) for the response to treatment. CONCLUSIONS: In asthmatics with low sputum EOS, inhaled glucocorticoid therapy for 3 months failed to improve pulmonary function. The result confirmed that low sputum EOS was the best predictor for poor glucocorticoid effect in asthma.