沙美特罗氟替卡松对稳定期慢性阻塞性肺疾病患者诱导痰及血浆白介素32表达的影响

Effect of salmeterol/fluticasone on interleukin-32 expression in induced sputum and plasma of stable chronic obstructive pulmonary disease

目的已有研究证实白介素32（IL-32）在慢性阻塞性肺疾病（COPD）患者肺组织中表达增高且与气流受限程度相关，提示IL-32可能与COPD的异常炎症反应和疾病进展有关。本研究拟观察沙美特罗氟替卡松对稳定期COPD患者IL-32表达的影响，探讨IL-32在COPD发病中的作用。方法所有受试者共分为4组：稳定期COPD患者32例，健康吸烟者18人，健康非吸烟者18人。其中稳定期COPD患者随机分为2组，分别为接受沙美特罗／氟替卡松治疗（50ug／500ug，2次／d）及沙丁胺醇／异丙托溴铵（21ug／120ug，4次／d）治疗随访3个月。随访前后收集临床资料、肺功能、诱导痰、血浆，采用酶联免疫吸附试验方法检测诱导痰上清及血浆中IL-32及肿瘤坏死因子a（TNF-a）的浓度。结果治疗前各组受试者间诱导痰及血浆中IL-32浓度及浓度的差异均无统计学意义。COPD组患者的诱导痰Il-32浓度与痰巨噬细胞及中性粒细胞计数、第1秒用力呼气容积（FEV1）占预计值百分比及圣乔治呼吸评分（SGRQ）均无相关性。COPD组血浆TNF—a浓度显著高于对照组且与血浆IL-32浓度呈正相关（r=0．68，P〈0．001）。治疗3个月后随访结果显示：两组患者治疗前后诱导痰及血浆IL-32浓度、诱导痰细胞总数、中性粒细胞计数、巨噬细胞计数及肺功能FEV1的差异均无统计学意义。沙美特罗／氟替卡松组治疗后SGRQ较治疗前显著下降，其差异有统计学意义（P〈0．001），而沙丁胺醇／异丙托溴铵组治疗前后SGRQ无显著差异。结论IL-32与COPD患者诱导痰炎症细胞增多无明显相关性，但可能参与了（COPD全身炎症反应。沙美特罗／氟替卡松可改善COPD患者的临床症状并提高生活质量，但其对IL-32的表达无显著影响。

Objective The interleukin-32 （IL- 32）, a newly discovered cytokine, was reported to have increased expressions in the lung tissue of patients with chronic obstructive pulmonary disease （COPD） and correlated with the degree of airflow obstructions. This study was to undertake a randomized controlled trail to evaluate combined salmeterol/fluticasone on IL- 32 and inflammatory ceils in induced sputum and plasma of COPI） patients and discuss whether IL- 32 is related to the inflammatory disorder of COPD patients. Methods Using enzyme linked immunosorbent assay, the expression of IL- 39 in induced sputum and plasma was respectively examined to the following groups： 32 patients with stable COPD, 18 asymptomatic smokers, and 18 nonsmokers. COPD patients were treated in an open labeled, randomized, parallel group and controlled trial with either a combination of 50 ug salmeterol and 500 ug fluticasone twice daily （SF, n =18） or 21 ug salbutamol and 120 ug ipratropine quartic daily （IS, n = 18） for 3 months. At the start and end of treatment induced sputum was performed and the level of IL- 32 was measured. Results IL-32 level in sputum and plasma of the four groups did not show significant differences. IL -32 level in sputum had no correlation to maerophage and neutrophil count in sputum, FEV1% predicted and SGRQ. IL-32 level in plasma of COPI） patients had positive correlation to TNF-a level in plasma （r=0.65, P〈0.001）. In addition, SGRQwas significantlyrednced by SF （P〈0.001） which was not seen with IS. SF did not significantly change IL-32 level in sputum and plasma, macrophage and neutrophil count in sputum and FEV 1% predicted compared with IS. Conclusions The results of this study suggested that although IL-32 was not related to the increase of inflammatory cells in induced sputum of COPD patients, ii might be implicated in the systematic inflammatory disorder of COPD patients. SF improved the health status but did not significantly change IL- 32 level and inflammatory cells in induced sputum of COPD patients.