吸入激素联合治疗COPD的有效亚型及茶碱的逆转作用  

Treatment of inhaled corticosteroids combined with theophylline in COPD based on effective phenotypes

作　　者：孙娴雯[1] 李庆云[1] 顾淑一[1] 万欢英[1] 邓伟吾[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院呼吸科,200025

出　　处：《国际呼吸杂志》2017年第1期35-40,共6页International Journal of Respiration

基　　金：中华医学会临床医学科研专项资金项目（07010210029）;上海市科学技术委员会科研计划项目（14411950900）;上海市气象与健康重点实验室开放基金课题（QXJK201403）

摘　　要：目的COPD治疗的关键是抗炎、缓解症状、延缓肺功能恶化。敏感性是影响糖皮质激素疗效的主要原因，故有必要筛选激素治疗敏感的COPD亚型并对不敏感者采取相应措施。研究发现茶碱可提高组蛋白去乙酰化酶2活性，进而改善激素的抗炎作用。因此本研究拟进一步探讨小剂量茶碱对激素不敏感的逆转作用。方法采用高分辨率CT（high-resolution computed tomography,HRCT）对63例稳定期COPD患者行病理改变的综合评估分型，A型：无肺气肿或轻微肺气肿合并或不合并支气管管壁增厚；E型：肺气肿不合并支气管管壁增厚；M型：肺气肿合并支气管管壁增厚。各型患者分为吸入激素或联合口服茶碱治疗组。监测12周、24周治疗后患者的临床症状评分及肺功能变化。结果各型COPD患者临床特征和肺功能检查结果存在差异。A型患者联合治疗后的临床症状评分优于E型；E型患者联合治疗后的临床症状评分显著改善；M型患者吸入激素治疗后的临床症状评分显著改善。A型患者吸入激素或联合治疗后的肺功能及改善率均高于其余2型患者；E型患者联合治疗后肺功能及改善率均高于单一吸入激素治疗。结论HRCT分型中A型、M型可能是糖皮质激素治疗COPD的有效亚型，而联合茶碱治疗可提高激素疗效。Objective Chronic obstructive pulmonary disease （COPD） phenotypes may have individual characteristics and different responses to corticosteroids treatment. Recent advances have provided hope for a therapeutic strategy that restores corticosteroid sensitivity by increasing histone deacetylase-2 activity by low dose theophylline. We conducted a study to identify phenotypes with good responses to inhaled corticosteroids by high-resolution computed tomography （HRCT） and explored the effect of low-dose theophylline on corticosteroid sensitivity. Methods Sixty-three stable COPD patients were examined by HRCT and classified into three phenotypes： absence of emphysema, with little emphysema with or without bronchial wall thickening （A phenotype）, emphysema without bronchial wall thickening （E phenotype）, and emphysema with bronchial wall thickening （M phenotype）. They were treated with fluticasone propionate/salmeterol with or without theophylline for twenty-four-week follow- up. Results The patients of phenotype A and M responded well to corticosteroid treatment, whereas patients of phenotype E responded poorly. Anti-inflammatory sensitivity of inhaled corticosteroid was increased in the phenotype E treated with low-dose theophylline combination therapy. Conclusions Low- dose theophylline may improve the corticosteroids sensitivities based on HRCT phenotypes of COPD.

关 键 词：慢性阻塞性肺疾病 高分辨率CT 吸入糖皮质激素 茶碱 亚型 

分 类 号：R563.9[医药卫生—呼吸系统]