中重度慢阻肺病人ICS撤退后气道炎症增加-5年随访研究
2017/01/20
摘要
研究背景及目的：长期吸入糖皮质激素（ICS）可能减低某些类型慢阻肺病人肺功能下降和降低气道炎症，撤退ICS治疗将导致进一步肺功能下降。Kunz L等研究假设慢阻肺病人长期ICS治疗后撤退ICS将增加气道炎症水平。
方法：GLUCOLD-研究（GL1）研究中，入组114例中重度慢阻肺病人，病人随机分配到6月和30月氟替卡松治疗（500 µg，一天2次），30月氟替卡松/沙美特罗（500/50 µg，一天2次）或者安慰剂组。5年随访研究（GL2）中，随访这些病人临床治疗情况。在基线及30月（GL1结束时）及7.5年（GL2结束时）进行支气管活检和诱导痰检查，评估炎症情况。应用线性混合效应模型分析结果。
结果：GL1期间使用ICS及GL2期间ICS使用时间（0–50%）的病人，GL2时支气管粘膜炎症细胞显著增高，包括CD3（每年差异改变通过GL2-GL1计算，2.68, 95% CI 1.87–3.84)、CD4(1.91, 95% CI 1.33–2.75)、CD8 (1.71, 95% CI 1.15–2.53)及肥大细胞(1.91, 95% CI 1.36–2.68)。GL2时痰总细胞数目显著增高(1.90, 95% CI 1.42–2.54)，其中巨噬细胞（2.10, 95% CI 1.55–2.86)，中性粒细胞(1.92, 95% CI 1.39–2.65)及淋巴细胞(2.01, 95% CI 1.46–2.78)。
结论：ICS撤退增加中重度慢阻肺病人气道炎症，提示慢阻肺病ICS的抗炎作用在ICS撤退后不能够维持。
关键词：慢阻肺，气道炎症，ICS撤离
Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids
Kunz L, ten Hacken Nick, Lapperre T S. et al.
European Respiratory Journal 2016; DOI: 10.1183/13993003.00839-2016
Abstract：
The research background and purpose: Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.
METHODS:In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo.During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.
RESULTS：In patients using ICS during GL1 and using ICS 0–50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3+ (fold change per year calculated as GL2 minus GL1 2.68, 95% CI 1.87–3.84), CD4+ (1.91, 95% CI 1.33–2.75) and CD8+ cells (1.71, 95% CI 1.15–2.53), and mast cells (1.91, 95% CI 1.36–2.68). The sputum total cell counts increased significantly in GL2 (1.90, 95% CI 1.42–2.54), as did counts of macrophages (2.10, 95% CI 1.55–2.86), neutrophils (1.92, 95% CI 1.39–2.65) and lymphocytes (2.01, 95% CI 1.46–2.78).
CONCLUSIONS:ICS discontinuation increases airway inflammation in patients with moderate-severe COPD, suggesting that the anti-inflammatory effects of ICS in COPD are not maintained after ICS discontinuation.
研究背景及目的：长期吸入糖皮质激素（ICS）可能减低某些类型慢阻肺病人肺功能下降和降低气道炎症，撤退ICS治疗将导致进一步肺功能下降。Kunz L等研究假设慢阻肺病人长期ICS治疗后撤退ICS将增加气道炎症水平。
方法：GLUCOLD-研究（GL1）研究中，入组114例中重度慢阻肺病人，病人随机分配到6月和30月氟替卡松治疗（500 µg，一天2次），30月氟替卡松/沙美特罗（500/50 µg，一天2次）或者安慰剂组。5年随访研究（GL2）中，随访这些病人临床治疗情况。在基线及30月（GL1结束时）及7.5年（GL2结束时）进行支气管活检和诱导痰检查，评估炎症情况。应用线性混合效应模型分析结果。
结果：GL1期间使用ICS及GL2期间ICS使用时间（0–50%）的病人，GL2时支气管粘膜炎症细胞显著增高，包括CD3（每年差异改变通过GL2-GL1计算，2.68, 95% CI 1.87–3.84)、CD4(1.91, 95% CI 1.33–2.75)、CD8 (1.71, 95% CI 1.15–2.53)及肥大细胞(1.91, 95% CI 1.36–2.68)。GL2时痰总细胞数目显著增高(1.90, 95% CI 1.42–2.54)，其中巨噬细胞（2.10, 95% CI 1.55–2.86)，中性粒细胞(1.92, 95% CI 1.39–2.65)及淋巴细胞(2.01, 95% CI 1.46–2.78)。
结论：ICS撤退增加中重度慢阻肺病人气道炎症，提示慢阻肺病ICS的抗炎作用在ICS撤退后不能够维持。
关键词：慢阻肺，气道炎症，ICS撤离
（王燕红 赵海金 南方医科大学南方医院 510515 摘译）
European Respiratory Journal 2016; DOI: 10.1183/13993003.00839-2016
European Respiratory Journal 2016; DOI: 10.1183/13993003.00839-2016
Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids
Kunz L, ten Hacken Nick, Lapperre T S. et al.
European Respiratory Journal 2016; DOI: 10.1183/13993003.00839-2016
Abstract：
The research background and purpose: Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.
METHODS:In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo.During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.
RESULTS：In patients using ICS during GL1 and using ICS 0–50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3+ (fold change per year calculated as GL2 minus GL1 2.68, 95% CI 1.87–3.84), CD4+ (1.91, 95% CI 1.33–2.75) and CD8+ cells (1.71, 95% CI 1.15–2.53), and mast cells (1.91, 95% CI 1.36–2.68). The sputum total cell counts increased significantly in GL2 (1.90, 95% CI 1.42–2.54), as did counts of macrophages (2.10, 95% CI 1.55–2.86), neutrophils (1.92, 95% CI 1.39–2.65) and lymphocytes (2.01, 95% CI 1.46–2.78).
CONCLUSIONS:ICS discontinuation increases airway inflammation in patients with moderate-severe COPD, suggesting that the anti-inflammatory effects of ICS in COPD are not maintained after ICS discontinuation.
上一篇：
NOX4过度表达与中性粒细胞哮喘患者上皮纤毛功能障碍相关
下一篇：
重症嗜酸粒细胞性哮喘患者中上皮细胞因子信号通路抑制因子1降低
