活性维生素D3对老年慢性阻塞性肺疾病维生素D缺乏患者气道重塑的保护作用

Protective effect of active vitamin D3 on airway remodelling in elderly patients with chronic obstructive pulmonary disease and vitamin D deficiency

目的探讨活性维生素D;(阿法骨化醇)对老年慢性阻塞性肺疾病(简称慢阻肺)维生素D缺乏者气道重塑的保护作用。方法选取成都医学院第二附属医院2019年1月—2020年1月健康人群(健康对照组)40例及年龄≥60岁的25羟维生素D[25(OH)D]水平低于20 ng/mL的稳定期慢阻肺患者146例。慢阻肺患者采用随机数字法分为3组,分别为高剂量组(48例)、低剂量组(49例)及对照组(49例),在入组时、3个月及6个月后分别测定患者的血液25(OH)D、基质金属蛋白酶9(MMP-9)、转化生长因子-β1(TGF-β1)、金属蛋白酶组织抑制因子-1(TIMP-1),高分辨率CT测量支气管管壁厚度与外径比值(T/D)及气道壁面积占气道总截面积百分比(WA%)。结果慢阻肺组患者25(OH)D水平[(13.47±5.32)ng/mL]明显低于健康对照组[(20.35±8.34)ng/mL,P<0.05];而MMP-9、TGF-β1、TIMP-1、T/D、WA%显著高于健康对照组(均P<0.05)。低剂量组补充3个月后25(OH)D、MMP-9、TGF-β1及WA%较补充前有明显改善(均P<0.05),补充6个月后TIMP-1和T/D较补充前也有改善(均P<0.05)。高剂量组补充3个月及6个月治疗后,患者的25(OH)D水平及上述气道重塑指标均较治疗前有显著改善(均P<0.05),其中补充6个月后的25(OH)D、TGF-β1及WA%与同期的低剂量组比较差异有统计学意义(均P<0.05)。25(OH)D水平与MMP-9、TGF-β1、WA%呈负相关(r值分别为-0.287、-0.311、-0.389,均P<0.05)。结论老年慢阻肺维生素D缺乏者每天补充阿法骨化醇对25(OH)D水平的提升及气道重塑有较好的保护作用,高剂量连续补充6个月效果更佳。

Objective To explore the protective effect of active vitamin D3(alfacalcidol)on airway remodelling in elderly patients with chronic obstructive pulmonary disease(COPD)and vitamin D deficiency.Methods Forty healthy people(healthy control group)and 146 stable COPD patients with 25(OH)D level lower than 20 ng/mL were selected from January 2019 to January 2020.Patients with chronic obstructive pulmonary disease were randomly divided into three groups:high-dose group(n=48),low-dose group(n=49)and control group(n=49).The levels of 25(OH)D,matrix metalloproteinase-9(MMP-9),transforming growth factorβ1(TGF-β1),tissue inhibitor of metallo-proteinase-1(TIMP-1)in blood and HRCT were measured.The ratio of bronchial wall thickness to outer diameter(T/D)and the percentage of airway wall area to total airway cross-sectional area(WA%)were measured at the time of admission and at 3 and 6 months later.Results The 25(OH)D level in the COPD group was(13.47±5.32)ng/mL,which was significantly lower than that in the healthy control group[(20.35±8.34)ng/mL],P<0.05.Meanwhile,the levels of MMP-9,TGFβ-1,TIMP-1,T/D and WA%were significantly higher in the COPD group than in the healthy control group(P<0.05).The levels of 25(OH)D,MMP-9,TGF-β1 and WA%in the low-dose group significantly improved after 3 months of supplementation(P<0.05),and the levels of TIMP-1 and T/D in the low-dose group significantly improved after 6 months of supplementation(P<0.05).The level of 25(OH)D and all airway remodelling indexes in the high-dose group after 3 and 6 months of treatment improved(all P<0.05).The levels of 25(OH)D,TGF-β1 and WA%after 6 months of treatment were different from those in the low-dose group(P<0.05).The 25(OH)D level negatively correlated with MMP-9,TGF-β1 and WA%(r=-0.287,-0.311,-0.389,respectively,all P<0.05).Conclusion In elderly patients with COPD vitamin D deficiency,daily supplement of alfacalcidol exerts a better protective effect on the improvement of 25(OH)D level and airway remodelling,and high-dose supplement for 6 months exerts a better effect.