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

  目的  探讨活性维生素D₃(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D25(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。 

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

  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 factor β1 (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, TGF β-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.