Effect of acetylcysteine combined with glucocorticoid on severe adenovirus pneumonia-induced bronchiolitis obliterans in children and the effect on IL-18 and IL-17
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摘要: 目的 探究乙酰半胱氨酸联合糖皮质激素对重症腺病毒肺炎致闭塞性细支气管炎(PIBO)患儿的效果及对IL-18、IL-17的影响。方法 选取2017年1月-2021年12月我院84例重症腺病毒肺炎致PIBO患儿，结合不同治疗方法分为试验组、对照组，各42例。对照组予以吸入用布地奈德混悬液，试验组在对照组基础上增加乙酰半胱氨酸。比较两组疗效、症状改善时间、治疗前后肺功能[呼吸阻力(Rrsc)、达峰容积比(VPTEF/VE)、潮气量(TV)、达峰时间比(tPTEF/tE)、呼吸比(Ti/Te)]、炎性因子水平[可溶性血管细胞黏附分子1(sVCAM-1)、IL-18、IL-17、半胱氨酰白三烯(CysLTs)]、血清基质金属蛋白酶-9(MMP-9)、金属蛋白酶抑制剂-1(TIMP-1)水平、不良反应发生率。结果 试验组总有效率为92.86%，较对照组的76.19%高，两组疗效比较差异有统计学意义(P< 0.05)；试验组症状改善时间较对照组短，差异有统计学意义(P< 0.05)；治疗后试验组Rrsc较对照组低，VPTEF/VE、TV、tPTEF/tE、Ti/Te较对照组高，差异有统计学意义(P< 0.05)；治疗后试验组血清IL-18、IL-17、sVCAM-1、CysLTs、MMP-9、TIMP-1水平较对照组低，差异有统计学意义(P< 0.05)；比较两组不良反应情况，差异无统计学意义(P> 0.05)。结论 乙酰半胱氨酸联合糖皮质激素治疗重症腺病毒肺炎致PIBO患儿效果显著，可有效促使症状改善，改善肺功能，减轻机体炎症，调节血清MMP-9、TIMP-1水平，且安全性高。Abstract: Objective To explore the effect of acetylcysteine combined with glucocorticoid on severe adenovirus pneumonia-induced bronchiolitis obliterans(PIBO) in children and the effect on interleukin-18(IL-18) and IL-17.Methods A total of 84 children with PIBO caused by severe adenovirus pneumonia in our hospital from January 2017 to December 2021 were selected and randomly divided into experimental group and control group, with 42 cases in each group. The control group was treated with budesonide suspension for inhalation, the test group was treated with acetylcysteine on the basis of the control group. The curative effect, time of symptom improvement, lung function[respiratory resistance(Rrsc), peak volume ratio(VPTEF/VE), tidal volume(TV), peak time ratio(tPTEF/tE), respiration ratio(Ti/Te)], levels of inflammatory factors[soluble vascular cell adhesion molecule 1(sVCAM-1), IL-18, IL-17, cysteinyl leukotrienes(CysLTs)], serum matrix metalloproteinase-9(MMP-9) metalloproteinase inhibitor-1(TIMP-1) before and after treatment and the incidence of adverse reactions were compared between the two groups.Results The total effective rate of 92.86% in the test group was higher than that of 76.19% in the control group(P< 0.05); The symptom improvement time of the test group was shorter than that of the control group(P< 0.05); After treatment, the Rrsc of the test group was lower than that of the control group, and VPTEF/VE, TV, tPTEF/tE, and Ti/Te were higher than those of the control group(P< 0.05); After treatment, the serum levels of IL-18, IL-17, sVCAM-1, CysLTs, MMP-9 and TIMP-1 in the test group were lower than those in the control group(P< 0.05); There was no statistically significant difference in the incidence of adverse reactions between the two groups(P> 0.05).Conclusion Acetylcysteine combined with glucocorticoids is effective in treating PIBO children with severe adenovirus pneumonia. That can effectively improve symptoms, improve lung function, reduce body inflammation, regulate serum MMP-9 and TIMP-1 levels, and has high safety.
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表 1 两组患者基线资料比较
X±S 基线资料 试验组 对照组 t/χ2 P 例数 42 42 性别 0.194 0.659 男 25 23 女 17 19 年龄/岁 1~5(3.02±0.87) 1~6(3.14±0.91) 0.618 0.539 体重/kg 9~21(15.21±2.85) 8~23(15.98±2.56) 1.303 0.196 体温/℃ 37.4~40.3(38.89±0.51) 37.6~40.1(38.72±0.48) 1.573 0.120 有创机械通气/例(%) 12(28.57) 9(21.43) 0.571 0.450 病程/周 6~10(8.42±0.84) 6~11(8.27±0.79) 0.843 0.402 
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表 2 两组疗效比较
例(%) 组别 例数 显效 有效 无效 总有效 试验组 42 21(50.00) 18(42.86) 3(7.14) 39(92.86) 对照组 42 16(38.10) 16(38.10) 10(23.81) 32(76.19) χ2 4.459 P 0.035
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表 3 两组症状改善时间比较
d，X±S 组别 例数 喘憋改善时间 气促改善时间 咳嗽改善时间 肺部啰音改善时间 试验组 42 8.68±2.06 10.81±2.15 9.42±2.11 13.54±2.71 对照组 42 10.09±3.53 12.07±2.43 11.08±2.42 15.87±3.35 t 2.236 2.518 3.351 3.504 P 0.028 0.014 0.001 0.001
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表 4 两组肺功能比较
X±S 时间 例数 Rrsc/(kPa·s-1) VPTEF/VE/% TV/(mL·kg-1) tPTEF/tE/% Ti/Te/ng 治疗前 试验组 42 5.95±1.06 17.26±3.07 6.45±1.22 13.96±2.72 0.59±0.12 对照组 42 5.86±1.13 17.09±3.18 6.27±1.17 13.43±2.89 0.55±0.19 t 0.377 0.249 0.690 0.866 1.154 P 0.708 0.804 0.492 0.389 0.252 治疗后 试验组 42 3.58±0.731) 27.35±3.961) 9.73±1.801) 22.28±4.821) 0.87±0.271) 对照组 42 4.01±0.851) 25.57±3.641) 8.80±1.651) 19.91±4.061) 0.70±0.241) t 2.487 2.145 2.468 2.437 3.050 P 0.015 0.035 0.016 0.017 0.003 与同组治疗前比较，1)P < 0.05。
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表 5 两组炎性因子水平比较
X±S 时间 例数 IL-18/ng IL-17/ng sVCAM-1/(mg·L-1) CysLTs/(μg·L-1) 治疗前 试验组 42 17.26±2.25 2.95±0.62 2.18±0.53 50.97±6.87 对照组 42 17.08±2.39 2.86±0.73 2.06±0.67 52.05±7.19 t 0.355 0.609 0.910 0.704 P 0.723 0.544 0.365 0.484 治疗后 试验组 42 14.85±1.981) 1.49±0.311) 0.78±0.181) 37.58±4.161) 对照组 42 16.07±2.171) 1.72±0.481) 0.92±0.221) 40.02±4.871) t 2.692 2.609 3.192 2.469 P 0.009 0.011 0.002 0.016 与同组治疗前比较，1)P < 0.05。
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表 6 两组血清MMP-9、TIMP-1水平比较
μg/L，X±S 时间 例数 MMP-9 TIMP-1 治疗前 试验组 42 2842.32±254.05 264.68±32.48 对照组 42 2804.76±229.49 275.94±28.95 t 0.711 1.677 P 0.479 0.097 治疗后 试验组 42 1341.59±201.181) 213.65±22.261) 对照组 42 1498.74±219.491) 230.18±20.151) t 3.421 3.568 P 0.001 0.001 与同组治疗前比较，1)P < 0.05
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表 7 两组不良反应发生率比较
例(%) 组别 例数 呕吐 皮疹 食欲不振 发绀 试验组 42 2(4.76) 1(2.38) 2(4.76) 1(2.38) 对照组 42 1(2.38) 0(0.00) 3(7.14) 1(2.38) χ2 0.000 - 0.000 - P 1.000 1.000 1.000 1.000 注：“-”表示采用确切概率法计算。
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