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中华妇幼临床医学杂志(电子版)

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2024, Vol. 20 ›› Issue (03): 292 -301. doi: 10.3877/cma.j.issn.1673-5250.2024.03.008

Original Article

Longitudinal study of pulmonary and motor function in children with ambulatory Duchenne muscular dystrophy treated with corticosteroids

Yueting Wu1, Linyuhan Zhou1, Qin Hu1, Huayan Xu2, Min Huang1, Xiaoyong Chen1, Meng Zhang1, Zhonghui Li3, Liang Ru4, Qiu Wang1,†(), Xiaotang Cai1,†()   

  1. 1. Department of Rehabilitation Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    2. Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    3. Department of Pediatric Genetics, Endocrinology and Metabolism, Chengdu Women′s and Children′s Central Hospital, Chengdu 610073, Sichuan Province, China
    4. Department of Pediatric Medicine, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uyghur Autonomous Region, China
  • Received:2024-02-07 Revised:2024-05-12 Published:2024-06-01
  • Corresponding author: Qiu Wang, Xiaotang Cai
  • Supported by:
    Project of Sichuan Provincial Central Government Guidance for Local Science and Technology Development(2023ZYD0121, 2023ZYD0100); Science and Technology Plan Project of Sichuan Province (Key Research and Development Project)(2023YFG0284); Medical Technology Project of Health Commission of Sichuan Province(21PJ048); Science and Technology Project of Tibet Autonomous Region(XZ202201ZY0049G)
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Objective

To explore the changes of pulmonary and motor function indexes in children with ambulatory Duchenne muscular dystrophy (DMD) treated with corticosteroids (CS) for at least one year.

Methods

A total of 32 DMD children admitted to the outpatient department of West China Second University Hospital of Sichuan University, Chengdu Women′s and Children′s Central Hospital, and the First Affiliated Hospital of Xinjiang Medical University from April 2020 to May 2021 were selected into this study. According to the age of children when they initially received treatment with CS, they were divided into ≤7 years group (n=13) and >7 years group (n=19). A 2-year retrospective longitudinal study of these 32 children was conducted after initial treatment. And the children′s pulmonary function [forced vital capacity percent predicted value (FVC%), forced expiratory volume in one second percent predicted value (FEV1%), ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC), peak expiratory flow percent predicted value (PEF%)] was assessed by spirometry at initial treatment and at 1 and 2 years after initial treatment (recorded as T0, T1 and T2, respectively). The North Star Ambulatory Assessment (NSAA) score and three key monitor function indexes timing tests (the time required to complete supine-up, 10 m walk/run, and climb 4 stairs test once each) were performed to evaluate the children′s motor function at T0, T1 and T2. Repeated measures analysis of variance or Friedman test was used to compare the 4 pulmonary function indexes and NSAA score and three key monitor function indexes of all DMD children, ≤7 years group and >7 years group at different time points. Multiple linear regression analysis was used to analyze the effect of NSAA score and three key monitor function indexes on FVC% among 32 DMD children. This study was approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Ethics No. 2023-303).

Results

① Among the 32 DMD children, there were no significant differences in FVC%, FEV1% and FEV1/FVC at T0, T1 and T2 (P>0.05), while the PEF% showed a upward trend, and the difference was statistically significant (F=4.40, P=0.016). Further pairwise comparison showed that FVC% at T1 was 8.3% higher than that at T0, and the difference was statistically significant (Z=-2.09, P=0.036), FEV1% and PEF% at T2 was 8.2% and 9.2% higher than these at T0, and both the differences were statistically significant (Z=-2.15, P=0.032; t=-2.69, P=0.011). ② At T0, T1, and T2, the NSAA score of 32 DMD children showed a downward trend, while the time required to complete supine-up and 10 m walk/run tests showed an increasing trend, and the differences were statistically significant (F=4.33, P=0.017; χ2=32.32, P<0.001; χ2=6.74, P=0.034). ③ Results of multiple linear regression analysis showed that NSAA score at T0 was an independent protective factor for the increase of FVC% in DMD children (b=0.817, P=0.027). ④ In ≤7 years group, FVC%, FEV1%, and PEF% showed an upward trend at T0, T1, and T2, and the differences were statistically significant (F=10.87, 12.24, 11.03; P=0.004, 0.003, 0.003). The time required to complete supine-up test at T0, T1, and T2 was also statistically significant (χ2=15.17, P=0.001). ⑤ In >7 years group, there were no statistically significant differences in FVC%, FEV1%, FEV1/FVC, and PEF% at T0, T1, and T2 (P>0.05). While the NSAA score at T0, T1 and T2 showed a downward trend, and the time required to complete supine-up and 10 m walk/run tests at T0, T1 and T2 showed an increasing trend, and all the differences were statistically significant (χ2=6.50, P=0.039; χ2=20.99, P<0.001; χ2=10.11, P=0.006).

Conclusions

Among children with ambulatory DMD treated with CS, the pulmonary function of those with initial treatment ≤ 7 years show an upward trend within 2 years after initial treatment, but remain stable within 2 years after the initial treatment for those with initial treatment > 7 years. The motor function of children with initial treatment ≤ 7 years and > 7 years all show a downward trend, and the decline is more obvious in children with initial treatment > 7 years. There is a correlation between NSAA score and pulmonary function in ambulatory DMD children.

Key words: Muscular dystrophy, Duchenne, Respiratory function tests, Pulmonary function, Vital capacity, Forced expiratory volume, Peak expiratory flow rate, Motor function, Child
表1 T0、T1、T2时，本研究32例DMD患儿4项肺功能指标比较(%)
不同时间点 例数 FVC%[M(Q1，Q3)] FEV1%[M(Q1，Q3)] FEV1/FVC(±s) PEF%(±s)
T0 32 92.7(87.5，106.1) 99.5(93.9，111.0) 89.8±3.9 91.5±14.3
T1 32 100.4(90.5，111.9) 106.4(96.9，116.5) 89.4±4.8 96.0±12.8
T2 32 100.8(92.8，110.9) 107.7(100.3，118.3) 89.6±3.5 99.9±12.3
总体比较(统计量/P值)   χ2＝1.94/0.380 χ2＝4.19/0.123 F＝0.14/0.871 F＝4.40/0.016
两两比较(统计量/P值)          
T0 vs T1   Z＝－2.09/0.036 Z＝－1.63/0.104 t＝0.50/0.619 t＝－1.59/0.122
T0 vs T2   Z＝－1.94/0.052 Z＝－2.15/0.032 t＝0.35/0.729 t＝－2.69/0.011
T1 vs T2   Z＝－0.16/0.874 Z＝－0.57/0.568 t＝－0.18/0.857 t＝－1.55/0.132
表2 T0、T1、T2时，本研究32例DMD患儿NSAA评分和3项关键运动功能指标比较
不同时间点 例数 NSAA评分(分，±s) 完成仰卧-站立所需时间[s，M(Q1，Q3)] 完成10 m走/跑所需时间[s，M(Q1，Q3)] 完成上4级楼梯所需时间[s，M(Q1，Q3)]
T0 32 22.2±7.5 3.8(2.3，5.0) 4.7(4.4，5.6) 2.3(1.9，5.4)
T1 32 21.1±8.8 5.4(3.4，8.8) 5.3(4.6，7.7) 3.3(1.3，6.9)
T2 32 19.5±9.9 5.8(3.3，16.7) 5.1(3.9，8.4) 3.1(1.5，6.0)
总体比较(统计量/P值)   F＝4.33/0.017 χ2＝32.32/<0.001 χ2＝6.74/0.034 χ2＝0.96/0.618
两两比较(统计量/P值)          
T0 vs T1   t＝1.38/0.177 Z＝－4.35/<0.001 Z＝－3.35/<0.001 Z＝－1.65/0.980
T0 vs T2   t＝2.57/0.015 Z＝－4.37/<0.001 Z＝－2.28/0.022 Z＝－1.66/0.960
T1 vs T2   t＝1.76/0.088 Z＝－3.53/<0.001 Z＝－1.03/0.304 Z＝－1.64/0.101
表3 本研究32例DMD患儿FVC%影响因素的多重线性回归分析
变量 偏回归系数 偏回归系数标准误 标准偏回归系数 t值 P值
常数项 64.997 20.262 — 3.208 0.002
年龄a 1.272 1.086 0.145 1.172 0.245
BMIa 0.282 0.628 0.049 0.449 0.655
NSAA评分a 0.817 0.362 0.420 2.254 0.027
完成仰卧-站立测试所需时间a 0.044 1.312 0.026 0.154 0.878
完成10 m走/跑测试所需时间a 0.119 0.287 0.018 0.091 0.928
完成上4级楼梯测试所需时间a 0.161 0.689 0.043 0.233 0.816
表4 T0、T1、T2时，≤7岁组与>7岁组DMD患儿4项肺功能指标比较(%)
不同时间点 ≤7岁组
例数 FVC%(±s) FEV1%(±s) FEV1/FVC(±s) PEF%(±s)
T0 11 96.4±12.7 99.6±12.4 88.6±4.3 89.4±10.1
T1 11 107.9±12.9 112.4±13.2 88.6±6.6 92.2±14.5
T2 11 112.4±11.0 117.8±11.0 88.9±2.7 105.1±13.5
总体比较(统计量/P值)   F＝10.87/0.004 F＝12.24/0.003 F＝0.02/0.981 F＝11.03/0.003
两两比较(统计量/P值)          
T0 vs T1   t＝－2.86/0.017 t＝－2.80/0.019 t＝0.03/0.981 t＝－0.62/0.552
T0 vs T2   t＝－3.78/0.004 t＝－4.24/0.002 t＝－0.18/0.857 t＝－4.54/0.001
T1 vs T2   t＝－2.41/0.037 t＝－2.92/0.015 t＝－0.18/0.860 t＝－5.53/<0.001
不同时间点 >7岁组
例数 FVC%[M(Q1，Q3)] FEV1%[M(Q1，Q3)] FEV1/FVC(±s) PEF%[M(Q1，Q3)]
T0 21 92.7(86.1，111.3) 100.6(94.3，118.0) 90.4±3.7 99.7(80.3，104.8)
T1 21 96.4(89.7，106.6) 100.9(96.3，112.4) 89.9±3.6 94.5(90.0，102.6)
T2 21 94.8(89.8，102.3) 101.8(96.7，106.9) 89.9±3.8 97.0(91.6，108.3)
总体比较(统计量/P值)   χ2＝0.86/0.651 χ2<0.01/0.999 F＝0.29/0.749 χ2＝0.86/0.651
两两比较(统计量/P值)          
T0 vs T1   Z＝－0.85/0.394 Z＝－0.33/0.741 t＝0.77/0.449 Z＝－1.22/0.224
T0 vs T2   Z＝－0.05/0.958 Z＝－0.23/0.821 t＝0.58/0.566 Z＝－1.03/0.305
T1 vs T2   Z＝－1.13/0.258 Z＝－0.73/0.465 t＝－0.07/0.943 Z＝－0.23/0.821
表5 T0、T1、T2时，≤7岁组与>7岁组DMD患儿NSAA评分和3项关键运动功能指标比较[M(Q1，Q3)]
不同时间点 ≤7岁组
例数 NSAA评分(分) 完成仰卧-站立所需时间(s) 完成10 m走/跑所需时间(s) 完成上4级楼梯所需时间(s)
T0 11 28.0(23.0，30.0) 2.2(1.8，2.6) 4.4(4.3，4.6) 1.9(1.2，2.0)
T1 11 27.0(27.0，31.0) 3.7(2.6，5.0) 4.9(4.4，5.3) 1.7(1.1，2.8)
T2 11 27.0(23.0，33.0) 4.5(2.8，5.5) 3.9(3.7，5.2) 1.5(1.1，2.6)
总体比较(χ2值/P值)   1.02/0.599 11.40/0.003 2.89/0.236 0.20/0.905
两两比较(Z值/P值)          
T0 vs T1   －0.40/0.687 －2.50/0.013 －1.78/0.074 －0.56/0.575
T0 vs T2   <0.01/0.999 －2.80/0.005 －0.53/0.594 －0.56/0.575
T1 vs T2   －0.59/0.553 －1.51/0.131 －2.09/0.037 －0.04/0.965
不同时间点 >7岁组
例数 NSAA评分(分) 完成仰卧-站立所需时间(s) 完成10 m走/跑所需时间(s) 完成上4级楼梯所需时间(s)
T0 21 22.0(15.0，25.5) 4.4(2.8，6.5) 5.2(4.5，5.7) 3.3(2.3，7.4)
T1 21 20.0(10.5，24.0) 8.0(4.4，12.6) 5.5(4.7，8.6) 3.9(2.1，9.9)
T2 21 18.0(13.0，23.0) 10.6(4.8，21.0) 5.6(4.6，8.5) 4.6(2.0，6.3)
总体比较(χ2值/P值)   6.50/0.039 20.99/<0.001 10.11/0.006 2.73/0.255
两两比较(Z值/P值)          
T0 vs T1   －1.48/0.140 －3.59/<0.001 －2.85/0.004 －1.45/0.147
T0 vs T2   －2.51/0.012 －3.48/0.001 －2.98/0.003 －1.33/0.184
T1 vs T2   －2.13/0.034 －3.15/0.002 －0.17/0.867 －1.80/0.072
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