结核性胸膜炎患者化疗时是否加用糖皮质激素对肺功能动态变化的对比研究

doi:10.3969/j.issn.1000-6621.2021.01.012

摘要/Abstract

摘要：

目的探讨结核性胸膜炎患者化疗时是否加用糖皮质激素对肺功能的动态变化。方法回顾性分析首都医科大学附属北京胸科医院2015年5月至2018年5月收治的结核性胸膜炎患者172例,对患者的肺通气、容积、弥散功能和呼吸肌力学指标在化疗前,以及化疗第1、6、12个月末进行4次检测;根据在抗结核药品化疗方案的基础上是否加用糖皮质激素分为两组,即加用组60例(醋酸泼尼松+2H-R-Z-E/10H-R-E)和未加用组112例(2H-R-Z-E/10H-R-E)。肺通气功能的检测指标为患者用力肺活量检测值占正常预计值的百分比(FVC)、第1秒用力呼气容积检测值占正常预计值的百分比(FEV₁% pred)、第1秒钟用力呼气容积/用力肺活量比值占正常预计值的百分比(FEV₁/FVC% pred)、用力呼出75%肺总量时瞬间呼气流量检测值占正常预计值的百分比(FEF₇₅)、最大分钟通气量检测值占正常预计值的百分比(MVV% pred);肺容积功能的检测指标为残气量检测值占正常预计值的百分比(RV% pred)、肺总量检测值占正常预计值的百分比(TLC% pred)、残气量/肺总量比值占正常预计值的百分比(RV/TLC% pred);弥散功能的检测指标为肺弥散量检测值占正常预计值的百分比(D_LCO)和肺泡容量校正的肺弥散率检测值占正常预计值的百分比(D_LCO/VA% pred);呼吸肌力学的检测指标为气道阻力检测值占正常预计值的百分比(Rtot% pred、呼气峰流量检测值占正常预计值的百分比(PEF% pred)、吸气峰值流量实测值(PIF),通过对检测指标的观察,了解肺功能的变化。肺功能测定结果按“测定值/正常预计值×100%”表示(除PIF为实测值),符合正态分布的计量资料采用“$\overline{x}$±s”进行统计描述,统计学处理采用t检验;不符合正态分布的计量资料采用中位数(四分位数)[M(Q₁,Q₃)] 表示,统计学处理采用Z检验,P<0.05为差异有统计学意义。结果 (1)结核性胸膜炎患者化疗前,以限制性通气功能障碍为主,FVC% pred为(62.1±13.4)%,FEV₁% pred为(64.4±15.5)%,FEV₁/FVC% pred为(87.0±11.1)%,MVV% pred (65.7±21.1)%,FEF₇₅% pred为61.6(41.6,83.0)%,RV% pred为111.3(89.8,131.4)%, TLC% pred为 (77.0±16.9)%,RV/TLC% pred为(146.9±35.9)%, D_LCO% pred为(62.6±18.3)%,D_LCO/VA% pred为(92.3±16.6)%,PEF% pred为(64.1±18.13)%,PIF为 3.2(2.3,4.1)L/s,Rtot% pred为96.0(69.3,118.9)%]。(2)化疗过程中,第1、6、12个月末 FVC<80%的患者分别为80.2%(138/172)、75.0%(129/172)、0.0%(0/0);化疗第6个月末D_LCO<80%的患者为44.2%(76/172)); (3)加用组和未加用组患者在化疗前、化疗第1、6、12个月末FEF₇₅% pred[分别为(68.7(49.8,84.1)%和60.7(39.4,80.7)%);87.1(70.5,94.4)%和73.1(51.9,87.0)%;80.1(66.5,111.9)%和66.8(59.9,87.2)%;90.4(55.3,102.9)%和78.4(54.6,87.3)%],两组比较差异均无统计学意义值分别为-1.091、-0.111、-1.609、-1.171,P值均>0.05); MVV% pred[分别为(65.8±19.4)%和(65.5±18.6)%);(86.9±18.6)%和(79.5±18.7)%;(90.3±16.0)%和(86.3±16.0)%;(96.8±11.1)%和(87.3±19.8)],两组比较差异均无统计学意义(t值分别为1.043、0.444、0.708、1.113,P值均>0.05)。结论结核性胸膜炎患者治疗前、治疗第1个月末肺功能减退主要表现为限制性通气功能障碍和弥散功能减退,治疗第6个月末仅通气功能恢复正常,而弥散功能在治疗第12个月末恢复正常;早期糖皮质激素辅助治疗对结核性胸膜炎患者的肺功能无明显影响。

关键词: 结核,胸膜, 抗结核药, 糖皮质激素类, 药物疗法,联合, 呼吸功能试验, 疗效比较研究

Abstract:

Objective To investigate the dynamic changes of pulmonary function in patients with tuberculous pleurisy after chemotherapy with glucocorticoid. Methods All of 172 patients with tuberculous pleurisy admitted to Beijing Chest Hospital affiliated to Capital Medical University from May 2015 to May 2018 were retrospectively analyzed. The pulmonary ventilation, volume, diffusion function and respiratory muscle mechanics indexes of patients were tested for 4 times: before treatment, at the end of the 1st, 6th and 12th months of treatment. On the basis of anti-tuberculosis drug treatment regimen, patients were divided into two groups: 60 patients in the plus group (prednisone acetate +2H-R-Z-E/10H-R-E) and 112 patients in the non-plus group (2H-R-Z-E/10H-R-E).Pulmonary ventilation function of patients were tested with percentage of forced vital capacity values over the expected value (expected value of pulmonary function factory default value formula), percentage of forced expiratory volume in 1 second readings over the expected value, percentage of forced expiratory volume in 1 second readings versus a forced vital capacity values, percentage of forcibly exhale 75% total lung moment expiratory flow values over the expected value (FEF₇₅% pred), percentage of the maximum values of the expected minute ventilation (MVV% pred);The measurement index of lung volume function were percentage of residual volume detected value over the estimated value, percentage of total lung detected value over the estimated value, and percentage of residual volume/total lung ratio over the estimated value.The measurement index of dispersion function were percentage of the detected lung dispersion amount over the predicted value and percentage of the detected lung dispersion rate in the corrected alveolar volume over the predicted value.The measurement indexes of respiratory muscle mechanics were percentage of airway resistance detected, percentage of peak expiratory flow detected and the measured value of peak inspiratory flow. Results (1)Before chemotherapy, patients with tuberculous pleurisy were mainly affected by restricted ventilation dysfunction (FVC (62.1±13.4) %, FEV₁ (64.4±15.5) %, FEV₁/FVC (87.0±11.1) %, MVV (65.7±21.1) %, FEF₇₅ (61.6 (41.6,83.0) %, RV (111.3 (89.8,131.4) %, TLC (77.0±16.9) %, RV/TLC (146.9±35.9) %,D_LCO (62.6±18.3) %, D_LCO/VA (92.3±16.6) %, PEF (64.1±18.13) %, PIF (3.2 (2.3,4.1) %, Rtot 96.0 (69.3,118.9) %).(2) During the course of treatment, 80.2% (138/172), 75.0% (129/172), and 0.0% (0/0) of patients were tested as having FVC <80% at the end of 1st, 6th, and 12th months. At the end of the 6th month of treatment, up to 44.2% (76/172) of patients had D_LCO <80%. (3) FEF₇₅ for glucocorticoid plus group and non plus group patients before treatment, at 1, 6, 12 months of treatment were (68.7 (49.8,84.1)% and 60.7 (39.4, 80.7) %;87.1 (70.5, 94.4) % and 73.1 (51.9, 87.0) %; 80.1 (66.5, 111.9) % and 66.8 (59.9, 87.2) %;90.4 (55.3, 102.9) % and 78.4 (54.6,87.3) % respectively, improvements after treatment were not significant (Z values were -1.091, -0.111, -1.609, -1.171, all P values were >0.05). MVV% pred were (65.8±19.4) % and (65.5±18.6) %; (86.9±18.6) % and (79.5±18.7) %; (90.3±16.0) % and (86.3±16.0) %;(96.8±11.1) % and (87.3±19.8) %) respectively, the improvement were not significant too(t values were 1.043, 0.444, 0.708, 1.113, all P values were >0.05). Conclusion Patients with tuberculous pleurisy showed restrictive ventilation dysfunction and diffusion function decline before treatment and at the end of the first month of treatment. At the end of 6 months’ treatment, only ventilation function returned to normal. Dispersion function returned to normal at the end of 12 months’ treatment. Early adjuvant treatment of glucocorticoid had no significant effect on pulmonary function in patients with tuberculous pleurisy.

Key words: Tuberculosis,pleural, Antitubercular agents, Glucocorticoids, Drug therapy,combination, Respiratory function tests, Comparative effectiveness research

阮洪云, 李琦, 陈效友, 段鸿飞, 郭超, 操敏, 梁清涛, 王志茹, 杨扬, 孙桂新, 李华, 邓玲, 绍玲玲, 邢维祥, 张芸, 杨新婷. 结核性胸膜炎患者化疗时是否加用糖皮质激素对肺功能动态变化的对比研究[J]. 中国防痨杂志, 2021, 43(1): 58-65. doi: 10.3969/j.issn.1000-6621.2021.01.012

RUAN Hong-yun, LI Qi, CHEN Xiao-you, DUAN Hong-fei, GUO Chao, CAO Min, LIANG Qing-tao, WANG Zhi-ru, YANG Yang, SUN Gui-xin, LI Hua, DENG Ling, SHAO Ling-ling, XING Wei-xiang, ZHANG Yun, YANG Xin-ting. Dynamic changes of lung function and hormone-assisted therapy in patients with tuberculous pleurisy[J]. Chinese Journal of Antituberculosis, 2021, 43(1): 58-65. doi: 10.3969/j.issn.1000-6621.2021.01.012

图/表 4

表1

表2

172例结核性胸膜炎患者化疗前、化疗第1、6、12个月末肺功能情况

检测时间	FVC ( $x ˉ$ ±s, %)	FEV₁ ( $x ˉ$ ±s, %)	FEV₁/FVC ( $x ˉ$ ±s, %)	MVV ( $x ˉ$ ±s, %)	FEF₇₅ [M(Q₁, Q₃),%]	RV% [M(Q₁, Q₃),%]	TLC ( $x ˉ$ ±s, %)	RV/TLC ( $x ˉ$ ±s, %)	D_LCO ( $x ˉ$ ±s, %)	D_LCO/VA ( $x ˉ$ ±s, %)	PEF ( $x ˉ$ ±s, %)	PIF [M(Q₁, Q₃), L/s]	Rtot % [M(Q₁, Q₃),%]
化疗前	62.1± 13.4	64.4± 15.5	87.0± 11.1,	65.7± 21.1	61.6 (41.6, 83.0)	111.3 (89.8, 131.4)	77.0± 16.9	146.9± 35.9	62.6± 18.3	92.3± 16.6	64.1± 18.3	3.2 (2.3, 4.1)	96.0 (69.3, 118.9)
第1月	76.5± 15.2	78.3± 14.9	86.8± 10.2	82.6± 18.6	70.2 (54.5, 142.1)	109.1 (90.5, 142.1)	86.2± 15.1	133.8± 32.6	70.2± 15.4	91.9± 17.0	79.4± 18.1	4.5 (3.4, 5.5)	80.0 (64.4, 103.1)
第6月	89.6± 18.7	89.3± 13.2	86.1± 8.2	89.3± 17.1	75.9 (60.4, 101.7)	100.6 (85.2, 126.2)	91.1± 13.2	113.4± 24.1	78.4± 13.7	93.1± 18.4	84.9± 19.6	4.4 (3.6, 5.7)	88.7 (67.3, 106.3)
第12月	94.8± 11.8	91.7± 13.3	82.8± 9.7	89.6± 18.7	78.7 (55.1, 90.6)	104.3 (82.9, 122.7)	94.9± 14.3	107.6± 23.0	81.4± 9.0	91.8± 15.6	89.1± 19.7	4.3 (3.2, 4.9)	89.0 (63.9, 110.8)
统计检验值	F= 81.212	F= 64.146	F= 1.592	F= 32.971	H= 3.831	H= 2.336	F= 21.400	F= 23.876	F= 22.501	F= 0.070	F= 30.831	H= 5.280	H= 3.060
P值	<0.001	<0.001	0.191	<0.001	0.01	0.074	<0.001	<0.001	<0.001	0.976	<0.001	0.001	0.028

表2

图1

表3

糖皮质激素加用组与未加用组患者化疗前、化疗第1、6、12个月末肺功能比较

组别及治疗时间	FVC ( $x ˉ$ ±s, %)	FEV₁ ( $x ˉ$ ±s, %)	FEV₁/FVC ( $x ˉ$ ±s, %)	MVV ( $x ˉ$ ±s, %)	FEF₇₅ [M(Q₁, Q₃),%]	RV [M(Q₁, Q₃),%]	TLC ( $x ˉ$ ±s, %)	RV/TLC [M(Q₁, Q₃),%]	D_LCO ( $x ˉ$ ±s), %	D_LCO/VA ( $x ˉ$ ±s), %	PEF ( $x ˉ$ ±s), %	PIF [M(Q₁, Q₃), L/s]	Rtot [M(Q₁, Q₃),%]
加用组治疗前	60.0± 14.0	63.0± 14.9	89.7± 10.3	65.8± 19.4	68.7 (49.8, 84.1)	106.1 (83.5, 129.1)	75.9± 21.4	144.4 (120.4, 165.3)	65.0± 24.2	94.3± 17.6	62.6± 19.4	3.2 (2.2, 4.0)	94.5 (77.6, 121.4)
未加用组治疗前	62.7± 12.6	64.6± 15.4	85.6± 11.4	65.5± 18.6	60.7 (39.4, 80.7)	113.3 (93.3, 132.2)	77.3± 14.4	149.2 (123.1, 172.9)	61.1± 14.3	91.4± 16.1	65.0± 17.8	3.2 (2.3, 4.3)	97.0 (68.7, 117.7)
统计检验值	t= 2.136	t= 0.002	t= 1.076	t= 1.043	Z= -1.091	Z= -1.439	t= 2.550	Z= -0.939	t= 3.393	t= 0.829	t= 0.224	Z= -0.387	Z= -0.537
P值	0.146	0.964	0.301	0.309	0.275	0.150	0.112	0.348	0.067	0.364	0.637	0.699	0.592
加用组第1个月	77.1± 14.6	79.1± 15.1	86.7± 9.7	86.9± 18.6	87.1 (70.5, 94.4)	103.8 (88.1, 129.8)	86.9± 15.7	124.8 (103.0, 146.9)	72.9± 16.9	96.1± 20.1	84.8± 27.6	4.6 (3.5, 5.6)	80.6 (67.0, 103.1)
未加用组第1个月	76.3± 16.0	77.7± 15.0	86.6± 10.5	79.5± 18.7	73.1 (51.9, 87.0)	117.5 (96.0, 149.3)	86.7± 14.7	135.1 (109.6, 162.6)	68.3± 14.2	89.8± 13.9	80.7± 23.6	4.5 (3.0, 5.5)	79.9 (61.5, 103.1)
统计检验值	t= 0.033	t= 0.067	t= 0.053	t= 0.444	Z= -0.111	Z= -1.232	t= 0.027	Z= -1.267	t= 2.005	t= 4.603	t= 1.039	Z= -0.907	Z= -0.414
P值	0.856	0.797	0.819	0.508	0.911	0.218	0.871	0.205	0.160	0.350	0.311	0.364	0.679
加用组第6个月	86.5± 16.0	90.2± 14.5	88.4± 6.4	90.3± 16.0	80.1 (66.5, 111.9)	99.1 (87.7, 115.8)	89.2± 11.9	114.1 (92.3, 131.3)	72.9± 16.9	96.1± 20.1	84.8± 27.6	4.7 (4.1, 5.7)	83.2 (64.4, 116.0)
未加用组第6个月	91.6± 20.2	88.6± 12.6	84.5± 8.8	86.3± 16.0	66.8 (59.9, 87.2)	105.1 (84.4, 132.0)	92.3± 14.1	106.7 (94.2, 131.5)	68.3± 14.2	89.8± 13.9	80.7± 23.6	4.2 (3.4, 6.0)	92.6 (69.1, 103.6)
统计检验值	t= 0.016	t= 0.942	t= 3.084	t= 0.708	Z= -1.609	Z= -0.566	t= 1.344	Z= 1.84	t= 0.747	t= 2.399	t= 0.065	Z= -0.814	Z= -0.414
P值	0.900	0.335	0.084	0.403	0.108	0.0571	0.251	0.854	0.391	0.126	0.800	0.416	0.679
加用组第12个月	101.1± 12.8	96.9± 17.3	85.0± 11.0	96.8± 11.1	90.4 (55.3, 102.9)	102.1 (75.4, 103.4)	92.8± 11.6	96.1 (80.1, 107.8)	85.9± 24.1	96.2± 15.3	96.6± 10.2	4.4 (4.4, 4.9)	88.3 (62.2, 111.7)
未加用组第12个月	94..4± 12.3	91.5± 13.5	84.5± 13.0	87.3± 19.8	78.4 (54.6, 87.3)	108.4 (83.4, 136.6)	96.0± 14.8	106.8 (96.3, 131.6)	81.0± 9.2	91.2± 15.7	88.7± 19.8	4.2 (2.7, 4.9)	89.6 (64.5, 111.7)
统计检验值	t= 0.046	t= 1.155	t= 2.168	t= 1.113	Z= -1.171	Z= -1.512	t= 0.984	Z= 1.427	t= 0.681	t= 0.024	t= 0.083	Z= -1.193	Z= -0.277
P值	0.831	0.291	0.151	0.300	0.241	0.131	0.329	0.154	0.415	0.878	0.775	0.233	0.782

表3

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患者情况	例数	未加用组		加用组		χ²值	P值
患者情况	例数	例数	构成比(%)	例数	构成比(%)	χ²值	P值
性别						0.098	0.755
男	112	72	64.3	40	66.7
女	60	40	35.7	20	33.3
年龄(岁)						-	0.563^a
≤60	164	105	93.8	59	98.3
>60	8	7	6.3	1	1.7
吸烟						0.274	0.600
从未吸烟	119	79	70.5	40	66.7
吸烟	53	33	29.5	20	33.3
并发症						0.228	0.633
无	143	92	82.1	51	85.0
有^b	29	20	17.9	9	15.0

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