中性粒细胞弹性蛋白酶活性与支气管扩张症患者疾病严重程度及恶化风险相关性研究

doi:10.3877/cma.j.issn.1674-6902.2025.05.011

中华肺部疾病杂志(电子版) ›› 2025, Vol. 18 ›› Issue (05) : 727 -731. doi: 10.3877/cma.j.issn.1674-6902.2025.05.011

论著

中性粒细胞弹性蛋白酶活性与支气管扩张症患者疾病严重程度及恶化风险相关性研究

黄佩琦¹, 黄方舟¹, 王加栋¹, 冯习¹, 周金华¹, 黄艳¹^,^†(

), 饶文姣², 袁浩²

¹410000　长沙，湖南师范大学附属长沙医院急诊急救中心
²410000　长沙，湖南师范大学附属长沙医院呼吸与重症医学科

收稿日期:2025-04-21 出版日期:2025-10-25
通信作者: 黄艳
基金资助:
湖南省卫生健康委科研计划项目(202210003022)

Study on the correlation between neutrophil elastase activity and disease severity and exacerbation risk in patients with bronchiectasis

Peiqi Huang¹, Fangzhou Huang¹, Jiadong Wang¹, Xi Feng¹, Jinhua Zhou¹, Yan Huang¹^,^†(), Wenjiao Rao², Hao Yuan²

¹Department of Emergency, Hunan Normal University Affiliated Changsha Hospital, Changsha 410000, China
²Department of Respiratory and Critical Care Medicine, Hunan Normal University Affiliated Changsha Hospital, Changsha 410000, China

Received:2025-04-21 Published:2025-10-25
Corresponding author: Yan Huang

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引用本文：

黄佩琦, 黄方舟, 王加栋, 冯习, 周金华, 黄艳, 饶文姣, 袁浩. 中性粒细胞弹性蛋白酶活性与支气管扩张症患者疾病严重程度及恶化风险相关性研究[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 727-731.

Peiqi Huang, Fangzhou Huang, Jiadong Wang, Xi Feng, Jinhua Zhou, Yan Huang, Wenjiao Rao, Hao Yuan. Study on the correlation between neutrophil elastase activity and disease severity and exacerbation risk in patients with bronchiectasis[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(05): 727-731.

目的

分析中性粒细胞弹性蛋白酶(neutrophil elastase)活性与支气管扩张患者疾病严重程度和恶化风险的相关性。

方法

选择2020年1月至2023年12月我院收治的103例非囊性纤维化(cystic fibrosis, CF)支气管扩张患者为对象，比较患者HRCT评分、支气管扩张严重指数(bronchiectasis severity index, BSI)、肺功能；采用免疫测定法检测血清中性粒细胞弹性蛋白酶活性，随访1年，观察支气管扩张恶化情况。采用多元线性回归和COX风险比例分析血清中性粒细胞弹性蛋白酶与患者疾病严重程度和恶化关系。

结果

103例中轻度支气管扩张41例、中度39例及重度23例，轻度、中度和重度支气管扩张患者血清中性粒细胞弹性蛋白酶活性分别为2.51(1.29，3.29)μg/ml、3.22(1.80，4.55)μg/ml、5.77(4.42，9.95)μg/ml(H＝35.618，P<0.001)。性别(β＝2.791，95%CI：1.182~4.401，P＝0.001)、体质量指数(body mass index, BMI)(β＝－0.261，95%CI：－0.443~－0.079，P＝0.006)、近1年急性加重次数(β＝0.001，95%CI: 0.616，P＝0.245~0.987)、用力肺活量(forced vital capacity, FVC)(β＝－5.744，95%CI：－10.933~－0.555，P＝0.030)和血清中性粒细胞弹性蛋白酶活性(β＝0.248，95%CI：0.093~0.402，P＝0.002)与BSI相关(P<0.05)。高血清中性粒细胞弹性蛋白酶活性(HR＝1.312，95%CI：1.202~1.431，P<0.001)与支气管扩张恶化有关。随访1年，恶化事件≥1次50例；103例CF患者中生存94例(91.26%)，死亡者9例(8.74%)，死因为支气管扩张加重6例、慢性阻塞性肺疾病2例、呼吸道感染1例。Kaplan-Meier曲线显示，与血清中性粒细胞弹性蛋白酶低活性者比较(<3.22 μg/ml)，血清中性粒细胞弹性蛋白酶高活性者(≥3.22 μg/ml)无恶化生存时间短(Log-Rank＝40.557，P<0.001)。

结论

血清中性粒细胞弹性蛋白酶活性与非CF支气管扩张患者疾病严重程度和恶化相关。

关键词: 中性粒细胞弹性蛋白酶, 支气管扩张症, 支气管扩张严重指数, 恶化风险

Objective

To analyze the correlation between neutrophil elastase activity and disease severity and exacerbation in patients with bronchiectasis.

Methods

A total of 103 patients with non-cystic fibrosis (CF) bronchiectasis admitted to our hospital from January, 2020, to December, 2023, were selected as subjects. Their HRCT scores, bronchiectasis severity index (BSI), and lung function were compared. Serum neutrophil elastase activity was measured using an activity-based immunoassay, and patients were followed for one year to observe bronchiectasis exacerbations. Multiple linear regression and COX proportional hazards analysis were used to analyze the relationship between serum neutrophil elastase and disease severity and exacerbation.

Results

Among the 103 patients, 41 had mild bronchiectasis, 39 had moderate bronchiectasis, and 23 had severe bronchiectasis. The serum neutrophil elastase activities in patients with mild, moderate, and severe bronchiectasis were 2.51(1.29, 3.29)μg/ml, 3.22(1.80, 4.55)μg/ml, and 5.77(4.42, 9.95)μg/ml, respectively (H=35.618, P<0.001). Gender (β=2.791, 95%CI: 1.182~4.401, P=0.001), body mass index (BMI) (β=-0.261, 95%CI: -0.443~-0.079, P=0.006), number of acute exacerbations in the past year (β=0.001, 95%CI: 0.616, P=0.245~0.987), forced vital capacity (FVC) (β=-5.744, 95%CI: -10.933~-0.555, P=0.030), and serum neutrophil elastase activity (β=0.248, 95%CI: 0.093~0.402, P=0.002) were associated with BSI (P<0.05). High serum neutrophil elastase activity (HR=1.312, 95%CI: 1.202~1.431, P<0.001) was associated with exacerbation in bronchiectasis patients during the one-year follow-up period. During the one-year follow-up, 50 patients experienced ≥1 exacerbation event; 94 cases(91.26%)survived, 9 patients died (8.74%), with causes of death including bronchiectasis exacerbation (6 cases), chronic obstructive pulmonary disease (2 cases), and respiratory infection (1 case). Kaplan-Meier curves showed that compared to patients with low serum neutrophil elastase activity (<3.22 μg/ml), those with high serum neutrophil elastase activity (≥3.22 μg/ml) had a shorter time to exacerbation-free survival (Log-Rank=40.557, P<0.001).

Conclusion

Serum neutrophil elastase activity is associated with disease severity and the risk of exacerbation in non-CF bronchiectasis patients.

Key words: Neutrophil elastase, Bronchiectasis, Bronchiectasis severity index, Deterioration

表1 不同病情严重程度支气管扩张患者临床资料

临床资料	轻度(n＝41)	中度(n＝39)	重度(n＝23)	F/H/χ²	P值
性别[n(%)]				6.634	0.036
男	12(29.27)	22(56.41)^a	12(32.17)
女	29(70.73)	17(43.59)	11(47.83)
BMI[kg/m²，(±s)]	21.72±2.74	20.99±3.40	18.82±3.43^ab	6.342	0.003
用药史[n(%)]
吸入性糖皮质激素	5(12.20)	6(15.38)	3(13.04)	0.181	0.914
化痰剂	9(21.95)	9(23.08)	5(21.74)	0.021	0.990
抗生素	8(19.51)	9(23.08)	5(21.74)	0.154	0.926
病因[n(%)]				1.091	0.896
特发性	18(43.90)	16(41.03)	12(32.17)
感染后	12(29.26)	13(33.33)	5(21.74)
其它	11(26.83)	10(25.64)	6(26.09)
痰细菌[n(%)]				2.363	0.669
共生菌	9(21.95)	11(28.21)	9(39.13)
铜绿假单胞菌	19(46.34)	15(38.46)	8(34.78)
其它菌	13(31.70)	13(33.33)	6(26.09)
近1年加重次数[次，M₅₀(P₂₅，P₇₅)]	1.00(0.50，2.00)	2.00(1.00，3.00)^a	2.00(1.00，3.00)^a	13.335	0.001
支气管扩张肺叶[个，M₅₀(P₂₅，P₇₅)]	3.00(2.00，5.00)	4.00(2.00，6.00)^a	6.00(5.00，6.00)^a	22.438	0.000
HRCT评分[分，M₅₀(P₂₅，P₇₅)]	6.00(4.00，8.00)	8.00(4.00，11.00)	11.00(8.00，13.00)^ab	25.304	0.000
肺脓肿[n(%)]	27(65.85)	29(74.36)	21(91.30)	5.063	0.080

表1 不同病情严重程度支气管扩张患者临床资料

临床资料	轻度(n＝41)	中度(n＝39)	重度(n＝23)	F/H/χ²	P值
性别[n(%)]				6.634	0.036
男	12(29.27)	22(56.41)^a	12(32.17)
女	29(70.73)	17(43.59)	11(47.83)
BMI[kg/m²，(±s)]	21.72±2.74	20.99±3.40	18.82±3.43^ab	6.342	0.003
用药史[n(%)]
吸入性糖皮质激素	5(12.20)	6(15.38)	3(13.04)	0.181	0.914
化痰剂	9(21.95)	9(23.08)	5(21.74)	0.021	0.990
抗生素	8(19.51)	9(23.08)	5(21.74)	0.154	0.926
病因[n(%)]				1.091	0.896
特发性	18(43.90)	16(41.03)	12(32.17)
感染后	12(29.26)	13(33.33)	5(21.74)
其它	11(26.83)	10(25.64)	6(26.09)
痰细菌[n(%)]				2.363	0.669
共生菌	9(21.95)	11(28.21)	9(39.13)
铜绿假单胞菌	19(46.34)	15(38.46)	8(34.78)
其它菌	13(31.70)	13(33.33)	6(26.09)
近1年加重次数[次，M₅₀(P₂₅，P₇₅)]	1.00(0.50，2.00)	2.00(1.00，3.00)^a	2.00(1.00，3.00)^a	13.335	0.001
支气管扩张肺叶[个，M₅₀(P₂₅，P₇₅)]	3.00(2.00，5.00)	4.00(2.00，6.00)^a	6.00(5.00，6.00)^a	22.438	0.000
HRCT评分[分，M₅₀(P₂₅，P₇₅)]	6.00(4.00，8.00)	8.00(4.00，11.00)	11.00(8.00，13.00)^ab	25.304	0.000
肺脓肿[n(%)]	27(65.85)	29(74.36)	21(91.30)	5.063	0.080

表2 不同病情严重程度支气管扩张患者肺功能

肺功能	轻度(n＝41)	中度(n＝39)	重度(n＝23)	F/H/χ²	P值
FVC(L)	2.63±0.77	2.82±0.78	2.17±0.89^ab	4.909	0.009
FVC pred%	82.39±15.27	88.00±22.57	67.32±24.99^ab	7.418	0.001
FEV₁(L)	1.96±0.66	1.91±0.73	1.34±0.59^ab	7.085	0.001
FEV₁ pred%	73.46±19.36	72.19±26.50	50.55±23.29^ab	8.304	0.000
FEV₁/FVC	75.60±12.93	69.85±15.88	62.53±13.20^a	6.328	0.003
MMEF50 pred%	46.91(32.50，61.19)	38.86(19.57，64.37)	20.98(11.24，36.60)^ab	11.944	0.003
MMEF25 pred%	40.82(28.52，58.88)	37.33(19.11，50.13)	17.48(11.38，34.76)^ab	14.486	0.001

表2 不同病情严重程度支气管扩张患者肺功能

肺功能	轻度(n＝41)	中度(n＝39)	重度(n＝23)	F/H/χ²	P值
FVC(L)	2.63±0.77	2.82±0.78	2.17±0.89^ab	4.909	0.009
FVC pred%	82.39±15.27	88.00±22.57	67.32±24.99^ab	7.418	0.001
FEV₁(L)	1.96±0.66	1.91±0.73	1.34±0.59^ab	7.085	0.001
FEV₁ pred%	73.46±19.36	72.19±26.50	50.55±23.29^ab	8.304	0.000
FEV₁/FVC	75.60±12.93	69.85±15.88	62.53±13.20^a	6.328	0.003
MMEF50 pred%	46.91(32.50，61.19)	38.86(19.57，64.37)	20.98(11.24，36.60)^ab	11.944	0.003
MMEF25 pred%	40.82(28.52，58.88)	37.33(19.11，50.13)	17.48(11.38，34.76)^ab	14.486	0.001

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Study on the correlation between neutrophil elastase activity and disease severity and exacerbation risk in patients with bronchiectasis