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

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

Abstract

Abstract:

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

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]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(05): 727-731.

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References 30

1	亓倩，郝田宇，徐嘉蔚，等. 山东地区呼吸科医师对支气管扩张症诊治认知的现状调查[J]. 山东大学学报(医学版), 2023, 61(7): 63-71.
2	桂真，蒲红兵，张蓓，等. 嗜酸性粒细胞水平与支气管扩张吸入性糖皮质激素疗效的相关性[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(6): 1020-1023.
3	Morton M, Wilson N, Homer TM, et al. Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis[J]. BMJ Open, 2023, 13(8): e071906.
4	杨智晖，赵宇博，许倩，等. 经鼻高流量湿化氧疗治疗支气管扩张症伴感染临床分析[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(2): 206-208.
5	余灵灵，闫范书，王黎君，等. 2004-2021年中国支气管扩张相关的死亡特征分析[J]. 中国慢性病预防与控制，2024, 32(2): 86-89.
6	Oriano M, Gramegna A, Terranova L, et al. Sputum neutrophil elastase associates with microbiota and Pseudomonas aeruginosa in bronchiectasis[J]. Eur Respir J, 2020, 56(4): 2000769.
7	Johnson E, Long MB, Chalmers JD. Biomarkers in bronchiectasis[J]. Eur Respir Rev, 2024, 33(173): 230234.
8	Chalmers JD, Burgel PR, Daley CL, et al. Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics[J]. ERJ Open Res, 2024, 10(4): 00151-2024.
9	陈红波，陈丽萍，金永明，等. COPD不同HRCT表型患者血清中性粒细胞弹性蛋白酶、总抗氧化能力比较[J]. 昆明医科大学学报，2020, 41(12): 108-111.
10	Voynow JA, Shinbashi M. Neutrophil elastase and chronic lung disease[J]. Biomolecules, 2021, 11(8): 1065.
11	Ali HA, Fouda EM, Salem MA, et al. Sputum neutrophil elastase and its relation to pediatric bronchiectasis severity: A cross-sectional study[J]. Health Sci Rep, 2022, 5(3): e581.
12	Oriano M, Amati F, Gramegna A, et al. Protease-antiprotease imbalance in bronchiectasis[J]. Int J Mol Sci, 2021, 22(11): 5996.
13	支气管扩张症专家共识撰写协作组，中华医学会呼吸病学分会感染学组. 中国成人支气管扩张症诊断与治疗专家共识[J]. 中华结核和呼吸杂志，2021, 44(4): 311-321.
14	Howarth T, Gibbs C, Abeyaratne A, et al. Applicability and validity of the "bronchiectasis severity Index" (BSI) and "FACED" score in adult aboriginal australians[J]. Int J Chron Obstruct Pulmon Dis, 2024, 19: 2611-2628.
15	Alzeer AH. HRCT score in bronchiectasis: correlation with pulmonary function tests and pulmonary artery pressure[J]. Ann Thorac Med, 2008, 3(3): 82-86.
16	Johnson E, Long MB, Chalmers JD. Biomarkers in bronchiectasis[J]. Eur Respir Rev, 2024, 33(173): 230234.
17	Choi H, McShane PJ, Aliberti S, et al. Bronchiectasis management in adults: state of the art and future directions[J]. Eur Respir J, 2024, 63(6): 2400518.
18	Elborn JS, Blasi F, Haworth CS, et al. Bronchiectasis and inhaled tobramycin: A literature review[J]. Respir Med, 2022, 192: 106728.
19	Choate R, Aksamit TR, Mannino D, et al. Pseudomonas aeruginosa associated with severity of non-cystic fibrosis bronchiectasis measured by the modified bronchiectasis severity score (BSI) and the FACED: The US bronchiectasis and NTM Research Registry (BRR) study[J]. Respir Med, 2021, 177: 106285.
20	Im Y, Chalmers JD, Choi H. Disease severity and activity in bronchiectasis: a paradigm shift in bronchiectasis management[J]. Tuberc Respir Dis (Seoul), 2025, 88(1): 109-119.
21	Chalmers JD, Mall MA, Chotirmall SH, et al. Targeting neutrophil serine proteases in bronchiectasis[J]. Eur Respir J, 2025, 65(1): 2401050.
22	Chalmers JD, Metersky M, Aliberti S, et al. Neutrophilic inflammation in bronchiectasis[J]. Eur Respir Rev, 2025, 34(176): 240179.
23	Keir HR, Chalmers JD. Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy[J]. Eur Respir Rev, 2022, 31(163): 210241.
24	Martins M, Keir HR, Chalmers JD. Endotypes in bronchiectasis: moving towards precision medicine a narrative review[J]. Pulmonology, 2023, 29(6): 505-517.
25	Keir HR, Chalmers JD. Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy[J]. Eur Respir Rev, 2022, 31(163): 210241.
26	董右青，朱星，沈俊希，等. 补肺汤对COPD大鼠模型中性粒细胞胞外诱捕网及维生素D的影响[J]. 中药药理与临床，2024, 40(4): 47-53.
27	Voynow JA, Shinbashi M. Neutrophil elastase and chronic lung disease[J]. Biomolecules, 2021, 11(8): 1065.
28	Garratt LW, Breuer O, Schofield CJ, et al. Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis[J]. J Cyst Fibros, 2021, 20(6): 941-948.
29	Gao Y, Richardson H, Dicker AJ, et al. Endotypes of exacerbation in bronchiectasis: An observational cohort study[J]. Am J Respir Crit Care Med, 2024, 210(1): 77-86.
30	Chalmers JD, Moffitt KL, Suarez-Cuartin G, et al. Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis[J]. Am J Respir Crit Care Med, 2017, 195(10): 1384-1393.

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

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

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

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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