气道高反应性与哮喘气道TSLP相关，独立于嗜酸性粒细胞炎症
2024/01/26
摘要
背景：胸腺基质淋巴生成素(TSLP)在各种环境触发下从气道上皮释放，诱导2型炎症反应，并与气道炎症、气道高反应性(AHR)和加重有关。TSLP也可能通过对气道平滑肌和肥大细胞的直接作用诱导AHR，独立于2型炎症，尽管气道TSLP和AHR在哮喘表型之间的关联很少被描述。
目的：本研究旨在探讨伴有或不伴有2型炎症的哮喘患者血清、痰液和支气管肺泡灌洗液中AHR与TSLP水平之间的关系。
方法：一种新的超灵敏测定法用于测量哮喘患者（血清，n = 182;痰液，n = 81;支气管肺泡灌洗，n = 85）和健康对照（血清，n = 47）的TSLP水平。评估气道和全身性 TSLP 之间的分布和关联、AHR 测量、2 型炎症和疾病严重程度。
结果：痰液中 TSLP 与 AHR 相关，与嗜酸性粒细胞和呼出气一氧化氮分数水平无关 （ρ = 0.49，P =0.005）。与健康对照组相比，嗜酸性粒细胞高和嗜酸性粒细胞低哮喘的血清TSLP均较高，几何平均值分别为：1600 fg/mL（95% CI：1468-1744 fg/mL）和 1294 fg/mL（95% CI：1167-1435 fg/mL）对比健康对照组为846 fg/mL（95% CI：661-1082 fg/mL），但与 AHR 水平无关。年龄、男性和血液中嗜酸性粒细胞的增加与血清中 TSLP 水平升高有关，而肺功能、吸入皮质类固醇剂量和症状评分与TSLP水平升高无关。
结论：无论2型炎症标志物如何，痰中TSLP与AHR之间的关联进一步支持了TSLP在AHR中的作用，其部分独立于嗜酸性粒细胞炎症。
Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation.
Andreasson LM, Dyhre-Petersen N, Hvidtfeldt M,
Abstrast
Background: Thymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a type-2 inflammatory response, and is associated with airway inflammation, airway hyperresponsiveness (AHR), and exacerbations. TSLP may also induce AHR via a direct effect on airway smooth muscle and mast cells, independently of type-2 inflammation, although association between airway TSLP and AHR across asthma phenotypes has been described sparsely.
Objectives: This study sought to investigate the association between AHR and levels of TSLP in serum, sputum, and bronchoalveolar lavage in patients with asthma with and without type-2 inflammation.
Methods: A novel ultrasensitive assay was used to measure levels of TSLP in patients with asthma (serum, n = 182; sputum, n = 81; bronchoalveolar lavage, n = 85) and healthy controls (serum, n = 47). The distribution and association among airway and systemic TSLP, measures of AHR, type-2 inflammation, and severity of disease were assessed.
Results: TSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide (ρ = 0.49, P =0 .005). Serum TSLP was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: geometric mean: 1600 fg/mL (95% CI: 1468-1744 fg/mL) and 1294 fg/mL (95% CI: 1167-1435 fg/mL) versus 846 fg/mL (95% CI: 661-1082 fg/mL), but did not correlate with the level of AHR. Increasing age, male sex, and eosinophils in blood were associated with higher levels of TSLP in serum, whereas lung function, inhaled corticosteroid dose, and symptom score were not.
Conclusions: The association between TSLP in sputum and AHR to mannitol irrespective of markers of type-2 inflammation further supports a role of TSLP in AHR that is partially independent of eosinophilic inflammation.
背景：胸腺基质淋巴生成素(TSLP)在各种环境触发下从气道上皮释放，诱导2型炎症反应，并与气道炎症、气道高反应性(AHR)和加重有关。TSLP也可能通过对气道平滑肌和肥大细胞的直接作用诱导AHR，独立于2型炎症，尽管气道TSLP和AHR在哮喘表型之间的关联很少被描述。
目的：本研究旨在探讨伴有或不伴有2型炎症的哮喘患者血清、痰液和支气管肺泡灌洗液中AHR与TSLP水平之间的关系。
方法：一种新的超灵敏测定法用于测量哮喘患者（血清，n = 182;痰液，n = 81;支气管肺泡灌洗，n = 85）和健康对照（血清，n = 47）的TSLP水平。评估气道和全身性 TSLP 之间的分布和关联、AHR 测量、2 型炎症和疾病严重程度。
结果：痰液中 TSLP 与 AHR 相关，与嗜酸性粒细胞和呼出气一氧化氮分数水平无关 （ρ = 0.49，P =0.005）。与健康对照组相比，嗜酸性粒细胞高和嗜酸性粒细胞低哮喘的血清TSLP均较高，几何平均值分别为：1600 fg/mL（95% CI：1468-1744 fg/mL）和 1294 fg/mL（95% CI：1167-1435 fg/mL）对比健康对照组为846 fg/mL（95% CI：661-1082 fg/mL），但与 AHR 水平无关。年龄、男性和血液中嗜酸性粒细胞的增加与血清中 TSLP 水平升高有关，而肺功能、吸入皮质类固醇剂量和症状评分与TSLP水平升高无关。
结论：无论2型炎症标志物如何，痰中TSLP与AHR之间的关联进一步支持了TSLP在AHR中的作用，其部分独立于嗜酸性粒细胞炎症。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(J Allergy Clin Immunol 2023 Dec 09;doi: 10.1016/j.jaci.2023.11.915. IF: 10.228)
(J Allergy Clin Immunol 2023 Dec 09;doi: 10.1016/j.jaci.2023.11.915. IF: 10.228)
Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation.
Andreasson LM, Dyhre-Petersen N, Hvidtfeldt M,
Abstrast
Background: Thymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a type-2 inflammatory response, and is associated with airway inflammation, airway hyperresponsiveness (AHR), and exacerbations. TSLP may also induce AHR via a direct effect on airway smooth muscle and mast cells, independently of type-2 inflammation, although association between airway TSLP and AHR across asthma phenotypes has been described sparsely.
Objectives: This study sought to investigate the association between AHR and levels of TSLP in serum, sputum, and bronchoalveolar lavage in patients with asthma with and without type-2 inflammation.
Methods: A novel ultrasensitive assay was used to measure levels of TSLP in patients with asthma (serum, n = 182; sputum, n = 81; bronchoalveolar lavage, n = 85) and healthy controls (serum, n = 47). The distribution and association among airway and systemic TSLP, measures of AHR, type-2 inflammation, and severity of disease were assessed.
Results: TSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide (ρ = 0.49, P =0 .005). Serum TSLP was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: geometric mean: 1600 fg/mL (95% CI: 1468-1744 fg/mL) and 1294 fg/mL (95% CI: 1167-1435 fg/mL) versus 846 fg/mL (95% CI: 661-1082 fg/mL), but did not correlate with the level of AHR. Increasing age, male sex, and eosinophils in blood were associated with higher levels of TSLP in serum, whereas lung function, inhaled corticosteroid dose, and symptom score were not.
Conclusions: The association between TSLP in sputum and AHR to mannitol irrespective of markers of type-2 inflammation further supports a role of TSLP in AHR that is partially independent of eosinophilic inflammation.
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儿童期成分分辨诊断与青少年早期哮喘预测：一项出生队列研究
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重度和非重度哮喘中炎症小体反应的特征和抑制
