痰中炎症、神经和重塑介质在嗜酸性粒细胞和非嗜酸性粒细胞哮喘中的作用。

Sputum inflammatory, neural, and remodeling mediators in eosinophilic and noneosinophilic asthma.

机构信息

Research Centre for Hauora and Health Research Massey University, Wellington, New Zealand.

出版信息

Ann Allergy Asthma Immunol. 2023 Jun;130(6):776-783.e3. doi: 10.1016/j.anai.2023.03.015. Epub 2023 Mar 21.

DOI:10.1016/j.anai.2023.03.015

PMID:36958472

Abstract

BACKGROUND

Neural and remodeling mechanisms may play a role in asthma, particularly noneosinophilic asthma (NEA).

OBJECTIVE

To assess sputum mediators associated with neural, remodeling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and participants without asthma.

METHODS

A total of 111 participants with and 62 without asthma (14-21 years old) underwent sputum induction, exhaled nitric oxide, atopy, and spirometry tests. There were 24 mediators measured in sputum using enzyme-linked immunosorbent assay or bead array. Eosinophilic asthma (n = 52) and NEA (n = 59) were defined using a sputum eosinophil level cut-point of greater than or equal to 2.5%.

RESULTS

Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, P = .03), periostin (33.8 vs 9.4 ng/mL, P = .01), and ECP; (220.1 vs 83.7 ng/mL, P = .03) were found in patients with asthma compared with those without asthma. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, P = .02) compared with participants without asthma. Eosinophilic asthma had higher levels of inflammatory mediators (ECP: 495.5 vs 100.3 ng/mL, P ≤ .01; interleukin-1β: 285.3 vs 209.3 pg/mL, P = .03; histamine: 5805.0 vs 3172.5 pg/mL, P < .01) and remodeling mediators (VEGF-A); 3.3 vs 2.5 ng/mL, P = .03; periostin: 47.7 vs 22.1 ng/mL, P = .04) than NEA. Whereas macrophages were associated with neural mediators, for example, neurokinin A (r = 0.27, P = .01) and nociceptin (r = 0.30, P = .02), granulocytes were associated with inflammatory and remodeling mediators (eg, ECP and VEGF-A correlated with neutrophils (r = 0.53 and r = 0.33, respectively, P < .01) and eosinophils (r = 0.53 and r = 0.29 respectively, P ≤ .01).

CONCLUSION

Elevated levels of nociceptin and inflammatory and remodeling markers were found in EA, but no evidence for neural and remodeling pathways was found in NEA. Neural and remodeling mechanisms seem to coexist with inflammation.

摘要

背景

神经和重塑机制可能在哮喘中发挥作用，尤其是非嗜酸性粒细胞性哮喘（NEA）。

目的

评估与嗜酸性粒细胞性哮喘（EA）、NEA 和无哮喘参与者的神经、重塑和炎症机制相关的痰液介质。

方法

共纳入 111 名哮喘患者和 62 名无哮喘患者（14-21 岁）进行痰液诱导、呼气一氧化氮、变应原和肺量测定。使用酶联免疫吸附试验或珠阵列法测量痰液中的 24 种介质。根据痰液嗜酸性粒细胞水平大于或等于 2.5%，将嗜酸性粒细胞性哮喘（n=52）和 NEA（n=59）定义为。

结果

与无哮喘患者相比，哮喘患者的神经肽（中位数：39.1 比 22.4 ng/ml，P=0.03）、periostin（33.8 比 9.4 ng/ml，P=0.01）和 ECP（220.1 比 83.7 ng/ml，P=0.03）水平升高。与无哮喘患者相比，EA 患者的神经肽水平升高（54.8 比 22.4 ng/ml，P=0.02）。嗜酸性粒细胞性哮喘患者的炎症介质（ECP：495.5 比 100.3 ng/ml，P≤0.01；白细胞介素-1β：285.3 比 209.3 pg/ml，P=0.03；组胺：5805.0 比 3172.5 pg/ml，P<0.01）和重塑介质（VEGF-A）；3.3 比 2.5 ng/ml，P=0.03；periostin：47.7 比 22.1 ng/ml，P=0.04）水平高于 NEA。虽然巨噬细胞与神经介质相关，例如神经激肽 A（r=0.27，P=0.01）和神经肽（r=0.30，P=0.02），但嗜中性粒细胞与炎症和重塑介质相关（例如，ECP 和 VEGF-A 与嗜中性粒细胞（r=0.53 和 r=0.33，分别，P<0.01）和嗜酸性粒细胞（r=0.53 和 r=0.29，分别，P≤0.01）相关。