重症难治性哮喘患者的支气管热成形术的效果：临床和组织病理学的相关性
2016/11/09
摘要
背景：支气管热成形术（BT）的效果已经在重症哮喘中有过报道，但在不同的支气管结构中的影响仍然是未知的。
目的：检测BT对支气管结构的影响，探讨其与难治性哮喘的临床疗效的关系。
方法：对15个严重失控哮喘患者在BT手术之前和手术3个月之后进行支气管活检（N = 300）。免疫组化染色切片用来检测气道平滑肌（ASM）、上皮下基底膜厚度、神经纤维和神经内分泌细胞的上皮细胞。组织病理学检查结果用临床参数进行校正。
结果：BT在第3个月和第12个月明显改善哮喘控制和生活质量，并减少严重病情加重和口服糖皮质激素的数量。在第3个月，临床效益伴随着以下指标均降低：气道平滑肌面积（BT之前和之后的中位数[ 25-75 [IQR]，分别为19.7% [15.9-22.4]和5.3%[3.5-10.1]，P＜0.001）、上皮下基底膜增厚（4.4μM [ 4.0-4.7 ]和3.9μm [ 3.7-4.6 ]，P = 0.02）、黏膜下神经（1‰免疫反应性[0.7-1.3]和0.3‰免疫反应性[0.1-0.5]，P＜0.001）、ASM相关的神经（452.6免疫反应性像素每平方毫米 [196.0-811.2]和62.7免疫反应性像素每平方毫米 [0.0-230.3] P = 0.02）和上皮细胞神经内分泌细胞（4.9每平方毫米[0-16.4]和0.0每平方毫米[0-0]，P = 0.02）。BT手术后3个月和12个月，组织病理学参数与哮喘控制测试、病情加重数目、急救部门就诊有关（P均≤0.02）。
结论：支气管热成形术（BT）是重症治疗难治性哮喘的一个选择，它可下调气道狭窄和气道反应性，特别是ASM、神经内分泌上皮细胞和支气管神经末梢等有关的选择性结构异常。
关键词：难治性哮喘；气道重塑；气道平滑肌；哮喘控制；支气管上皮细胞；神经内分泌细胞上皮细胞；黏膜神经
（杨冬 审校）
J Allergy Clin Immunol. 2016 Sep 5. pii: S0091-6749(16)30896-X. doi: 10.1016/j.jaci.2016.08.009. [Epub ahead of print]
Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: clinical and histopathological correlations.
Pretolani M1, Bergqvist A2, Thabut G3, Dombret MC4, Knapp D5, Hamidi F1, Alavoine L6, Taillé C4, Chanez P7, Erjefält JS2, Aubier M8.
Author information
Abstract
BACKGROUND:The effectiveness of bronchial thermoplasty (BT) has been reported in severe asthma, yet its impact on the different bronchial structures remains unknown.
OBJECTIVE:To examine the effect of BT on bronchial structures and to explore their association with clinical outcome in severe refractory asthmatics.
METHODS:Bronchial biopsies (n = 300) were collected from 15 severe uncontrolled asthmatics before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, sub-epithelial basement membrane thickness, nerve fibers and epithelium neuroendocrine cells. Histopathological findings were correlated with clinical parameters.
RESULTS:BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values [25-75 IQR] before and after BT, respectively, 19.7% [15.9-22.4] and 5.3% [3.5-10.1], P < 0.001), in sub-epithelial basement membrane thickening (4.4 μm [4.0-4.7] and 3.9 μm [3.7-4.6], P = 0.02), in sub-mucosal nerves (1.0 ‰ immunoreactivity [0.7-1.3] and 0.3 ‰ immunoreactivity [0.1-0.5], P < 0.001), in ASM-associated nerves (452.6 immunoreactive pixels per mm2 [196.0-811.2] and 62.7 immunoreactive pixels per mm2 [0.0-230.3], P = 0.02) and in epithelium neuroendocrine cells (4.9 per mm2 [0-16.4] and 0.0 per mm2 [0-0], P = 0.02). Histopathological parameters were associated with asthma control test, number of exacerbations, and visits to emergency department (all P ≤ 0.02), 3 and 12 months after BT.
CONCLUSION:BT is a treatment option in severe therapy-refractory asthma that down-regulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells and bronchial nerve endings.
Copyright © 2016. Published by Elsevier Inc.
KEYWORDS:Refractory asthma; airway remodeling; airway smooth muscle; asthma control; bronchial epithelium; epithelium neuroendocrine cells; mucosal nerves
J Allergy Clin Immunol. 2016 Sep 5. pii: S0091-6749(16)30896-X. doi: 10.1016/j.jaci.2016.08.009. [Epub ahead of print]
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