Inserm UMR1152, Physiopathology and Epidemiology of Respiratory Diseases, Paris, France; Paris Diderot University, Faculty of Medicine, Bichat campus, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité, and DHU FIRE, Paris, France.
Unit of Airway Inflammation, Lund University, Lund, Sweden.
J Allergy Clin Immunol. 2017 Apr;139(4):1176-1185. doi: 10.1016/j.jaci.2016.08.009. Epub 2016 Sep 5.
The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown.
We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma.
Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters.
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 before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 μm [25th-75th IQR, 4.0-4.7 μm] and 3.9 μm [25th-75th IQR, 3.7-4.6 μm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm, P = .02), and epithelial neuroendocrine cells (4.9/mm [25th-75th IQR, 0-16.4/mm] and 0.0/mm [25th-75th IQR, 0-0/mm], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT.
BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.
支气管热成形术（BT）在重度哮喘患者中的有效性已得到报道，但它对不同支气管结构的影响尚不清楚。
我们旨在研究 BT 对支气管结构的影响，并探讨其与重度难治性哮喘患者临床结局的关系。
我们从 15 例重度未控制哮喘患者中在 BT 治疗前和治疗后 3 个月分别采集支气管活检标本（n=300）。用免疫组化染色评估气道平滑肌（ASM）面积、黏膜下基底膜厚度、神经纤维和上皮神经内分泌细胞。组织病理学发现与临床参数相关。
BT 治疗后 3 个月和 12 个月时哮喘控制和生活质量均显著改善，重度加重发作次数和口服皮质类固醇剂量减少。3 个月时，这种临床获益伴随着 ASM 面积的减少（BT 治疗前后中位数分别为 19.7%[25%至 75%四分位数间距（IQR），15.9%至 22.4%]和 5.3%[25%至 75% IQR，3.5%至 10.1%]，P<0.001）、黏膜下基底膜增厚（4.4μm[25%至 75% IQR，4.0 至 4.7μm]和 3.9μm[25%至 75% IQR，3.7 至 4.6μm]，P=0.02）、黏膜下神经（1.0‰[25%至 75% IQR，0.7 至 1.3‰]免疫反应性和 0.3‰[25%至 75% IQR，0.1 至 0.5‰]免疫反应性，P<0.001）、ASM 相关神经（452.6[25%至 75% IQR，196.0 至 811.2]个/mm 免疫反应性像素和 62.7[25%至 75% IQR，0.0 至 230.3]个/mm 免疫反应性像素，P=0.02）和上皮神经内分泌细胞（4.9/mm[25%至 75% IQR，0 至 16.4/mm]和 0.0/mm[25%至 75% IQR，0 至 0/mm]，P=0.02）。BT 治疗后 3 个月和 12 个月，组织病理学参数与哮喘控制测试评分、加重发作次数和急诊科就诊次数相关（均 P≤0.02）。
BT 是一种治疗重度治疗抵抗性哮喘的选择，可下调与气道狭窄和支气管反应性相关的结构异常，特别是 ASM、上皮神经内分泌细胞和支气管神经末梢。
