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Long-term modulation of airway remodelling in severe asthma following bronchial thermoplasty
European Respiratory Journal ( IF 24.3 ) Pub Date : 2021-12-31 , DOI: 10.1183/13993003.00622-2021
Nicholas Jendzjowsky 1, 2, 3 , Austin Laing 1, 3, 4 , Michelle Malig 1, 4 , John Matyas 5 , Elaine de Heuvel 1 , Curtis Dumonceaux 1 , Elaine Dumoulin 6 , Alain Tremblay 6 , Richard Leigh 1, 6 , Alex Chee 3, 6 , Margaret M Kelly 3, 4, 7
Affiliation  

Rationale

Bronchial thermoplasty is a mechanical therapeutic intervention that has been advocated as an effective treatment option for severe asthma. The mechanism is promoted as being related to the attenuation of airway smooth muscle which has been shown to occur in the short-term. However, long-term studies of the effects of bronchial thermoplasty on airway remodelling are few, with only limited assessment of airway remodelling indices.

Objectives

To evaluate the effect of bronchial thermoplasty on 1) airway epithelial and smooth muscle cells in culture and 2) airway remodelling in patients with severe asthma who have been prescribed bronchial thermoplasty up to 12 months post-treatment.

Methods

The distribution of heat within the airway by bronchial thermoplasty was assessed in a porcine model. Culture of human airway smooth muscle cells and bronchial epithelial cells evaluated the impact of thermal injury. Histological evaluation and morphometric assessment were performed on bronchial biopsies obtained from severe asthma patients at baseline, 6 weeks and 12 months following bronchial thermoplasty.

Results

Bronchial thermoplasty resulted in heterogeneous heating of the airway wall. Airway smooth muscle cell cultures sustained thermal injury, whilst bronchial epithelial cells were relatively resistant to heat. Airway smooth muscle and neural bundles were significantly reduced at 6 weeks and 12 months post-treatment. At 6 weeks post-treatment, submucosal collagen was reduced and vessel density increased, with both indices returning to baseline at 12 months. Goblet cell numbers, submucosal gland area and sub-basement membrane thickness were not significantly altered at any time point examined.

Conclusions

Bronchial thermoplasty primarily affects airway smooth muscle and nerves with the effects still present at 12 months post-treatment.



中文翻译:

支气管热成形术后严重哮喘气道重塑的长期调节

基本原理

支气管热成形术是一种机械治疗干预措施,已被提倡作为严重哮喘的有效治疗选择。该机制被认为与气道平滑肌的衰减有关,这已被证明在短期内发生。然而,关于支气管热成形术对气道重塑影响的长期研究很少,对气道重塑指数的评估也很有限。

目标

评估支气管热成形术对 1) 培养中的气道上皮细胞和平滑肌细胞和 2) 在治疗后长达 12 个月内接受支气管热成形术的严重哮喘患者的气道重塑的影响。

方法

在猪模型中评估通过支气管热成形术在气道内的热量分布。人气道平滑肌细胞和支气管上皮细胞的培养评估了热损伤的影响。在基线、支气管热成形术后 6 周和 12 个月对从严重哮喘患者获得的支气管活检进行组织学评估和形态学评估。

结果

支气管热成形术导致气道壁的不均匀加热。气道平滑肌细胞培养物持续热损伤,而支气管上皮细胞相对耐热。气道平滑肌和神经束在治疗后 6 周和 12 个月显着减少。在治疗后 6 周,黏膜下胶原蛋白减少,血管密度增加,两个指标在 12 个月时恢复到基线。在检查的任何时间点,杯状细胞数量、粘膜下腺面积和亚基底膜厚度均未显着改变。

结论

支气管热成形术主要影响气道平滑肌和神经,治疗后 12 个月仍存在影响。

更新日期:2021-12-31
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