重度哮喘支气管热成形术后气道重塑的长期调节
2021/06/18
摘要
背景：支气管热成形术是一种机械治疗干预，被提倡为重度哮喘的有效治疗选择。认为其机制与短期内发生的气道平滑肌衰减有关。然而，关于支气管热成形术对气道重塑的影响的长期研究很少，仅对气道重塑指标进行了有限地评估。
目的：评估支气管热成形术对培养的气道上皮细胞和平滑肌细胞的影响，以及对行支气管热成形术治疗后12个月的重度哮喘患者气道重塑的影响。
方法：在猪模型中，通过支气管热成形术评估气道内的热量分布。培养人气道平滑肌细胞和支气管上皮细胞，以评估热损伤的影响。支气管热成形术治疗后基线、6周和12个月，对重度哮喘患者支气管活检进行组织学评价和形态计量学评价。
结果：支气管热成形术导致气道壁不均匀受热。气道平滑肌细胞持续遭受热损伤，而支气管上皮细胞相对耐热。治疗后6周和12个月，气道平滑肌和神经束显著减少。治疗6周后，粘膜下胶原蛋白减少，血管密度增加，治疗12个月时这两项指标均恢复至基线水平。在任何时间点检测杯状细胞数量、粘膜下腺面积和基底膜厚度均无明显变化。
结论：支气管热成形术主要影响气道平滑肌和神经，且该影响持续至治疗后12个月。
Long-term modulation of airway remodeling in severe asthma following bronchial thermoplasty
Nicholas Jendzjowsky, Austin Laing, Michelle Malig, John Matyas, Elaine de Heuvel 4, Curtis Dumonceaux, Elaine Dumoulin, Alain Tremblay, Richard Leigh , Alex Chee, Margaret M Kelly
Abstract
BACKGROUND: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 remodeling are few with only limited assessment of airway remodeling indices.
OBJECTIVES:To evaluate the effect of bronchial thermoplasty on (a) airway epithelial and smooth muscle cells in culture, and (b), airway remodeling 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 heterogenous 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 subbasement membrane thickness, were not significantly altered at any timepoint examined.
CONCLUSIONS:Bronchial thermoplasty primarily affects airway smooth muscle and nerves with the effects still present at 12-months post-treatment.
背景：支气管热成形术是一种机械治疗干预，被提倡为重度哮喘的有效治疗选择。认为其机制与短期内发生的气道平滑肌衰减有关。然而，关于支气管热成形术对气道重塑的影响的长期研究很少，仅对气道重塑指标进行了有限地评估。
目的：评估支气管热成形术对培养的气道上皮细胞和平滑肌细胞的影响，以及对行支气管热成形术治疗后12个月的重度哮喘患者气道重塑的影响。
方法：在猪模型中，通过支气管热成形术评估气道内的热量分布。培养人气道平滑肌细胞和支气管上皮细胞，以评估热损伤的影响。支气管热成形术治疗后基线、6周和12个月，对重度哮喘患者支气管活检进行组织学评价和形态计量学评价。
结果：支气管热成形术导致气道壁不均匀受热。气道平滑肌细胞持续遭受热损伤，而支气管上皮细胞相对耐热。治疗后6周和12个月，气道平滑肌和神经束显著减少。治疗6周后，粘膜下胶原蛋白减少，血管密度增加，治疗12个月时这两项指标均恢复至基线水平。在任何时间点检测杯状细胞数量、粘膜下腺面积和基底膜厚度均无明显变化。
结论：支气管热成形术主要影响气道平滑肌和神经，且该影响持续至治疗后12个月。
(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)
(Eur Respir J.2021 May 28;2100622. doi: 10.1183/13993003.00622-2021.)
(Eur Respir J.2021 May 28;2100622. doi: 10.1183/13993003.00622-2021.)
Long-term modulation of airway remodeling in severe asthma following bronchial thermoplasty
Nicholas Jendzjowsky, Austin Laing, Michelle Malig, John Matyas, Elaine de Heuvel 4, Curtis Dumonceaux, Elaine Dumoulin, Alain Tremblay, Richard Leigh , Alex Chee, Margaret M Kelly
Abstract
BACKGROUND: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 remodeling are few with only limited assessment of airway remodeling indices.
OBJECTIVES:To evaluate the effect of bronchial thermoplasty on (a) airway epithelial and smooth muscle cells in culture, and (b), airway remodeling 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 heterogenous 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 subbasement membrane thickness, were not significantly altered at any timepoint examined.
CONCLUSIONS:Bronchial thermoplasty primarily affects airway smooth muscle and nerves with the effects still present at 12-months post-treatment.
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