In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss.
In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss.
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DOI：
10.1183/13993003.01680-2017
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Brightling CE
中科院分区：
文献类型：
--
作者：
Chernyavsky IL;Russell RJ;Saunders RM;Morris GE;Berair R;Singapuri A;Chachi L;Mansur AH;Howarth PH;Dennison P;Chaudhuri R;Bicknell S;Rose FRAJ;Siddiqui S;Brook BS;Brightling CE
支气管热成形术是治疗哮喘的方法。目前尚不清楚其组织病理学影响是否可以通过暴露于影响细胞存活所需温度的气道壁比例来充分解释。将气道平滑肌和支气管上皮细胞暴露于介质（37-70°C）10秒以模拟热成形。在计算机中，我们开发了热成形术后气道热量分布的数学模型。在体内，我们测定了 14 名严重哮喘患者热成形术前后的气道平滑肌质量和上皮完整性。添加加热至 ≥65°C 的培养基后，体外气道平滑肌和上皮细胞数量显着减少。计算机模拟显示，在较大的气道中，不均匀的热量分布被放大，在内半径为 ∼4 mm 的气道中，<10% 的气道壁被加热到 >60°C。热成形术后 6 周的体内哮喘控制有所改善（通过哮喘控制问卷 6 进行测量；平均差 0.7，95% CI 0.1–1.3；p=0.03），气道平滑肌质量下降（绝对中值减少 5%，四分位距 (IQR) 0–10；p=0.03），上皮完整性增加（14%， IQR 6-29；p=0.007)。后两个结果均与哮喘控制的改善无关。综合体外和计算机模型表明，热成形术后气道平滑肌的减少不能完全用急性加热来解释，而且这种减少也没有带来哮喘控制的更大改善。支气管热成形术治疗哮喘具有意想不到的可能作用机制 http://ow.ly/ZcuE30jsaSa
Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival. Airway smooth muscle and bronchial epithelial cells were exposed to media (37–70°C) for 10 s to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution post-thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma. In vitro airway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to ≥65°C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60°C in airways with an inner radius of ∼4 mm. In vivo at 6 weeks post-thermoplasty, there was an improvement in asthma control (measured via Asthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1–1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0–10; p=0.03) and epithelial integrity increased (14%, IQR 6–29; p=0.007). Neither of the latter two outcomes was related to improved asthma control. Integrated in vitro and in silico modelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control. Bronchial thermoplasty treatment for asthma has unexpected possible mechanisms of action http://ow.ly/ZcuE30jsaSa
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DOI：
10.4049/jimmunol.181.4.2772
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hollins F;Kaur D;Yang W;Cruse G;Saunders R;Sutcliffe A;Berger P;Ito A;Brightling CE;Bradding P
通讯作者：
Bradding P
影响因子：
8.3
作者：
Chakir, Jamila;Haj-Salem, Ikhlass;Laviolette, Michel
通讯作者：
Laviolette, Michel
影响因子：
3.9
作者：
Jarrard, Jerry;Wizeman, Bill;Mitzner, Wayne
通讯作者：
Mitzner, Wayne
DOI：
10.1183/13993003.01507-2016
发表时间：
2017-05
期刊：
The European respiratory journal
影响因子：
--
作者：
Berair R;Hartley R;Mistry V;Sheshadri A;Gupta S;Singapuri A;Gonem S;Marshall RP;Sousa AR;Shikotra A;Kay R;Wardlaw A;Bradding P;Siddiqui S;Castro M;Brightling CE
通讯作者：
Brightling CE
DOI：
10.1164/rccm.200603-394oc
发表时间：
2006-12-01
影响因子：
24.7
作者：
Kaur, Davinder;Saunders, Ruth;Brightling, Christopher E.
通讯作者：
Brightling, Christopher E.