Human diaphragm remodeling associated with chronic obstructive pulmonary disease - Clinical implications

Human diaphragm remodeling associated with chronic obstructive pulmonary disease - Clinical implications
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DOI:
10.1164/rccm.200209-1070oc
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发表时间:
2003-09-15
影响因子:
24.7
通讯作者:
Shrager, JB
Shrager, JB
中科院分区:
医学1区
文献类型:
--
作者:
Levine, S;Nguyen, T;Shrager, JB

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与慢性阻塞性肺疾病(COPD)相关的膈肌重塑包括快到慢的纤维类型转换以及每种纤维类型内的适应。为了解释文献中关于纤维类型比例和FEV 1之间关系的不同发现,我们对40名受试者进行了肋膈活检,其FEV 1范围为预测正常值的118 - 16%。首先,我们注意到,我们的指数回归模型表明,FEV 1的变化可以解释I型纤维比例变化的72%。其次,为了评估COPID对膈肌力产生的影响,我们测量了由两名肺功能正常患者和两名严重COPD患者的膈肌制备的单透化纤维产生的最大比力。我们注意到,由严重COPD患者的横膈膜制备的纤维产生的比力低于对照纤维(p < 0.001),并且I型纤维产生的比力低于11型纤维(p < 0.001)。我们发现I型纤维的比例和FEV 1之间的指数关系解释了文献中的差异。此外,我们的单纤维的结果表明,COPD相关的膈肌重塑减少了每种纤维类型内的适应以及纤维类型的转换,产生的反作用力。
Diaphragm remodeling associated with chronic obstructive pulmonary-disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsieson 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPID on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type 11 fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.