Paré P D, Roberts C R, Bai T R, Wiggs B J
Respiratory Health Network of Centres of Excellence, University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Monaldi Arch Chest Dis. 1997 Dec;52(6):589-96.
Structural changes in the airway walls involving extracellular matrix remodelling are prominent features of asthma. These changes are probably driven by mediators released as a consequence of chronic allergic inflammation. It is clear that changes in the extracellular matrix have the capacity to influence airway function in asthma. However, it is not clear how each of the many changes that occur in the airway wall contribute to altered airway function in asthma. Collagen deposition in the subepithelial matrix, and hyaluronan and versican deposition around and internal to the smooth muscle would be expected to oppose the effect of smooth muscle contraction. Conversely, geometric considerations would result in exaggerated airway narrowing for a given degree of smooth muscle shortening, as the airway wall is thickened by the deposition of these molecules internal to the smooth muscle. Elastin and cartilage reorganization and degradation in the airway walls would be expected to result in decreased airway wall stiffness and increased airway narrowing for a given amount of force generated by the smooth muscle. Degradation of matrix associated with the smooth muscle may both decrease the stiffness of the parallel elastic component and uncouple smooth muscle from the load provided by lung recoil, allowing exaggerated smooth muscle shortening. Increase in muscle mass may be associated with an increase, a decrease or no change in smooth muscle contractility. If an increase in muscle mass was associated with preservation of its contractile capacity modelling studies suggest that it could be the most important contributor to exaggerated airway narrowing. Modelling studies also suggest that the pattern of mucosal folding during smooth muscle contraction may be an important determinant of airway narrowing. The greater the number of folds, and the stiffer the subepithelial collagenous layer the more resistant the airway will be to narrowing.
气道壁涉及细胞外基质重塑的结构变化是哮喘的显著特征。这些变化可能是由慢性过敏性炎症释放的介质驱动的。显然，细胞外基质的变化有能力影响哮喘患者的气道功能。然而，尚不清楚气道壁发生的众多变化中的每一个如何导致哮喘患者气道功能改变。上皮下基质中的胶原蛋白沉积，以及平滑肌周围和内部的透明质酸和多功能蛋白聚糖沉积，预计会对抗平滑肌收缩的作用。相反，从几何学角度考虑，由于平滑肌内部这些分子的沉积使气道壁增厚，对于给定程度的平滑肌缩短，气道狭窄会加剧。气道壁中的弹性蛋白和软骨重组及降解预计会导致气道壁硬度降低，并且对于平滑肌产生的给定力量，气道狭窄会增加。与平滑肌相关的基质降解可能既会降低平行弹性成分的硬度，又会使平滑肌与肺回缩提供的负荷解耦联，从而使平滑肌过度缩短。肌肉质量增加可能与平滑肌收缩力增加、降低或无变化有关。如果肌肉质量增加与收缩能力的保留相关，模型研究表明这可能是气道过度狭窄的最重要因素。模型研究还表明，平滑肌收缩过程中黏膜折叠的模式可能是气道狭窄的重要决定因素。褶皱数量越多，上皮下胶原层越硬，气道对狭窄的抵抗力就越强。
