Lang M R, Fiaux G W, Gillooly M, Stewart J A, Hulmes D J, Lamb D
Department of Pathology, Medical School, University of Edinburgh.
Thorax. 1994 Apr;49(4):319-26. doi: 10.1136/thx.49.4.319.
Emphysema is currently defined as "a condition of the lung characterised by abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious fibrosis." The functional and morphological changes that occur in emphysema have largely been attributed to changes in alveolar elastin rather than in collagen. A study was performed to determine whether the amount of collagen in the alveolar wall changes with age in the lungs of non-smokers and of smokers with different types of macroscopically defined emphysema in relation to a microscopic measurement of lung structure.
Total alveolar wall collagen was measured (as hydroxyproline) in known volumes of distended lung tissue (by reverse phase high pressure liquid chromatography) in the lungs of non-smokers (n = 23) and in regions sampled away from emphysematous lesions in the lungs of 36 smokers (four with no emphysema, 13 with centriacinar emphysema (CAE), nine with panacinar emphysema (PAE), and 10 with a mixture (MIX) of both PAE and CAE). Mean lung airspace wall surface area per unit volume (AWUV) was calculated from at least six random blocks per lung and on histological sections immediately adjacent to those prepared for collagen measurement with a rapid scanning device (fast interval processor).
In non-smokers there was no significant correlation between the amount of collagen in the alveolar wall tissue and either mean lung AWUV or increasing patient age when amounts of collagen were expressed either per unit volume of distended lung (40 mm3 sample) or per unit surface area of airspace wall tissue. Smokers without emphysema had similar amounts of collagen to non-smokers. Lungs with PAE and MIX, but not CAE alone, contained significantly more collagen than normal when expressed per unit volume of airspace wall tissue whereas all groups, including CAE, contained significantly raised amounts of collagen when expressed per unit surface area.
There is no significant age related change in the collagen content of the lungs of non-smokers which suggests that, as AWUV is lost with age, the main collagenous framework is maintained. However, in smokers with emphysema there is a loss of airspace wall tissue in regions remote from the macroscopic lesions that is accompanied by a net increase in collagen mass. The greater accumulation of collagen in MIX lungs than in CAE lungs suggests a greater degree of structural damage, indicative of an alternative pathogenetic mechanism operating between the different types of emphysema. Our results suggest an active alveolar wall fibrosis in emphysema as a consequence of cigarette smoking. It is suggested that the definition of emphysema may require further revision to include such change.
目前，肺气肿被定义为“一种肺部疾病，其特征为终末细支气管远端的气腔异常、永久性扩大，伴有其壁的破坏，且无明显纤维化”。肺气肿中发生的功能和形态学变化在很大程度上归因于肺泡弹性蛋白而非胶原蛋白的变化。本研究旨在确定非吸烟者以及患有不同类型宏观定义肺气肿的吸烟者的肺中，肺泡壁胶原蛋白的含量是否随年龄变化，并与肺结构的微观测量相关。
通过反相高压液相色谱法，在已知体积的扩张肺组织中（非吸烟者(n = 23)例）以及在36例吸烟者的肺中远离肺气肿病变的区域（4例无肺气肿者、13例有小叶中心型肺气肿（CAE）者、9例有全小叶型肺气肿（PAE）者以及10例同时有PAE和CAE混合类型（MIX）者）测量总肺泡壁胶原蛋白（以羟脯氨酸计）。使用快速扫描设备（快速间隔处理器），从每侧肺至少六个随机切片块以及与用于胶原蛋白测量的切片紧邻的组织学切片上计算每单位体积的平均肺气腔壁表面积（AWUV）。
在非吸烟者中，当以扩张肺的每单位体积（(40 mm^3)样本）或气腔壁组织的每单位表面积表示胶原蛋白含量时，肺泡壁组织中的胶原蛋白含量与平均肺AWUV或患者年龄增加之间均无显著相关性。无肺气肿的吸烟者的胶原蛋白含量与非吸烟者相似。当以气腔壁组织的每单位体积表示时，PAE和MIX类型的肺（而非仅CAE类型的肺）比正常肺含有显著更多的胶原蛋白，而当以每单位表面积表示时，所有组（包括CAE组）的胶原蛋白含量均显著升高。
非吸烟者肺中胶原蛋白含量无显著的年龄相关变化，这表明随着年龄增长AWUV降低时，主要的胶原框架得以维持。然而，在患有肺气肿的吸烟者中，远离宏观病变区域的气腔壁组织减少，同时胶原蛋白总量净增加。MIX类型的肺中胶原蛋白积累比CAE类型的肺更多，这表明结构损伤程度更大，提示不同类型肺气肿之间存在另一种致病机制。我们的结果表明，吸烟导致肺气肿时存在活跃的肺泡壁纤维化。建议肺气肿的定义可能需要进一步修订以纳入此类变化。
