Kilburn K H
Environ Health Perspect. 1984 Apr;55:97-109. doi: 10.1289/ehp.845597.
The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and quantify our preliminary picture of the pathogenesis of lung disease by particles, but a useful start has been made.
肺对吸入颗粒的反应模式有限。所观察到的疾病取决于颗粒沉积的位置:传导气道、终末细支气管和肺泡,以及所引发炎症的性质:急性、亚急性或慢性。许多不同的因素可导致传导气道狭窄(哮喘),其中一些因素还会导致气道永久性变形或闭塞。终末细支气管似乎对某些颗粒特别敏感,这些颗粒会导致杯状细胞化生、黏液阻塞,并最终导致细支气管周围纤维化。癌症是支气管层面的最终后果,似乎取决于气道持续暴露于或留存某种物质,以及受影响细胞无法脱落,这可能是由于鳞状化生所致。肺泡由内皮细胞、I型或扁平上皮细胞以及具有代谢活性的立方状II型细胞组成,II型细胞可产生肺特异性表面活性剂二棕榈酰卵磷脂。表面活性剂紊乱会导致肺远端水肿,而过敏反应或烟雾引起的喉水肿可能导致窒息。难消化颗粒的物理留存或免疫记忆反应导致的留存可能引发透明膜形成,刺激肺泡蛋白沉着症,最终导致纤维化。这种后期结缔组织的过度沉积在职业性尘肺尤其是矽肺和石棉肺中得到了最好的研究。相比之下,肺气肿是一种分解代谢反应,似乎常常是在香烟烟雾颗粒的处理过程中,溶酶体蛋白酶泄漏或释放到肺中所致。由颗粒引起的最隐匿且可能最重要的人类肺部疾病是细支气管阻塞和闭塞,导致气流逐渐受损。致病颗粒是难消化脂质、复合碳水化合物与活性化学物质的复杂组合,我们称之为香烟烟雾。需要进行更多研究来完善、修正和量化我们对颗粒所致肺部疾病发病机制的初步认识,但已经有了一个有益的开端。