Cigarette Smoke Makes Airway and Early Parenchymal Asbestos-Induced Lung Disease Worse in the Guinea Pig

Abstract

In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic exposure to high levels of particulate air pollution and small airway remodeling.

“…Smoking produces lesions similar in location and appearance [pigmentation, inflammation, and fibrosis of the walls of the membranous and to a certain extent the RB (Wright et al 1992)] to those caused by dusts, although smoke-induced lesions tend to be more proximal in the bronchioles and dust-induced lesions more distal. Synergistic interactions between smoke and dust may amplify dust effects as indicated in animal models (Tron et al 1987); thus, determining what effects really are chronic ambient PM effects is not straightforward.…”

Cigarette Smoke Potentiates Asbestos-Induced Airflow Abnormalities

“…We have discussed elsewhere [2] the significance of our observation that asbestos, either alone or with cigarette smoke, produces enlarged airspaces (i.e., emphysema [27]) in this model, and we suggested that the process may be related to chronic low-grade inflammation with release of proteolytic enzymes, in much the same way as smoke is thought to produce emphysema. Inorganic dusts are traditionally associated with fibrotic reactions and restrictive functional profiles, but Becklake [28] recently reviewed the epidemiologic data on airflow obstruction in workers with occupational exposure to a variety of inorganic agents and concluded that workers with many types of dust exposure appear to have evidence of airflow obstruction (structural basis unknown) even in the absence of smoking.…”

“…Table 2 shows a series of corelations generated using the morphological data [2] and functional data from these animals. There is a strong positive correlation between increases in wall thickness of respiratory bronchioles or alveolar size and increases in FRC and RV, as well as a strong and consistently negative correlation between increases in wall thickness and the measurements of flow.…”

“…To produce equal size groups, 12 animals were randomly selected from the smoking controls and amosite nonsmokers. All animals underwent a series of pulmonary function tests as detailed below and were then exsanguinated and the lungs collected for morphological and biochemical studies, which are described elsewhere [2]. …”

“…However, not all reports have shown such an effect [l], and there are neither morphological nor functional data in humans to prove or disprove the issue. We previously demonstrated that exposure of guinea pigs to both asbestos and cigarette smoke produces morphological evidence of increased airway fibrosis along with early interstitial fibrosis and increased lung collagen content compared to animals exposed to asbestos alone; the combined effects of the two agents are largely synergistic [2]. In this study we have used the same model to examine the effects of asbestos and cigarette smoke on pulmonary function and to correlate structural and functional changes.…”