Subspecialty in Translational Medicine
Asbestos-induced lung diseases: an update

https://doi.org/10.1016/j.trsl.2009.01.004Get rights and content

Asbestos causes asbestosis (pulmonary fibrosis caused by asbestos inhalation) and malignancies (bronchogenic carcinoma and mesothelioma) by mechanisms that are not fully elucidated. Despite a dramatic reduction in asbestos use worldwide, asbestos-induced lung diseases remain a substantial health concern primarily because of the vast amounts of fibers that have been mined, processed, and used during the 20th century combined with the long latency period of up to 40 years between exposure and disease presentation. This review summarizes the important new epidemiologic and pathogenic information that has emerged over the past several years. Whereas the development of asbestosis is directly associated with the magnitude and duration of asbestos exposure, the development of a malignant clone of cells can occur in the setting of low-level asbestos exposure. Emphasis is placed on the recent epidemiologic investigations that explore the malignancy risk that occurs from nonoccupational, environmental asbestos exposure. Accumulating studies are shedding light on novel mechanistic pathways by which asbestos damages the lung. Attention is focused on the importance of alveolar epithelial cell (AEC) injury and repair, the role of iron-derived reactive oxygen species (ROS), and apoptosis by the p53- and mitochondria-regulated death pathways. Furthermore, recent evidence underscores crucial roles for specific cellular signaling pathways that regulate the production of cytokines and growth factors. An evolving role for epithelial-mesenchymal transition (EMT) is also reviewed. The translational significance of these studies is evident in providing the molecular basis for developing novel therapeutic strategies for asbestos-related lung diseases and, importantly, other pulmonary diseases, such as interstitial pulmonary fibrosis and lung cancer.

Section snippets

Epidemiology

Despite a dramatic decline in asbestos use in industrialized countries since the 1970s, asbestos-induced lung diseases remain a significant health concern for several reasons. First, more than 30 million tons of asbestos have been mined, processed, and used in the United States since the early 1900s.2 An estimated 27 million workers in the United States were exposed to aerosolized asbestos fibers between 1940 and 1979.7 Globally, Lin et al8 recently demonstrated a direct relationship between

Pathophysiology—What's New?

It is well established that the toxic effects of asbestos inhalation depend on the cumulative dose, the elapsed time since the initial exposure, and the physical-chemical properties of the different asbestos fibers.1, 2, 3, 30 Amphibole fibers, as compared with chrysotile, are generally more toxic in part because amphibole fibers accumulate more readily in the distal lung parenchyma, are not cleared as effectively, and are more durable (estimated half-life in the lungs on the order of decades

Conclusions

Asbestos-related lung diseases remain a significant challenge to health care providers as well as to investigators studying the basic mechanisms that underlie asbestos-induced pulmonary toxicity. Given the long latency between asbestos exposure and disease as well as the direct relationship between asbestos consumption and mortality from asbestos-related lung diseases, a total worldwide asbestos ban is strongly supported.6, 8, 17, 18 If asbestos use continues in countries where it is less

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