Inorganic dust pneumonias: the metal-related parenchymal disorders.

Abstract

In recent years the greatest progress in our understanding of pneumoconioses, other than those produced by asbestos, silica, and coal, has been in the arena of metal-induced parenchymal lung disorders. Inhalation of metal dusts and fumes can induce a wide range of lung pathology, including airways disorders, cancer, and parenchymal diseases. The emphasis of this update is on parenchymal diseases caused by metal inhalation, including granulomatous disease, giant cell interstitial pneumonitis, chemical pneumonitis, and interstitial fibrosis, among others. The clinical characteristics, epidemiology, and pathogenesis of disorders arising from exposure to aluminum, beryllium, cadmium, cobalt, copper, iron, mercury, and nickel are presented in detail. Metal fume fever, an inhalation fever syndrome attributed to exposure to a number of metals, is also discussed. Advances in our knowledge of antigen-specific immunologic reactions in the lung are particularly evident in disorders secondary to beryllium and nickel exposure, where immunologic mechanisms have been well characterized. For example, current evidence suggests that beryllium acts as an antigen, or hapten, and is presented by antigen-presenting cells to CD4+ T cells, which possess specific surface antigen receptors. Other metals such as cadmium and mercury induce nonspecific damage, probably by initiating production of reactive oxygen species. Additionally, genetic susceptibility markers associated with increased risk have been identified in some metal-related diseases such as chronic beryllium disease and hard metal disease. Future research needs include development of biologic markers of metal-induced immunologic disease, detailed characterization of human exposure, examination of gene alleles that might confer risk, and association of exposure data with that of genetic susceptibility. Key words: aluminum, beryllium, cadmium, cobalt, copper, hard metal disease, iron, mercury, metal fume fever, nickel, pneumoconiosis. The term pneumoconiosis, first introduced in the 19th century, refers to diseases and pathologic consequences from inhalation of particulate dusts. In recent years the greatest progress in our understanding of pneumoconioses, other than those produced by asbestos, silica, and coal, has been in the arena of metalinduced parenchymal lung disorders. As presented in Table 1 (1). A major theme that emerges in reviewing recent developments in metal-related lung toxicity is the extent to which various metals are capable of inducing both antigen-specific immunologic reactions in the lung and nonspecific "innate" immune system responses characterized by inflammation frequently triggered by oxidant injury. With the recognition of these immune and inflammatory effects comes a growing awareness of the potential hazards to the lung at low levels of exposure. There is also increasing research being conducted on the interaction between metal exposure and the human genome. In the cases of beryllium and cobalt, for example, there is emerging recognition of the spec...

Depletion of Intracellular Ascorbate by the Carcinogenic Metals Nickel and Cobalt Results in the Induction of Hypoxic Stress

“…The hydroxylase reaction was carried out using 30 g of protein in the reaction buffer containing 40 mM Tris-HCl, pH 7.5, 50 M FeSO 4 , 0.1 mM L- [5-14 C]␣-ketoglutaric acid, 200 M ODD peptide (amino acids 556 -575 of HIF-1␣) (Advanced ChemTech, Louisville, KY), 0.25 mM ascorbate, 0.4 mg/ml catalase, 0.5 mM dithiothreitol. Samples were incubated for 1 h at 37°C in a final volume of 50 l. After incubation, 25 l of mixture of 20 mM succinate and 2OG was added, followed by the addition of 25 l of 0.16 M 2,4-dinitrophenylhydrazine in 30% HClO 4 . The samples were allowed to sit for 30 min at room temperature following the addition of 50 l of 1 M 2OG.…”

“…Additionally, burning of fossil fuels pollutes the air with metalcontaining particles, up to 35% of which could be composed of nickel (3). Environmental or occupational exposure to particles containing nickel or cobalt causes various forms of lung injury including pneumonitis, asthma, and fibrosis (4). Both metals are carcinogenic in animals (5,6), and nickel has been recognized as a human carcinogen (7).…”

Aluminio en el Tracto Respiratorio Bajo de Residentes de la Ciudad de México

“…Las investigaciones muestran que el nivel de toxicidad del Al puede ser muy bajo (21) y puede provocar enfermedades respiratorias (4,16,21,22), neurológicas (15,17,23) y recientemente se ha reportado su efecto cancerígeno (24,25).…”

“…Los efectos respiratorios se han observado principalmente en trabajadores expuestos (4,5,26,27) y estudios experimentales indican que la presencia de Al se correlaciona con proceso inflamatorio pulmonar (22,28).…”

“…Se S e ha demostrado que las partículas atmosféricas inducen incremento de la mortalidad (1,2) y morbilidad (2,3) en la población expuesta por causas tanto respiratorias (2-5) como cardiovasculares (2,6,7) y del sis-identificaron 17 metales, de los cuales es llamativo la presencia de Al en las muestras de tejido analizadas por varias razones. En primer lugar por su alta concentración, en segundo lugar porque se ha informado que es uno de los metales más frecuentemente encontrados en las partículas del aire de la ciudad de México (14) y, en tercer lugar, porque se sabe que el Al no cumple con ninguna función biológica, por el contrario la inhalación de polvo de Al puede causar patologías muy severas a nivel respiratorio (4,15,16) y neurológico (16,17).…”