Inhalation of dust from contaminated organic materials may result in acute respiratory tract illness. Possible mechanisms include toxic and cellular reactions to microbial and other organic products or immunologic responses after prior sensitization to an antigen. A case is presented of a 52 year old male who developed fever, myalgia, and marked dyspnea 12 hr after shoveling composted wood chips and leaves. Inspiratory crackles, hypoxemia, and bilateral patchy pulmonary infiltrates were seen. Precipitating antibody tests for the usual antigens were inconclusive. He improved over 3 days. In order to assess the environmental conditions the patient had experienced, we returned to the site to reproduce and measure respiratory exposures during hand loading of the compost. Visible clouds of fine particulate were easily generated during handling activities. Microscopic examination of these dusts indicated a predominance of spores. Endotoxin concentrations from inspirable and respirable dust samples ranged from 636 to 16,300 endotoxin units/m3. Levels of contaminants found were consistent with those associated with respiratory illness in other agricultural settings. Two respiratory disorders, hypersensitivity pneumonitis (HP) and organic dust toxic syndrome (ODTS), may occur after exposure to organic dusts containing fungal spores and endotoxins. Despite extensive clinical and environmental investigations, we were unable to differentiate these two disorders, and suggest they may represent parts of a spectrum of responses to complex organic dusts, rather than completely distinct clinical entities.

In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide ('NO) production by BALC, and an increase in 'NOdependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silicaexposed lungs but is not significantly elevated in lavaged lung tissue. In vitro exposure of AM to silica does not stimulate 'NO production or enhance iNOS message. However, treatment of naive AM with conditioned media from BALC harvested from silica-exposed rats does increase iNOS message and 'NO production by these AM. The potency of this conditioned medium is dependent on interaction between AM and PMN. In the rat model, a relationship exists between the ability of various dusts to cause PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > carbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest radiograph, and a silica-exposed coal miner with an abnormal chest radiograph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of 'NO-dependent CL from AM. These data suggest that 'NO may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced 'NO production in response to an inflammatory insult.

In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. In vitro exposure of AM to silica does not stimulate .NO production or enhance iNOS message. However, treatment of naive AM with conditioned media from BALC harvested from silica-exposed rats does increase iNOS message and .NO production by these AM. The potency of this conditioned medium is dependent on interaction between AM and PMN. In the rat model, a relationship exists between the ability of various dusts to cause PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > carbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest radiograph, and a silica-exposed coal miner with an abnormal chest radiograph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of .NO-dependent CL from AM. These data suggest that .NO may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced .NO production in response to an inflammatory insult.ImagesFigure 1Figure 2Figure 5Figure 6

The mechanism of bleomycin-induced pulmonary fibrosis is not yet clear. Recent studies have shown that alveolar macrophages (AM) can be stimulated by bleomycin in vitro releasing inflammatory cytokines, suggesting that the interaction of bleomycin with AM is an important step in the druginduced fibrotic process. Bleomycin is known to bind DNA and generate oxygen radicals through complexation with Fe2+ and oxygen. To provide more insight into the cellular oxidative property of bleomycin, we have developed a fluoromicroscopic method using 2',7'-dichlorofluorescin diacetate (DCFHDA) as an oxidative fluorescence probe to study the bleomycin-induced intracellular oxidation in rat AM and the inhibition of the oxidation by taurine, a compound known to inhibit the bleomycin-induced fibrosis. Bleomycin at 5 to 20 pg/ml has a moderate stimulatory effect (1.87-to 2.66-fold) on the secretion of superoxide anion. A high concentration of bleomycin (20 pg/ml), however, inhibits cell response to zymosan-induced secretion of superoxide anion. At 4 pg/ml, bleomycin has no effect on cell membrane integrity or morphology but results in a significant increase in intracellular oxidation. This oxidative process is Fe2-dependent and is accompanied by an increase in intracellular calcium (35 nM). Both the intracellular oxidation and calcium rise induced by internalized bleomycin are inhibited by pretreatment of cells with varying concentrations of taurine (25, 125, and 187.5 pM). The inhibitory effect on intracellular oxidation was found to be 36, 57, and 60%, respectively. These results demonstrate a stimulation-inhibition relationship between bleomycin and taurine on the cellular oxidation at a subcytotoxic dose of bleomycin, suggesting that the oxidative effect of the intracellular bleomycin-Fe2+ complex is important in the initiation of the fibrotic process. -Environ Health Perspect 102(Suppl 10): 91-96 (1994)

The mechanism of bleomycin-induced pulmonary fibrosis is not yet clear. Recent studies have shown that alveolar macrophages (AM) can be stimulated by bleomycin in vitro releasing inflammatory cytokines, suggesting that the interaction of bleomycin with AM is an important step in the drug-induced fibrotic process. Bleomycin is known to bind DNA and generate oxygen radicals through complexation with Fe2+ and oxygen. To provide more insight into the cellular oxidative property of bleomycin, we have developed a fluoromicroscopic method using 2',7'-dichlorofluorescin diacetate (DCFHDA) as an oxidative fluorescence probe to study the bleomycin-induced intracellular oxidation in rat AM and the inhibition of the oxidation by taurine, a compound known to inhibit the bleomycin-induced fibrosis. Bleomycin at 5 to 20 micrograms/ml has a moderate stimulatory effect (1.87- to 2.66-fold) on the secretion of superoxide anion. A high concentration of bleomycin (20 micrograms/ml), however, inhibits cell response to zymosan-induced secretion of superoxide anion. At 4 micrograms/ml, bleomycin has no effect on cell membrane integrity or morphology but results in a significant increase in intracellular oxidation. This oxidative process is Fe(2+)-dependent and is accompanied by an increase in intracellular calcium (35 nM). Both the intracellular oxidation and calcium rise induced by internalized bleomycin are inhibited by pretreatment of cells with varying concentrations of taurine (25, 125, and 187.5 microM). The inhibitory effect on intracellular oxidation was found to be 36, 57, and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)