AN EXPERIMENTAL HUMAN-MODEL OF METAL FUME FEVER

Objective: To examine the pathogenesis of metal fume fever in humans by studying functional, cellular, and biochemical responses after exposure to zinc welding fume. Design: Clinical experimental study. Participants: We studied 14 welders recruited through public advertisements. Interventions: Participants welded galvanized steel. Measurements: We measured lung volumes, airflow, diffusing capacity for carbon monoxide, and airway reactivity at baseline as well as either 6 or 20 hours after welding. We carried out bronchoalveolar lavage either 8 hours (early follow-up, 5 participants) or 22 hours (late follow-up, 9 participants) after welding, assaying the fluid for total and differential cell counts and bronchoalveolar lavage supernatant concentrations of interleukin-1 and tumor necrosis factor (TNF). Main Results: Changes in pulmonary function and airway reactivity were minimal. Cumulative zinc exposure and polymorphonuclear leukocyte count in bronchoalveolar lavage fluid at late (r = 0.87; P < 0.01) and early (r = 0.93; P < 0.05)follow-up were positively correlated. Among the late follow-up group, the mean proportion of polymorphonuclear leukocytes was 37% (range, 19% to 63%), a statistically greater proportion than the 9% (range, 2% to 21%) seen among the early follow-up group (P < 0.05). We did not detect TNF or more than a trace amount of interleukin-1 in the bronchoalveolar lavage supernatant. Conclusions: Zinc oxide welding fume was associated with a marked dose-dependent increase in the number of polymorphonuclear leukocytes recovered in bronchoalveolar lavage fluid 22 hours after exposure but was not associated with a clinically significant change in pulmonary function or airway reactivity. Although we did not identify increases in either interleukin-1 or TNF levels in bronchoalveolar lavage fluid, cytokines or a cytokine-like mechanism may mediate the syndrome of metal fume fever.