Metal fume fever is a flulike illness caused by zinc oxide inhalation and accompanied by an impressive pulmonary cellular response. We hypothesized that the syndrome is mediated by cytokines released in the lung after exposure to zinc oxide fume. We carried out 26 experimental welding exposures in 23 volunteer subjects, performing postexposure bronchoalveolar lavage (BAL) 3 h (n = 6), 8 h (n = 11), or 22 h (n = 9) after exposure. We detected tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) varying in a time- and exposure-related manner. The concentration of TNF in the BAL fluid supernatant was significantly greater at 3 h than at 8 h or 22 h after exposure (p < 0.05), exhibiting a statistically significant exposure-response relationship to airborne zinc at each follow-up time period (p < 0.05). TNF concentrations were statistically correlated with those of IL-6 in BAL supernatant obtained at 22 h (r = 0.78, p = 0.01) and with concentrations of IL-8 in BAL 8 h after exposure (r = 0.85, p = 0.001). IL-6 displayed a significant exposure-response relationship to zinc (p < 0.05) at 22 h. IL-8 exhibited a significant exposure-response relationship to zinc (p < 0.05) at 8 h after exposure, a time at which IL-8 correlated with marked increases in BAL fluid polymorphonuclear leukocytes (PMN) (r = 0.7, p = 0.01). Although we also detected interleukin-1 (IL-1) in BAL samples, this cytokine did not demonstrate a statistically significant exposure response. TNF, IL-6, and IL-8 in BAL fluid supernatant concentrations increased in a time and exposure-dependent fashion after zinc oxide welding fume exposure. The time course of increased cytokines, their correlations with one another and with PMN in the BAL fluid, and the consistency of our findings with the known kinetics and actions of these cytokines support the hypothesis that a network of cytokines is involved in the pathogenesis of metal fume fever.

No abstract

This position statement reviews several aspects of spirometric testing in the workplace, where spirometry is employed in the primary, secondary, and tertiary prevention of occupational lung disease. Primary prevention includes pre-placement and fitness-for-duty examinations as well as research and monitoring of health status in groups of exposed workers; secondary prevention includes periodic medical screening of individual workers for early effects of exposure to known occupational hazards; and tertiary prevention includes clinical evaluation and impairment/disability assessment. For all of these purposes, valid spirometry measurements are critical, requiring: documented spirometer accuracy and precision, a rigorous and standardized testing technique, standardized measurement of pulmonary function values from the spirogram, adequate initial and refresher training of spirometry technicians, and, ideally, quality assessment of samples of spirograms. Interpretation of spirometric results usually includes comparison with predicted values and should also evaluate changes in lung function over time. Response to inhaled bronchodilators and changes in relation to workplace exposure may also be assessed. Each of these interpretations should begin with an assessment of test quality and, based on the most recent ATS recommendations, should rely on a few reproducible indices of pulmonary function (FEV1, FVC, and FEV1/FVC.) The use of FEF rates (e.g., the FEF25-75%) in interpreting results for individuals is strongly discouraged except when confirming borderline airways obstruction. Finally, the use of serial PEF measurements is emerging as a method for confirming associations between reduced or variable pulmonary function and workplace exposures in the diagnosis of occupational asthma. Throughout this position statement, ACOEM makes detailed recommendations to ensure that each of these areas of test performance and interpretation follow current recommendations/standards in the pulmonary and regulatory fields. Submitted by the Occupational and Environmental Lung Disorder Committee on November 16,1999. Approved by the ACOEM Board of Directors on January 4,2000.

Organic Dust Toxic Syndrome (ODTS) is a flu-like syndrome that can occur after inhalation of cotton, grain, wood chip dusts, or other organic dusts or aerosols. We investigated whether inflammatory pulmonary responses occur, even after relatively brief, low-level wood chip mulch exposure. Six volunteers were exposed to wood chip mulch dust. Total dust and/or endotoxin levels were measured in five subjects. Pulmonary function and peripheral blood counts were measured before and after exposure in each subject. Bronchoalveolar lavage (BAL) was performed in each subject after exposure, and cell, cytokine, and protein concentrations were measured. Control BAL without previous exposure was also performed on three of the subjects. Three of six subjects had symptoms consistent with ODTS. No clinically relevant or statistically significant changes in pulmonary function tests after exposure were found. Three subjects manifested a marked elevation in neutrophil percentage in their BAL (range, 10 to 57%). When these three subjects underwent control BAL, the postexposure comparison demonstrated an increase in neutrophil levels of 154 +/- 89 x 10(3)/mL (mean +/- standard error; P = 0.22). The mean increase in BAL interleukin-8 levels after exposure, compared with paired control values, was 11.2 +/- SE 2.5 pg/mL (P = 0.047). There was also an increase in BAL interleukin-6 levels that reached borderline significance (6.4 +/- SE 2.0 pg/mL; P = 0.08). Tumor necrosis factor levels were increased in all three subjects' BAL as well (0.4 +/- SE 0.2 pg/mL), but this change was not statistically significant (P = 0.2). Our findings of increased BAL proinflammatory cytokine and neutrophil levels are consistent with the theory that cytokine networking in the lung may mediate ODTS.

There is uncertainty in Great Britain (GB) about what constitutes appropriate health surveillance for silica-exposed workers, despite evidence that new cases of silicosis are occurring. The latter is supported by data from UK-based, HSE funded, national surveillance systems for work-related illness. There is also evidence to suggest that the risk of silicosis is finite at current permissible exposure levels. Many of the industries in GB in which exposure to Respirable Crystalline Silica (RCS) may arise have signed up to a Social Dialogue Agreement (SDA), a pan-European initiative to improve the control of silica dust exposure. In part, this agreement is a commitment to undertake health surveillance where this is necessary because of a potential continuing risk of silicosis, even when recommended engineering and other controls are in place. The appropriate target population for this surveillance would likely include all workers who are exposed to levels of crystalline silica that place them at risk of developing silicosis or other silica-related lung diseases. Consequently, the GB regulator wishes to establish a standard for the health surveillance of silica-exposed workers, in order to assess whether dutyholders are complying with their duties under appropriate legislation. This report and the work it describes were funded by the Health and Safety Executive (HSE). Its contents, including any opinions and/or conclusions expressed, are those of the authors alone and do not necessarily reflect HSE policy.