Introduction: Workplace clusters of rare lung disease can provide insights into disease pathogenesis and may ultimately have implications for treatment and prevention. Methods: Four coworkers at a machine fabrication facility with 300 production employees experienced chronic respiratory symptoms. We reviewed their clinical presentations and physiologic, radiologic, and pathologic patterns for commonalities. We evaluated the workplace for potential causative exposures. We collected samples of two metalworking fluids (MWF), a mineral oil-based solution and a synthetic fluid, used for cooling and lubrication during metal machining. MWF was analyzed for microbial contamination using culture and non-culture techniques. Results: At time of symptom onset (1995 to 2007), the four affected workers, all non-smokers, had employment tenures of 4-17 years. Three were based in the machine shop and one in the adjacent assembly area. All four reported a history of hunting, but otherwise did not share social factors. The workers experienced cough and dyspnea on exertion that increased gradually over years; three reported wheeze. Spirometry demonstrated moderate to very severe obstruction, with variable response to bronchodilator. One worker experienced a 1.7 L improvement in FEV1 in four months away from work while on oral steroid therapy. Diffusing capacity was mildly to severely reduced. Chest CT showed emphysematous changes and/or air trapping. Three workers underwent surgical lung biopsy, which revealed lymphocytic bronchiolitis consisting predominantly of B cells. In one of these cases, extensive lymphoid hyperplasia prompted evaluation for lymphoma. Immunohistochemical staining confirmed B cells were from the marginal zone. Monoclonality of the immunoglobulin heavy chain was not present. The fourth case underwent transbronchial biopsy that revealed non-specific peribronchial inflammation. Workplace evaluation suggested opportunities for exposure to metals (carbon steel, aluminum), paper dust, vacuum pump exhaust, paint, lacquer thinner, and MWF. Culture demonstrated MWF samples were contaminated with a variety of bacteria (up to 109 CFU/ml) and fungi; endotoxin concentrations were elevated. Ribosomal RNA analyses demonstrated presence of additional bacterial and fungal species not identified with culture. Mycobacterial DNA was not detected with quantitative polymerase chain reaction. Conclusions: MALT in the adult lung is abnormal and may form in response to infection, allergens, environmental antigens, particulate exposures, and autoimmunity. The experience with MALT lymphoma in other organ systems has demonstrated the role of chronic antigenic stimulation and infection in lymphomagenesis. The occurrence of this disease cluster in a workplace with contaminated MWF raises the possibility that exposure to bioaerosols played a pathogenic role and warrants further investigation.
Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-disease; Lymphocytes; Lung-cells; Pathogenesis; Disease-incidence; Disease-prevention; Chronic-inflammation; Machine-shop-workers; Fabricated-plate-work; Metalworking-fluids; Metalworking; Metalworking-industry; Spirometry; Pulmonary-function-tests; Airway-obstruction; Biopsy; Bacteria; Fungi; Endotoxins; Biological-agents; Aerosols; Antigens
K. J. Cummings, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV