Endotoxin is one of the principal components of grain dust that causes acute reversible airflow obstruction and airway inflammation. To determine whether endotoxin responsiveness influences the development of chronic grain dust-induced airway disease, physiological and airway inflammation remodeling parameters were evaluated after an 8-wk exposure to corn dust extract (CDE) and again after a 4-wk recovery period in a strain of mice sensitive to (C3H/HeBFeJ) and one resistant to (C3H/HeJ) endotoxin. After the CDE exposure, both strains of mice had equal airway hyperreactivity to a methacholine challenge; however, airway hyperreactivity persisted only in the C3H/HeBFeJ mice after the recovery period. Only the C3H/HeBFeJ mice showed significant inflammation of the lower airway after the 8-wk exposure to CDE. After the recovery period, this inflammatory response completely resolved. Lung stereological measurements indicate that an 8-wk exposure to CDE resulted in persistent expansion of the airway submucosal cross-sectional area only in the C3H/HeBFeJ mice. Collagen type III and an influx of cells into the subepithelial area participated in the expansion of the submucosa. Our findings demonstrate that subchronic inhalation of grain dust extract results in the development of chronic airway disease only in mice sensitive to endotoxin but not in mice that are genetically hyporesponsive to endotoxin, suggesting that endotoxin is important in the development of chronic airway disease.

Research scientists, laboratory technicians, and animal handlers who work with animals frequently report respiratory and skin symptoms from exposure to laboratory animals (LA). However, on the basis of prick skin tests or RASTs, only half are sensitized to LA. We hypothesized that aerosolized endotoxin from mouse work is responsible for symptoms in nonsensitized workers. We performed a cross-sectional study of 269/310 (87%) workers at a research institution. Subjects completed a questionnaire and underwent prick skin tests (n = 254) or RASTs (n = 16) for environmental and LA allergens. We measured airborne mouse allergen and endotoxin in the animal facility and in research laboratories. Of 212 workers not sensitized to mice, 34 (16%) reported symptoms compared with 26 (46%) of mouse-sensitized workers (p < 0.001). Symptomatic workers were more likely to be atopic, regardless of mouse sensitization status. Symptomatic non-mouse-sensitized workers spent more time performing animal experiments in the animal facility (p = 0.0001) and in their own laboratories (p < 0.0001) and had higher daily endotoxin exposure (p = 0.008) compared with asymptomatic coworkers. In a multivariate model, daily endotoxin exposure most strongly predicted symptoms to mice in non-mouse-sensitized workers (odds ratio = 30.8, p = 0.003). We conclude that airborne endotoxin is associated with respiratory symptoms to mice in non-mouse-sensitized scientists and technicians.

To determine factors that influence the occurrence of congenital cytomegalovirus (CMV) infection, the authors surveyed prospectively 8,254 infants born in eastern Iowa between October 1989 and June 1994. The authors conducted a case-control study to identify maternal risk factors, matching each CMV-infected infant with three uninfected infants according to hospital and date of birth. CMV strains were compared by using the polymerase chain reaction (PCR) to identify common sources of infection. Of the 7,229 infants cultured successfully for CMV, 35 (0.48%) were congenitally infected. Mothers of CMV-infected infants were more likely to be single (odds ratio (OR) = 3.05, p = 0.016), to work in sales (OR = 4.93, p = 0.008), or to be students (OR = 5.01, p = 0.017). Conversely, women who worked in health-care professions were less likely to have a congenitally infected infant (OR = 0.14, p = 0.049). PCR analysis indicated 27 distinct strains of CMV, but two groups of infants (two infants per group) excreted strains with indistinguishable molecular patterns. One of these pairs of infants had older siblings who attended the same child-care center during their mothers' pregnancies. The authors concluded that demographic and occupational factors influenced the risk of giving birth to an infant with congenital CMV infection. Many distinct CMV strains were identified, suggesting that major point source outbreaks had not occurred. Nonetheless, point source acquisition of CMV from child-care environments did account for some cases of congenital CMV infection in eastern Iowa.

No abstract