Grain dust-induced airflow obstruction and inflammation of the lower respiratory tract

Abstract

To investigate the relationship between the physiologic and biologic effects of grain dust inhalation, we exposed 15 nonsmoking, nonasthmatic, nonatopic male grain handlers to buffered saline and aqueous corn dust extract by inhalation challenge in a crossover study. The inhalation challenges to buffered saline and corn dust extract were separated by at least 14 d. Compared with buffered saline, inhalation of corn dust extract resulted in significant airflow obstruction, which was observed within 30 min of exposure and persisted for 5 h. Inhalation of corn dust extract resulted in an acute inflammatory response characterized by higher concentrations of neutrophils (p = 0.001), IL-1β (p = 0.001), IL-1RA (p = 0.001), IL-6 (p = 0.001), IL-8 (p = 0.001), and TNF-α (p = 0.04) in bronchoalveolar lavage (BAL) fluid. mRNA levels specific for IL-1β, IL-1RA, IL-6, and IL-8 from cells present in the BAL fluid were significantly greater after challenge with corn dust extract than after challenge with buffered saline. Importantly, no significant differences were observed in the concentration of lymphocytes or eosinophils in the BAL fluid following inhalation of corn dust extract, and the concentrations of histamine and 15-HETE were similar in BAL fluid after the two challenges. The maximal percentage decrease in FEV1 was significantly associated with the absolute neutrophil concentration in the BAL fluid (p = 0.001), as well as the concentration of TNF-α (p = 0.03), IL- 1β (p = 0.005), IL-1RA (p = 0.001), IL-6 (p = 0.001), and IL-8 (p = 0.001) in the BAL fluid. These findings indicate that grain workers who inhale corn dust extract develop airflow obstruction in association with a brisk neutrophilic inflammatory response, as well as increased levels of proinflammatory cytokines in the lower respiratory tract. Furthermore, cytokine release is accompanied by upregulation of the corresponding mRNA. These physiologic and biologic responses to inhaled corn dust are not dependent on preexisting asthma or the presence of atopy, and our results suggest that classic immunological mechanisms do not initiate this inflammatory response. In fact, our results suggest that the airway response to grain dust represents an acute inflammatory response to an inhaled toxin, such as endotoxin.