GRAIN DUST-INDUCED AIR-FLOW OBSTRUCTION AND INFLAMMATION OF THE LOWERRESPIRATORY-TRACT

To investigate the relationship between the physiologic and biologic e ffects of grain dust inhalation, we exposed 15 nonsmoking, nonasthmati c, nonatopic male grain handlers to buffered saline and aqueous corn d ust extract by inhalation challenge in a crossover study. The inhalati on challenges to buffered saline and corn dust extract were separated by at least 14 d. Compared with buffered saline, inhalation of corn du st extract resulted in significant airflow obstruction, which was obse rved within 30 min of exposure and persisted for 5 h. Inhalation of co rn dust extract resulted in an acute inflammatory response characteriz ed by higher concentrations of neutrophils (p = 0.001), IL-1 beta (p = 0.001), IL-1RA (p = 0.001), IL-6 (p = 0.001), IL-8 (p = 0.001), and T NF-alpha (p = 0.04) in bronchoalveolar lavage (BAL) fluid. mRNA levels specific for IL-1 beta, IL-1RA, IL-6, and IL-8 from cells present in the BAL fluid were significantly greater after challenge with corn dus t extract than after challenge with buffered saline. Importantly, no s ignificant differences were observed in the concentration of lymphocyt es or eosinophils in the BAL fluid following inhalation of corn dust e xtract, and the concentrations of histamine and 15-HETE were similar i n BAL fluid after the two challenges. The maximal percentage decrease in FEV(1) was significantly associated with the absolute neutrophil co ncentration in the BAL fluid (p = 0.001), as well as the concentration of TNF-alpha (p = 0.03), IL-1 beta (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 i ndicate that grain workers who inhale corn dust extract develop airflo w obstruction in association with a brisk neutrophilic inflammatory re sponse, as well as increased levels of proinflammatory cytokines in th e lower respiratory tract. Furthermore, cytokine release is accompanie d by upregulation of the corresponding mRNA. These physiologic and bio logic 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. I n fact, our results suggest that the airway response to grain dust rep resents an acute inflammatory response to an inhaled toxin, such as en dotoxin.