Identification of Persons Who Are Responsive To Wood Smoke Particle-Induced Airway Inflammation With Assessment of The Effect of GSTM1, Asthma Status And Sex On This Response.

Abstract

Background: We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6 and 24 hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (>10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (N=52) at both 6 and 24hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP. Results: In the entire cohort, we found a significant, but very small, decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased at 24 hours post exposure, the latter finding was also significantly correlated with sputum IL-1b, IL-6, IL-8, and PMN/mg; a similar response was not found at the 6 hour %PMN response. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1b, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (p<0.05) enhanced the %PMN response at 6 hours in the entire cohort, by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the entire cohort and in the 6- and 24-hour responders. Sex had no effect on %PMN response. Conclusions: The 24 hour time point was more informative than the 6 hour time point in optimally defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.