Impact of GSTM1 Genotype on Airway Response to Inhaled Wood Smoke Particles

RATIONALE: Wood smoke particles (WSP) derived from wildland fires cause abrupt increases in ambient air particulate matter (PM_2.5) and can have negative effects on pulmonary health even in healthy people. Glutathione-S-transferase Mu1 (GSTM1) null genotype increases susceptibility to ambient air ozone. The aim of this study is to determine if GSTM1 genotype determines susceptibility to WSP-induced airway inflammation.

METHODS: Healthy volunteers underwent exposure to 500 µg/m³ WSP for 2 hours with alternating 15-minute periods of exercise and rest to achieve minute ventilation of 20 L/min/m². Induced sputum samples were obtained prior to and 6 hours after exposure for assessment of inflammatory cells and cytokines. Participants were genotyped for GSTM1 status.

RESULTS: Fifteen healthy volunteers provided qualifying sputum. Six participants were GSTM1 null. WSP exposure significantly increased mean sputum percent neutrophils (PMNs) [47% ± 18 (post) vs 31% ±18 (pre), n=15; p=.002] and PMNs/mg of sputum [370 ±152 (post) vs. 212 ±154 (pre), n=15; p=.003]. Sputum IL-8 concentration was significantly increased from baseline at 24 hours post-exposure [8714 pg/mL ± 9663 (post) vs. 3158 pg/mL ± 3151 (pre), n=14; p=.05]. No significant difference was seen in sputum neutrophils or IL-8 concentration between GSTM1 null and sufficient participant samples.

CONCLUSIONS: Exposure to 500 µg/m³ WSP increases airway neutrophilic inflammatory responses, and this effect appears to be independent of GSTM1 genotype. This is an ongoing study, and a larger sample size is needed to draw definitive conclusions about the role of GSTM1 genotype as a modifier of oxidative stress and resultant health effects associated with WSP.