Cysteinyl Leukotriene Receptor 1 and Health Effects of Particulate Exposure in Asthma

Rationale: Acute exposure to ambient particle matter is associated with increased levels of the cysteinyl leukotriene (CysLT) biomarker, urinary leukotriene E4 (uLTE4), in subjects with asthma.Objectives: The role of CysLTs in mediating asthma worsening after particulate matter exposures was explored.Methods: Daily concentrations of particulate matter of 2.5 μm and smaller diameter (PM2.5) and repeated measurements of albuterol use over a 5-month period were collected in 44 urban school children with persistent asthma. DNA was analyzed for gene polymorphisms on genes involved in the CysLT pathway to identify gene–environment interactions. An experimental challenge study in 16 adults with mild, nonpersistent asthma was performed to define biological pathways explaining these gene–environment interactions. Subjects in the challenge study were exposed on two different days to filtered air or diesel exhaust (300 μg PM2.5/m3). FEV1 and CysLT-related gene DNA methylation and messenger RNA expression changes wer...