Effect of GST variants on lung function following diesel exhaust and allergen co-exposure in a controlled human crossover study

Abstract

BackgroundIsolated exposure to diesel exhaust (DE) or allergen can cause decrements in lung function that are impacted by the presence of genetic variants in the glutathione-S-transferase (GST) family but the effect of GST interactions with DE-allergen co-exposure on lung function is unknown. We aimed to assess the impact of DE and allergen co-exposure on lung function and the influence of GSTM1 or GSTT1 variation MethodsWe used a blinded crossover study design with 17 atopic subjects exposed to filtered air (FA; the control for DE) or DE for 2h. One hour following each exposure to DE or FA, bronchoscopy was performed to deliver a diluent-controlled segmental allergen challenge (SAC). Methacholine challenge and forced expiratory volume in 1s (FEV1) was performed pre-exposure (baseline airway responsiveness) and 24h post-exposure (effect of co-exposure). Additionally, FEV1 was performed hourly after DE/FA exposure and protein carbonyl content was measured in plasma as an oxidative stress marker. ResultsChanges in FEV1 from baseline were dependent on time following allergen exposure. DE, as opposed to FA, led to a significant change in FEV1 at 2h post-allergen exposure in GSTT1 variants only (24.5±19.6% reduction in GSTT1 null individuals vs. 9.2±7.3% reduction in GSTT1 present individuals). Moreover, plasma protein carbonyl level 4h after co-exposure was higher in the individuals who have the GSTT1 null genotype. ConclusionsThis suggests a gene-environment interaction that endangers susceptible populations co-exposed to DE and allergen.