Evidence for enhanced oxidative stress in smokers with severe asthma

Abstract

Background As part of the U-BIOPRED project, extensive clinical and biomarker information was collected from cohorts of adult severe asthma smokers/ex-smokers (SAs/ex) and severe asthmatic non-smokers (SAn). Oxidative stress in SAs/ex vs SAn patients was investigated by analysing urinary 8-iso-PGF2a and the mRNA expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant (SODs; CAT; GPX1) enzymes in the airways, in relation to clinical outcomes. Methods Urine and induced sputum (IS) were obtained from severe asthma patients. A bronchoscopy to obtain bronchial biopsy (BB) and brushing (BBr) was performed in a subset of patients. Urinary 8-iso-PGF2a was quantified using mass spectrometry. IS, BB and BBr were processed for mRNA expression microarray analysis.

Results Urinary 8-iso-PGF2a was increased in SAs/ex compared to SAn (p< 0.001) and in current smokers vs ex-smokers and non-smokers (p= 0.004). Sputum mRNA expression of NOX2 were increased in SAs/ex compared to SAn (three probe-sets with p< 0.05). The mRNA expression of antioxidant enzymes was similar between the two severe asthma cohorts in all airway samples. NOS2 mRNA expression was decreased in BBr of SAs/ex compared to SAn (p= 0.029). NOS2 mRNA expression in BBr correlated with FeNO (p< 0.001). FeNO was lower in current-smokers than in ex-smokers (p= 0.007) indicating an effect of active smoking. Conclusions The data suggests evidence of greater systemic oxidative stress in SAs/ex with significant effects on the mRNA expression of NOX2 and NOS2 in the airways of severe asthmatic patients.