Evaluation of lung oxidative stress and inflammatory state using exhaled breath condensate analysis in early-life arsenic exposure

Millions of people worldwide are exposed to environmental arsenic in drinking water, resulting in both malignant and nonmalignant diseases. Interestingly, early life exposure by itself is sufficient to produce higher incidences of these diseases later in life. Based on the delayed onset of disease, we hypothesized that early life arsenic exposure would also induce long-term alterations in the metabolic profile. The objective of this study was to examine metabolomic biomarkers in exhaled breath condensate (EBC) of individuals exposed to arsenic in drinking water early in life, but not later. One hundred and fifty subjects (75 males and 75 females) were initially recruited from Antofagasta, Chile, some of whom were exposed to high water arsenic levels (⩾870<i>µ</i>g l^-1; HighAE group), and others, low water arsenic levels (⩽110<i>µ</i>g l^-1; LowAE group) early in life (1958-1970). EBC samples were collected for targeted and untargeted metabolomic biomarker analysis. The results showed significantly shorter individuals and reduced pulmonary functions (forced vital capacity, FVC and forced expiratory volume in 1 s, FEV₁) in both males and females in the high-arsenic groups. Males exposed to high arsenic levels also had reduced red blood cell concentrations, as well as higher concentrations of the oxidative stress metabolites 8-OH-2dG and 8-iso-PGF2<i>α</i>. Females in the high-arsenic group showed reductions in 8-OH-2dG. Untargeted analysis revealed metabolomic markers that differentiated the HighAE group from the LowAE group, with a subgroup of markers whose concentrations were proportional to the level of arsenic exposure. Targeted and untargeted analyses of EBC using liquid chromatography-mass spectrometry indicated that adults exposed to high arsenic levels in drinking water in utero and during early childhood retained a modified metabolic profile 47 years after the end of exposure.