Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel

Abstract

Airborne particulate matter (PM) components from fossil fuel combustion can induce oxidative stress initiated by reactive oxygen species (ROS). Reported associations between worsening asthma and PM2.5 mass could be related to PM oxidative potential to induce airway oxidative stress and inflammation (hallmarks of asthma pathology). We followed 45 schoolchildren with persistent asthma in their southern California homes daily over 10 days with offline fractional exhaled nitric oxide (FENO), a biomarker of airway inflammation. Ambient exposures included daily average PM2.5, PM2.5 elemental and organic carbon (EC, OC), NO2, O3, and endotoxin. We assessed PM2.5 oxidative potential using both an abiotic and an in vitro bioassay on aqueous extracts of daily particle filters: (1) dithiothreitol (DTT) assay (abiotic), representing chemically produced ROS; and (2) ROS generated intracellularly in a rat alveolar macrophage model using the fluorescent probe 2′7′-dicholorohidroflourescin diacetate. We analyzed relations of FENO to air pollutants in mixed linear regression models. FENO was significantly positively associated with lag 1-day and 2-day averages of traffic-related markers (EC, OC, and NO2), DTT and macrophage ROS, but not PM2.5 mass. DTT associations were nearly twice as strong as other exposures per interquartile range: median FENO increased 8.7–9.9% per 0.43 nmole/min/m3 DTT. Findings suggest that future research in oxidative stress-related illnesses such as asthma and PM exposure would benefit from assessments of PM oxidative potential and composition.

Relationship between chemical composition and oxidative potential of secondary organic aerosol from polycyclic aromatic hydrocarbons

“…DTT assay is one of the most commonly used OP evaluation methods since DTT is a potent surrogate for the total thio-pools (glutathione and protein thiols), and this assay can be conducted under biologically relevant conditions (37 • C, pH = 7.4) with relatively simple procedures (Cleland, 1964;Hansen et al, 2009;McWhinney et al, 2011). OP levels measured by this assay have been found to correlate well with cellular ROS expression as well as several airway inflammation biomarkers, such as HO-1, tumor necrosis factor-α (TNF-α) and fractional exhaled nitric oxide (FE NO ) (Delfino et al, 2013;Li et al, 2003b;Tuet et al, 2017a).…”

A method for measuring total aerosol oxidative potential (OP) with the dithiothreitol (DTT) assay and comparisons between an urban and roadside site of water-soluble and total OP

“…The mechanisms of PM toxicity are complex and not completely understood. One view is that PM toxicity occurs through inducement of oxidative stress (Delfino et al, 2005(Delfino et al, , 2013Nel, 2005): a state of biochemical imbalance in which the presence and formation of reactive oxygen species (ROS) in the human body overwhelms antioxidant defenses, eventually leading to various adverse health outcomes (Delfino et al, 2011;Donaldson et al, 2001;Li et al, 2003a). ROS can be either transported on inhaled particles to the air-lung interface or generated in vivo by interaction between deposited PM and physiological chemical components (Lakey et al, 2016).…”

“…When this reaction is monitored under conditions of excess DTT, the DTT consumption over time is proportional to the concentration of PM redox-active species, quantified as OP DTT . OP DTT per volume of air sampled has been found to correlate with biological markers, such as cellular heme oxygenase (HO-1) expression (Li et al, 2003b) and fractional exhaled nitric oxide (FE NO ) in human subjects (Delfino et al, 2013;Janssen et al, 2015). Epidemiological studies have linked OP DTT to adverse health outcomes, such as asthma, rhinitis (Yang et al, 2016), asthma or wheezing, and congestive heart failure Fang et al, 2016).…”

A semi-automated system for quantifying the oxidative potential of ambient particles in aqueous extracts using the dithiothreitol (DTT) assay: results from the Southeastern Center for Air Pollution and Epidemiology (SCAPE)

“…Acellular methods require less-controlled environments and provide faster readouts of PM oxidative potential. One of the most widely used cell-free measures of particles oxidative potential is the DTT (dithiothreitol, HSCH 2 (CH(OH)) 2 CH 2 SH)) assay (Charrier and Anastasio, 2012;Verma et al, 2012Verma et al, , 2009aCho et al, 2005;Kumagai et al, 2002;Delfino et al, 2013). Typically, ROS in vivo are mainly produced in mitochondria and endoplasmic reticulum (ER) where molecular oxygen (O 2 ) are reduced to superoxide anion (O − 2 ) by accepting electrons from cellular reductants, such as NADPH, or during the ER protein folding process (Alfadda and Sallam, 2012).…”