PM10 Oxidative Properties and Asthma and COPD

Abstract

To the Editor: Oxidative stress is a possible mechanism to explain the toxic effects of particulate matter (PM). Conceptually, PM oxidative burden is an appealing exposure metric because it captures a biological process thought to be responsible for PM-induced airway inflammation. However, few epidemiologic studies have examined this exposure metric, and results have been inconsistent.1 Direct measurement of PM oxidative properties could improve the ability to estimate PM effects and enhance the understanding of its mechanism of action, potentially leading to targeted public health strategies aimed at removing the most toxic PM components. We previously reported adverse effects of PM10 (mean aerodynamic diameter <10 μm) mass on asthma and chronic obstructive pulmonary disease (COPD) exacerbations, increased by low antioxidant status (vitamin C) and variation in antioxidant genes.2 Here, we investigate the effects of PM10 oxidative properties on respiratory exacerbations. We conducted a bi-directional case-crossover study in patients admitted to the hospital for asthma/COPD exacerbation, comparing PM10 oxidative potential (OP) on the admission day with that on 14 days before/after (controls). PM10 was collected using a high-volume sampler located near the hospital, and oxidative potential was measured as depletion of three antioxidants (ascorbic acid, AA; glutathione, GSH; uric acid, UA) in a synthetic respiratory tract lining fluid model. The oxidative potential effects were estimated using conditional logistic regressions for paired data, adjusting for PM10 mass, temperature, and humidity. Effect modification by vitamin C serum levels was also assessed. Details on study methods are provided in the eAppendix (https://links.lww.com/EDE/A776). The analyses included 160 exacerbations in 151 patients with data available from at least one case and one control filter. Patients’ characteristics are presented in eTable 1; https://links.lww.com/EDE/A776. With the exception of a high positive correlation between OPAA and OPGSH (r = 0.69), there was no substantial correlation between the three oxidative potential readings and PM10 mass. PM10 oxidative potentials showed no association with asthma/COPD admissions, with similarly negative results after adjustment for PM10 mass (Table) and when stratifying by vitamin C serum levels (eTable 2; https://links.lww.com/EDE/A776).TABLE: Associationa of Asthma/COPD Exacerbations with a Unit Increase in OP m−3 for Each Antioxidant (n = 160 Exacerbations; n = 156 Filters)Our findings suggest that intrinsic oxidative properties are not driving the adverse effect of PM10 effects on respiratory exacerbations.2 PM10 effects could be due instead to indirect oxidative effects mediated by host reactions through cellular activation,1,3 such as that resulting in an influx of activated inflammatory cells to the lung, which cannot be captured by our particles’ oxidative potential measurement method based on oxidation reactions in an acellular respiratory tract lining fluid model. The association between particles’ oxidative potential and respiratory outcomes was evaluated in three recent epidemiologic panel studies.4–6 Only one of these studies found a positive association of outdoor PM2.5 oxidative potential, but not mass, with airway inflammation in 45 asthmatic children.6 The other two, using a semi-experimental design in 31 volunteers exposed to various levels of ambient PM, found no association of either PM mass or oxidative potential with lung function and exhaled nitric oxide4 or acute nasal airway inflammation.5 Although 85% of the patients in our study lived around the Chelsea and Westminster Hospital where PM10 was sampled,2 the use of monitoring sites to derive individual exposure is problematic due to temporal and spatial variation in PM oxidative properties, with higher oxidative potential in proximity to traffic.7,8 PM personal-sampling methods are more accurate but are not an option in a case-crossover design. Also, we measured the oxidative potential of PM10, and smaller particles may have different oxidative properties. However, previous measurements in London showed greater oxidative potential for PM10, suggesting an enrichment of redox-active components in the coarse fraction.7 Further studies with larger sample sizes, more accurate measurements of exposure (such as personal sampling), sampling several PM fractions, and comparing assays to measure oxidative potential are needed to establish the exact mechanism of PM oxidative potential on respiratory exacerbations. Cristina Canova Department of Molecular Medicine University of Padova Padova, Italy Imperial College London, United Kingdom [email protected]; [email protected] Cosetta Minelli Imperial College London, United Kingdom Christina Dunster Frank Kelly King’s College London, United Kingdom Pallav L. Shah NHLI, Imperial College London, United Kingdom Chelsea and Westminster Hospital London, United Kingdom Cielito Caneja Chelsea and Westminster Hospital London, United Kingdom Michael K. Tumilty Peter Burney Imperial College London, United Kingdom