TY - JOUR T1 - Direct activation of sensory afferents by diesel exhaust particles can trigger respiratory symptoms JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA5071 VL - 48 IS - suppl 60 SP - PA5071 AU - Ryan Robinson AU - Mark Birrell AU - Michael Wortley AU - Eric Dubuis AU - Shu Chen AU - Catriona McGilvery AU - Sheng Hu AU - Sara Bonvini AU - Sarah Maher AU - John Adcock AU - Ian Mudway AU - Alexandra Porter AU - Terry Tetley AU - Maria Belvisi Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA5071.abstract N2 - Urban air pollution, specifically particulate matter (PM), is a global health issue. Diesel exhaust particles (DEP) are a key component of PM and epidemiological evidence links exposure with respiratory symptoms. Activation of airway sensory afferents drives respiratory reflexes. Transient receptor potential (TRP) channels expressed on airway afferents can be activated by various stimuli to initiate reflexes, such as cough or bronchoconstriction (Birrell et al. AJRCCM:2009,1042–1047). We aimed to determine whether DEP activated airway sensory nerves and whether TRP channels were involved.DEP subunits were ∼50nm in diameter with aggregates up to 2μm. DEP was ∼2% metallic, ∼15% organic and ∼83% carbon. In anaesthetised guinea pigs, intratracheal administration of DEP activated chemosensitive airway single nerve fibres (8.3±0.3 action potential impulses.sec-1). Only the organic extract (DEP-OE) activated sensory nerves (measured as depolarisation) of the isolated guinea pig and human vagus and this was inhibited by 83.4±10.2% by a TRPA1 antagonist. DEP generates oxidative stress, a known TRPA1 activator. The antioxidant N-acetyl cysteine (NAC) abolished responses to DEP-OE and polycyclic aromatic hydrocarbons (PAH) found in DEP activate the vagus nerve. The aryl hydrocarbon receptor (AhR) and subsequent mitochondrial ROS, which can activate TRPA1 on nociceptive C-fibres (Nesuashvili et al. MolPharm:2013,83,1007-1019), are central to the response.To conclude, DEP can activate airway sensory nerves via activation of chemosensitive afferents. These findings provide the first mechanistic insights into how exposure to urban air pollution leads to respiratory symptoms. ER -