Surfactant Found in Cleaning Products, 4-Tert-octylphenol, Causes Airway Sensory Nerves Firing and Airway Smooth Muscle Contraction

Research suggests that cleaning product exposure has adverse effects on respiratory health (Svanes, Ø. et al. AJRCCM 2018;197:1157-1163). This could be attributed to the activation of airway sensory nerves, which cause reflex coughing, and bronchospasm with associated shortness of breath. We hypothesised that alkylphenols, which are commonly used as non-ionic surfactants in cleaning products (Suen, J.L. et al. KJMS 2012;28:43-48), may induce adverse respiratory effects following exposure. The prevalent alkylphenol, 4-tert-octylphenol (4-t-OP), was investigated in vitro using vagus nerve and airway smooth muscle tissue from guinea pigs and in vivo using electrophysiology recordings of single afferent nerve fibres. 4-t-OP caused depolarisation of vagus nerves in vitro and single nerve firing in vivo, suggesting it can activate airway sensory nerves. 4-t-OP also increased tracheal pressure in vivo and airway smooth muscle contraction in vitro, indicating it can induce bronchospasm. We then pharmacologically investigated ion channels known to play a role in airway reflexes and determined that antagonists for TRPM3 (isosakuranetin, 5µM) and TRPV4 (GSK2193874, 10µM) inhibited 4-t-OP (10µM)-induced nerve depolarisation by 56% and 44% respectively. The same antagonists inhibited 4-t-OP-induced smooth muscle contraction by 39% and 30%. This suggests that 4-t-OP acts via two distinct pathways involving TRPM3 and TRPV4. Our data shows that 4-t-OP interacts with airway sensory nerves and airway smooth muscle via activation of TRPM3 and TRPV4, suggesting a novel mechanism by which alkylphenols may contribute to respiratory symptoms following cleaning product exposure.