Experimental Constraints on the Respiratory Health Hazard Posed by Crystalline Silica-bearing Volcanic Ash

Since volcanic ash from the 1980 eruption of Mount St Helens, USA, impacted on a million inhabitants in the Pacific Northwest, it is known that a substantial fraction of volcanic ejecta is respirable and therefore capable of being a human health hazard. Exacerbation of airway problems, such as asthma and chronic bronchitis, due to an increase in ambient particulate matter following the eruption, was an expected finding; however, a significant amount of cristobalite, a toxic mineral, in the ash was unforeseen and led to repeated toxicological testing of the ash to establish the hazard posed to human health. Those results together with studies on cristobalite-bearing ash from other major eruptions suggest that volcanic cristobalite is minimally reactive relative to pure phase standards. This finding adheres to a well-established thesis on the variable pathogenicity of crystalline silica, whereby intrinsic characteristics and extrinsic modifications of the crystalline silica govern reactivity. Indeed, chemical impurities (up to 4 wt% aluminum) and substantial structural defects have been implicated in the reduced potency of volcanic cristobalite. However, whilst not overtly toxic, volcanic ash exposure can initiate a sample-dependent inflammatory response in macrophages, a cell type that provides a first line of defense against inhaled particles. Inflammation plays a pivotal role in crystal-driven disease progression and can be observed in patients with particle-induced lung disease. We demonstrate that ash can induce inflammation by stimulating the NLRP3 inflammasome, a cytosolic receptor complex that drives the inflammatory response to several endo- and exogenous crystalline materials. The impact of inflammasome activation mediated by inhaled ash particles and its potential relevance in chronic pulmonary diseases was confirmed in primary human cells; however, it is not yet known whether the response resolves in vivo. The NLRP3 inflammasome as an ash-responsive element is predominantly mediated by the crystalline silica phase, although other common phases present in volcanic ash induce a low level response. As the componentry of volcanic ash is variable and intrinsically linked to eruption history, these data strengthen our efforts to provide health risk assessments during future eruptions.