Characterizing the effects of mining dust particulate matter exposure on respiratory health

The re-emergence of coal workers pneumoconiosis (CWP) in coal mining workers in Australia and abroad highlights major deficiencies in safety practices in the coal mining sector. CWP and other occupational lung diseases are complex that involve biological responses and interactions between multiple cell types in the lung and systemically. Importantly, different chemically distinct dust are likely to have different effects on disease processes. A greater understanding of how different types of dust exposures generated during mining operations cause disease is required to inform better safe exposure limits, identify early diagnostic markers of disease and inform potential therapies. During my PhD, I collected six different coal dust samples from real-world coal mining operations/locations and developed a dry screening technique to screen different PM fractions. The screened dust PM samples were partially characterized using advanced analytical techniques, and PM10 fractions were used to develop a series of in vivo and in vitro models to study the pathophysiological effects of chemically distinct dust PM. I show that exposure to different dust types/exposures has resulted in differential effects on lung health, such as declined carbon monoxide intake (DFco), increased AHR, structural changes (increased alveolar destruction & airway remodelling and coal macule formation). In addition, I also show that dust-PM rich in inorganic contaminants (initial stages) like crystalline silica and Fe showed increased inflammation, whereas PM rich in elemental carbon (final stages) had no effect. Further, using a real-time PCR, I show that acute exposure to increasing doses of carbon-rich dust-PM resulted in a dose-dependent knockdown of key inflammatory cytokines genes and altered iron and cell cycle regulatory genes. Finally, I show that exposure to dust PM resulted in the decreased phagocytic ability of macrophages with increased AHR during infection. My innovative approach uses highly representative whole organism exposures to model interactions that cannot be investigated in people or individual cell exposure systems. The developed models can provide a platform and ability to assess the detrimental health effects of different dust types, identify early disease markers and potential targets for therapies for better health.