Models to evaluate the pulmonary toxicity of desert dust and what we have learned from them so far: a mini-review.

Millions of people worldwide are exposed to aerosolised desert dust and are at risk of the adverse respiratory health effects it causes. This mini-review gives an overview of the study types that can be used to assess the respiratory toxicity of desert dust and the insights gained from these studies. We highlight the main advantages and disadvantages of epidemiological, in vivo, and in vitro studies. Regarding in vitro studies, we discuss models of increasing complexity, i.e., traditional submerged cell cultures, air-liquid interface cultures, organ-on-a-chip models, organoids, and precision-cut lung slices. Epidemiological studies have shown increased short-term mortality and exacerbated acute and chronic respiratory diseases after desert dust events. In contrast, a connection to the onset of chronic diseases is more difficult to prove. In vivo and in vitro studies have particularly addressed the cellular and molecular effects of desert dust. It was found that desert dust activates immune cells and induces the expression of inflammatory cytokines and oxidative stress markers. The specific effects and their extent vary between dust samples from different sources. The investigation of the role of the composition is still immature and needs further effort including more extensive screenings. The advancement of easy-to-handle and realistic pulmonary in vitro models is required to automate screenings, support mechanistic insights, and enable the assessment of long-term exposure scenarios. In agreement with striving to develop new approach methodologies, such advancements can reduce and replace animal experiments and strongly benefit the translatability of research outcomes to human health protection.