Emissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments.

The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 American Thoracic Society Workshop on Precision-Cut Lung Slices (PCLSs) brought together 35 experts to discuss and address the role of human tissue–derived PCLSs as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, together with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts. The current document recommends standard reporting criteria and emphasizes the requirement for careful collection and integration of clinical metadata. We further discuss current clinically relevant readouts that can be applied to PCLSs and highlight recent developments and future steps for implementing novel technologies for PCLS modeling and analysis. The collection and correlation of clinical metadata and multiomic analysis will further advance the integration of this preclinical platform into patient endotyping and the development of tailored therapies for patients with lung disease.

Background: Acute and chronic exposures to biomass wildfire smoke pose significant health risks to firefighters and impacted communities. Susceptible populations such as asthmatics may be particularly sensitive to wildfire effects. We examined pulmonary responses to biomass smoke generated from combustion of peat, oak, or eucalyptus in control and house dust mite (HDM)-allergic mice. Methods: Mice were exposed 1 h/d for 2 consecutive days to emissions from each fuel type under smoldering or flaming conditions (∼40 or ∼3.3 mg PM/m³, respectively) while maintaining comparable CO levels (∼60–120 ppm). Results: Control and allergic mice reduced breathing frequency during exposure to all biomass emissions compared with pre-exposure to clean air. Smoldering eucalyptus and oak, but not peat, further reduced frequency compared to flaming conditions in control and allergic groups, while also reducing minute volume and peak inspiratory flow in control mice. Several biochemical and cellular markers of lung injury and inflammation were suppressed by all biomass emission types in both HDM-allergic and control mice. Control mice exposed to flaming eucalyptus at different PM concentrations (C) and times (T) with the same C × T product had a greater decrease in breathing frequency with high concentration acute exposure compared with lower concentration episodic exposure. This decrease was ameliorated by PM HEPA filtration, indicating that the respiratory changes were partially mediated by biomass smoke particles. Conclusion: These data show that exposure to smoldering eucalyptus or oak smoke inhibits respiratory responses to a greater degree than peat smoke. Anti-inflammatory effects of CO may possibly contribute to smoke-induced suppression of allergic inflammatory responses.

Although engineered nanomaterials (ENM) are currently regulated either in the context of a new chemical, or as a new use of an existing chemical, hazard assessment is still to a large extent reliant on information from historical toxicity studies of the parent compound, and may not take into account special properties related to the small size and high surface area of ENM. While it is important to properly screen and predict the potential toxicity of ENM, there is also concern that current toxicity tests will require even heavier use of experimental animals, and reliable alternatives should be developed and validated. Here we assessed the comparative respiratory toxicity of ENM in three different methods which employed in vivo, in vitro and ex vivo toxicity testing approaches. Toxicity of five ENM (SiO₂ (10), CeO₂ (23), CeO₂ (88), TiO₂ (10), and TiO₂ (200); parentheses indicate average ENM diameter in nm) were tested in this study. CD-1 mice were exposed to the ENM by oropharyngeal aspiration at a dose of 100 μg. Mouse lung tissue slices and alveolar macrophages were also exposed to the ENM at concentrations of 22–132 and 3.1-100 μg/mL, respectively. Biomarkers of lung injury and inflammation were assessed at 4 and/or 24 hr post-exposure. Small-sized ENM (SiO₂ (10), CeO₂ (23), but not TiO₂ (10)) significantly elicited pro-inflammatory responses in mice (in vivo), suggesting that the observed toxicity in the lungs was dependent on size and chemical composition. Similarly, SiO₂ (10) and/or CeO₂ (23) were also more toxic in the lung tissue slices (ex vivo) and alveolar macrophages (in vitro) compared to other ENM. A similar pattern of inflammatory response (e.g., interleukin-6) was observed in both ex vivo and in vitro when a dose metric based on cell surface area (μg/cm²), but not culture medium volume (μg/mL) was employed. Exposure to ENM induced acute lung inflammatory effects in a size- and chemical composition-dependent manner. The cell culture and lung slice techniques provided similar profiles of effect and help bridge the gap in our understanding of in vivo, ex vivo, and in vitro toxicity outcomes.