B97-10 Impact of Prednisone on Sputum Macrophage Uptake of Carbon Black Following a Controlled Acute Exposure to Wood Smoke Particles

Abstract Rationale Exposure to woodsmoke particles (WSP) from wildfires induces airways inflammation and contributes to both acute and chronic respiratory morbidity. We have previously reported that prednisone administered immediately after a controlled WSP exposure reduced WSP-induced neutrophilic inflammation in healthy adults known to be neutrophil responsive to WSP [1]. The effect of this interventions however, on particulate matter burden in the airways, as measured by carbon black (CB) content of induced sputum airway macrophages (AM), is unknown. Methods We measured the CB content of AM from two previous WSP controlled-exposure studies, the first of which identified a cohort (N = 20) of healthy adult subjects who were neutrophil (PMN) responsive to WSP defined as ≥ 10% increase in sputum %PMN 24 hrs after a 2-hr exposure to 500µg/m3 WSP[2]. A sub-set of this PMN responsive cohort (N = 11) underwent a second WSP exposure protocol under the same exposure conditions as the first but received a single dose (60mg) of prednisone vs. placebo immediately post exposure, in a randomized crossover design. Sputum was collected 24hr post WSPs and sputum cytospin slides were generated and imaged for AM CB content using NIS Elements Imaging Software Basic Research 5.00.00. Fifty intact macrophages were counted per slide and the mean cytoplasmic CB content per AM was quantified by a) total number of CB particles within an AM, b) total area occupied by CB within an AM (µm2), and c) the percentage of the AM area occupied by CB (%). Results As previously reported, prednisone significantly reduced %PMN at 24 hours post WSP in 8 of 11 subjects who demonstrated PMN responsiveness after placebo (P = 0.05). Adequate cytospin slides for CB analysis were available for N = 10 subjects from the prednisone study. Following prednisone, CB content, as measured by total AM area occupied by CB (um2), was significantly negatively correlated with sputum % PMN (R = -0.71, p < 0.05). Conclusion Blunting airways neutrophilic inflammation immediately following an acute exposure to WSP may enhance AM CB uptake thereby decreasing the overall burden of inhaled WSP exposure to the airways. Airways inflammation appears to be a modifying factor in the response to inhaled WSP. Anti-inflammatory therapies given immediately after WSP exposure may be a feasible mechanism to reverse the acute impact of WSP to the airways by enhancing macrophage uptake of WSP. [1] J Allergy Clin Immunol Glob. 2024 Oct 10;4(1):100347. doi: 10.1016/j.jacig.2024.100347 [2] Inhal Toxicol. 2022 Aug 15;34(11-12):329-339. doi: 10.1080/08958378.2022.2110334 This abstract is funded by: NIH