Deposition Patterns of Carbon Black Nanoparticles in Pulmonary Lobes and Airway Generations: Implications for Lung Remodeling.

Carbon black nanoparticles (CBNPs) pose respiratory risks due to occupational and environmental exposure, yet their spatially heterogeneous effects on lung remodeling remain unclear. We quantified remodeling patterns using high-resolution computerized tomography (HRCT) in 69 carbon black packers and 107 controls, with carbon content in airway macrophages (CCAM) serving as a bioeffective dosimeter. CBNP-exposed workers exhibited elevated mean lung density in the left (β = 7.75 HU) and right upper lobe (β = 6.22 HU, all p values ≤ 0.047), showing clear dose-dependent trends with CBNP internal dose. Thickened airway wall area percentage (WA%) was observed in the sixth- and ninth-generation bronchi of the upper lobes, including the sixth-generation left B1 + 2 bronchus (β = 3.76%) and the right B1 bronchus to the carina (β = 4.43%; all p values ≤ 0.006). Dose-response trends linked CCAM with WA% thickening in larger sixth-generation bronchi of bilateral upper lobes (all p_trend values ≤ 0.008), absent in ninth-generation airways. Computational modeling revealed 45.2% higher particle deposition in bilateral upper lobes and 3-fold greater deposition in sixth-generation airways, governed by inertial impaction, which dominates in proximal small airways. This study visualizes region-specific pulmonary remodeling associated with CBNP exposure in humans, identifying the bilateral upper lobes and proximal small airways as key vulnerability hotspots. By linking deposition physics-dominated by inertial impaction-to selective regional targeting, these findings provide mechanistic insight into how nanoparticle deposition patterns translate into heterogeneous lung remodeling. The combined use of quantitative HRCT biomarkers and respiratory tract deposition modeling offers a framework for early surveillance and risk assessment of nanomaterial-induced lung injury.