LPS induced inflammation depends on particles size

Inhaled lipopolysaccharide (LPS) is a usual inflammatory respiratory model. Particle size is a key parameter in defining the bioavailability of inhaled material. The objectives were to compare the lung deposition of a fixed LPS dose delivered by 3 aerosols devices characterized by different droplet size distributions: Microcirrus (C), MB2 (M) and Pari (P) given by a Mefar dosimeter and to evaluate the induced systemic inflammatory response. Each aerosol of LPS was first labeled with 99m Technetium and characterized by a Next Generation Impactor. Six healthy subjects (2F/4M) inhaled randomly 3 bolus of 20 μg 99m Tc-LPS delivered by each aerosol after a 14 days wash-out period. LPS lung deposition was quantified with planar gamma-scintigraphy. Serum samples were obtained after 24h to evaluate systemic inflammatory response (CRP). The mass median aerodynamic diameters (MMAD) of each aerosol were different (p<0.01) about 2.0 ± 0.2 µm, 3.2 ± 0.2 µm and 7.9 ± 0.5 µm for C, M and P, respectively. LPS lung deposition was different (p<0.01) for each aerosols (C: 84,6 ± 26,6 cpm/pixel; M: 190,5 ± 89,2 cpm/pixel; P: 237,7 ± 125,2 cpm/pixel). For the same aerosol device, deposition varied between subjects, particularly for M (up to 250%) which is the standard used nebulizer. CRP at 24h was greater for large droplets (M: 23,3 ± 10,3 mg/l; P: 28,3 ± 20,1 mg/l) compared to small ones (C: 8,9 ± 7,2 mg/l) (p < 0.05 after log transformation). Interestingly, results showed a correlation between lung deposition and CRP (n=15, r² 0,574, p < 0.005). LPS lung deposition varies in function of the MMAD of inhaled droplets and inflammatory response correlates with the lung deposition. Therefore, the choice of the aerosol nebulizer seems to be important.