title: Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers.
abstract: In drug development, the anti-inflammatory properties of new molecules in the lung are currently tested using the inhaled lipopolysaccharide (LPS) model. The total and regional lung bioavailability of inhaled particles depends significantly on their size. The objective of the present study was to compare inflammatory responses in healthy volunteers after the inhalation of LPS of varying droplet size.
  
  
  
  Three nebulizers were characterized by different droplet size distributions [mean mass median aerodynamic diameters: Microcirrus (2.0 μm), MB2 (3.2 μm) and Pari (7.9 μm)]. Participants inhaled three boluses of a 20 μg (technetium 99 m-labelled) solution of LPS, randomly delivered by each nebulizer. We measured the lung deposition of the nebulized LPS by gamma-scintigraphy, while blood and sputum biomarkers were evaluated before and after challenges.
  
  
  
  MB2 and Pari achieved greater lung deposition than Microcirrus [171.5 (±72.9) and 217.6 (±97.8) counts pixel-1, respectively, vs. 67.9 (±20.6) counts pixel-1; P < 0.01]. MB2 and Pari caused higher levels of blood C-reactive protein and more total cells and neutrophils in sputum compared with Microcirrus (P < 0.05). C-reactive protein levels correlated positively with lung deposition (P < 0.01).
  
  
  
  Inhalation of large droplets of LPS gave rise to greater lung deposition and induced a more pronounced systemic and bronchial inflammatory response than small droplets. The systemic inflammatory response correlated with lung deposition. NCT01081392.
authors.affiliation: Clinic of Immuno-allergology, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium. vdoyen@ulb.ac.be.
authors.forename: Virginie
authors.initials: V
authors.lastname: Doyen
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, ULB, Brussels, Belgium.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Pilcer
authors.affiliation: Clinic of Immuno-allergology, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium.|Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.
authors.forename: Phong Huy Duc
authors.initials: PH
authors.lastname: Dinh
authors.affiliation: Laboratory of Immunology, CHU Brugmann, ULB, Brussels, Belgium.
authors.forename: Francis
authors.initials: F
authors.lastname: Corazza
authors.affiliation: Unit of Toxicology and Applied Pharmacology, Faculty of Medicine, ULB, Brussels, Belgium.
authors.forename: Alfred
authors.initials: A
authors.lastname: Bernard
authors.affiliation: Nuclear medicine department, CHU Brugmann, ULB, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bergmann
authors.affiliation: Clinic of Pulmonology, Allergology and Cystic Fibrosis, Hôpital Universitaire des Enfants Reine Fabiola, ULB, Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lefevre
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, ULB, Brussels, Belgium.
authors.forename: Karim
authors.initials: K
authors.lastname: Amighi
authors.affiliation: Clinic of Immuno-allergology, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Michel
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism*; D002452:Cell Count; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D009504:Neutrophils / Q000187:drug effects*; D010316:Particle Size; D011877:Radionuclide Imaging; D013183:Sputum / Q000166:cytology; D013667:Technetium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D013667:Technetium; D002097:C-Reactive Protein
keywords: asthma; endotoxin; inflammation; lung deposition; particle size