Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers

Abstract

AIMSIn 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. METHODSThree 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 gammascintigraphy, while blood and sputum biomarkers were evaluated before and after challenges. RESULTSMB2 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). CONCLUSIONSInhalation 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. British Journal of Clinical Pharmacology WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Inhaled lipopolysaccharide (LPS) challenge induces neutrophilic airway inflammation. The size of inhaled droplets is a physical parameter that affects total and regional deposition in the respiratory system. WHAT THIS STUDY ADDS• The current study demonstrates a link between inhaled LPS droplet size, lung deposition and the amplitude of the neutrophilic inflammatory response. The size of inhaled LPS droplets is a significant factor when investigating the mechanisms of inflammation and response to pharmacological inhibitors.

Distinct Clinical Pathology and Microbiota in Chronic Rhinosinusitis With Nasal Polyps Endotypes

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“…lipopolysaccharides help to induce neutrophilic asthma in a mouse model 55 . In humans, inhalation of lipopolysaccharides induces neutrophilic inflammation 56 . Hence, lipopolysaccharides could be correlated with neutrophilic inflaming.…”

High temperatures trigger suicide mortality in Brussels, Belgium: A case-crossover study (2002–2011)

“…The CC16 protein protects the respiratory tract against oxidative stress and is a potent anti-inflammatory agent (Janicova et al, 2019;Pang et al, 2017). The inflammatory reaction occurring in the lungs, leads to an increased production of CC16, resulting in increased levels of serum CC16 (Arsalane et al, 2000;Barregard et al, 2008;Doyen et al, 2016;Seys et al, 2015). The time needed for this increase to occur and to be observed, can vary depending on the source and the levels of the toxicant causing the inflammation.…”

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“…Relatie tussen de waargenomen longdepositie van endotoxine en het optreden van een systemische ontstekingsreactie, bepaald als CRP (C-reactief proteïne) concentratie in bloed, 24 uur na inhalatie van endotoxine. Figuur overgenomen (met toestemming) uit Doyen et al (2016).…”