JG Filep

JM Erlich

MR Looney

WM Kuebler

U Imran Hamid

J Conlon

S Spence

A Krasnodembskaya

A Kissenpfennig

DF McAuley

CM O'Kane

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POSTER PRESENTATION Open Access0995. Aspirin reduces neutrophilic pulmonaryinflammation in a human model of acuterespiratory distress syndrome induced by inhaledlipopolysaccharideU Imran Hamid*, J Conlon, S Spence, A Krasnodembskaya, A Kissenpfennig, DF McAuley, CM O’KaneFrom ESICM LIVES 2014Barcelona, Spain. 27 September - 1 October 2014IntroductionAcute respiratory distress syndrome (ARDS) is charac-terized by damage to the alveolar epithelial-endothelialbarrier resulting in neutrophil influx and pulmonaryoedema. The activation of platelet and secondary cap-ture of neutrophils may play an important role in propa-gation of inflammation in ARDS [1]. Various animalstudies have shown that aspirin therapy reduces pul-monary oedema and development of lung injury [2]. Inobservational studies, patients on aspirin therapy priorto hospital admission had a reduced incidence of ARDS[3]. By acetylating cyclooxygenase, aspirin inhibits plate-let aggregation and generates anti-inflammatory mole-cules which modulate neutrophilic inflammation [4].ObjectiveTo test the hypothesis that aspirin reduces pulmonaryinflammation in an in vivo human model of acuterespiratory distress syndrome, induced by inhaled lipo-polysaccharide (LPS).MethodsHealthy subjects were enrolled in a double-blind,placebo-controlled study and were randomised to receiveaspirin 75mg or aspirin 1200mg or placebo (1:1:1) forseven days prior to LPS inhalation. Measurements wereperformed in bronchoalveolar lavage (BAL) fluidobtained at 6 hours after inhaling 50 micrograms of LPS.Results33 healthy subjects were enrolled. There was no signifi-cant difference between aspirin 75mg and aspirin1200mg. Data for both aspirin groups were combined.Aspirin pre-treatment reduced LPS induced BAL neutro-philia (figure 1) and BAL concentrations of both theneutrophil-specific protease MMP-8, and the pro-inflam-matory cytokine TNF-a. There was a non-significanttrend towards reduction in a range of inflammatory cyto-kines (table 1).Centre for Infection and Immunity, School of Medicine, Dentistry andBiomedical Sciences, Queen’s University of Belfast, Belfast, UKFigure 1 Aspirin reduces LPS induced BAL neurtophilia.Hamid et al. Intensive Care Medicine Experimental 2014, 2(Suppl 1):P80http://www.icm-experimental.com/content/2/S1/P80© 2014 Hamid et al; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons AttributionLicense (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium,provided the original work is properly cited.ConclusionThis study shows for the first time that aspirin canreduce neutrophilic inflammation in the lung in humans.Further clinical studies are warranted to assess its abilityto reduce neutrophil mediated inflammation in ARDS.Grant acknowledgementThis work was funded by the UK Intensive Care Society.ClinicalTrials.gov identifier: NCT01659307.Published: 26 September 2014References1. Kuebler WM: J Clin Invest 2006, 116(12):3106-8.2. Looney MR, et al: J Clin Invest 2009, 119(11):3450-61.3. Erlich JM, et al: Chest 2011, 139(2):289-95.4. Filep JG, et al: Prostaglandins Leukot Essent Fatty Acids 2005, 73(3-4):257-62.doi:10.1186/2197-425X-2-S1-P80Cite this article as: Hamid et al.: 0995. Aspirin reduces neutrophilicpulmonary inflammation in a human model of acute respiratorydistress syndrome induced by inhaled lipopolysaccharide. Intensive CareMedicine Experimental 2014 2(Suppl 1):P80.Submit your manuscript to a journal and benefi t from:7 Convenient online submission7 Rigorous peer review7 Immediate publication on acceptance7 Open access: articles freely available online7 High visibility within the fi eld7 Retaining the copyright to your article    Submit your next manuscript at 7 springeropen.comTable 1 Effect of aspirin on markes of pulmonary inflammationBALPlacebo (n=13) Aspirin (n=20) % reduction p-valuePMN (105cells/ml) 2.25 (1.18, 4.67) 1.48 (0.32, 6.21) 34.2 0.03TNF-a (pg/ml) 105.7 (73.49, 358.5) 79.72 (37.34, 276.6) 24.5 0.02IL-6 (pg/ml) 856.5 (535.9, 2285) 647.9 (224.6, 1582) 24.1 0.07MMP-8 (pg/ml) 6342 (1932, 9574) 2902 (862.8, 6758) 54 0.03MMP-9 (pg/ml) 48493 (23126, 99780) 33717 (10471, 72334) 30.4 0.03IL-8 (pg/ml) 447.5 (236.9, 1250) 345.9 (175.5, 1522) 22.7 0.11IL-1b (pg/ml) 42.74 (25.98, 98.76) 37.03 (18.73, 54.88) 13 0.16Hamid et al. Intensive Care Medicine Experimental 2014, 2(Suppl 1):P80http://www.icm-experimental.com/content/2/S1/P80Page 2 of 2

Intensive Care Medicine Experimental

0995. Aspirin reduces neutrophilic pulmonary inflammation in a human model of acute respiratory distress syndrome induced by inhaled lipopolysaccharide

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0995. Aspirin reduces neutrophilic pulmonary inflammation in a human model of acute respiratory distress syndrome induced by inhaled lipopolysaccharide

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