TY - JOUR T1 - Quantitative assessment of cysteinyl leukotrienes in human sputum during the allergen-induced asthmatic response and the effect of GSK2190915, a 5-lipoxygenase activating protein (FLAP) inhibitor JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4080 AU - Ginger L. Milne AU - Warda Amin AU - Stephanie C. Sanchez AU - Andrew F. Preece Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4080.abstract N2 - Accurate measurement of the cysteinyl leukotrienes (cLTs) LTC4, LTD4, and LTE4 in human sputum may be useful for assessing airway inflammation. GSK2190915 is a potent FLAP inhibitor that inhibits the synthesis of cLTs. The objective of this study was to assess the effect of GSK2190915 on the production of cLTs in human sputum using ultra pressure liquid chromatography-mass spectrometry.In this double-blind, placebo-controlled, crossover study subjects took 100mg GSK219095 and placebo orally once daily for 5 days, in randomized order. On Day 3 they had an inhaled allergen challenge and on Days 4 and 5 they had induced sputum collection. Sputum was frozen at –80°C until measurement. For analysis, 200-500μL of sputum supernatant was diluted into 1mL of water spiked with [2H3]-LTE4 internal standard and was extracted using an Empore C-18 solid phase extraction disk prior to analysis.The limit of detection for each analyte was 1pg/mL. LTD4 and LTE4 were detected in most samples while LTC4 was generally below the limit of detection:Measurement of cLTs using this method allows for the accurate and reliable quantitation in human sputum and may allow a better understanding of the role of these molecules in airway inflammation.Study funded by GlaxoSmithKline. GSK study LPA111834. Clinicaltrials.gov identifier NCT00748306. ER -