Effects of a FLAP inhibitor, GSK2190915, in asthmatics with high sputum neutrophils

Pulmonary Pharmacology and Therapeutics

Volumn 27, Issue 1, 2014, Pages 62-69

  Chaudhuri, R ^a   Norris, V ^b   Kelly, K ^b   Zhu, C Q ^b   Ambery, C ^b   Lafferty, J ^a   Cameron, E ^a   Thomson, N C ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

5 Lipoxygenase activating protein (FLAP) inhibitor; Asthma; GSK2190915; Sputum neutrophilia

Indexed keywords

FIBOFLAPON; LEUKOTRIENE B4; LEUKOTRIENE E4; PLACEBO;

ADULT; AGED; ARTICLE; ASTHMA; CLINICAL ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG SAFETY; FEMALE; HUMAN; LUNG FUNCTION; MALE; MIDDLE AGED; MULTIPLE CYCLE TREATMENT; NEUTROPHIL; NEUTROPHIL COUNT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SPUTUM CULTURE; TREATMENT OUTCOME; YOUNG ADULT;

5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITOR; ASTHMA; GSK2190915; SPUTUM NEUTROPHILIA;

5-LIPOXYGENASE-ACTIVATING PROTEIN INHIBITORS; ADULT; AGED; ASTHMA; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INDOLES; LEUKOCYTE COUNT; MALE; MIDDLE AGED; NEUTROPHILS; PENTANOIC ACIDS; SPUTUM; TIME FACTORS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84892435915     PISSN: 10945539     EISSN: 15229629     Source Type: Journal    
DOI: 10.1016/j.pupt.2013.11.007     Document Type: Article

References (30)

1. Global strategy for asthma management and prevention (updated 2011). Global Initiative for Asthma (GINA). URL: http://www.ginasthma.com.
2. Gibson P.G. Tackling asthma phenotypes in community studies. Thorax 2009, 64:369-370.
3. Wenzel S.E. Asthma: defining of the persistent adult phenotypes. Lancet 2006, 368:804-813.
4. Douwes J., Gibson P., Pekkanen J., Pearce N. Non-eosinophilic asthma: importance and possible mechanisms. Thorax 2002, 57:643-648.
5. Fahy J.V. Eosinophilic and neutrophilic inflammation in asthma. Insights from clinical studies. Proc Am Thorac Soc 2009, 6:2256-2259.
6. Mann B.S., Chung K.F. Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy. Respir Res 2006, 7:59.
7. McGrath K.W., Icitovic N., Boushey H.A., Lazarus S.C., Rand Sutherland E., Chinchilli V.M., et al. A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med 2012, 185:612-619.
8. Wang F., He X.Y., Baines K.J., Gunawardhana L.P., Simpson J.L., Li F., et al. Different inflammatory phenotypes in adults and children with acute asthma. Eur Respir J 2011, 38:567-574.
9. Sampson A.P. The role of eosinophils and neutrophils in inflammation. Clin Exp Allergy 2000, 30(Suppl. 1):22-27.
10. Pavord I.D., Brightling C.E., Woltmann G., Wardlaw A.J. Non-eosinophilic corticosteroid unresponsive asthma. Lancet 1999, 353:2213-2214.
11. Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol 1995, 154:4719-4725.
12. Wenzel S. Mechanisms of severe asthma. Clin Exp Allergy 2003, 33:1622-1628.
13. Sampson A.P. FLAP inhibitors for the treatment of inflammatory diseases. Curr Opin Investig Drugs 2009, 10:1163-1172.
14. Lorrain D.S., Bain G., Correa L.D., Chapman C., Broadhead A.R., Santini A.M., et al. Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models of acute inflammation. Eur J Pharmacol 2010, 640:211-218.
15. Bain G., King C.D., Schaab K., Rewolinski M., Norris V., Ambery C., et al. Pharmacodynamics, pharmacokinetics and safety of GSK2190915, a novel oral anti-inflammatory 5-lipoxygenase-activating protein inhibitor. Br J Clin Pharmacol 2013, 75:779-790.
16. Kent S.E., Boyce M., Diamant Z., Singh D., O'Connor B.J., Saggu P.S., et al. The 5-lipoxygenase activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma. Clin Exp Allergy 2013, 43:177-186.
17. Pavord I.D., Pizzichini M.M.M., Pizzichini E., Hargreave F.E. The use of induced sputum to investigate airway inflammation. Thorax 1997, 52:498-501.
18. Pizzichini E., Pizzichini M.M., Efthimiadis A., Evans S., Morris M.M., Squillace D., et al. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med 1996, 154:308-317.
19. Miller M.R., Hankinson J., Brusasco V., Burgos F., Casaburi R., Coates A., et al. Standardisation of spirometry. Eur Respir J 2005, 26:319-338.
20. Juniper E.F., O'Byrne P.M., Guyatt G.H., Ferrie P.J., King D.R. Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999, 14:902-907.
21. Daley-Yates P, Norris V, Ambery C, Preece A. Early clinical evaluation of a novel 5-lipoxygenase activating protein (FLAP) inhibitor (GSK2190915A). Pharmacokinetics, bioavailability and dose form selection: influence of age, food, drug interactions and regional absorption (LPA112071, LPA112362, LPA114604). In: BPS winter meeting 2012: proceedings of the British Pharmacological Society at http://www.pa2online.org/abstracts/vol10issue4abst078p.pdf.
22. 2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial. Clin Exp Allergy 2012, 42:1097-1103. on behalf of the study investigators.
23. Kobayashi S.D., Voyich J.M., Whitney A.R., DeLeo F.R. Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor. J Leukoc Biol 2005, 78:1408-1418.
24. Evans D.J., Barnes P.J., Spaethe S.M., van Alstyne E.L., Mitchell M.I., O'Connor B.J. Effect of a leukotriene B4 receptor antagonist, LY293111, on allergen induced responses in asthma. Thorax 1996, 51:1178-1184.
25. Simpson J.L., Powell H., Boyle M.J., Scott R.J., Gibson P.G. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med 2008, 177:148-155.
26. Maneechotesuwan K., Essilfie-Quaye S., Meah S., Kelly C., Kharitonov S.A., Adcock I.M., et al. Formoterol attenuates neutrophilic airway inflammation in asthma. Chest 2005, 128:1936-1942.
27. Gompertz S., Stockley R.A. A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD. Chest 2002, 122:289-294.
28. Grönke L., Beeh K.M., Cameron R., Kornmann O., Beier J., Shaw M., et al. Effect of the oral leukotriene B4 receptor antagonist LTB019 on inflammatory sputum markers in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2008, 21:409-417.
29. Follows R.M.A., Snowise N.G., Ho S.-Y., Ambery C.L., Smart K., McQuade B.A. Efficacy, safety and tolerability of GSK2190915, a 5-lipoxygenase activating protein inhibitor, in adults and adolescents with persistent asthma: a randomised dose-ranging study. Respir Res 2013, 14:54.
30. Snowise N.G., Clements D., Ho S.-Y., Follows R.M.A. Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma. Curr Med Res Opin 2013, 10.1185/03007995.2013.842163.