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  • 1. Barnes PJ. Chronic obstructive pulmonary disease: A growing but neglected global epidemic. PLOS Med. 2007 May;4(5):e112.
  • 2. Akinbami LJ, Moorman JE, Bailey C, Zahran HS, King M, Johnson CA et al. Trends in asthma prevalence, health care use, and mortality in the United States, 2001-2010. NCHS Data Brief. 2012 May(94):1-8.
  • 3. Barnes PJ. New anti-inflammatory targets for chronic obstructive pulmonary disease. Nat Rev Drug Discov. 2013 July;12(7):543-559.
  • 4. Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 February 15; 187(4):347-365.
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  • 6. Suissa S, Barnes PJ. Inhaled corticosteroids in COPD: The case against. Eur Respir J. 2009 July;34(1):13-16.
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  • 18. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008 March;8(3):183-192.
  • 19. Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest. 2013 July;144(1):266-273.
  • 20. Usmani OS, Barnes PJ. Assessing and treating small airways disease in asthma and chronic obstructive pulmonary disease. Ann Med. 2012 March;44(2):146-156.
  • 21. Lee EY, Lee ZH, Song YW. The interaction between CXCL10 and cytokines in chronic inflammatory arthritis. Autoimmun Rev. 2013 March;12(5):554-557.
  • 22. Donnelly LE, Barnes PJ. Chemokine receptors as therapeutic targets in chronic obstructive pulmonary disease. Trends Pharmacol Sci. 2006 October;27(10):546-553.
  • 23. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009 September 1;180(5):388-395.
  • 24. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009 March 5;360(10):985-993.
  • 25. Barnes PJ. New therapies for chronic obstructive pulmonary disease. Med Princ Pract. 2010;19(5):330-338.
  • 26. Holz O, Khalilieh S, Ludwig-Sengpiel A, Watz H, Stryszak P, Soni P et al. SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Eur Respir J. 2010 March;35(3):564-570.
  • 27. Costa C, Rufino R, Traves SL, Lapa ESJR, Barnes PJ, Donnelly LE. CXCR3 and CCR5 che- mokines in induced sputum from patients with COPD. Chest. 2008 January;133(1):26-33.
  • 28. Mahler DA, Huang S, Tabrizi M, Bell GM. Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: A pilot study. Chest. 2004 September;126(3):926-934.
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  • 33. Paul-Pletzer K. Tocilizumab: Blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today (Bare). 2006 September;42(9):559-576.
  • 34. De Sanctis JB, Garmendia JV, Moreno D, Larocca N, Mijares M, Di Giulio C et al. Pharmacological modulation of Th17. Recent Pat Inflamm Allergy Drug Diseov. 2009 June;3(2): 149-156.
  • 35. Abboud RT, Vimalanathan S. Pathogenesis of COPD. Part I. The role of protease- antiprotease imbalance in emphysema. Int J Tubere Lung Dis. 2008 April; 12(4):361-367.
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  • 37. Churg A, Wang R, Wang X, Onnervik PO, Thim K, Wright JL. Effect of an MMP-9/ MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs. Thorax. 2007 August;62(8):706-713.
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  • 39. Tomita K, Barnes PJ, Adcock IM. The effect of oxidative stress on histone acetylation and IL-8 release. Bioehem Biophys Res Commun. 2003 February 7;301(2):572-577.
  • 40. Puente-Maestu L, Perez-Parra J, Godoy R, Moreno N, Tejedor A, Gonzalez-Aragoneses F et al. Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients. Eur Respir J. 2009 May;33(5):1045-1052.
  • 41. Malhotra D, Thimmulappa R, Navas-Acien A, Sandford A, Elliott M, Singh A et al. Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am J Respir Crit Care Med. 2008 September 15;178(6):592-604.
  • 42. Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K et al. Placebo- controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 September 20;367(12):1098-1107.
  • 43. Rossing P. Diabetic nephropathy: Could problems with bardoxolone methyl have been predicted? Nat Rev Nephrol. 2013 March;9(3):128-130.
  • 44. Chatzopoulou M, Pegklidou K, Papastavrou N, Demopoulos VJ. Development of aldose reductase inhibitors for the treatment of inflammatory disorders. Expert Opin Drug Diseov. 2013 November;8(11):1365-1380.
  • 45. Giembycz MA. Can the anti-inflammatory potential of PDE4 inhibitors be realized: Guarded optimism or wishful thinking? Br JPharmaeol. 2008 October;155(3):288-290.
  • 46. Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbroker D et al. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007 December;62(12):1081-1087.
  • 47. Calverley PM, Sanchez-Toril F, McIvor A, Teichmann P, Bredenbroeker D, Fabbri LM. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007 July 15;176(2):154-161.
  • 48. Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: Two randomised clinical trials. Laneet. 2009 August 29;374(9691):695-703.
  • 49. Watz H, Mistry SJ, Lazaar AL, for the IPC101939 investigators. Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD. Pulm Pharmacol Ther. 2013;26:588-595.
  • 50. Giembycz MA. Phosphodiesterase-4: Selective and dual-specificity inhibitors for the therapy of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(4):326-333; discussion 40-41.
  • 51. Banner KH, Press NJ. Dual PDE3/4 inhibitors as therapeutic agents for chronic obstructive pulmonary disease. Br J Pharmacol. 2009 July;157(6):892-906.
  • 52. Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP. The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6, 7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2- (2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquino lin-4-one]. J Pharmacol Exp Ther. 2006 August;318(2):840-848.
  • 53. Cazzola M, Page CP, Calzetta L, Matera MG. Emerging anti-inflammatory strategies for chronic obstructive pulmonary disease. Eur Respir J. 2012 April 10; 40(3):724-741.
  • 54. Medina-Tato DA, Ward SG, Watson ML. Phosphoinositide 3-kinase signalling in lung disease: Leucocytes and beyond. Immunology. 2007 August;121(4):448-461.
  • 55. Marwick JA, Caramori G, Stevenson CS, Casolari P, Jazrawi E, Barnes PJ et al. Inhibition of PI3Kdelta restores glucocorticoid function in smoking-induced airway inflammation in mice. Am J Respir Crit Care Med. 2009 April 1;179(7):542-548.
  • 56. Doukas J, Eide L, Stebbins K, Racanelli-Layton A, Dellamary L, Martin M et al. Aerosolized phosphoinositide 3-kinase gamma/delta inhibitor TG100-115 [3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a therapeutic candidate for asthma and chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2009 March;328(3):758-765.
  • 57. Reutershan J, Saprito MS, Wu D, Ruckle T, Ley K. Phosphoinositide 3-kinase gamma required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung. Eur Respir J. 2010 May;35(5):1137-1147.
  • 58. Ward S, Sotsios Y, Dowden J, Bruce I, Finan P. Therapeutic potential of phosphoinositide 3-kinase inhibitors. Chem Biol. 2003 March;10(3):207-213.
  • 59. Sturgeon SA, Jones C, Angus JA, Wright CE. Advantages of a selective beta-isoform phosphoinositide 3-kinase antagonist, an anti-thrombotic agent devoid of other cardiovascular actions in the rat. Eur J Pharmacol. 2008 June 10;587(1-3):209-215.
  • 60. Renda T, Baraldo S, Pelaia G, Bazzan E, Turato G, Papi A et al. Increased activation of p38 MAPK in COPD. Eur Respir J. 2008 January;31(1):62-69.
  • 61. Medicherla S, Fitzgerald MF, Spicer D, Woodman P, Ma JY, Kapoun AM et al. p3 8alpha- selective mitogen-activated protein kinase inhibitor SD-282 reduces inflammation in a subchronic model of tobacco smoke-induced airway inflammation. J Pharmacol Exp Ther. 2008 March;324(3):921-929.
  • 62. Lomas DA, Lipson DA, Miller BE, Willits L, Keene O, Barnacle H et al. An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. J Clin Pharmacol. 2012 March;52(3):416-424.
  • 63. Chung KF. p38 mitogen-activated protein kinase pathways in asthma and COPD. Chest. 2011 June;139(6):1470-1479.
  • 64. Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008 April 15;177(8):861-870.
  • 65. Birrell MA, Wong S, Hardaker EL, Catley MC, McCluskie K, Collins M et al. IkappaB kinase-2-independent and -dependent inflammation in airway disease models: Relevance of IKK-2 inhibition to the clinic. Mol Pharmacol. 2006 June;69(6):1791-1800.
  • 66. Keslacy S, Tliba O, Baidouri H, Amrani Y. Inhibition of tumor necrosis factor- alpha-inducible inflammatory genes by interferon-gamma is associated with altered nuclear factor-kappaB transactivation and enhanced histone deacetylase activity. Mol Pharmacol. 2007 February;71(2):609-618.
  • 67. Catley MC, Sukkar MB, Chung KF, Jaffee B, Liao SM, Coyle AJ et al. Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle. Mol Pharmacol. 2006 August;70(2):697-705.
  • 68. Courtine E, Pene F, Cagnard N, Toubiana J, Fitting C, Brocheton J et al. Critical role of cRel subunit of NF-kappaB in sepsis survival. Infect Immun. 2011 May;79(5):1848-1854.
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  • 70. Sugawara A, Sueki A, Hirose T, Nagai K, Gouda H, Hirono S et al. Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for antiinflammatory and/or immunomodulatory agents. Bioorg Med Chem Lett. 2011 June 1; 21(11):3373-3376.
  • 71. Nakamaru Y, Vuppusetty C, Wada H, Milne JC, Ito M, Rossios C et al. A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J. 2009 September;23(9):2810-2819.
  • 72. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE et al. Rapamycin slows aging in mice. Aging Cell. 2012 August;11(4):675-682.
  • 73. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 November 16; 444(7117):337-342.
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