American Journal of Respiratory and Critical Care Medicine

1. Barnes PJ. New anti-inflammatory targets for chronic obstructive pulmonary disease. Nat Rev Drug Discov 2013;12:543559.
2. Cazzola M, Matera MG. Bronchodilators: current and future. Clin Chest Med 2014;35:191201.
3. Singh D, Schröder-Babo W, Cohuet G, Muraro A, Bonnet-Gonod F, Petruzzelli S, Hoffmann M, Siergiejko Z; TRIDENT Study Investigators. The bronchodilator effects of extrafine glycopyrronium added to combination treatment with beclometasone dipropionate plus formoterol in COPD: a randomised crossover study (the TRIDENT Study). Respir Med 2016;114:8490.
4. Cazzola M, Lopez-Campos JL, Puente-Maestu L. The MABA approach: a new option to improve bronchodilator therapy. Eur Respir J 2013;42:885887.
5. Grassin-Delyle S, Abrial C, Fayad-Kobeissi S, Brollo M, Faisy C, Alvarez JC, Naline E, Devillier P. The expression and relaxant effect of bitter taste receptors in human bronchi. Respir Res 2013;14:134.
6. Yarova PL, Stewart AL, Sathish V, Britt RD Jr, Thompson MA, Lowe APP, Freeman M, Aravamudan B, Kita H, Brennan SC, et al. Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma. Sci Transl Med 2015;7:284ra260.
7. Sundahl N, Bridelance J, Libert C, De Bosscher K, Beck IM. Selective glucocorticoid receptor modulation: new directions with non-steroidal scaffolds. Pharmacol Ther 2015;152:2841.
8. Leaker BR, O’Connor B, Singh D, Barnes PJ. The novel inhaled glucocorticoid receptor agonist GW870086X protects against adenosine-induced bronchoconstriction in asthma. J Allergy Clin Immunol 2015;136:5012.e6.
9. Beghè B, Rabe KF, Fabbri LM. Phosphodiesterase-4 inhibitor therapy for lung diseases. Am J Respir Crit Care Med 2013;188:271278.
10. Wedzicha JA, Calverley PM, Rabe KF. Roflumilast: a review of its use in the treatment of COPD. Int J Chron Obstruct Pulmon Dis 2016;11:8190.
11. Mulhall AM, Droege CA, Ernst NE, Panos RJ, Zafar MA. Phosphodiesterase 4 inhibitors for the treatment of chronic obstructive pulmonary disease: a review of current and developing drugs. Expert Opin Investig Drugs 2015;24:15971611.
12. Watz H, Mistry SJ, Lazaar AL; IPC101939 Investigators. Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD. Pulm Pharmacol Ther 2013;26:588595.
13. Singh D, Leaker B, Boyce M, Nandeuil MA, Collarini S, Mariotti F, Santoro D, Barnes PJ. A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients. Pulm Pharmacol Ther 2016;40:16.
14. Franciosi LG, Diamant Z, Banner KH, Zuiker R, Morelli N, Kamerling IM, de Kam ML, Burggraaf J, Cohen AF, Cazzola M, et al. Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials. Lancet Respir Med 2013;1:714727.
15. Barnes PJ. Kinases as novel therapeutic targets in asthma and COPD. Pharmacol Rev 2016;68:788815.
16. Norman P. Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs 2015;24:383392.
17. Mercado N, Hakim A, Kobayashi Y, Meah S, Usmani OS, Chung KF, Barnes PJ, Ito K. Restoration of corticosteroid sensitivity by p38 mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma. PLoS One 2012;7:e41582.
18. Watz H, Barnacle H, Hartley BF, Chan R. Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2014;2:6372.
19. MacNee W, Allan RJ, Jones I, De Salvo MC, Tan LF. Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax 2013;68:738745.
20. Singh D, Siew L, Christensen J, Plumb J, Clarke GW, Greenaway S, Perros-Huguet C, Clarke N, Kilty I, Tan L. Oral and inhaled p38 MAPK inhibitors: effects on inhaled LPS challenge in healthy subjects. Eur J Clin Pharmacol 2015;71:11751184.
21. Vanhaesebroeck B, Whitehead MA, Piñeiro R. Molecules in medicine mini-review: isoforms of PI3K in biology and disease. J Mol Med (Berl) 2016;94:511.
22. To Y, Ito K, Kizawa Y, Failla M, Ito M, Kusama T, Elliot M, Hogg JC, Adcock IM, Barnes PJ. Targeting phosphoinositide-3-kinase-δ with theophylline reverses corticosteroid insensitivity in COPD. Am J Respir Crit Care Med 2010;182:897904.
23. Mitani A, Ito K, Vuppusetty C, Barnes PJ, Mercado N. Restoration of corticosteroid sensitivity in chronic obstructive pulmonary disease by inhibition of mammalian target of rapamycin. Am J Respir Crit Care Med 2016;193:143153.
24. Lee KS, Jeong JS, Kim SR, Cho SH, Kolliputi N, Ko YH, Lee KB, Park SC, Park HJ, Lee YC. Phosphoinositide 3-kinase-δ regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress. Thorax 2016;71:5263.
25. Wilson R, Cahn AAD, McSherry L, Rambaran C, Sousa A, Wilbraham D. Safety, tolerability and pharmacokinetics (PK) of single and repeat nebulised doses of a novel phosphoinositide 3-kinase δ inhibitor (PI3Kδ), GSK2269557, administered to healthy male subjects in a phase I study. Eur Respir J 2013;42(Suppl 57):P729.
26. Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, et al. Optimization of novel indazoles as highly potent and selective inhibitors of phosphoinositide 3-kinase δ for the treatment of respiratory disease. J Med Chem 2015;58:73817399.
27. Fenwick PS, Macedo P, Kilty IC, Barnes PJ, Donnelly LE. Effect of JAK inhibitors on release of CXCL9, CXCL10 and CXCL11 from human airway epithelial cells. PLoS One 2015;10:e0128757.
28. Ramis I, Calama E, Domènech A, Carreño C, Calaf E, Cordoba M, Alberti J, De Alba J, Bach J, Prats N, et al. New inhaled JAK inhibitor LAS194046 inhibits allergen-induced airway inflammation in Brown Norway rats. Eur Respir J 2014;44(Suppl 58):22.
29. Geahlen RL. Getting Syk: spleen tyrosine kinase as a therapeutic target. Trends Pharmacol Sci 2014;35:414422.
30. Ramis I, Otal R, Carreño C, Domènech A, Eichhorn P, Orellana A, Maldonado M, De Alba J, Prats N, Fernández JC, et al. A novel inhaled Syk inhibitor blocks mast cell degranulation and early asthmatic response. Pharmacol Res 2015;99:116124.
31. Gonem S, Berair R, Singapuri A, Hartley R, Laurencin MF, Bacher G, Holzhauer B, Bourne M, Mistry V, Pavord ID, et al. Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med 2016;4:699707.
32. Erpenbeck VJ, Popov TA, Miller D, Weinstein SF, Spector S, Magnusson B, Osuntokun W, Goldsmith P, Weiss M, Beier J. The oral CRTh2 antagonist QAW039 (fevipiprant): a phase II study in uncontrolled allergic asthma. Pulm Pharmacol Ther 2016;39:5463.
33. Chung KF. Targeting the interleukin pathway in the treatment of asthma. Lancet 2015;386:10861096.
34. Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, Pirozzi G, Sutherland ER, Evans RR, Joish VN, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet 2016;388:3144.
35. Barnes PJ. Therapeutic approaches to asthma–chronic obstructive pulmonary disease overlap syndromes. J Allergy Clin Immunol 2015;136:531545.
36. Krug N, Hohlfeld JM, Kirsten AM, Kornmann O, Beeh KM, Kappeler D, Korn S, Ignatenko S, Timmer W, Rogon C, et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med 2015;372:19871995.
37. Busse WW, Holgate S, Kerwin E, Chon Y, Feng J, Lin J, Lin SL. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti–IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med 2013;188:12941302.
38. Nair P, Gaga M, Zervas E, Alagha K, Hargreave FE, O’Byrne PM, Stryszak P, Gann L, Sadeh J, Chanez P; Study Investigators. Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial. Clin Exp Allergy 2012;42:10971103.
39. Rennard SI, Dale DC, Donohue JF, Kanniess F, Magnussen H, Sutherland ER, Watz H, Lu S, Stryszak P, Rosenberg E, et al. CXCR2 antagonist MK-7123: a phase 2 proof-of-concept trial for chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015;191:10011011.
40. Holz O, Khalilieh S, Ludwig-Sengpiel A, Watz H, Stryszak P, Soni P, Tsai M, Sadeh J, Magnussen H. SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Eur Respir J 2010;35:564570.
41. Leaker BR, Barnes PJ, O’Connor B. Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist. Respir Res 2013;14:137.
42. Lee S, Suh GY, Ryter SW, Choi AM. Regulation and function of the nucleotide binding domain leucine-rich repeat-containing receptor, pyrin domain–containing-3 inflammasome in lung disease. Am J Respir Cell Mol Biol 2016;54:151160.
43. Coll RC, Robertson AA, Chae JJ, Higgins SC, Munoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med 2015;21:248–255.
44. 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;62:706713.
45. Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest 2013;144:266273.
46. Borbély G, Szabadkai I, Horváth Z, Markó P, Varga Z, Breza N, Baska F, Vántus T, Huszár M, Geiszt M, et al. Small-molecule inhibitors of NADPH oxidase 4. J Med Chem 2010;53:67586762.
47. Murphy MP. Antioxidants as therapies: can we improve on nature? Free Radic Biol Med 2014;66:2023.
48. Suzuki T, Motohashi H, Yamamoto M. Toward clinical application of the Keap1–Nrf2 pathway. Trends Pharmacol Sci 2013;34:340346.
49. Akdis CA, Akdis M. Advances in allergen immunotherapy: aiming for complete tolerance to allergens. Sci Transl Med 2015;7:280ps6.
50. Molfino A, Amabile MI, Rossi Fanelli F, Muscaritoli M. Novel therapeutic options for cachexia and sarcopenia. Expert Opin Biol Ther 2016;16:12391244.
51. Usmani OS, Barnes PJ. Assessing and treating small airways disease in asthma and chronic obstructive pulmonary disease. Ann Med 2012;44:146156.
52. Fabbri LM, Kerwin EM, Spangenthal S, Ferguson GT, Rodriguez-Roisin R, Pearle J, Sethi S, Orevillo C, Darken P, St Rose E, et al. Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension™ delivery technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD. Respir Res 2016;17:109.
53. Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol 2013;131:636645.
54. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature 2014;510:92101.
55. Adegunsoye A, Strek ME. Therapeutic approach to adult fibrotic lung diseases. Chest 2016;150:13711386.
56. Liu X, Fang Q, Kim H. Preclinical studies of mesenchymal stem cell (MSC) administration in chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis. PLoS One 2016;11:e0157099.
57. Barnes PJ. Mechanisms of development of multimorbidity in the elderly. Eur Respir J 2015;45:790806.
58. Barnes PJ. Senescence in COPD and its comorbidities. Annu Rev Physiol [online ahead of print] 9 Dec 2016; DOI: 10.1146/annurev-physiol-022516-034314.
59. Barnes PJ, Bonini S, Seeger W, Belvisi MG, Ward B, Holmes A. Barriers to new drug development in respiratory disease. Eur Respir J 2015;45:11971207.
60. Pavord ID, Lettis S, Locantore N, Pascoe S, Jones PW, Wedzicha JA, Barnes NC. Blood eosinophils and inhaled corticosteroid/long-acting β2 agonist efficacy in COPD. Thorax 2016;71:118125.


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American Journal of Respiratory and Critical Care Medicine

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