New drugs for exacerbations of chronic obstructive pulmonary disease

The Lancet

Volumn 374, Issue 9691, 2009, Pages 744-755

  Hansel, Trevor T ^a   Barnes, Peter J ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACLIDINIUM BROMIDE; ALPHA DEFENSIN; ANTIBIOTIC AGENT; ANTIOXIDANT; ANTIVIRUS AGENT; ARFORMOTEROL; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; BETA DEFENSIN; BRONCHODILATING AGENT; CARMOTEROL; CATHELICIDIN; CHEMOKINE RECEPTOR ANTAGONIST; CILOMILAST; CORTICOSTEROID; CYTOKINE RECEPTOR ANTAGONIST; ERYTHROMYCIN DERIVATIVE; FORMOTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDACATEROL; MONOCLONAL ANTIBODY; MUSCARINIC RECEPTOR BLOCKING AGENT; OSELTAMIVIR; PALIVIZUMAB; PHOSPHODIESTERASE IV INHIBITOR; PROTEINASE INHIBITOR; STEROID; THEOPHYLLINE; TIOTROPIUM BROMIDE; UNINDEXED DRUG; ZANAMIVIR;

ACUTE PHASE RESPONSE; AGING; AUTOIMMUNITY; BACTERIAL INFECTION; BRONCHIOLITIS; CHRONIC OBSTRUCTIVE LUNG DISEASE; DIARRHEA; DISEASE EXACERBATION; DRUG INDUCED HEADACHE; EMPHYSEMA; HUMAN; INFLAMMATION; INFLUENZA; INJURY; INNATE IMMUNITY; LOW DRUG DOSE; LUNG FIBROBLAST; LUNG FIBROSIS; LYMPHOCYTE SUBPOPULATION; MACROPHAGE; NAUSEA; NEUTROPHIL; PRIORITY JOURNAL; PROTEIN DEGRADATION; RESPIRATORY SYNCYTIAL PNEUMOVIRUS; RESPIRATORY SYSTEM; REVIEW; VIRUS INFECTION;

EID: 69249117423     PISSN: 01406736     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0140-6736(09)61342-8     Document Type: Review

References (147)

1. Celli B.R., and Barnes P.J. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J 29 (2007) 1224-1238
2. Wedzicha J.A., and Seemungal T. COPD exacerbations: defining their cause and prevention. Lancet 370 (2007) 786-796
3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. http://www.goldcopd.org/Guidelineitem.asp?l1=2&l2=1&intId=2003 (accessed Aug 6, 2009).
4. Fletcher C., and Peto R. The natural history of chronic airflow obstruction. Br Med J 1 (1977) 1645-1648
5. Mannino D.M., Watt G., Hole D., et al. The natural history of chronic obstructive pulmonary disease. Eur Respir J 27 (2006) 627-643
6. 1 decline in current smokers but not ex-smokers with chronic obstructive pulmonary disease: results from Lung Health Study. Am J Respir Crit Care Med 164 (2001) 358-364
7. Donaldson G.C., Seemungal T.A., Bhowmik A., and Wedzicha J.A. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 57 (2002) 847-852
8. Silverman E.K. Exacerbations in chronic obstructive pulmonary disease: do they contribute to disease progression?. Proc Am Thorac Soc 4 (2007) 586-590
9. Celli B.R., Cote C.G., Marin J.M., et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 350 (2004) 1005-1012
10. Barnes P.J., and Celli B.R. Systemic manifestations and comorbidities of COPD. Eur Respir J 33 (2009) 1165-1185
11. Cookson W. Genetics and genomics of chronic obstructive pulmonary disease. Proc Am Thorac Soc 3 (2008) 473-477
12. Hersh C.P., DeMeo D.L., and Silverman E.K. National emphysema treatment trial state of the art: genetics of emphysema. Proc Am Thorac Soc 5 (2008) 486-493
13. Foreman M.G., DeMeo D.L., Hersh C.P., et al. Polymorphic variation in surfactant protein B is associated with COPD exacerbations. Eur Respir J 32 (2008) 938-944
14. Yang I.A., Seeney S.L., Wolter J.M., et al. Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections. Genes Immun 4 (2003) 269-274
15. Hogg J.C., Chu F., Utokaparch S., et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 350 (2004) 2645-2653
16. Kelsen S.G., Aksoy M.O., Georgy M., et al. Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3. Am J Respir Crit Care Med 179 (2009) 799-805
17. van der Strate B.W., Postma D.S., Brandsma C.A., et al. Cigarette smoke-induced emphysema: a role for the B cell?. Am J Respir Crit Care Med 173 (2006) 751-758
18. Mak J.C. Pathogenesis of COPD. Part II. Oxidative-antioxidative imbalance. Int J Tuberc Lung Dis 12 (2008) 368-374
19. Kovacic P., and Somanathan R. Pulmonary toxicity and environmental contamination: radicals, electron transfer, and protection by antioxidants. Rev Environ Contam Toxicol 201 (2009) 41-69
20. 2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ-lyase. Science 322 (2008) 587-590
21. Stampfli M.R., and Anderson G.P. How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Nat Rev Immunol 9 (2009) 377-384
22. Baglole C.J., Maggirwar S.B., Gasiewicz T.A., Thatcher T.H., Phipps R.P., and Sime P.J. The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-κB family member RelB. J Biol Chem 283 (2008) 28944-28957
23. Ling S.H., and van Eeden S.F. Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 4 (2009) 233-243
24. Sykes A., Mallia P., and Johnston S.L. Diagnosis of pathogens in exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc 4 (2007) 642-646
25. Varkey J.B., and Varkey B. Viral infections in patients with chronic obstructive pulmonary disease. Curr Opin Pulm Med 14 (2008) 89-94
26. Brownlee J.W., and Turner R.B. New developments in the epidemiology and clinical spectrum of rhinovirus infections. Curr Opin Pediatr 20 (2008) 67-71
27. Patel I.S., Roberts N.J., Lloyd-Owen S.J., Sapsford R.J., and Wedzicha J.A. Airway epithelial inflammatory responses and clinical parameters in COPD. Eur Respir J 22 (2003) 94-99
28. Papi A., Contoli M., Caramori G., Mallia P., and Johnston S.L. Models of infection and exacerbations in COPD. Curr Opin Pharmacol 7 (2007) 259-265
29. Ramaswamy M., Groskreutz D.J., and Look D.C. Recognizing the importance of respiratory syncytial virus in chronic obstructive pulmonary disease. COPD 6 (2009) 64-75
30. Sikkel M.B., Quint J.K., Mallia P., Wedzicha J.A., and Johnston S.L. Respiratory syncytial virus persistence in chronic obstructive pulmonary disease. Pediatr Infect Dis J 27 suppl (2008) S63-S70
31. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360 (2009) 2605-2615
32. Murphy T.F. The role of bacteria in airway inflammation in exacerbations of chronic obstructive pulmonary disease. Curr Opin Infect Dis 19 (2006) 225-230
33. Sethi S., Maloney J., Grove L., Wrona C., and Berenson C.S. Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 173 (2006) 991-998
34. Patel I.S., Seemungal T.A., Wilks M., Lloyd-Owen S.J., Donaldson G.C., and Wedzicha J.A. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 57 (2002) 759-764
35. Nseir S., and Ader F. Prevalence and outcome of severe chronic obstructive pulmonary disease exacerbations caused by multidrug-resistant bacteria. Curr Opin Pulm Med 14 (2008) 95-100
36. Bozinovski S., Hutchinson A., Thompson M., et al. Serum amyloid A is a biomarker of acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 177 (2008) 269-278
37. Barnes P.J. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 118 (2008) 3546-3556
38. Zemans R.L., Colgan S.P., and Downey G.P. Transepithelial migration of neutrophils: mechanisms and implications for acute lung injury. Am J Respir Cell Mol Biol 40 (2009) 519-535
39. Mosser D.M., and Edwards J.P. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8 (2008) 958-969
40. Hammad H., and Lambrecht B.N. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol 8 (2008) 193-204
41. Borchers M.T., Wesselkamper S.C., Curull V., et al. Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease. J Clin Invest 119 (2009) 636-649
42. Makris D., Lazarou S., Alexandrakis M., et al. Tc2 response at the onset of COPD exacerbations. Chest 134 (2008) 483-488
43. H17 cells in health and disease. J Allergy Clin Immunol 123 (2009) 1004-1011
44. Cosio M.G., Saetta M., and Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med 360 (2009) 2445-2454
45. Feghali-Bostwick C.A., Gadgil A.S., Otterbein L.E., et al. Autoantibodies in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 177 (2008) 156-163
46. Lee S.H., Goswami S., Grudo A., et al. Antielastin autoimmunity in tobacco smoking-induced emphysema. Nat Med 13 (2007) 567-569
47. Gaestel M., Kotlyarov A., and Kracht M. Targeting innate immunity protein kinase signalling in inflammation. Nat Rev Drug Discov 8 (2009) 480-499
48. Wilson M.S., and Wynn T.A. Pulmonary fibrosis: pathogenesis, etiology and regulation. Mucosal Immunol 2 (2009) 103-121
49. Laurent G.J., McAnulty R.J., Hill M., and Chambers R. Escape from the matrix: multiple mechanisms for fibroblast activation in pulmonary fibrosis. Proc Am Thorac Soc 5 (2008) 311-315
50. Scotton C.J., and Chambers R.C. Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest 132 (2007) 1311-1321
51. Marciniak S.J., and Lomas D.A. What can naturally occurring mutations tell us about the pathogenesis of COPD?. Thorax 64 (2009) 359-364
52. Taraseviciene-Stewart L., and Voelkel N.F. Molecular pathogenesis of emphysema. J Clin Invest 118 (2008) 394-402
53. Owen C.A. Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 3 (2008) 253-268
54. Muroski M.E., Roycik M.D., Newcomer R.G., et al. Matrix metalloproteinase-9/gelatinase B is a putative therapeutic target of chronic obstructive pulmonary disease and multiple sclerosis. Curr Pharm Biotechnol 9 (2008) 34-46
55. Lagente V., Le Q.C., and Boichot E. Macrophage metalloelastase (MMP-12) as a target for inflammatory respiratory diseases. Expert Opin Ther Targets 13 (2009) 287-295
56. Sarir H., Henricks P.A., van Houwelingen A.H., Nijkamp F.P., and Folkerts G. Cells, mediators and toll-like receptors in COPD. Eur J Pharmacol 585 (2008) 346-353
57. Raymond T., Schaller M., Hogaboam C.M., Lukacs N.W., Rochford R., and Kunkel S.L. Toll-like receptors, notch ligands, and cytokines drive the chronicity of lung inflammation. Proc Am Thorac Soc 4 (2007) 635-641
58. O'Neill L.A. The interleukin-1 receptor/toll-like receptor superfamily: 10 years of progress. Immunol Rev 226 (2008) 10-18
59. Kumar H., Kawai T., and Akira S. Pathogen recognition in the innate immune response. Biochem J 420 (2009) 1-16
60. Matzinger P. Friendly and dangerous signals: is the tissue in control?. Nat Immunol 8 (2007) 11-13
61. Paul-Clark M.J., McMaster S.K., Sorrentino R., et al. Toll-like receptor 2 is essential for the sensing of oxidants during inflammation. Am J Respir Crit Care Med 179 (2009) 299-306
62. Williams A.S., Leung S.Y., Nath P., et al. Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophilia. J Appl Physiol 103 (2007) 1189-1195
63. Doz E., Noulin N., Boichot E., et al. Cigarette smoke-induced pulmonary inflammation is TLR4/MyD88 and IL-1R1/MyD88 signaling dependent. J Immunol 180 (2008) 1169-1178
64. Foell D., Wittkowski H., and Roth J. Mechanisms of disease: a 'DAMP' view of inflammatory arthritis. Nat Clin Pract Rheumatol 3 (2007) 382-390
65. Bianchi M.E. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81 (2007) 1-5
66. Areschoug T., and Gordon S. Scavenger receptors: role in innate immunity and microbial pathogenesis. Cell Microbiol 11 (2009) 1160-1169
67. Klune J.R., Dhupar R., Cardinal J., Billiar T.R., and Tsung A. HMGB1: endogenous danger signaling. Mol Med 14 (2008) 476-484
68. Ramasamy R., Yan S.F., and Schmidt A.M. RAGE: therapeutic target and biomarker of the inflammatory response-the evidence mounts. J Leukoc Biol (2009) 10.1189/jlb.0409230 published online May 27.
69. Sukkar M.B., Xie S., Khorasani N.M., et al. Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle. J Allergy Clin Immunol 118 (2006) 641-648
70. Churg A., Cosio M., and Wright J.L. Mechanisms of cigarette smoke-induced COPD: insights from animal models. Am J Physiol Lung Cell Mol Physiol 294 (2008) L612-L631
71. Hoogerwerf J.J., de Vos A.F., Bresser P., et al. Lung inflammation induced by lipoteichoic acid or lipopolysaccharide in humans. Am J Respir Crit Care Med 178 (2008) 34-41
72. Cazzola M., MacNee W., Martinez F.J., et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 31 (2008) 416-469
73. Quon B.S., Gan W.Q., and Sin D.D. Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest 133 (2008) 756-766
74. Decramer M., Nici L., Nardini S., et al. Targeting the COPD exacerbation. Respir Med 102 suppl 1 (2008) S3-S15
75. Black P.N., and McDonald C.F. Interventions to reduce the frequency of exacerbations of chronic obstructive pulmonary disease. Postgrad Med J 85 (2009) 141-147
76. Adcock I.M., and Barnes P.J. Molecular mechanisms of corticosteroid resistance. Chest 134 (2008) 394-401
77. Celli B.R. Update on the management of COPD. Chest 133 (2008) 1451-1462
78. Leff A.R., and Munoz N.M. Future treatment to lessen exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc 4 (2007) 659-666
79. US Department of Health and Human Services. Guidance for industry. Chronic obstructive pulmonary disease: developing drugs for treatment. Draft guidance. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/ucm071575.pdf (accessed Aug 6, 2009).
80. Hanania N.A., and Donohue J.F. Pharmacologic interventions in chronic obstructive pulmonary disease: bronchodilators. Proc Am Thorac Soc 4 (2007) 526-534
81. Baumgartner R.A., Hanania N.A., Calhoun W.J., Sahn S.A., Sciarappa K., and Hanrahan J.P. Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. Clin Ther 29 (2007) 261-278
82. Cazzola M. Aclidinium bromide, a novel long-acting muscarinic M3 antagonist for the treatment of COPD. Curr Opin Investig Drugs 10 (2009) 482-490
83. Seemungal T.A., and Wedzicha J.A. Acute exacerbations of COPD: the challenge is early treatment. COPD 6 (2009) 79-81
84. Carrera M., Marin J.M., Anton A., et al. A controlled trial of noninvasive ventilation for chronic obstructive pulmonary disease exacerbations. J Crit Care (2009) published online Jan 17. 1016/j.jrc.2008.08.007
85. de Jong Y.P., Uil S.M., Grotjohan H.P., Postma D.S., Kerstjens H.A., and van den Berg J.W. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest 132 (2007) 1741-1747
86. Cosio B.G., Iglesias A., Rios A., et al. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax 64 (2009) 424-429
87. Cosio B.G., Tsaprouni L., Ito K., Jazrawi E., Adcock I.M., and Barnes P.J. Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med 200 (2004) 689-695
88. Kirkham P., and Rahman I. Antioxidant therapeutic strategies. In: Hansel T.T., and Barnes P.J. (Eds). New drugs and targets for respiratory diseases (2009), Thomson-Reuters, London
89. Li L., Salto-Tellez M., Tan C.H., Whiteman M., and Moore P.K. GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat 1. Free Radic Biol Med 47 (2009) 103-113
90. Rohde G. Drug targets in rhinoviral infections. Infect Disord Drug Targets 9 (2009) 126-132
91. Zhu L., Lee P.K., Lee W.M., Zhao Y., Yu D., and Chen Y. Rhinovirus-induced major airway mucin production involves a novel TLR3-EGFR-dependent pathway. Am J Respir Cell Mol Biol 40 (2009) 610-619
92. Olszewska W., and Openshaw P. Emerging drugs for respiratory syncytial virus infection. Expert Opin Emerg Drugs 14 (2009) 207-217
93. Glezen W.P. Clinical practice. Prevention and treatment of seasonal influenza. N Engl J Med 359 (2008) 2579-2585
94. Hayden F. Developing new antiviral agents for influenza treatment: what does the future hold?. Clin Infect Dis 48 suppl 1 (2009) S3-S13
95. Hanlon G.W. Bacteriophages: an appraisal of their role in the treatment of bacterial infections. Int J Antimicrob Agents 30 (2007) 118-128
96. Serhan C.N., Chiang N., and Van Dyke T.E. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8 (2008) 349-361
97. Doss M., White M.R., Tecle T., et al. Interactions of α-, β-, and θ-defensins with influenza A virus and surfactant protein D. J Immunol 182 (2009) 7878-7887
98. Tamaoki J., Kadota J., and Takizawa H. Clinical implications of the immunomodulatory effects of macrolides. Am J Med 117 suppl 9A (2004) 5S-11S
99. Li Y.J., Azuma A., Usuki J., et al. EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-β signaling in lung fibroblasts. Respir Res 7 (2006) 16
100. Murawski M.R., Bowen G.N., Cerny A.M., et al. Respiratory syncytial virus activates innate immunity through toll-like receptor 2. J Virol 83 (2009) 1492-1500
101. Xie X.H., Law H.K., Wang L.J., Li X., Yang X.Q., and Liu E.M. Lipopolysaccharide induces IL-6 production in respiratory syncytial virus-infected airway epithelial cells through the toll-like receptor 4 signaling pathway. Pediatr Res 65 (2009) 156-162
102. Heltzer M.L., Coffin S.E., Maurer K., et al. Immune dysregulation in severe influenza. J Leukoc Biol 85 (2009) 1036-1043
103. Presicce P., Giannelli S., Taddeo A., Villa M.L., and Della B.S. Human defensins activate monocyte-derived dendritic cells, promote the production of proinflammatory cytokines, and up-regulate the surface expression of CD91. J Leukoc Biol (2009) 10.1189/jlb.0708412 published online June 15.
104. O'Neill L.A., Bryant C.E., and Doyle S.L. Therapeutic targeting of toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev 61 (2009) 177-197
105. Chaudhuri N., Whyte M.K., and Sabroe I. Reducing the toll of inflammatory lung disease. Chest 131 (2007) 1550-1556
106. Kenny E.F., and O'Neill L.A. Signalling adaptors used by toll-like receptors: an update. Cytokine 43 (2008) 342-349
107. Hunninghake D.B. Cardiovascular disease in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2 (2005) 44-49
108. Jain M.K., and Ridker P.M. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4 (2005) 977-987
109. Frost F.J., Petersen H., Tollestrup K., and Skipper B. Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest 131 (2007) 1006-1012
110. Mancini G.B., Etminan M., Zhang B., Levesque L.E., Fitzgerald J.M., and Brophy J.M. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 47 (2006) 2554-2560
111. Soyseth V., Brekke P.H., Smith P., and Omland T. Statin use is associated with reduced mortality in COPD. Eur Respir J 29 (2007) 279-283
112. van Gestel Y.R., Hoeks S.E., Sin D.D., et al. Effect of statin therapy on mortality in patients with peripheral arterial disease and comparison of those with versus without associated chronic obstructive pulmonary disease. Am J Cardiol 102 (2008) 192-196
113. Blamoun A.I., Batty G.N., DeBari V.A., Rashid A.O., Sheikh M., and Khan M.A. Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study. Int J Clin Pract 62 (2008) 1373-1378
114. Janda S., Park K., Fitzgerald J.M., Etminan M., and Swiston J. Statins in COPD: a systematic review. Chest (2009) 10.1378/chest.09-0194 published online April 17.
115. Currie G.P., Butler C.A., Anderson W.J., and Skinner C. Phosphodiesterase 4 inhibitors in chronic obstructive pulmonary disease: a new approach to oral treatment. Br J Clin Pharmacol 65 (2008) 803-810
116. Giembycz M.A. Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking?. Br J Pharmacol 155 (2008) 288-290
117. Compton C.H., Gubb J., Nieman R., et al. Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study. Lancet 358 (2001) 265-270
118. Rennard S.I., Schachter N., Strek M., Rickard K., and Amit O. Cilomilast for COPD: results of a 6-month, placebo-controlled study of a potent, selective inhibitor of phosphodiesterase 4. Chest 129 (2006) 56-66
119. Rabe K.F., Bateman E.D., O'Donnell D., Witte S., Bredenbröker D., and Bethke T.D. Roflumilast-an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 366 (2005) 563-571
120. Calverley P.M., Sanchez-Toril F., McIvor A., Teichmann P., Bredenbroeker D., and Fabbri L.M. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 176 (2007) 154-161
121. Woodruff P.G., Koth L.L., Yang Y.H., et al. A distinctive alveolar macrophage activation state induced by cigarette smoking. Am J Respir Crit Care Med 172 (2005) 1383-1392
122. Kim E.Y., Battaile J.T., Patel A.C., et al. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med 14 (2008) 633-640
123. Barcelo B., Pons J., Ferrer J.M., Sauleda J., Fuster A., and Agusti A.G. Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco smoking. Eur Respir J 31 (2008) 555-562
124. Harrison O.J., Foley J., Bolognese B.J., Long III E., Podolin P.L., and Walsh P.T. Airway infiltration of CD4+ CCR6+ Th17 type cells associated with chronic cigarette smoke induced airspace enlargement. Immunol Lett 121 (2008) 13-21
125. Rennard S.I., Fogarty C., Kelsen S., et al. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175 (2007) 926-934
126. Barnes P.J. Unexpected failure of anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175 (2007) 866-867
127. Wenzel S.E., Barnes P.J., Bleecker E.R., et al. A randomized, double-blind, placebo-controlled study of TNF-α blockade in severe persistent asthma. Am J Respir Crit Care Med 179 (2009) 549-558
128. Laan M., Bozinovski S., and Anderson G.P. Cigarette smoke inhibits lipopolysaccharide-induced production of inflammatory cytokines by suppressing the activation of activator protein-1 in bronchial epithelial cells. J Immunol 173 (2004) 4164-4170
129. Berclaz P.Y., Carey B., Fillipi M.D., et al. GM-CSF regulates a PU.1-dependent transcriptional program determining the pulmonary response to LPS. Am J Respir Cell Mol Biol 36 (2007) 114-121
130. Paul-Pletzer K. Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today (Barc) 42 (2006) 559-576
131. Ivanov S., and Linden A. Targeting interleukin-17 in the lungs. In: Hansel T.T., and Barnes P.J. (Eds). New drugs and targets for respiratory diseases (2009), Thomson-Reuters, London
132. Prause O., Bossios A., Silverpil E., et al. IL-17-producing T lymphocytes in lung tissue and in the bronchoalveolar space after exposure to endotoxin from Escherichia coli in vivo-effects of anti-inflammatory pharmacotherapy. Pulm Pharmacol Ther 22 (2009) 199-207
133. O'Connor B.J., Leaker B.R., Barnes P.J., et al. Inhibition of LPS-induced neutrophilic inflammation in healthy volunteers. Eur Resp J 30 suppl 51 (2007) 1294
134. 4. Chest 123 (2003) 1240-1247
135. Edwards M.R., Bartlett N.W., Clarke D., Birrell M., Belvisi M., and Johnston S.L. Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease. Pharmacol Ther 121 (2009) 1-13
136. Birrell M.A., Wong S., Hardaker E.L., et al. IκB kinase-2-independent and -dependent inflammation in airway disease models: relevance of IKK-2 inhibition to the clinic. Mol Pharmacol 69 (2006) 1791-1800
137. Marwick J.A., Caramori G., Stevenson C.S., et al. Inhibition of PI3Kδ restores glucocorticoid function in smoking-induced airway inflammation in mice. Am J Respir Crit Care Med 179 (2009) 542-548
138. Decramer M., Rutten-van Mölken M., Dekhuijzen P.N.R., et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet 365 (2005) 1552-1560
139. Zheng J.-P., Kang J., Huang S.-G., et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study. Lancet 371 (2008) 2013-2018
140. Rogers D.F. Mucoactive agents for airway mucus hypersecretory diseases. Respir Care 52 (2007) 1176-1193
141. Foreman M.G., DeMeo D.L., Hersh C.P., et al. Polymorphic variation in surfactant protein B is associated with COPD exacerbations. Eur Respir J 32 (2008) 938-944
142. Hudson T.J. Dornase in treatment of chronic bronchitis. Ann Pharmacother 30 (1996) 674-675
143. Ito K., and Barnes P.J. COPD as a disease of accelerated lung aging. Chest 135 (2009) 173-180
144. Jiang D., Liang J., Fan J., et al. Regulation of lung injury and repair by toll-like receptors and hyaluronan. Nat Med 11 (2005) 1173-1179
145. Turino G.M., and Cantor J.O. Hyaluronan in respiratory injury and repair. Am J Respir Crit Care Med 167 (2003) 1169-1175
146. Roth M.D., Connett J.E., D'Armiento J.M., et al. Feasibility of retinoids for the treatment of emphysema study. Chest 130 (2006) 1334-1345
147. Klimanskaya I., Rosenthal N., and Lanza R. Derive and conquer: sourcing and differentiating stem cells for therapeutic applications. Nat Rev Drug Discov 7 (2008) 131-142