Future directions in the pharmacologic therapy of chronic obstructive pulmonary disease

Proceedings of the American Thoracic Society

Volumn 2, Issue 1, 2005, Pages 83-93

  Buhl, Roland ^a   Farmer, Stephen G ^b  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^b NONE

Author keywords

COPD; Drug development; Pulmonary inflammation; Systemic inflammation; Therapy

Indexed keywords

2 CYCLOPENTYL 2 [4 (2 QUINOLINYLMETHOXY)PHENYL]ACETIC ACID; AD 237; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BIMOSIAMOSE; BRONCHODILATING AGENT; CHOLINERGIC RECEPTOR BLOCKING AGENT; CICLESONIDE; CILOMILAST; CORTICOSTEROID; ENDOTHELIN RECEPTOR ANTAGONIST; EXPECTORANT AGENT; FORMOTEROL; GLUCOCORTICOID RECEPTOR ANTAGONIST; HYALURONIC ACID; INDACATEROL; IPRATROPIUM BROMIDE; LAS 34273; LEUKOTRIENE B4 RECEPTOR ANTAGONIST; LONG ACTING DRUG; METHYLXANTHINE DERIVATIVE; MONTELUKAST; MUCOLYTIC AGENT; MUSCARINIC RECEPTOR BLOCKING AGENT; PHOSPHODIESTERASE IV INHIBITOR; RETINOIC ACID; ROFLUMILAST; SALMETEROL; THEOPHYLLINE; TIOTROPIUM BROMIDE; UNCLASSIFIED DRUG; ZILEUTON;

ABDOMINAL PAIN; AGING; APOPTOSIS; ASTHMA; CARDIOVASCULAR DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; CONFERENCE PAPER; CORTICOSTEROID THERAPY; DIARRHEA; DISEASE ASSOCIATION; DISEASE COURSE; HEADACHE; HEART ARRHYTHMIA; HUMAN; HYPERCOAGULABILITY; HYPOXIA; LUNG FUNCTION; NAUSEA; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; PNEUMONIA; PROTEIN TARGETING; SEIZURE; SIDE EFFECT; SLEEP DISORDER; VOMITING; WEIGHT REDUCTION;

ADMINISTRATION, INHALATION; ADRENERGIC BETA-AGONISTS; ANTI-INFLAMMATORY AGENTS; ANTIBODIES, MONOCLONAL; ANTIOXIDANTS; BRONCHODILATOR AGENTS; GLUCOCORTICOIDS; HUMANS; PHOSPHODIESTERASE INHIBITORS; PROTEASE INHIBITORS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; QUALITY OF LIFE; SMOKING CESSATION;

EID: 17644364775     PISSN: 15463222     EISSN: None     Source Type: Conference Proceeding    
DOI: 10.1513/pats.200411-054SF     Document Type: Conference Paper

References (151)

1. Pauwels R, Buist AS, Calverley PMA, Jenkins CR, Hurd SS, for the GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001; 163:1256-1276.
2. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. NHLBI/WHO workshop report. Bethesda, MD: National Heart, Lung and Blood Institute; 2001. Update of the management sections, GOLD Web site (www.goldcopd.com). Date updated: July 2004.
3. Fabbri LM, Hurd SS, for the GOLD Scientific Committee. Global strategy for the diagnosis, management and prevention of COPD: 2003 update. Eur Respir J 2003;22:1-2.
4. Rodriguez-Roisin R. Toward a consensus definition for COPD exacerbations. Chest 2000;117:398S-401S.
5. Hurd S. The impact of COPD on lung health worldwide: epidemiology and incidence. Chest 2000;117:1S-4S.
6. Feenstra TL, van Genugten ML, Hoogenveen RT, Wouters EF, Ruttenvan Molken MP. The impact of aging and smoking on the future burden of chronic obstructive pulmonary disease: a model analysis in the Netherlands. Am J Respir Crit Care Med 2001;164:590-596.
7. Cano NJ, Pichard C, Roth H. Court-Fortune, Cynober L, Gerard-Boncompain M, Cuvelier A, Laaban JP, Melchior JC, Raphael JC, Pison CM. C-reactive protein and body mass index predict outcome in end-stage respiratory failure. Chest 2004;126:540-546.
8. Celli BR, Cote CG, Marin JM, Casanova C, de Montes O, Mendez RA, Pinto Plata V, Cabral HJ. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005-1012.
9. Kony S, Zureik M, Driss F, Neukirch C, Leynaert B, Neukirch F. Association of bronchial hyperresponsiveness and lung function with C-reactive protein (CRP): a population based study. Thorax 2004;59:892-896.
10. Sin DD, Lacy P, York E, Man SF. Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:760-765.
11. Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation 2003;107:1514-1519.
12. Sin DD, Man JP, Man SF. The risk of osteoporosis in Caucasian men and women with obstructive airways disease. Am J Med 2003;114:10-14.
13. Tracy RP, Psaty BM, Macy E, Bovill EG, Cushman M, Cornell ES, Kuller LH. Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects. Arterioscler Thromb Vasc Biol 1997;17:2167-2176.
14. Barnes PJ. Therapy of chronic obstructive pulmonary disease. Pharmacol Ther 2003;97:87-94.
15. Wouters EF. Management of severe COPD. Lancet 2004;364:883-895.
16. Selroos O. The place of inhaled corticosteroids in chronic obstructive pulmonary disease. Curr Med Res Opin 2004;20:1579-1593.
17. Tashkin DP, Cooper CB. The role of long-acting bronchodilators in the management of stable COPD. Chest 2004;125:249-259.
18. Buhl R, Farmer SG. Current and future pharmacologic therapy of exacerbations in chronic obstructive pulmonary disease and asthma. Proc Am Thorac Soc 2004;1:136-142.
19. Celik G, Kayacan O, Beder S, Durmaz G. Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: a cross-over, placebo-controlled comparison of onset and duration of action. Respiration (Herrlisheim) 1999;66:434-439.
20. Beeh K-M, Weite T, Buhl R. Anticholinergics in the treatment of chronic obstructive pulmonary disease. Respiration (Herrlisheim) 2002;69:372-379.
21. Barnes PJ. The pharmacological properties of tiotropium. Chest 2000;117:63S-66S.
22. Casaburi R, Mahler DA, Jones PW, Wanner A, San Pedro G, ZuWallack RL, Menjoge SS, Serby CW, Witek T. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J 2002;19:217-224.
23. Vincken W, Van Noord JA, Greefhorst APM, Bantje TA, Kesten S, Korducki L, Cornelissen PJG, for the Dutch/Belgian Tiotropium Study Group. Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium. Eur Respir J 2002;19:209-216.
24. Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson J, Maden C. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003;361:449-456.
25. Szafranski W, Cukier A, Ramirez A, Menga G, Sansores R, Nahabedian S, Peterson S, Olsson H. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J 2003;21:74-81.
26. Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003;22:912-919.
27. Moayyedi P, Congleton J, Page RL, Pearson SB, Muers MF. Comparison of nebulized salbutamol and ipratropium bromide with salbutamol alone in the treatment of chronic obstructive pulmonary disease. Thorax 1995;50:834-837.
28. Fernandez A, Munoz J, de la Calle B, Alia I, Ezpeleta A, de la Cal MA, Reyes A. Comparison of one versus two bronchodilators in ventilated COPD patients. Intensive Care Med 1994;20:199-202.
29. Siafakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, Yernault JC, Decramer M, Higenbottam T, Postma DS, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J 1995;8:1398-1420.
30. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:S77-S121.
31. Pearson MG, Alderslade R, Allen SC, Apps MCP, Barnes G, Bellamy D, Boote G, Calverley PMA. The COPD Guidelines Group of the Standards of Care Committee of the BTS. BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax 1997;52: S1-S28.
32. The COMBIVENT Inhalation Solution Study Group. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. Chest 1994,105:1411-1419.
33. Gross N, Tashkin D, Miller R, Oren J, Coleman W, Linberg S. Inhalation by nebulization of albuterol-ipratropium combination (Dey combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary. Respiration (Herrlisheim) 1998;65:354-362.
34. D'Urzo AD, De Salvo MC, Ramirez-Rivera A, Almeida J, Sichletidis L, Rapatz G, Kottakis J. In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium: a 3-week, randomized, double-blind, within-patient, multicenter study. Chest 2001;119:1347-1356.
35. Van Noord JA, de Munck DR, Bantje TA, Hop WC, Akveld ML, Bommer AM. Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium. Eur Respir J 2000;15:878-885.
36. Van Noord JA, Aumann J, Janssens E, Folgering H, Mueller A, Cornelissen PJG. Tiotropium maintenance therapy in patients with COPD and the 24-h spiromerric benefit of adding once or twice daily formoterol during 2-week treatment periods [abstract]. Am J Respir Crit Care Med 2003;167:A95.
37. Cazzola M, Marco FD, Santus P, Boveri B, Verga M, Matera MG, Centanni S. The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD. Pulm Pharmacol Ther 2004;17:35-39.
38. Handley DA, Senanayake CH, Dutczak W, Benovic JL, Walle T, Penn RB, Wilkinson HS, Tanoury GJ, Andersson RG, Johansson F, et al. Biological actions of formoterol isomers. Pulm Pharmacol Ther 2002;15:135-145.
39. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645-2653.
40. Sin DD, Tu JV. Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164:580-584.
41. Soriano JB, Vestbo J, Pride NB, Kiri V, Maden C, Maier WC. Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practice. Eur Respir J 2002;20:819-825.
42. Sin DD, Man SF. Inhaled corticosteroids and survival in chronic obstructive pulmonary disease: does the dose matter? Eur Respir J 2003;21: 260-266.
43. Suissa S. Effectiveness of inhaled corticosteroids in COPD: immortal time bias in observational studies. Am J Respir Crit Care Med 2003; 168:49-53.
44. Fan VS, Bryson CL, Curtis JR, Fihn SD, Bridevaux P-O, McDonell MB, Au DH. Inhaled corticosteroid use over time and risk of death in COPD patients [abstract]. Am J Respir Crit Care Med 2003;167:A89.
45. Vestbo J. The TORCH (TOwards a Revolution in COPD Health) survival study protocol. Eur Respir J 2004;24:206-210.
46. Schacke H, Rehwinkel H. Dissociated glucocorticoid receptor ligands. Curr Opin Investig Drugs 2004;5:524-528.
47. Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med 2000; 343:269-280.
48. Croxton TL, Weinmann GG, Senior RM, Wise RA, Crapo JD, Buist AS. Clinical research in chronic obstructive pulmonary disease: needs and opportunities. Am J Respir Crit Care Med 2003;167:1142-1149.
49. Barnes PJ. COPD: is there light at the end of the tunnel? Curr Opin Pharmacol 2004;4:263-272.
50. Barnes PJ, Hansel TT. Prospects for new drugs for chronic obstructive pulmonary disease. Lancet 2004;364:985-996.
51. Anthonisen NR, Connett JE, Murray RP. Smoking and lung function of Lung Health Study participants after 11 years. Am J Respir Crit Care Med 2002;166:675-679.
52. Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-691.
53. Tashkin D, Kanner R, Bailey W, Buist S, Anderson P, Nides M, Gonzales D, Dozier G, Patel MK, Jamerson B. Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial. Lancet 2001;357:1571-1575.
54. Fogarty M. Depending on cigarettes, counting on science. Scientist 2003; 17:21.
55. Fagerstrom K. New perspectives in the treatment of tobacco dependence. Monaldi Arch Chest Dis 2003;60:179-183.
56. Gamble E, Grootendorst DC, Brightling CE, Troy S, Qiu Y, Zhu J, Parker D, Matin D, Majumdar S, Vignola AM, et al. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;168:976-982.
57. Reid P. Roflumilast Altana Pharma. Curr Opin Investig Drugs 2002;3: 1165-1170.
58. Giembycz MA. Development status of second generation PDE4 inhibitors for asthma and COPD: the story so far. Monaldi Arch Chest Dis 2002;57:48-64.
59. Vignola AM. PDE4 inhibitors in COPD - a more selective approach to treatment. Respir Med 2004;98:495-503.
60. Spina D. The potential of PDE4 inhibitors in respiratory disease. Curr Drug Targets Inflamm Allergy 2004;3:231-236.
61. Leichtl S, Syed J, Bredenbröker D, Rathgeb F, Wurst W. Efficacy of once-daily roflumilast, a new orally active, selective phosphodiesterase 4 inhibitor in chronic obstructive pulmonary disease [abstract]. Am J Respir Crit Care Med 2002;165:A229.
62. Compton CH, Gubb J, Nieman R, Edelson J, Amit O, Bakst A, Ayres JG, Creemers JP, Schultze-Werninghaus G, Brambilla C, et al. Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study. Lancet 2001;358:265-270.
63. Beeh KM, Lerch C, Beier J, Kornmann O, Buhl R. Effect of piklamilast, a selective phosphodiesterase (IV)-inhibitor, theophylline and prednisone on FMLP-induced respiratory burst of peripheral blood neutrophils and sputum cells from COPD patients [abstract]. Am J Respir Crit Care Med 2003;167:A320.
64. Profita M, Chiappara G, Mirabella F, Di Giorgi R, Chimenti L, Costanzo G, Riccobono L, Bellia V, Bousquet J, Vignola AM. Effect of cilomilast (Ariflo) on TNF-alpha, IL-8, and GM-CSF release by airway cells of patients with COPD. Thorax 2003;58:573-579.
65. Larson JL, Pino MV, Geiger LE, Simeone CR. The toxicity of repeated exposures to rolipram, a type IV phosphodiesterase inhibitor, in rats. Pharmacol Toxicol 1996;78:44-49.
66. Losco PE, Evans EW, Barat SA, Blackshear PE, Reyderman L, Fine JS, Bober LA, Anthes JC, Mirro EJ, Cuss FM. The toxicity of SCH 351591, a novel phosphodiesterase-4 inhibitor, in Cynomolgus monkeys. Toxicol Pathol 2004;32:295-308.
67. Hill AT, Bayley D, Stockley RA. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Respir Crit Care Med 1999;160:893-898.
68. Beeh KM, Kornmann O, Buhl R, Culpitt SV, Giembycz MA, Barnes PJ. Neutrophil chemotactic activity of sputum from patients with COPD: role of interleukin 8 and leukotriene B4. Chest 2003;123:1240-1247.
69. Grönke L, Beeh KM, Cameron R, Kornmann O, Beier J, Wang JH, Brauburger J, Mücke M, Holz O, Buhl R, et al. LTB 019 A, a leukotriene B4 receptor antagonist, has no effect on the levels of neutrophils, mMPO, IL-8 and TNF-a in induced sputum of COPD patients in vivo [abstract]. Am J Respir Crit Care Med 2002;165:A598.
70. Yokomizo T, Kato K, Terawaki K, Izumi T, Shimizu T. A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. J Exp Med 2000;192:421-432.
71. Cazzola M, Boveri B, Carlucci P, Santus P, DiMarco F, Centanni S, Allegra L. Lung function improvement in smokers suffering from COPD with zafirlukast, a CysLT(1)-receptor antagonist. Pulm Pharmacol Ther 2000;13:301-305.
72. Gompertz S, Stockley RA. A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD. Chest 2002;122:289-294.
73. Donohue JF. Therapeutic responses in asthma and COPD: bronchodilators. Chest 2004;126:125S-137S.
74. Richman-Eisenstat JB, Jorens PG, Hebert CA, Ueki I, Nadel JA. Interleukin-8: an important chemoattractant in sputum of patients with chronic inflammatory airway diseases. Am J Physiol 1993;264:L413-L418.
75. Keatings VM, Collins PD, Scott DM, Barnes PJ. Differences in interleukin-8 and tumor necrosis factor-α in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996;153:530-534.
76. Mikami M, Llewellyn-Jones CG, Bayley D, Hill SL, Stockley RA. The chemotactic activity of sputum from patients with bronchiectasis. Am J Respir Crit Care Med 1998;157:723-728.
77. Yang XD, Corvalan JR, Wang P, Roy CM, Davis CG. Fully human anti-interleukin-8 monoclonal antibodies: potential therapeutics for the treatment of inflammatory disease states. J Leukoc Biol 1999;66: 401-410.
78. 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;126:926-934.
79. Widdowson KL, Elliott JD, Veber DF, Nie H, Rutledge MC, McCleland BW, Xiang JN, Jurewicz AJ, Hertzberg RP, Foley JJ, et al. Evaluation of potent and selective small-molecule antagonists for the CXCR2 chemokine receptor. J Med Chem 2004;47:1319-1321.
80. De Boer WJ. Cytokines and therapy in COPD: a promising combination? Chest 2002;121:209S-218S.
81. de Godoy I, Donahoe M, Calhoun WJ, Mancino J, Rogers RM. Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients. Am J Respir Crit Care Med 1996;153:633-637.
82. Vernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF. Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 2002;166:1218-1224.
83. Olsen NJ, Stein CM. New drugs for rheumatoid arthritis. N Engl J Med 2004;350:2167-2179.
84. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004;350:876-885.
85. Rabinowitz MH, Andrews RC, Becherer JD, Bickett DM, Bubacz DG, Conway JG, Cowan DJ, Gaul M, Glennon K, Lambert MH, et al. Design of selective and soluble inhibitors of tumor necrosis factor-alpha converting enzyme (TACE). J Med Chem 2001;44:4252-4267.
86. Blease K, Raymon HK. Small molecule inhibitors of cell signalling: novel future therapeutics for asthma and chronic obstructive pulmonary diseases. Curr Opin Investig Drugs 2003;4:544-551.
87. Karin M, Takahashi T, Kapahi P, Delhase M, Chen Y, Makris C, Rothwarf D, Baud V, Natoli G, Guido F, et al. Oxidative stress and gene expression: the AP-1 and NF-kappaB connections. Biofactors 2001;15: 87-89.
88. Delhase M, Li N, Karin M. Kinase regulation in inflammatory response. Nature 2000;406:367-368.
89. Adams JL, Badger AM, Kumar S, Lee JC. p38 MAP kinase: molecular target for the inhibition of pro-inflammatory cytokines. Prog Med Chem 2001;38:1-60.
90. Di Stefano A, Caramori G, Ricciardolo FL, Capelli A, Adcock IM, Donner CF. Cellular and molecular mechanisms in chronic obstructive pulmonary disease: an overview. Clin Exp Allergy 2004;34:1156-1167.
91. Di Stefano A, Caramori G, Capelli A, Gnemmi I, Ricciardolo FL, Oates T, Donner CF, Chung KF, Barnes PJ, Adcock IM. STAT4 activation in smokers and patients with chronic obstructive pulmonary disease. Eur Respir J 2004;24:78-85.
92. Myo S, Zhu X, Myou S, Meliton AY, Liu J, Boetticher E, Lambertino AT, Xu C, Munoz NM, Leff AR. Additive blockade of beta 2-integrin adhesion of eosinophils by salmeterol and fluticasone propionate. Eur Respir J 2004;23:511-517.
93. Sasaki T, Irie-Sasaki J, Jones RG, Oliveira-dos-Santos AJ, Stanford WL, Bolon B, Wakeham A, Itie A, Bouchard D, Kozieradzki I, et al. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science 2000;287:1040-1046.
94. Catley MC, Cambridge LM, Nasuhara Y, Ito K, Chivers JE, Beaton A, Holden NS, Bergmann MW, Barnes PJ, Newton R. Inhibitors of protein kinase C (PKC) prevent activated transcription: role of events downstream of NF-kappaB DNA binding. J Biol Chem 2004;279: 18457-18466.
95. Underwood DC, Osborn RR, Bochnowicz S, Webb EF, Rieman DJ, Lee JC, Romanic AM, Adams JL, Hay DW, Griswold DE. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol 2000;279:L895-L902.
96. Underwood DC, Osborn RR, Kotzer CJ, Adams JL, Lee JC, Webb EF, Carpenter DC, Bochnowicz S, Thomas HC, Hay DW, et al. SB 239063, a potent p38 MAP kinase inhibitor, reduces inflammatory cytokine production, airways eosinophil infiltration, and persistence. J Pharmacol Exp Ther 2000;293:281-288.
97. Juliano RL. Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. Annu Rev Pharmacol Toxicol 2002; 42:283-323.
98. Rosen SD, Bertozzi CR. The selectins and their ligands. Curr Opin Cell Biol 1994;6:663-673.
99. Slee DH, Romano SJ, Yu J, Nguyen TN, John JK, Raheja NK, Axe FU, Jones TK, Ripka WC. Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors with antiinftammatory activity. J Med Chem 2001;44:2094-2107.
100. Aydt E, Wolff G. Development of synthetic pan-selectin antagonists: a new treatment strategy for chronic inflammation in asthma. Pathobiology 2002;70:297-301.
101. Kansas GS. Selectins and their ligands: current concepts and controversies. Blood 1996;88:3259-3287.
102. Kogan TP, Dupre B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA. Novel synthetic inhibitors of selectin-medtated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)- 4-(2-alpha-D-mannopyranosyloxy)phenyl]hexane (TBC1269). J Med Chem 1998;41:1099-1111.
103. Onai Y, Suzuki J, Nishiwaki Y, Gotoh R, Berens K, Dixon R, Yoshida M, Ito H, Isobe M. Blockade of cell adhesion by a small molecule selectin antagonist attenuates myocardial ischemia/reperfusion injury. Eur J Pharmacol 2003;481:217-225.
104. Davenpeck KL, Berens KL, Dixon RA, Dupre B, Bochner BS. Inhibition of adhesion of human neutrophils and eosinophils to P-selectin by the sialyl Lewis antagonist TBC1269: preferential activity against neutrophil adhesion in vitro. J Allergy Clin Immunol 2000;105:769-775.
105. Radi ZA, Brogden KA, Dixon RA, Gallup JM, Ackermann MR. A selectin inhibitor decreases neutrophil infiltration during acute Mannheimia haemolytica pneumonia. Vet Pathol 2002;39:697-705.
106. Ramos-Kelly JR, Toledo-Pereyra LH, Jordan JA, Rivera-Chavez FA, Dixon RA, Ward PA. Upregulation of lung chemokines associated with hemorrhage is reversed with a small molecule multiple selectin inhibitor. J Am Coll Surg 1999;189:546-553.
107. Palma-Vargas JM, Toledo-Pereyra L, Dean RE, Harkema JM, Dixon RA, Kogan TP. Small-molecule selectin inhibitor protects against liver inflammatory response after ischemia and reperfusion. J Am Coll Surg 1997;185:365-372.
108. Beeh KM, Beier J, Buhl R, Zahlten R, Wolf G. Influence of inhaled bimosiamose (TBC 1269), a synthetic pan-selectin antagonist, on the allergen-induced late asthmatic response (LAR) in patients with mild allergic asthma [abstract]. Am J Respir Crit Care Med 2004;169:A321.
109. Barnes PJ. New treatments for COPD. Nat Rev 2002;1:437-446.
110. Anderson GP, Shinagawa K. Neutrophil elastase inhibitors as treatments for emphysema and chronic bronchitis. Curr Opin Antiinflamm Immunomod Drugs 1999;1:29-38.
111. White AJ, Gompertz S, Stockley RA. Chronic obstructive pulmonary disease. 6: The aetiology of exacerbations of chronic obstructive pulmonary disease. Thorax 2003;58:73-80.
112. Stoller JK. Alpha 1-antitrypsin deficiency. Thorax 2004;59:92-93.
113. Wencker M, Banik N, Buhl R, Seidel R, Konietzko N, for the WATL α1-AT Study Group. Long-term treatment of α1-antitrypsin deficiency-related pulmonary emphysema with human α1-antitrypsin. Eur Respir J 1998;11:428-433.
114. Survival and FEV1 decline in individuals with severe deficiency of α1-antitrypsin. Am J Respir Crit Care Med 1998;158:49-59.
115. Ohbayashi H. Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs 2002;11:965-980.
116. Wright JL, Farmer SG, Churg A. Synthetic serine elastase inhibitor reduces cigarette smoke-induced emphysema in guinea pigs. Am J Respir Crit Care Med 2002;166:954-960.
117. Wright JL, Farmer SG, Churg A. A neutrophil elastase inhibitor reduces cigarette smoke-induced remodelling of lung vessels. Eur Respir J 2003;22:77-81.
118. Tetley TD. Macrophages and the pathogenesis of COPD. Chest 2002;121: 156S-159S.
119. Beeh KM, Beier J, Kornmann O, Buhl R. Sputum matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med 2003;97:634-639.
120. Belvisi MG, Bottomley KM. The role of matrix metalloproteinases (MMPs) in the pathophysiology of chronic obstructive pulmonary disease (COPD): a therapeutic role for inhibitors of MMPs? Inflamm Res 2003;52:95-100.
121. Ramnath N, Creaven PJ. Matrix metalloproteinase inhibitors. Curr Oncol Rep 2004;6:96-102.
122. Cantor JO, Turino GM. Can exogenously administered hyaluronan improve respiratory function in patients with pulmonary emphysema? Chest 2004;125:288-292.
123. MacNee W. Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 2001;429:195-207.
124. Decramer ML, Rutten-van Molken M, Dekhuijzen RP, Troosters T, Lankhorst I. BRONCUS investigators. Effects of NAC on pulmonary function and exacerbation rate in COPD [abstract]. Am J Respir Crit Care Med 2004;169:A208.
125. Watson L, Margetts B, Howarth P, Dorward M, Thompson R, Little P. The association between diet and chronic obstructive pulmonary disease in subjects selected from general practice. Eur Respir J 2002;20:313-318.
126. Walda IC, Tabak C, Smit HA, Rasanen L, Fidanza F, Menotti A, Nissinen A, Feskens EJ, Kromhout D. Diet and 20-year chronic obstructive pulmonary disease mortality in middle-aged men from three European countries. Eur J Clin Nutr 2002;56:638-643.
127. Tabak C, Smit HA, Heederik D, Ocke MC, Kromhout D. Diet and chronic obstructive pulmonary disease: independent beneficial effects of fruits, whole grains, and alcohol (the MORGEN study). Clin Exp Allergy 2001;31:747-755.
128. Corradi M, Montuschi P, Donnelly LE, Pesci A, Kharitonov SA, Barnes PJ. Increased nitrosothiols in exhaled breath condensate in inflammatory airway diseases. Am J Respir Crit Care Med 2001;163:854-858.
129. Kanazawa H, Shoji S, Yoshikawa T, Hirata K, Yoshikawa J. Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease. Clin Exp Allergy 1998;28:1244-1250.
130. Jones KL, Bryan TW, Jinkins PA, Simpson KL, Grisham MB, Owens MW, Milligan SA, Markewitz BA, Robbins RA. Superoxide released from neutrophils causes a reduction in nitric oxide gas. Am J Physiol 1998;275:L1120-L1126.
131. Singh SP, Wishnok JS, Keshive M, Deen WM, Tannenbaum SR. The chemistry of the S-nitrosoglutathione/glutathione system. Proc Natl Acad Sci USA 1996;93:14428-14433.
132. Kharitonov SA, Barnes PJ. Nitric oxide, nitrotyrosine, and nitric oxide modulators in asthma and chronic obstructive pulmonary disease. Curr Allergy Asthma Rep 2003;3:121-129.
133. DeCarlo Massaro G, Massaro D. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat Med 1997;3:675-677.
134. McGowan SE. Contributions of retinoids to the generation and repair of the pulmonary alveolus. Chest 2002;121:206S-208S.
135. Kummer F. Of mice and men, or: a pill for emphysema? Respiration (Herrlisheim) 2003;70:135-136.
136. Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, et al. A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am J Respir Crit Care Med 2002;165:718-723.
137. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 2000; 106:1311-1319.
138. Kasahara Y, Tuder RM, Cool CD, Lynch DA, Flores SC, Voelkel NF. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med 2001;163:737-744.
139. Tuder RM, Petrache I, Elias JA, Voelkel NF, Henson PM. Apoptosis and emphysema: the missing link. Am J Respir Cell Mol Biol 2003; 28:551-554.
140. Massaro D, Massaro GD, Baras A, Hoffman EP, Clerch LB. Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression. Am J Physiol Lung Cell Mol Phvsiol 2004;286:L896-L906.
141. Massaro D, Massaro GD. Hunger disease and pulmonary emboli. Am J Respir Crit Care Med 2004;170:723-724.
142. Stockley RA. Neutrophils and the pathogenesis of COPD. Chest 2002;121:1515-1558.
143. Leikauf GD, Borchers MT, Prows DR, Simpson LG. Mucin apoprotein expression in COPD. Chest 2002;121:166S-182S.
144. Kellerman DJ. P2Y(2) receptor agonists: a new class of medication targeted at improved mucociliary clearance. Chest 2002;121:201S-205S.
145. Poole PJ, Black PN. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews; 2004, Issue 2, Art. No. CD001287.
146. Gerrits CMJM, Herings RMC, Leufkens HG, Lammers J-WJ. N-acetyl-cysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease. Eur Respir J 2003;21:795-798.
147. Berry JK, Baum C. Reversal of chronic obstructive pulmonary disease-associated weight loss: are there pharmacological treatment options? Drugs 2004;64:1041-1052.
148. Schols A. Nutritional modulation as part of the integrated management of chronic obstructive pulmonary disease. Proc Nutr Soc 2003;62:783-791.
149. Cosio MG, Guerassimov A. Chronic obstructive pulmonary disease: inflammation of small airways and lung parenchyma. Am J Respir Crit Care Med 1999;60:S1-S5.
150. Calverley P. Are inhaled corticosteroids systemic therapy for chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2004;170: 721-722.
151. Mallampalli A, Guntupalli KK. Smoking and systemic disease. Med Clin North Am 2004;88:1431-1451.