Roflumilast: systemic therapy for chronic obstructive pulmonary disease

References

• Weiss ST, DeMeo DL, Postma DS. COPD: problems in diagnosis and measurement. Eur. Respir. J.41(Suppl.), 4S–12S (2003).
   Google Scholar
• Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet349(9064), 1498–1504 (1997).
   PubMed Web of Science ®Google Scholar
• European Respiratory Society. European Lung White Book: Huddersfield, UK. European Respiratory Society Journals, Ltd (2003).
   Google Scholar
• Rennard SI. Antiinflammatory therapies other than corticosteroids. Proc. Am. Thorac. Soc.1(3), 282–287 (2004).
   PubMedGoogle Scholar
• Daheshia M. Pathogenesis of chronic obstructive pulmonary disease. Clin. Applied Immunol. Rev.5(1), 339–351 (2005).
   Google Scholar
• Sevenoaks MJ, Stockley RA. Chronic obstructive pulmonary disease, inflammation and co-morbidity – a common inflammatory phenotype? Respir. Res.7, 70–78 (2006).
   PubMed Web of Science ®Google Scholar
• Larsson K. Aspects on pathophysiological mechanisms in COPD. J. Intern. Med.262(3), 311–340 (2007).
   PubMed Web of Science ®Google Scholar
• Thompson AB, Daughton D, Robbins RA, Ghafouri MA, Oehlerking M, Rennard SI. Intraluminal airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters. Am. Rev. Respir. Dis.140(6), 1527–1537 (1989).
   PubMed Web of Science ®Google Scholar
• Rennard SI. Chronic obstructive pulmonary disease: linking outcomes and pathobiology of disease modification. Proc. Am. Thorac. Soc.3(3), 276–280 (2006).
   PubMedGoogle Scholar
• Hogg JC, Chu S, Utokaparch R. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med.350(26), 2645–2653 (2004).
   PubMed Web of Science ®Google Scholar
• Saetta M, Di Stefano A, Maestrelli P et al. Airway eosinophilia in chronic bronchitis during exacerbations. Am. J. Respir. Crit. Care Med.150(6 Pt 1), 1646–1652 (1994).
   PubMed Web of Science ®Google Scholar
• Kent L, Smyth L, Clayton C et al. Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages. Cytokine42(2), 205–216 (2008).
   PubMed Web of Science ®Google Scholar
• Saetta M, Di Stefano A, Turato G et al. CD8+ T-lymphocytes in the peripheral airways of smokers with COPD. Am. J. Respir. Crit. Care Med.157(3 Pt 1), 822–826 (1998).
   PubMed Web of Science ®Google Scholar
• Peinado VI, Barbera JA, Abate P et al. Inflammatory reaction in pulmonary muscular arteries of patients with mild COPD. Am. J. Respir. Crit. Care Med.159(5 Pt 1), 1605–1611 (1999).
   PubMed Web of Science ®Google Scholar
• Rennard SI. Clinical approach to patients with chronic obstructive pulmonary disease and cardiovascular disease. Proc. Am. Thorac. Soc.2(1), 94–100 (2005).
   PubMedGoogle Scholar
• Soriano JB, Visick GT, Muellerova H, Payvandi N, Hansell AL. Patterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest128(4), 2099–2107 (2005).
   PubMed Web of Science ®Google Scholar
• Agustí A. Systemic effects of chronic obstructive pulmonary disease: what we know and what we don’t know (but should). Proc. Am. Thorac. Soc.4(7), 522–525 (2007).
   PubMedGoogle Scholar
• Agusti A, Soriano JB. COPD as a systemic disease. COPD5(2), 133–138 (2008).
   PubMedGoogle Scholar
• Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax59(7), 574–580 (2004).
   PubMed Web of Science ®Google Scholar
• Pinto-Plata VM, Mullerova H, Toso JF et al. C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax61(1), 23–28 (2006).
   PubMed Web of Science ®Google Scholar
• Franciosi LG, Page CP, Celli BR et al. Markers of disease severity in chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther.19(3), 189–199 (2006).
   PubMed Web of Science ®Google Scholar
• Sin DD, Man SF. Why are patients with COPD at increased risk of cardiovascular disease? The potential role of systemic inflammation in COPD. Circulation107(11), 1514–1519 (2003).
   PubMed Web of Science ®Google Scholar
• Broekhuizen R, Wouters EF, Creutzberg EC, Schols AM. Raised CRP levels mark metabolic and functional impairment in advanced COPD. Thorax61(1), 17–22 (2006).
   PubMed Web of Science ®Google Scholar
• Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. Chest128(4), 2005–2011 (2005).
   PubMed Web of Science ®Google Scholar
• Curkendall SM, DeLuise C, Jones JK et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Am. J. Epidemiol.16(1), 63–70 (2006).
   Google Scholar
• Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome? Lancet370(9589), 797–799 (2007).
   PubMed Web of Science ®Google Scholar
• Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol. Ther.109(3), 366–398 (2006).
   PubMed Web of Science ®Google Scholar
• Vignola AM. PDE4 inhibitors in COPD – a more selective approach to treatment. Respir. Med.98(6), 495–503 (2004).
   PubMed Web of Science ®Google Scholar
• Tang HF, Chen JQ, Xie QM et al. The role of PDE4 in pulmonary inflammation and goblet cell hyperplasia in allergic rats. Biochim. Biophys. Acta1762(5), 525–532 (2006).
   PubMed Web of Science ®Google Scholar
• Buhl R, Farmer SG. Future directions in the pharmacologic therapy of chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc.2(1), 83–93 (2005).
   PubMedGoogle Scholar
• Fan Chung K. Phosphodiesterase inhibitors in airways disease. Eur. J. Pharmacol.533(1–3), 110–117 (2006).
   PubMed Web of Science ®Google Scholar
• Dinter H. Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis? BioDrugs13(2), 87–94 (2000).
   PubMed Web of Science ®Google Scholar
• Hamamoto M, Suga M, Takahashi Y et al. Suppressive effect of phosphodiesterase type 4 inhibition on systemic inflammatory responses after cardiopulmonary bypass. J. Artif. Organs9(3), 144–148 (2006).
   PubMedGoogle Scholar
• Growcott EJ, Spink KG, Ren X, Afzal S, Banner KH, Wharton J. Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells. Respir. Res.7, 9 (2006).
   PubMed Web of Science ®Google Scholar
• Schreiber S, Keshavarzian A, Isaacs KL et al. A randomized, placebo-controlled, Phase II study of tetomilast in active ulcerative colitis. Gastroenterology132(1), 76–86 (2007).
   PubMed Web of Science ®Google Scholar
• Gottlieb AB, Strober B, Krueger JG et al. An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr. Med. Res. Opin.24(5), 1529–1538 (2008).
   PubMed Web of Science ®Google Scholar
• Rabe KF, Bateman ED, O’Donnell D, Witte S, Bredenbröker D, Bethke TD. Roflumilast – an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet366(9485), 563–571 (2005).
   PubMed Web of Science ®Google Scholar
• Hatzelmann A, Schudt C. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. J. Pharmacol. Exp. Ther.297(1), 267–279 (2001).
   PubMed Web of Science ®Google Scholar
• Jones NA, Boswell-Smith V, Lever R, Page P. The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro. Pulm. Pharmacol. Ther.18(2), 93–101 (2005).
   PubMed Web of Science ®Google Scholar
• Martorana PA, Beume R, Lucattelli M, Wollin L, Lungarella G. Roflumilast fully prevents emphysema in mice chronically exposed to cigarette smoke. Am. J. Respir. Crit. Care Med.172(7), 848–853 (2005).
   PubMed Web of Science ®Google Scholar
• Hohlfeld JM, Schoenfeld K, Lavae-Mokhtari M et al. Roflumilast attenuates pulmonary inflammation upon segmental endotoxin challenge in healthy subjects: a randomized placebo-controlled trial. Pulm. Pharmacol. Ther.21(4), 616–623 (2008).
   PubMed Web of Science ®Google Scholar
• Grootendorst DC, Gauw SA, Verhoosel RM et al. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax62(12), 1081–1087 (2007).
   PubMed Web of Science ®Google Scholar
• Wollin L, Bundschuh DS, Wohlsen A, Marx D, Beume R. Inhibition of airway hyperresponsiveness and pulmonary inflammation by roflumilast and other PDE4 inhibitors. Pulm. Pharmacol. Ther19(5), 343–352 (2006).
   PubMed Web of Science ®Google Scholar
• Rogers DF. Physiology of airway mucus secretion and pathophysiology of hypersecretion. Respir. Care52(9), 1134–1146 (2007).
   PubMed Web of Science ®Google Scholar
• Mata M, Sarria B, Buenestado A, Cortijo J, Cerda M, Morcillo EJ. Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells. Thorax60(2), 144–152 (2005).
   PubMed Web of Science ®Google Scholar
• Kwak HJ, Song JS, Heo JY, Yang SD, Nam JY, Cheon HG. Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-κB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation. J. Pharmacol. Exp. Ther.315(3), 1188–1195 (2005).
   PubMed Web of Science ®Google Scholar
• Kwak HJ, Park KM, Choi HE, Chung KS, Lim HJ, Park HY. PDE4 inhibitor, roflumilast protects cardiomyocytes against NO-induced apoptosis via activation of PKA and Epac dual pathways. Cell Signal.20(5), 803–814 (2008).
   PubMed Web of Science ®Google Scholar
• Sanz MJ, Cortijo J, Taha MA et al. Roflumilast inhibits leukocyte–endothelial cell interactions, expression of adhesion molecules and microvascular permeability. Br. J. Pharmacol.152(4), 481–492 (2007).
   PubMed Web of Science ®Google Scholar
• O’Brien KD, McDonald TO, Chait A, Allen MD, Alpers CE. Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation93(4), 672–682 (1996).
   PubMed Web of Science ®Google Scholar
• Constans J, Conri C. Circulating markers of endothelial function in cardiovascular disease. Clin. Chim. Acta368(1–2), 33–47 (2006).
   PubMed Web of Science ®Google Scholar
• Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory process in Type 2 diabetes: the role of cytokines. Ann. NY Acad. Sci.1084, 89–117 (2006).
   PubMed Web of Science ®Google Scholar
• Zhao YF, Feng DD, Chen C. Contribution of adipocyte-derived factors to β-cell dysfunction in diabetes. Int. J. Biochem. Cell Biol.38(5–6), 804–819 (2006).
   PubMed Web of Science ®Google Scholar
• Mundy GR. Osteoporosis and inflammation. Nutr. Rev.65(Suppl. 12, Pt 2), S147–S151 (2007).
   PubMed Web of Science ®Google Scholar
• Means RT Jr. Advances in the anemia of chronic disease. Int. J. Hematol.70(1), 7–12 (1999).
   PubMed Web of Science ®Google Scholar
• David M, Zech K, Seiberling M, Weimar C, Bethke TD. Roflumilast, a novel, oral, selective PDE4 inhibitor, shows high absolute bioavailability. J. Allergy Clin. Immunol.113(1), S220–S221 (2000).
   Google Scholar
• Nassr N, Lahu G, von Richter O et al. Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects. Br. J. Clin. Pharmacol.63(3), 365–370 (2007).
   PubMed Web of Science ®Google Scholar
• Bundschuh DS, Eltze M, Barsig J, Wollin L, Hatzelmann A, Beume R. In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor. J. Pharmacol. Exp. Ther.297(1), 280–290 (2001).
   PubMed Web of Science ®Google Scholar
• Nassr N, Lahu G, Hünnemeyer A et al. Magnesium hydroxide/aluminium hydroxide-containing antacid does not affect the pharmacokinetics of the targeted phosphodiesterase 4 inhibitor roflumilast. J. Clin. Pharmacol.47(5), 660–666 (2007).
   PubMed Web of Science ®Google Scholar
• Hauns B, Hermann R, Hünnemeyer A et al. Investigation of a potential food effect on the pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, in healthy subjects. J. Clin. Pharmacol.46(10), 1146–1153 (2006).
   PubMed Web of Science ®Google Scholar
• Böhmer GM, Hermann R, Hauns B et al. Dose-proportional intraindividual single- and repeated-dose pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor. J. Clin. Pharmacol.47(1), 26–36 (2007).
   PubMed Web of Science ®Google Scholar
• Hermann R, Siegmund W, Giessmann T et al. The oral, once-daily phosphodiesterase 4 inhibitor roflumilast lacks relevant pharmacokinetic interactions with inhaled budesonide. J. Clin. Pharmacol.47(8), 1005–1013 (2007).
   PubMed Web of Science ®Google Scholar
• von Richter O, Lahu G, Huennemeyer A, Herzog R, Zech K, Hermann R. Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. Clin. Pharmacokinet.46(7), 613–622 (2007).
   PubMed Web of Science ®Google Scholar
• Bethke TD, Giessmann T, Westphal K et al. Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant pharmacokinetic interactions with inhaled salbutamol when co-administered in healthy subjects. Int. J. Clin. Pharmacol. Ther.44(11), 572–579 (2006).
   PubMed Web of Science ®Google Scholar
• 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.176(2), 154–161 (2007).
   PubMed Web of Science ®Google Scholar
• Rutten-van Mölken MP, van Nooten FE, Lindemann M, Caeser M, Calverley PM. A 1-year prospective cost-effectiveness analysis of roflumilast for the treatment of patients with severe chronic obstructive pulmonary disease. Pharmacoeconomics25(8), 695–711 (2007).
   PubMed Web of Science ®Google Scholar
• Man SF, Sin DD. Effects of corticosteroids on systemic inflammation in chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc.2(1), 78–82 (2005).
   PubMedGoogle Scholar
• Sin DD, Man SF, Marciniuk DD et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.177(11), 1207–1214 (2008).
   PubMed Web of Science ®Google Scholar
• Powrie DJ, Wilkinson TM, Donaldson GC et al. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur. Respir. J.30(3), 472–478 (2007).
   PubMed Web of Science ®Google Scholar
• Boswell-Smith V, Cazzola M, Page CP. Are phosphodiesterase 4 inhibitors just more theophylline? J. Allergy Clin. Immunol.117(6), 1237–1243 (2006).
   PubMed Web of Science ®Google Scholar
• Heaney LG, Lindsay JT, McGarvey LP. Inflammation in chronic obstructive pulmonary disease: implications for new treatment strategies. Curr. Med. Chem.14(7), 787–796 (2007).
   PubMed Web of Science ®Google Scholar
• Calverley PM, Anderson JA, Celli B et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N. Engl. J. Med.356(8), 775–789 (2007).
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Calverley PM, Seemungal TA et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am. J. Respir. Crit. Care Med.177(1), 19–26 (2008).
   PubMed Web of Science ®Google Scholar
• Moita J, Bárbara C, Cardoso J et al. Tiotropium improves FEV1 in patients with COPD irrespective of smoking status. Pulm. Pharmacol. Ther.21(1), 146–151 (2008).
   PubMed Web of Science ®Google Scholar
• Cazzola M, Ciaprini C, Page CP, Matera MG. Targeting systemic inflammation: novel therapies for the treatment of chronic obstructive pulmonary disease. Expert Opin. Ther. Targets11(10), 1273–1286 (2007).
   PubMed Web of Science ®Google Scholar
• Maclay JD, McAllister DA, Macnee W. Cardiovascular risk in chronic obstructive pulmonary disease. Respirology12(5), 634–641 (2007).
   PubMed Web of Science ®Google Scholar
• Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur. Respir. J.28(6), 1245–1257 (2006).
   PubMed Web of Science ®Google Scholar
• Bailey WC, Tashkin DP. Pharmacologic therapy: novel approaches for chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc.4(7), 543–548 (2007).
   PubMedGoogle Scholar