Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

References

• Cazzola M Page CP Rogliani P Matera MG β2-agonist therapy in lung disease Am J Respir Crit Care Med 2013 187 7 690 696 23348973
   PubMed Web of Science ®Google Scholar
• Johnson M Effects of β2-agonists on resident and infiltrating inflammatory cells J Allergy Clin Immunol 2002 110 Suppl 6 S282 S290 12464937
   PubMedGoogle Scholar
• Bosmann M Grailer JJ Zhu K Anti-inflammatory effects of β2 adrenergic receptor agonists in experimental acute lung injury FASEB J 2012 26 4 2137 2144 22318967
   PubMed Web of Science ®Google Scholar
• Hoyle GW Mitigation of chlorine lung injury by increasing cAMP levels Proc Am Thorac Soc 2012 7 4 284 289 20601633
   PubMedGoogle Scholar
• Fuso L Mores N Valente S Malerba M Montuschi P Long-acting beta-agonists and their association with inhaled corticosteroids in COPD Curr Med Chem 2013 20 12 1477 1495 23409722
   PubMed Web of Science ®Google Scholar
• Naline E Trifilieff A Fairhurst RA Advenier C Molimard M Effect of indacaterol, a novel long-acting β2-agonist, on isolated human bronchi Eur Respir J 2007 29 3 575 581 17135231
   PubMed Web of Science ®Google Scholar
• Woo AY Wang TB Zeng X Stereochemistry of an agonist determines coupling preference of b2-adrenoceptor to different G proteins in cardiomyocytes Mol Pharmacol 2009 75 1 158 165 18838481
   PubMed Web of Science ®Google Scholar
• Malerba M Radaeli A Morjaria JB Therapeutic potential for novel ultra long-acting β2-agonists in the management of COPD: biological and pharmacological aspects Drug Discov Today 2012 17 9–10 496 504 22119310
   PubMed Web of Science ®Google Scholar
• Tamm M Richards DH Beghé B Fabbri L Inhaled corticosteroid and long-acting β2-agonist pharmacological profiles: effective asthma therapy in practice Respir Med 2012 106 Suppl 1 S9 S19 23273165
   PubMed Web of Science ®Google Scholar
• Yorgancioglu A Indacaterol in chronic obstructive pulmonary disease: an update for clinicians Ther Adv Chronic Dis 2012 3 1 25 36 23251766
   PubMedGoogle Scholar
• DrugBank 3 0: a comprehensive resource for ‘omics’ research on drugs Nucleic Acids Res 2011 39 Database issue D1035 D1041 21059682
   PubMed Web of Science ®Google Scholar
• De Coupade C Gear RW Dazin PF Sroussi HY Green PG Levine JD Beta 2-Adrenergic receptor regulation of human neutrophil function is sexually dimorphic Br J Pharmacol 2004 143 8 1033 1041 15477226
   PubMed Web of Science ®Google Scholar
• Liggett SB Identification and characterization of a homologous population of beta 2-adrenergic receptors on human alveolar macrophages Am Rev Respir Dis 1989 139 2 552 555 2563322
   PubMed Web of Science ®Google Scholar
• Lonati-Galligani M Pirke KM Beta 2-adrenergic receptor regulation in circulating mononuclear leukocytes in anorexia nervosa and bulimia Psychiatry Res 1986 19 3 189 198 3025906
   PubMed Web of Science ®Google Scholar
• Chong LK Chess-Williams R Peachell PT Pharmacological characterisation of the β-adrenoceptor expressed by human lung mast cells Eur J Pharmacol 2002 437 1–2 1 7 11864632
   PubMed Web of Science ®Google Scholar
• Abraham G Kneuer C Ehrhardt C Honscha W Ungemach FR Expression of functional beta2-adrenergic receptors in the lung epithelial cell lines 16HBE14o(-), Calu-3 and A549 Biochim Biophys Acta 2004 1691 2–3 169 179 15110997
   PubMed Web of Science ®Google Scholar
• Yukawa T Ukena D Kroegel C Beta2-adrenergic receptors on eosinophils: binding and functional studies Am J Resp Crit Care Med 1990 141 6 1446 1452
   Google Scholar
• Landmann R Beta-adrenergic receptors in human leukocyte subpopulations Eur J Clin Invest 1992 22 Suppl 1 30 36 1333965
   PubMed Web of Science ®Google Scholar
• Anstead MI Hunt TA Carlson SL Burki NK Variability of peripheral blood lymphocyte beta-2-adrenergic receptor density in humans Am J Crit Care Med 1998 157 3 Pt 1 990 992
   Web of Science ®Google Scholar
• Oppenheimer J Nelson HS Safety of long-acting β-agonists in asthma: a review Curr Opin Pulm Med 2008 14 1 64 69 18043277
   PubMed Web of Science ®Google Scholar
• Rogers L Reibman J Stepping down asthma treatment: how and when Curr Opin Pulm Med 2012 18 1 70 75 22081088
   PubMed Web of Science ®Google Scholar
• Antoniu SA Effects of inhaled therapy on biomarkers of systemic inflammation in stable chronic obstructive pulmonary disease Biomarkers 2010 15 2 97 103 19929747
   PubMed Web of Science ®Google Scholar
• Taylor DR The beta-agonist saga and its clinical relevance: on and on it goes Am J Respir Crit Care Med 2009 179 11 976 978 19286624
   PubMed Web of Science ®Google Scholar
• Nelson HS Weiss ST Bleecker ER Yancey SW Dorinsky PM SMART Study Group The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol Chest 2006 129 1 15 26 16424409
   PubMed Web of Science ®Google Scholar
• Calverley PM Anderson JA Celli B Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease N Engl J Med 2007 356 8 775 789 17314337
   PubMed Web of Science ®Google Scholar
• Chung KF Caramori G Adcock IM Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future Eur J Clin Pharmacol 2009 65 9 853 871 19557399
   PubMed Web of Science ®Google Scholar
• Jarjour NN Wilson SJ Koenig SM Control of airway inflammation maintained at a lower steroid dose with 100/50 microg of fluticasone propionate/salmeterol J Allergy Clin Immunol 2006 118 1 44 52 16815137
   PubMed Web of Science ®Google Scholar
• Welte T Optimising treatment for COPD – new strategies for combination therapy Int J Clin Prac 2009 63 8 1136 1149
   PubMed Web of Science ®Google Scholar
• King P Role of arformoterol in the management of COPD Int JCOPD 2008 3 3 385 391
   Google Scholar
• Sin DD Man P Marciniuk DD The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease Am J Respir Crit Care Med 2008 177 11 1207 1214 18310480
   PubMed Web of Science ®Google Scholar
• Hanania NA The impact of inhaled corticosteroid and long acting β-agonist combination therapy on outcomes in COPD Pulm Pharmacol Therap 2008 21 3 540 550 18280761
   PubMed Web of Science ®Google Scholar
• Pandya CM Soubani AO Bronchiolitis obliterans following hematopoietic stem cell transplantation: a clinical update Clin Transplant 2012 24 3 291 306 19849704
   PubMed Web of Science ®Google Scholar
• Hildebrandt GC Fazekas T Lawitschka A Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD Bone Marrow Transplant 2011 46 10 1283 1295 21441964
   PubMed Web of Science ®Google Scholar
• Papazian L Con: β2-Adrenergic agonists in ALI-ARDS – not recommended or potentially harmful? Am J Resp Crit Care Med 2011 184 5 504 506 21885635
   PubMed Web of Science ®Google Scholar
• Roca O Gómez-Ollés S Cruz M-J Huñuz X Griffiths MJD Mascians JR Effects of salbutamol on exhaled breath condensate biomarkers in acute lung injury: prospective analysis Crit Care 2008 12 3 R72 18513388
   PubMed Web of Science ®Google Scholar
• National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury Am J Respir Crit Care 2011 184 5 561 568
   PubMed Web of Science ®Google Scholar
• Gao Smith F Perkins GD Gates S Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial Lancet 2012 379 9812 229 235 22166903
   PubMed Web of Science ®Google Scholar
• Barnes PJ Effect of β-agonists on inflammatory cells J Allergy Clin Immunol 1999 104 2 Pt 2 S10 S17 10452784
   PubMed Web of Science ®Google Scholar
• Hanania NA Moore RH Anti-inflammatory activities of beta 2-agonists Curr Drug Targets Inflamm Allergy 2004 3 3 271 277 15379595
   PubMedGoogle Scholar
• Anderson R Goolam Mahomed A Theron AJ Ramafi G Feldman C Effect of rolipram and dibutyryl cyclic AMP on resequestration of cytosolic calcium in FMLP-activated human neutrophils Br J Pharmacol 1998 124 3 547 555 9647480
   PubMed Web of Science ®Google Scholar
• Anderson R Visser SS Ramafi G Theron AJ Accelerated resequestration of cytosolic calcium and suppression of the pro-inflammatory activities of human neutrophils by CGS 21680 in vitro Br J Pharmacol 2000 130 4 717 724 10864876
   PubMed Web of Science ®Google Scholar
• Tintinger GR Steel HC Theron AJ Anderson R Pharmacological control of neutrophil-mediated inflammation: Strategies targeting calcium handling by activated polymorphonuclear leukocytes Drug Des Dev Ther 2009 2 95 104
   Google Scholar
• Gravett CM Theron AJ Steel HC Interactive inhibitory effects of formoterol and montelukast on activated human neutrophils Eur Respir J 2010 36 6 1417 1424 20413544
   PubMed Web of Science ®Google Scholar
• Ali H Sozzani S Fisher I Differential regulation of formyl peptide and platelet-activating factor receptors. Role of phospholipase Cβ3 phosphorylation by protein kinase A J Biol Chem 1998 273 18 11012 11016 9556582
   PubMed Web of Science ®Google Scholar
• Bai Y Sanderson MJ Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMPmediated inhibition of the IP3 receptor Respir Res 2006 7 34 16504084
   PubMed Web of Science ®Google Scholar
• Ay B Iyanoye A Sieck GC Prakash YS Pabelick CM Cyclic nucleotide regulation of store-operated Ca2+ influx in airway smooth muscle Am J Physiol Lung Cell Mol Physiol 2006 290 2 L278 L283 16155088
   PubMed Web of Science ®Google Scholar
• Flamand N Surette ME Picard S Bourgoin S Borgeat P Cyclic AMP-mediated inhibition of 5-lipoxygenase translocation and leukotriene biosynthesis in human neutrophils Mol Pharmacol 2002 62 2 250 256 12130675
   PubMed Web of Science ®Google Scholar
• Luo M Jones SM Flamand N Aronoff DM Peters-Golden M Brock TG Phosphorylation by protein kinase A inhibits nuclear import of 5-lipoxygenase J Biol Chem 2005 280 49 40609 40616 16230355
   PubMed Web of Science ®Google Scholar
• Iannnone MA Wolberg G Zimmerman TP Chemotactic peptide induces cAMP elevation in human neutrophils by amplification of the adenylate cyclase response to endogenously produced adenosine J Biol Chem 1989 264 34 20177 20180 2555342
   PubMed Web of Science ®Google Scholar
• Theron AJ Steel HC Tintinger GR Anderson R Endogenous adenosine regulates neutrophil pro-inflammatory activities by cyclic AMP-dependent accelerated clearance of cytosolic calcium Inflamm Res 2002 51 12 594 602 12558193
   PubMed Web of Science ®Google Scholar
• Parry GCN Mackman N Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-κB-mediated transcription J Immunol 1997 159 11 5450 5456 9548485
   PubMed Web of Science ®Google Scholar
• Tacon CR Newton R Proud D Leigh R Rhinovirus-induced MMP-9 expression is dependent on Fra-1, which is modulated by formoterol and dexamethasone J Immunol 2012 188 9 4621 4630 22461694
   PubMed Web of Science ®Google Scholar
• Cobelens PM Kavelaars A Vroon A The β2-adrenergic agonist salbutamol potentiates oral induction of tolerance, suppressing adjuvant arthritis and antigen-specific immunity J Immunol 2002 169 9 5028 5035 12391218
   PubMed Web of Science ®Google Scholar
• Park PH Huang H McMullen MR Bryan K Nagy LE Activation of cyclic-AMP response element binding protein contributes to adiponectin-stimulated interleukin-10 expression in RAW 264–267 macrophages J Leukoc Biol 2008 83 5 1258 1266 18263767
   PubMed Web of Science ®Google Scholar
• Alvarez Y Municio C Alonso S Sánchez Crespo M Fernández N The induction of IL-10 by zymosan in dendritic cells depends on CREB activation by the coactivators CREB-binding protein and TORC2 and autocrine PGE2 J Immunol 2009 183 2 1471 1479 19564345
   PubMed Web of Science ®Google Scholar
• Avni D Ernst O Philosoph A Zor T Role of CREB in modulation of TNFα and IL-10 expression in LPS-stimulated RAW264.7 macrophages Mol Immunol 2010 47 7–8 1396 1403 20303596
   PubMed Web of Science ®Google Scholar
• Tamassia N Zimmermann M Castellucci M Cutting edge: An inactive chromatin configuration at the IL-10 locus in human neutrophils J Immunol 2013 190 5 1921 1925 23355741
   PubMed Web of Science ®Google Scholar
• Giembycz MA Kaur M Leigh R Newton R A holy grail of asthma management: toward understanding how long-acting β2-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids Br J Pharmacol 2008 153 6 1090 1104 18071293
   PubMed Web of Science ®Google Scholar
• Ismaili N Garabedian MJ Modulation of glucocorticoid receptor function via phosphorylation Ann NY Acad Sci 2004 1024 86 101 15265775
   PubMed Web of Science ®Google Scholar
• Kumar R Calhoun WJ Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation Biologics 2008 2 4 845 854 19707462
   PubMedGoogle Scholar
• Haske T Nakao M Moudgil VK Phosphorylation of immunopurified rat liver glucocorticoid receptor by the catalytic subunit of cAMP-dependent protein kinase Mol Cell Biochem 1994 132 2 163 171 7969099
   PubMed Web of Science ®Google Scholar
• Peñuelas I Encío IJ López-Moratalla N Santiago E cAMP activates transcription of the human glucocorticoid receptor gene promoter J Steroid Biochem Mol Biol 1998 67 2 89 94 9877208
   PubMed Web of Science ®Google Scholar
• Eickelberg O Roth M Lörx R Ligand-independent activation of the glucocorticoid receptor by beta2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells J Biol Chem 1999 274 2 1005 1010 9873044
   PubMed Web of Science ®Google Scholar
• Roth M Johnson PR Rüdiger JJ Interaction between glucocorticoids and β2 agonists on bronchial airway smooth muscle cells through synchronised cellular signalling Lancet 2002 360 9342 1293 1299 12414205
   PubMed Web of Science ®Google Scholar
• Usmani OS Ito K Maneechotesuwan K Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy Am J Respir Crit Care Med 2005 172 6 704 712 15860753
   PubMed Web of Science ®Google Scholar
• Kaur M Chivers JE Giembycz MA Newton R Long-acting β2-adrenoceptor agonists synergistically enhance glucocorticoid-dependent transcription in human airway epithelial and smooth muscle cells Mol Pharmacol 2008 73 1 203 214 17901197
   PubMed Web of Science ®Google Scholar
• Anacker C Zunszain PA Cattaneo A Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor Mol Psych 2011 16 7 738 750
   PubMed Web of Science ®Google Scholar
• Pace TW Hu F Miller AH Activation of cAMP-protein kinase A abrogates STAT5-mediated inhibition of glucocorticoid receptor signaling by interferon-alpha Brain Behav Immun 2011 25 8 1716 1724 21798341
   PubMed Web of Science ®Google Scholar
• Barnes PJ Severe asthma: Advances in current management and future therapy J Allergy Clin Immunol 2012 129 1 48 59 22196524
   PubMed Web of Science ®Google Scholar
• Perng DW Su KC Chou KT Long-acting β2 agonists and corticosteroids restore the reduction of histone deacetylase activity and inhibit H2O2-induced mediator release from alveolar macrophages Pulm Pharmacol Ther 2012 25 4 312 318 22546485
   PubMed Web of Science ®Google Scholar
• Rossios C To Y Osoata G Ito M Barnes PJ Ito K Corticosteroid insensitivity is reversed by formoterol via phosphoinositide-3-kinase inhibition Br J Pharmacol 2012 167 4 775 786 22251095
   PubMed Web of Science ®Google Scholar
• Ohnishi H Miyahara N Gelfand EW The role of Leukotriene B4 in allergic diseases Allergol Int 2008 57 4 291 298 18797182
   PubMedGoogle Scholar
• Black JL Oliver BGG Roth M Molecular mechanisms of combination therapy with inhaled corticosteroids and long-acting β-agonists Chest 2009 136 4 1095 1100 19809050
   PubMed Web of Science ®Google Scholar
• Mercado N Hakim A Kobayashi Y Restoration of corticosteroid sensitivity by p38 mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma PLoS One 2012 7 7 e41582 22911818
   PubMed Web of Science ®Google Scholar
• Bos JL Epac proteins: multi-purpose cAMP targets Trends Biochem Sci 2006 31 12 680 686 17084085
   PubMed Web of Science ®Google Scholar
• Misra UK Kaczowka S Pizzo SV The cAMP-activated GTP exchange factor, Epac1 upregulates plasma membrane and nuclear Akt kinase activities in 8-CPT-2-O-Me-cAMP-stimulated macrophages: Gene silencing of the cAMP-activated GTP exchange Epac1 prevents 8-CPT-2-O-Me-cAMP activation of Akt activity in macrophages Cell Signal 2008 20 8 1459 1470 18495429
   PubMed Web of Science ®Google Scholar
• Liu J Zhao X Cao J Differential roles of PKA and Epac on the production of cytokines in the endotoxin-stimulated primary cultured microglia J Mol Neurosci 2011 45 2 186 193 20640531
   PubMed Web of Science ®Google Scholar
• Lovén J Svitacheva N Jerre A Miller-Larsson A Korn SH Anti-inflammatory activity of beta 2-agonists in primary lung epithelial cells is independent of glucocorticoid receptor Eur Respir J 2007 30 5 848 856 17596271
   PubMed Web of Science ®Google Scholar
• Donnelly LE Tudhope SJ Fenwick PS Barnes PJ Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages Eur Respir J 2010 36 1 178 186 19926732
   PubMed Web of Science ®Google Scholar
• Kobayashi Y Mercado N Miller-Larsson A Barnes PJ Ito K Increased corticosteroid sensitivity by a long acting β2 agonist formoterol via β2 adrenoceptor independent protein phosphatase 2A activation Pulm Pharmacol Ther 2012 25 3 201 207 22401993
   PubMed Web of Science ®Google Scholar
• Matthay MA Thompson BT Brower R Inflammation-induced desensitization of β-receptors in acute lung injury Am J Respir Crit Care Med 2012 185 8 894 895 22505755
   PubMed Web of Science ®Google Scholar
• Finney PA Belvisi MG Donnelly LE Albuterol-induced downregulation of Gsalpha accounts for pulmonary β2-adrenoceptor desensitization in vivo J Clin Invest 2000 106 1 125 135 10880056
   PubMed Web of Science ®Google Scholar
• Barnes PJ Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease J Allergy Clin Immunol 2013 131 3 636 645 23360759
   PubMed Web of Science ®Google Scholar
• Hu A Nino G Grunstein JS Fatma S Grunstein MM Prolonged heterologous β2-adrenoceptor desensitization promotes proasthmatic airway smooth muscle function via PKA/ERK1/2-mediated phosphodiesterase-4 induction Am J Physiol Lung Cell Mol Physiol 2008 294 6 L1055 L1067 18359889
   PubMed Web of Science ®Google Scholar
• Su Y Jackson EK Gorelik E Receptor desensitization and blockade of the suppressive effects of prostaglandin E2 and adenosine on the cytotoxic activity of human melanoma-infiltrating T lymphocytes Cancer Immunol Immunother 2011 60 1 111 122 20960188
   PubMed Web of Science ®Google Scholar
• Fogli S Stefanelli Martelli A Protective effect of high-dose montelukast on salbutamol-induced homologous desensitisation in airway smooth muscle Pulm Pharmacol Ther 2013 pii S1094-5539(13)00136-3
   Web of Science ®Google Scholar
• Pauwels RA Löfdahl CG Postma DS Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group N Engl J Med 1997 337 20 1405 1411 9358137
   PubMed Web of Science ®Google Scholar
• Donohue JF Combination therapy for chronic obstructive pulmonary disease: clinical aspects Proc Am Thorac Soc 2005 2 4 272 281 16267348
   PubMedGoogle Scholar
• Loukides S Bartziokas K Vestbo J Singh D Novel Anti-inflammatory agents in COPD: Targeting lung and systemic inflammation Curr Drug Targets 2013 14 2 235 245 23256720
   PubMed Web of Science ®Google Scholar
• Page CP Spina D Selective PDE inhibitors as novel treatments for respiratory diseases Curr Opin Pharmacol 2012 12 3 275 286 22497841
   PubMed Web of Science ®Google Scholar
• Moodley T Wilson S Joshi T Phosphodiesterase 4 inhibitors augment the ability of formoterol to enhance glucocorticoid-dependent gene transcription in human airway epithelial cells: A novel mechanism for the clinical efficacy of roflumilast in severe COPD Mol Pharmacol 2013 83 4 894 906 23389862
   PubMed Web of Science ®Google Scholar
• Anonymous Roflumilast: doubtful efficacy but clear harms in COPD Prescrire Int 2013 22 134 5 9 23367674
   PubMedGoogle Scholar
• Tintinger GR Feldman C Theron AJ Anderson R Montelukast: More than a cysteinyl leukotriene receptor agonist? Sci World J 2010 10 2403 2413
   Web of Science ®Google Scholar
• Anderson R Theron AJ Gravett CM Steel HC Tintinger GR Feldman C Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism Br J Pharmacol 2009 156 1 105 115 19068077
   PubMed Web of Science ®Google Scholar
• Keith PK Koch C Djandji M Montelukast as add-on therapy with inhaled corticosteroids alone or inhaled corticosteroids and long-acting beta-2-agonists in the management of patients diagnosed with asthma and concurrent allergic rhinitis (the RADAR trial) Can Respir J 2009 16 Suppl A 17A 31A
   PubMedGoogle Scholar
• Korn D Van den Brande P Potvin E Dramaix M Herbots E Peché R Efficacy of add-on montelukast in patients with non-controlled asthma: a Belgian open-label study Curr Med Res Opin 2009 25 2 489 497 19192994
   PubMed Web of Science ®Google Scholar
• Bjerg A Lundbäck B Lötvall J The future of combining inhaled drugs for COPD Curr Opin Pharmacol 2012 12 3 252 255 22465638
   PubMed Web of Science ®Google Scholar
• Calverley PM Boonsawat W Cseke Z Zhong N Peterson S Olsson H Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease Eur Respir J 2003 22 6 912 919 14680078
   PubMed Web of Science ®Google Scholar
• Kornmann O Dahl R Centanni S Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison Eur Respir J 2011 37 2 273 279 20693243
   PubMed Web of Science ®Google Scholar
• Szafranski W Cukier A Ramirez A Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease Eur Respir J 2003 21 1 74 81 12570112
   PubMed Web of Science ®Google Scholar
• Campbell M Eliraz A Johansson G Formoterol for maintenance and as-needed treatment of chronic obstructive pulmonary disease Respir Med 2005 99 12 1511 1520 16199148
   PubMed Web of Science ®Google Scholar
• Tashkin DP Rennard SI Martin P Efficacy and safety of budesonide and formoterol in one pressurized metered-dose inhaler in patients with moderate to very severe chronic obstructive pulmonary disease: results of a 6-month randomized clinical trial Drugs 2008 68 14 1975 2000 18778120
   PubMed Web of Science ®Google Scholar
• Tashkin DP Doherty DE Kerwin E Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial Int J Chron Obstruct Pulmon Dis 2012 7 43 55 22334768
   PubMed Web of Science ®Google Scholar
• Mahler DA Wire P Horstman D Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease Am J Respir Crit Care Med 2002 166 8 1084 1091 12379552
   PubMed Web of Science ®Google Scholar
• Chapman KR Arvidsson P Chuchalin AG The addition of salmeterol 50 microg bid to anticholinergic treatment in patients with COPD: a randomized, placebo controlled trial. Chronic obstructive pulmonary disease Can Respir J 2002 9 3 178 185 12068339
   PubMedGoogle Scholar
• Calverley P Pauwels R Vestbo J Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial Lancet 2003 361 9356 449 456 12583942
   PubMed Web of Science ®Google Scholar
• Brusasco V Hodder R Miravitlles M Korducki L Towse L Kesten S Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD Thorax 2003 58 5 399 404 12728159
   PubMed Web of Science ®Google Scholar
• Hanania NA Darken P Horstman D The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD Chest 2003 124 3 834 843 12970006
   PubMed Web of Science ®Google Scholar
• Stockley RA Chopra N Rice L Addition of salmeterol to existing treatment in patients with COPD: a 12 month study Thorax 2006 61 2 122 128 16443706
   PubMed Web of Science ®Google Scholar
• Donohue JF van Noord JA Bateman ED A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol Chest 2002 122 1 47 55 12114338
   PubMed Web of Science ®Google Scholar
• Decramer ML Hanania NA Lötvall JO Yawn BP The safety of long-acting beta2-agonists in the treatment of stable chronic obstructive pulmonary disease Int J Chron Obstruct Pulmon Dis 2013 8 53 64 23378756
   PubMed Web of Science ®Google Scholar
• Vogelmeier C Hederer B Glaab T Tiotropium versus salmeterol for the prevention of exacerbations of COPD N Engl J Med 2011 364 12 1093 1103 21428765
   PubMed Web of Science ®Google Scholar
• Wedzicha JA Calverley PM Seemungal TA The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide Am J Respir Crit Care Med 2008 177 1 19 26 17916806
   PubMed Web of Science ®Google Scholar
• Larsson K Janson C Lisspers K Combination of budesonide/formoterol more effective than fluticasone/salmeterol in preventing exacerbations in chronic obstructive pulmonary disease: the PATHOS study J Intern Med 2013 273 6 584 594 23495860
   PubMed Web of Science ®Google Scholar
• Niewoehner DE Rice K Cote C Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial Ann Intern Med 2005 143 5 317 326 16144890
   PubMed Web of Science ®Google Scholar
• Dusser D Bravo ML Iacono P The effect of tiotropium on exacerbations and airflow in patients with COPD Eur Respir J 2006 27 3 547 555 16507855
   PubMed Web of Science ®Google Scholar
• Powrie DJ Wilkinson TM Donaldson GC Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD Eur Respir J 2007 30 3 472 478 17504798
   PubMed Web of Science ®Google Scholar
• Chan CK Maltais F Sigouin C Haddon JM Ford GT SAFE Study Group A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease Can Respir J 2007 14 8 465 472 18060091
   PubMed Web of Science ®Google Scholar
• Casaburi R Mahler DA Jones PW A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease Eur Respir J 2002 19 2 217 224 11866001
   PubMed Web of Science ®Google Scholar
• Cazzola M Tashkin DP Combination of formoterol and tiotropium in the treatment of COPD: effects on lung function COPD 2009 6 5 405 415
   Google Scholar
• van Noord JA Aumann JL Janssens E Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD Eur Respir J 2005 26 2 214 222 16055868
   PubMed Web of Science ®Google Scholar
• van Noord JA Aumann JL Janssens E Effects of tiotropium with and without formoterol on airflow obstruction and resting hyper-inflation in patients with COPD Chest 2006 129 3 509 517 16537846
   PubMed Web of Science ®Google Scholar
• Tashkin DP Pearle J Iazzoni D Varghese ST Formoterol and tiotropium compared with tiotropium alone for COPD COPD 2009 6 1 17 25 19229704
   PubMedGoogle Scholar
• Tashkin DP Littner M Andrews CP Tomlinson L Rinehart M Denis-Mize K Concomitant treatment with nebulized formoterol and tiotropium in subjects with COPD: a placebo-controlled trial Respir Med 2008 102 4 479 487 18258423
   PubMed Web of Science ®Google Scholar
• Cazzola M Di Marco F Santus P The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD Pulm Pharmacol Ther 2004 17 1 35 39 14643169
   PubMed Web of Science ®Google Scholar
• Aaron S Vandemheen KL Fergusson D Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial Ann Intern Med 2007 146 8 545 555 17310045
   PubMed Web of Science ®Google Scholar
• Cazzola M Molimard M The scientific rationale for combining long-acting beta2-agonists and muscarinic antagonists in COPD Pulm Pharmacol Ther 2010 23 4 257 267 20381630
   PubMed Web of Science ®Google Scholar
• Short PM Williamson PA Elder DHJ Lipworth SI Schembri S Lipworth BJ The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting β-agonist therapy in COPD Chest 2012 141 1 81 86 21799028
   PubMed Web of Science ®Google Scholar
• Rossi A Polese G Indacaterol: a comprehensive review Int J Chron Obstruct Pulmon Dis 2013 8 353 363 23922496
   PubMed Web of Science ®Google Scholar
• Wollin L Pieper MP Tiotropium bromide exerts ant-inflammatory activity in a cigarette smoke mouse model of COPD Pulm Pharmacol Ther 2010 23 4 345 354 20362689
   PubMed Web of Science ®Google Scholar
• Karner C Cates CJ The effect of adding inhaled corticosteroids to tiotropium and long-acting beta2-agonists for chronic obstructive pulmonary disease Cochrane Database Syst Rev 2011 9 CD009039 21901729
   PubMed Web of Science ®Google Scholar
• Karner C Cates CJ Long-acting beta2-agonists in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease Cochrane Database Syst Rev 2012 4 CD008989 22513969
   PubMed Web of Science ®Google Scholar
• Mahler DA D’Urzo A Bateman ED Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison Thorax 2012 67 9 781 788 22544891
   PubMed Web of Science ®Google Scholar
• Profita M Bonanno A Montalbano AM β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD Biochim Biophys Acta 2012 1822 7 1079 1089 22440430
   PubMed Web of Science ®Google Scholar
• Kerstjens HA Disse B Schröder-Babo W Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial J Allergy Clin Immunol 2011 128 2 308 314 21636120
   PubMed Web of Science ®Google Scholar
• Bateman ED Kornmann O Ambery C Pharmacodynamics of GSK961081, a bi-functional molecule, in patients with COPD Pulm Pharmacol Ther 2013 26 5 581 587 23538170
   PubMed Web of Science ®Google Scholar
• Sears MR The FDA-mandated trial of safety of long-acting beta-agonists in asthma: finality or frutility? Thorax 2013 68 2 195 198 22858928
   PubMed Web of Science ®Google Scholar