478
Views
8
CrossRef citations to date
0
Altmetric
Review

Treatment options for moderate-to-very severe chronic obstructive pulmonary disease

, , &
Pages 977-988 | Received 07 Jan 2016, Accepted 15 Feb 2016, Published online: 21 Mar 2016

References

  • National Institute for Health and Clinical Excellence. Chronic obstructive pulmonary disease. NICE Guideline (Update) Consultation. London: National Institute for Health and Clinical Excellence; 2010.
  • Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155:179–191.
  • Miravitlles M, Soler-Cataluna JJ, Calle M, et al. Guia Espanola de la EPOC (GesEPOC). Tratamiento farmacologico de la EPOC estable. Arch Bronconeumol. 2012;48:247–257.
  • Koblizek V, Chlumsky J, Zindr V, et al. Chronic obstructive pulmonary disease: official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013;157:189–201.
  • Vestbo J, Hurd SS, Agustı´ AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187:347–365.
  • Khan JH, Lababidi HM, Al-Moamary MS, et al. The Saudi guidelines for the diagnosis and management of COPD. Ann Thorac Med. 2014;9:55–76.
  • Montes De Oca M, López VMV, Acuña A, et al. ALAT-2014 chronic obstructive pulmonary disease (COPD) clinical practice guidelines: questions and answers. Arch Bronconeumol. 2015;51:403–416.
  • Kankaanranta H, Harju T, Kilpeläinen M, et al. Diagnosis and pharmacotherapy of stable chronic obstructive pulmonary disease: the finnish guidelines. Basic Clin Pharmacol Toxicol. 2015;116:291–307.
  • Cazzola M, Page C. Long-acting bronchodilators in COPD: where are we now and where are we going? Breathe. 2014;10:110–112.
  • Patalano F, Banerji D, D’Andrea P, et al. Addressing unmet needs in the treatment of COPD. Eur Respir Rev. 2014;23:333–344.
  • Calverley PM. COPD: what is the unmet need? Br J Pharmacol. 2008;155:487–493.
  • Cazzola M, Matera MG. Bronchodilators: current and future. Clin Chest Med. 2014;35:191–201.
  • Cazzola M, Beeh KM, Price D, et al. Assessing the clinical value of fast onset and sustained duration of action of long-acting bronchodilators for COPD. Pulm Pharmacol Ther. 2015;31:68–78.
  • Ágh T, Inotai A, Mészáros Á. Factors associated with medication adherence in patients with chronic obstructive pulmonary disease. Respiration. 2011;82:328–334.
  • Price D, Lee AJ, Sims EJ, et al. Characteristics of patients preferring once-daily controller therapy for asthma and COPD: a retrospective cohort study. Prim Care Respir J. 2013;22:161–168.
  • Cazzola M, Bardaro F, Stirpe E. The role of indacaterol for chronic obstructive pulmonary disease (COPD). J Thorac Dis. 2013;5:559–566.
  • Matera MG, Rogliani P, Cazzola M. Indacaterol for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2015;16:107–115.
  • Geake JB, Dabscheck EJ, Wood-Baker R, et al. Indacaterol, a once-daily beta2-agonist, versus twice-daily beta₂-agonists or placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015;1:CD010139.
  • Matera MG, Ora J, Cazzola M. Differential pharmacology and clinical utility of long-acting bronchodilators in COPD - focus on olodaterol. Ther Clin Risk Manag. 2015;11:1805–1811.
  • Chaplin S. Striverdi respimat: once daily LABA for COPD. Prescriber. 2015;26:25–26.
  • Keating GM. Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease. Drugs. 2012;72:273–300.
  • Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;7:CD009285.
  • Cazzola M, Page C, Matera MG. Long-acting muscarinic receptor antagonists for the treatment of respiratory disease. Pulm Pharmacol Ther. 2013;26:307–317.
  • Matera MG, Rogliani P, Cazzola M. Muscarinic receptor antagonists for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2014;15:961–977.
  • Cazzola M, Page CP, Matera MG. Aclidinium bromide for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2013;14:1205–1214.
  • Ni H, Soe Z, Moe S. Aclidinium bromide for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;9:CD010509.
  • Lopez-Campos JL, Calero C, Lopez-Ramirez C, et al. Patient-reported outcomes and considerations in the management of COPD: focus on aclidinium. Patient Prefer Adherence. 2015;9:95–104.
  • Rogliani P, Calzetta L, Ora J, et al. Pharmacological assessment of the onset of action of aclidinium and glycopyrronium versus tiotropium in COPD patients and human isolated bronchi. Eur J Pharmacol. 2015;761:383–390.
  • Buhl R, Banerji D. Profile of glycopyrronium for once-daily treatment of moderate-to-severe COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:729–741.
  • Carter NJ. Inhaled glycopyrronium bromide: a review of its use in patients with moderate to severe chronic obstructive pulmonary disease. Drugs. 2013;73:741–753.
  • Trivedi R, Richard N, Mehta R, et al. Umeclidinium in patients with COPD: a randomised, placebo-controlled study. Eur Respir J. 2014;43:72–81.
  • Manickam R, Asija A, Aronow WS. Umeclidinium for treating COPD: an evaluation of pharmacologic properties, safety and clinical use. Expert Opin Drug Saf. 2014;13:1555–1561.
  • Segreti A, Calzetta L, Rogliani P, et al. Umeclidinium for the treatment of chronic obstructive pulmonary disease. Expert Rev Respir Med. 2014;8:665–671.
  • Tal-Singer R, Cahn A, Mehta R, et al. Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies. Eur J Pharmacol. 2013;701:40–48.
  • Van Der Molen T, Cazzola M. Beyond lung function in COPD management: effectiveness of LABA/LAMA combination therapy on patient-centred outcomes. Prim Care Respir J. 2012;21:101–108.
  • Calzetta L, Matera MG, Cazzola M. Pharmacological interaction between LABAs and LAMAs in the airways: optimizing synergy. Eur J Pharmacol. 2015;761:168–173.
  • Cazzola M, Calzetta L, Page CP, et al. Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi. Eur J Pharmacol. 2014;745:135–143.
  • Cazzola M, Calzetta L, Segreti A, et al. Translational study searching for synergy between glycopyrronium and indacaterol. Copd. 2015;12:175–181.
  • Matera MG, Rogliani P, Cazzola M. QVA149 (indacaterol/glycopyrronium) for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother. 2015;16:1079–1090.
  • Matera MG, Rogliani P, Rinaldi B, et al. Umeclidinium bromide + vilanterol for the treatment of chronic obstructive pulmonary disease. Expert Rev Clin Pharmacol. 2015;8:35–41.
  • Rodrigo GJ, Neffen H. A systematic review of the efficacy and safety of a fixed-dose combination of umeclidinium and vilanterol for the treatment of COPD. Chest. 2015;148:397–407.
  • Cazzola M, Rogliani P, Ora J, et al. Olodaterol + tiotropium bromide for the treatment of chronic obstructive pulmonary disease. Expert Rev Clin Pharmacol. 2015;8:529–539.
  • Dhillon S. Tiotropium/olodaterol: A review in COPD. Drugs. 2016;76:135–146.
  • Cazzola M, Calzetta L, Matera MG. Aclidinium/formoterol fixed-dose combination for the treatment of chronic obstructive pulmonary disease. Drugs Today (Barc). 2015;51:97–105.
  • Matera MG, Sanduzzi A, Cazzola M. Specific role of combination aclidinium: formoterol in the treatment of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2016;11:73–79.
  • D’Urzo T, Donohue JF, Price D, et al. Dual bronchodilator therapy with aclidinium bromide/formoterol fumarate for chronic obstructive pulmonary disease. Expert Rev Respir Med. 2015;9:519–532.
  • Cazzola M, Page CP, Calzetta L, et al. Emerging anti-inflammatory strategies for COPD. Eur Respir J. 2012;40:724–741.
  • Hanania NA, Ambrosino N, Calverley P, et al. Treatments for COPD. Respir Med. 2005;99(Suppl B):S28–40.
  • Calverley PM, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J. 2003;22:912–919.
  • Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–789.
  • Kardos P, Wencker M, Glaab T, et al. Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severechronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175:144–149.
  • Sobieraj DM, White CM, Coleman CI. Benefits and risks of adjunctive inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis. Clin Ther. 2008;30:1416–1425.
  • Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta2-agonist in one inhaler versus long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;9:CD006829.
  • Singh D, Nicolini G, Bindi E, et al. Extrafine beclomethasone/formoterol compared to fluticasone/salmeterol combination therapy in COPD. BMC Pulm Med. 2014;14:43.
  • Wedzicha JA, Singh D, Vestbo J, et al. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014;108:1153–1162.
  • Dransfield MT, Bourbeau J, Jones PW, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013;1:210–223.
  • Agustì A, De Teresa L, De Backer W, et al. A comparison of the efficacy and safety of once-daily fluticasone furoate/vilanterol with twice-daily fluticasone propionate/salmeterol in moderate to very severe COPD. Eur Respir J. 2014;43:763–767.
  • Dransfield MT, Feldman G, Korenblat P, et al. Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients. Respir Med. 2014;108:1171–1179.
  • Rogliani P, Matera MG, Cazzola M. Fluticasone furoate/vilanterol combination for the treatment of COPD and asthma. Drugs Today (Barc). 2015;51:469–478.
  • Kling J SUMMIT: no mortality benefit to Breo in COPD. [ cited 2016 Feb 13]. Available from: http://www.medscape.com/viewarticle/850900
  • Matera MG, Cardaci V, Cazzola M, et al. Safety of inhaled corticosteroids for treating chronic obstructive pulmonary disease. Expert Opin Drug Saf. 2015;14:533–541.
  • Suissa S, Patenaude V, Lapi F, et al. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68:1029–1036.
  • Suissa S, Coulombe J, Ernst P. Discontinuation of inhaled corticosteroids in COPD and the risk reduction of pneumonia. Chest. 2015;148:1177–1183.
  • Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of COPD (Updated 2016). [ cited 2016 Jan 2nd]. Available from: http://www.goldcopd.org/uploads/users/files/GOLD_Report%202016.pdf
  • Kerwin E, Siler T, Tombs L, et al. Triple therapy of umeclidinium and inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) vs placebo + ICS/LABA in GOLD D patients [abstract]. Eur Respir J. 2015;46(suppl 59):PA1490.
  • Vestbo J, Vogelmeier C, Small M, et al. Understanding the GOLD 2011 Strategy as applied to a real-world COPD population. Respir Med. 2014;108:729–736.
  • Miyazaki M, Nakamura H, Takahashi S, et al. The reasons for triple therapy in stable COPD patients in Japanese clinical practice. Int J Chron Obstruct Pulmon Dis. 2015;10:1053–1059.
  • Cazzola M, Matera MG. Triple combinations in chronic obstructive pulmonary disease - is three better than two? Expert Opin Pharmacother. 2014;15:2475–2478.
  • Hanania NA, Calverley PM, Dransfield MT, et al. Pooled subpopulation analyses of the effects of roflumilast on exacerbations and lung function in COPD. Respir Med. 2014;108:366–375.
  • Martinez FJ, Calverley PM, Goehring U-M, et al. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet. 2015;385:857–866.
  • Taegtmeyer AB, Leuppi JD, Kullak-Ublick GA. Roflumilast – a phosphodiesterase-4 inhibitor licensed for add-on therapy in severe COPD. Swiss Med Wkly. 2012;142:w13628.
  • Cazzola M, Page CP, Calzetta L, et al. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev. 2012;64:450–504.
  • Subramanian R, Jindal A, et al. The study of efficacy, tolerability and safety of theophylline given along with formoterol plus budesonide in COPD. J Clin Diagn Res. 2015;9:OC10–3.
  • Cosio BG, Iglesias A, Rios A, et al. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax. 2009;64:424–429.
  • Ford PA, Durham AL, Russell RE, et al. Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD. Chest. 2010;137:1338–1344.
  • Cyr M-C, Beauchesne M-F, Lemiere C, et al. Effect of theophylline on the rate of moderate to severe exacerbations among patients with chronic obstructive pulmonary disease. Br J Clin Pharmacol. 2008;65:40–45.
  • Horita N, Miyazawa N, Kojima R, et al. Chronic use of theophylline and mortality in chronic obstructive pulmonary disease: a meta- analysis. Arch Bronconeumol. 2015. doi:10.1016/j.arbres.2015.02.021.
  • Fexer J, Donnachie E, Schneider A, et al. The effects of theophylline on hospital admissions and exacerbations in COPD patients: audit data from the Bavarian disease management program. Dtsch Arztebl Int. 2014;111:293–300.
  • Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015;147:894–942.
  • Cazzola M, Calzetta L, Page C, et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015;24:451–461.
  • Dal Negro RW, Visconti M, Turco P. Efficacy of erdosteine 900 versus 600 mg/day in reducing oxidative stress in patients with COPD exacerbations: Results of a double blind, placebo-controlled trial. Pulm Pharmacol Ther. 2015;33:47–51.
  • Cazzola M, Capuano A, Rogliani P, et al. Bacterial lysates as a potentially effective approach in preventing acute exacerbation of COPD. Curr Opin Pharmacol. 2012;12:300–308.
  • Arandjus C, Black PN, Poole PJ, et al. Oral bacterial vaccines for the prevention of acute exacerbations in chronic obstructive pulmonary disease and chronic bronchitis. Respir Med. 2006;100:1671–1681.
  • Cazzola M, Anapurapu S, Page CP. Polyvalent mechanical bacterial lysate for the prevention of recurrent respiratory infections: a meta-analysis. Pulm Pharmacol Ther. 2012;25:62–68.
  • Braido F, Melioli G, Cazzola M, et al. Sub-lingual administration of a polyvalent mechanical bacterial lysate (PMBL) in patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD) according to the GOLD spirometric classification: A multicentre, double-blind, randomised, controlled, phase IV study (AIACE study: Advanced Immunological Approach in COPD Exacerbation). Pulm Pharmacol Ther. 2015;33:75–80.
  • Anzueto A. Alpha-1 antitrypsin deficiency-associated chronic obstructive pulmonary disease: A family perspective. Copd. 2015;12:462–467.
  • American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168:818–900.
  • Jonigk D, Al-Omari M, Maegel L, et al. Anti-inflammatory and immunomodulatory properties of α1-antitrypsin without inhibition of elastase. Proc Natl Acad Sci USA. 2013;110:15007–1.
  • Blasi F, Mantero M, Aliberti S. Antibiotics as immunomodulant agents in COPD. Curr Opin Pharmacol. 2012;12:293–299.
  • Altenburg J, De Graaff CS, Van Der Werf TS, et al. Immunomodulatory effects of macrolide antibiotics – part 1: biological mechanisms. Respiration. 2011;81:67–74.
  • Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;178:1139–1147.
  • Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689–698.
  • Uzun S, Djamin RS, Kluytmans JA, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014;2:361–368.
  • Sethi S, Jones PW, Theron MS, et al. Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Respir Res. 2010;11:10.
  • Herath SC, Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2013;11:CD009764.
  • Cazzola M, Bettoncelli G, Sessa E, et al. Prevalence of comorbidities in patients with chronic obstructive pulmonary disease. Respiration. 2010;80:112–119.
  • Wood AM, Tan SL, Stockley RA. Chronic obstructive pulmonary disease: towards pharmacogenetics. Genome Med. 2009;1:112.
  • Matera MG, Calzetta L, Rinaldi B, et al. Treatment of COPD: moving beyond the lungs. Curr Opin Pharmacol. 2012;12:315–322.
  • Cao C, Wu Y, Xu Z, et al. The effect of statins on chronic obstructive pulmonary disease exacerbation and mortality: a systematic review and meta-analysis of observational research. Sci Rep. 2015;5:16461.
  • Wang M, Lo Y, Tsai C, et al. Statin use and risk of COPD exacerbation requiring hospitalization. Am J Med. 2013;126:598–606.
  • Bartziokas K, Papaioannou A, Minas M, et al. Statins and outcome after hospitalization for COPD exacerbation: a prospective study. Pulm Pharmacol Ther. 2011;24:625–631.
  • Criner GJ, Connett JE, Aaron SD, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014;370:2201–2210.
  • Neukamm A, Hoiseth A, Einvik G, et al. Rosuvastatin treatment in stable chronic obstructive pulmonary disease (RODEO): a randomized controlled trial. J Intern Med. 2015;278:59–67.
  • Carlson AA, Smith EA, Reid DJ. The stats are in: an update on statin use in COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:2277–2284.
  • Shrikrishna D, Astin R, Kemp PR, et al. Renin-angiotensin system blockade: a novel therapeutic approach in chronic obstructive pulmonary disease. Clin Sci (Lond). 2012;123(8):487–498.
  • Petersen H, Sood A, Meek PM, et al. Rapid lung function decline in smokers is a risk factor for COPD and is attenuated by angiotensin-converting enzyme inhibitor use. Chest. 2014;145:695–703.
  • Mancini GB, Etminan M, Zhang B, et al. 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. 2006;47:2554–2560.
  • Mortensen EM, Copeland LA, Pugh MJ, et al. Impact of statins and ACE inhibitors on mortality after COPD exacerbations. Respir Res. 2009;10:45.
  • Andreas S, Herrmann-Lingen C, Raupach T, et al. Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial. Eur Respir J. 2006;27:972–979.
  • Cazzola M, Matera MG. Beta-blockers are safe in patients with chronic obstructive pulmonary disease, but only with caution. Am J Respir Crit Care Med. 2008;178:661–662.
  • Matera MG, Calzetta L, Cazzola M. β-Adrenoceptor modulation in chronic obstructive pulmonary disease: present and future perspectives. Drugs. 2013;73:1653–1663.
  • Puente-Maestu L, Calle M, Ortega-González A, et al. Multicentric study on the beta-blocker use and relation with exacerbations in COPD. Respir Med. 2014;108:737–744.
  • Van Gestel YR, Hoeks SE, Sin DD, et al. Impact of cardioselective beta-blockers on mortality in patients with chronic obstructive pulmonary disease and atherosclerosis. Am J Respir Crit Care Med. 2008;178:695–700.
  • Short PM, Lipworth SI, Elder DH, et al. Effect of blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. Bmj. 2011;342:d2549.
  • Farland MZ, Peters CJ, Williams JD, et al. β-Blocker use and incidence of chronic obstructive pulmonary disease exacerbations. Ann Pharmacother. 2013;47:651–656.
  • Ekstrom MP, Hermansson AB, Strom KE. Effects of cardiovascular drugs on mortality in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187:715–720.
  • Puente Maestu L, Alvarez-Sala LA, de Miguel-Díez J. Beta blockers in patients with chronic obstructive disease and coexistent cardiac illnesses. COPD Res Pract. 2015;1:11.
  • Bhatt SP, Wells JM, Kinney GL, et al. β-Blockers are associated with a reduction in COPD exacerbations. Thorax. 2016;71:8–14.
  • Andell P, Erlinge D, Smith JG, et al. β-blocker use and mortality in COPD patients after myocardial infarction: a Swedish nationwide observational study. J Am Heart Assoc. 2015;4:e001611.
  • Wurst KE, Punekar YS, Shukla A. Treatment evolution after COPD diagnosis in the UK primary care setting. PLoS One. 2014;9:e105296.
  • Woodruff PG, Agusti A, Roche N, et al. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management. Lancet. 2015;385:1789–1798.
  • Barnes PJ. Identifying molecular targets for new drug development for chronic obstructive pulmonary disease: what does the future hold? Semin Respir Crit Care Med. 2015;36:508–522.
  • Baker KE, Bonvini SJ, Donovan C, et al. Novel drug targets for asthma and COPD: lessons learned from in vitro and in vivo models. Pulm Pharmacol Ther. 2014;29:181–198.
  • Tam JT, Parker JL, Anastasopulos D, et al. Clinical trial risk in chronic obstructive pulmonary disease: the effects of drug class and inclusion criteria. Respiration. 2016;91:79–86.
  • Hay M, Thomas DW, Craighead JL, et al. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32:40–51.
  • Cazzola M, Segreti A, Rogliani P. Comparative effectiveness of drugs for chronic obstructive pulmonary disease. Drugs Today (Barc). 2012;48:785–794.
  • Cazzola M, Rogliani P, Matera MG. Escalation and de-escalation of therapy in COPD: myths, realities and perspectives. Drugs. 2015;75:1575–1585.
  • Rennard SI. The promise of observational studies (ECLIPSE, SPIROMICS, and COPDGene) in achieving the goal of personalized treatment of chronic obstructive pulmonary disease. Semin Respir Crit Care Med. 2015;36:478–490.
  • Vestbo J. COPD: definition and phenotypes. Clin Chest Med. 2014;35:1–6.
  • Segreti A, Stirpe E, Rogliani P, et al. Defining phenotypes in COPD: an aid to personalized healthcare. Mol Diagn Ther. 2014;18:381–388.
  • Montuschi P, Malerba M, Santini G, et al. Pharmacological treatment of chronic obstructive pulmonary disease: from evidence-based medicine to phenotyping. Drug Discov Today. 2014;19:1928–1935.
  • Miravitlles M, Soler-Catalunã JJ, Calle M, et al. Spanish guideline for COPD (GesEPOC). Update 2014. Arch Bronconeumol. 2014;50(Suppl 1):1–16.
  • Kim V, Han MK, Vance GB, et al. The chronic bronchitic phenotype of COPD: an analysis of the COPDGene study. Chest. 2011;140:626–633.
  • Rennard SI, Calverley PM, Goehring UM, et al. Reduction of exacerbations by the PDE4 inhibitor roflumilast – the importance of defining different subsets of patients with COPD. Respir Res. 2011;12:18.
  • Beeh KM, Beier J. The short, the long and the ‘‘ultra-long’’: why duration of bronchodilator action matters in chronic obstructive pulmonary disease. Adv Ther. 2010;27:150–159.
  • Reddel HK. Treatment of overlapping asthma-chronic obstructive pulmonary disease: can guidelines contribute in an evidence-free zone? J Allergy Clin Immunol. 2015;136:546–552.
  • Postma DS, Rabe KF. The Asthma-COPD overlap syndrome. N Engl J Med. 2015;373:1241–1249.
  • Zheng J-P, Wen F-Q, Bai C-X, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014;2:187–194.
  • De Backer J, Vos W, Van Holsbeke C, et al. Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients. Int J Chron Obstruct Pulmon Dis. 2013;8:569–579.
  • Matera MG, Calzetta L, Cazzola M. Oxidation pathway and exacerbations in COPD: the role of NAC. Expert Rev Respir Med. 2016;10:89–97.
  • Xuan J, Wang L, Yin H, et al. The cost-effectiveness of OM-85 in managing respiratory tract infections in China. J Med Econ. 2015;18:167–172.
  • Woodhead M, Blasi F, Ewig S, et al. Guidelines for the management of adult lower respiratory tract infections – full version. Clin Microbiol Infect. 2011;17(Suppl. 6):E1–59.
  • Garau J, Nicolau DP, Wullt B, et al. Antibiotic stewardship challenges in the management of community-acquired infections for prevention of escalating antibiotic resistance. J Glob Antimicrob Resist. 2014;2:245–253.
  • Tsiligianni IG, Kosmas E, Van Der Molen T, et al. Managing comorbidity in COPD: a difficult task. Curr Drug Targets. 2013;14:158–176.
  • Decramer M, Janssens W. Chronic obstructive pulmonary disease and comorbidities. Lancet Respir Med. 2013;1:73–83.
  • Cazzola M, Rogliani P, Matera MG. Cardiovascular disease in patients with COPD. Lancet Respir Med. 2015;3(8):593–595.
  • Stone IS, Barnes NC, James W-Y, et al. Lung deflation and cardiovascular structure and function in COPD: A randomized controlled trial. Am J Respir Crit Care Med. 2015. doi:10.1164/rccm.201508-1647OC.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.