Advertisement

Pharmacologic Treatment Strategies

  • Rachael A. Evans
  • Robert G. Varadi
  • Kambiz Mirzaei
  • Roger S. Goldstein
Chapter
Part of the Respiratory Medicine book series (RM)

Abstract

As COPD is characterized by only partially reversible airway obstruction, respiratory pharmacological agents focus primarily on addressing the airflow limitation, both by bronchodilatation and by reducing airway inflammation. However, the symptoms, morbidity and mortality associated with COPD are also associated with secondary impairments, such as skeletal muscle dysfunction, decreased bone density and alterations of mood. Patient management must also consider common co-morbidities such as cardiovascular disease and diabetes. Therefore pharmacological management must address both the consequences of the pulmonary disease, the secondary impairments and the co-morbidities. This chapter provides discussion of 1) the currently recommended pulmonary pharmacological treatment, 2) the interaction between COPD and cardiovascular disease, and the implications for pharmacological management, 3) an overview of the management of osteoporosis in COPD, 4) the interaction between COPD and diabetes, and the implications for pharmacological management, 5) the management of mood disorders, 6) future treatment directions.

Keywords

COPD Pharmacology Co-morbidity Cardiovascular disease Osteoporosis Anxiety and depression Diabetes 

References

  1. 1.
    Celli BR, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932–46.PubMedCrossRefGoogle Scholar
  2. 2.
    Maltais F, LeBlanc P, Jobin J, Casaburi R. Peripheral muscle dysfunction in chronic obstructive pulmonary disease. Clin Chest Med. 2000;21(4):665–77.PubMedCrossRefGoogle Scholar
  3. 3.
    Schols AM. Nutritional and metabolic modulation in chronic obstructive pulmonary disease management. Eur Respir J Suppl. 2003;46:81s–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Ionescu AA, Schoon E. Osteoporosis in chronic obstructive pulmonary disease. Eur Respir J Suppl. 2003;46:64s–75.PubMedCrossRefGoogle Scholar
  5. 5.
    Hill K, Geist R, Goldstein RS, Lacasse Y. Anxiety and depression in end-stage COPD. Eur Respir J. 2008;31(3):667–77.PubMedCrossRefGoogle Scholar
  6. 6.
    Van Vliet M, Spruit MA, Verleden G, Kasran A, Van Herck E, Pitta F, et al. Hypogonadism, quadriceps weakness, and exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;172(9):1105–11.PubMedCrossRefGoogle Scholar
  7. 7.
    Similowski T, Agusti A, MacNee W, Schonhofer B. The potential impact of anaemia of chronic disease in COPD. Eur Respir J. 2006;27(2):390–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Agusti A, Soriano JB. COPD as a systemic disease. COPD. 2008;5(2):133–8.PubMedCrossRefGoogle Scholar
  9. 9.
    NICE COPD guidelines. http://guidance.nice.org.uk/CG101. 2010.
  10. 10.
    Mahler DA, Donohue JF, Barbee RA, Goldman MD, Gross NJ, Wisniewski ME, et al. Efficacy of salmeterol xinafoate in the treatment of COPD. Chest. 1999;115(4):957–65.PubMedCrossRefGoogle Scholar
  11. 11.
    Dahl R, Greefhorst LA, Nowak D, Nonikov V, Byrne AM, Thomson MH, et al. Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164(5):778–84.PubMedGoogle Scholar
  12. 12.
    Vincken W, Van Noord JA, Greefhorst AP, Bantje TA, Kesten S, Korducki L, et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J. 2002;19(2):209–16.PubMedCrossRefGoogle Scholar
  13. 13.
    O’Donnell DE, Fluge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23(6):832–40.PubMedCrossRefGoogle Scholar
  14. 14.
    Di Marco F, Milic-Emili J, Boveri B, Carlucci P, Santus P, Casanova F, et al. Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD. Eur Respir J. 2003;21(1):86–94.PubMedCrossRefGoogle Scholar
  15. 15.
    Brouillard C, Pepin V, Milot J, Lacasse Y, Maltais F. Endurance shuttle walking test: responsiveness to salmeterol in COPD. Eur Respir J. 2008;31(3):579–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Mahler DA. The effect of inhaled beta2-agonists on clinical outcomes in chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2002;110(6 Suppl):S298–303.PubMedCrossRefGoogle Scholar
  17. 17.
    Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Stockley RA, Whitehead PJ, Williams MK. Improved outcomes in patients with chronic obstructive pulmonary disease treated with salmeterol compared with placebo/usual therapy: results of a meta-analysis. Respir Res. 2006;7:147.PubMedCrossRefGoogle Scholar
  19. 19.
    Niewoehner DE, Rice K, Cote C, Paulson D, Cooper Jr JA, Korducki L, et al. 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):317–26.PubMedGoogle Scholar
  20. 20.
    Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532–55.PubMedCrossRefGoogle Scholar
  21. 21.
    Yoshimura T, Kurita C, Nagao T, Usami E, Nakao T, Watanabe S, et al. Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells. Pharmacology. 1997;54(3):144–52.PubMedCrossRefGoogle Scholar
  22. 22.
    Barnes PJ. Effect of beta-agonists on inflammatory cells. J Allergy Clin Immunol. 1999;104(2 Pt 2):S10–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Bourbeau J, Christodoulopoulos P, Maltais F, Yamauchi Y, Olivenstein R, Hamid Q. Effect of salmeterol/fluticasone propionate on airway inflammation in COPD: a randomised controlled trial. Thorax. 2007;62(11):938–43.PubMedCrossRefGoogle Scholar
  24. 24.
    Grando SA, Kawashima K, Kirkpatrick CJ, Wessler I. Recent progress in understanding the non-neuronal cholinergic system in humans. Life Sci. 2007;80(24–25):2181–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Bateman ED, Rennard S, Barnes PJ, Dicpinigaitis PV, Gosens R, Gross NJ, et al. Alternative mechanisms for tiotropium. Pulm Pharmacol Ther. 2009;22(6):533–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Powrie DJ, Wilkinson TM, Donaldson GC, Jones P, Scrine K, Viel K, et al. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur Respir J. 2007;30(3):472–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Rajab P, Fox J, Riaz S, Tomlinson D, Ball D, Greenhaff PL. Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat. Am J Physiol Regul Integr Comp Physiol. 2000;279(3):R1076–81.PubMedGoogle Scholar
  28. 28.
    Koopman R, Ryall JG, Church JE, Lynch GS. The role of beta-adrenoceptor signaling in skeletal muscle: therapeutic implications for muscle wasting disorders. Curr Opin Clin Nutr Metab Care. 2009;12(6):601–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Yang IA, Fong KM, Sim EH, Black PN, Lasserson TJ. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2007;(2):CD002991.Google Scholar
  30. 30.
    Soriano JB, Sin DD, Zhang X, Camp PG, Anderson JA, Anthonisen NR, et al. A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo. Chest. 2007;131(3):682–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775–89.PubMedCrossRefGoogle Scholar
  32. 32.
    Nannini LJ, Cates CJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta-agonist in one inhaler versus inhaled steroids for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2007;(4):CD006826.Google Scholar
  33. 33.
    Nannini L, Cates CJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2007;(4):CD003794.Google Scholar
  34. 34.
    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):912–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting beta2-agonists and corticosteroids. Eur Respir J. 2002;19(1):182–91.PubMedCrossRefGoogle Scholar
  36. 36.
    Sin DD, Man SF, Marciniuk DD, Ford G, FitzGerald M, Wong E, 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. 2008;177(11):1207–14.PubMedCrossRefGoogle Scholar
  37. 37.
    Singh S, Loke YK. Risk of pneumonia associated with long-term use of inhaled corticosteroids in chronic obstructive pulmonary disease: a critical review and update. Curr Opin Pulm Med. 2010;16(2):118–22.PubMedCrossRefGoogle Scholar
  38. 38.
    Celli BR, Thomas NE, Anderson JA, Ferguson GT, Jenkins CR, Jones PW, et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med. 2008;178(4):332–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Celli B, Decramer M, Kesten S, Liu D, Mehra S, Tashkin DP. Mortality in the 4-year trial of tiotropium (UPLIFT) in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180(10):948–55.PubMedCrossRefGoogle Scholar
  40. 40.
    Decramer M, Celli B, Kesten S, Lystig T, Mehra S, Tashkin DP. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet. 2009;374(9696):1171–8.PubMedCrossRefGoogle Scholar
  41. 41.
  42. 42.
    Culpitt SV, de Matos C, Russell RE, Donnelly LE, Rogers DF, Barnes PJ. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;165(10):1371–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Barnes PJ. Theophylline in chronic obstructive pulmonary disease: new horizons. Proc Am Thorac Soc. 2005;2(4):334–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Cosio BG, Iglesias A, Rios A, Noguera A, Sala E, Ito K, et al. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax. 2009;64(5):424–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, et al. 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):545–55.PubMedGoogle Scholar
  46. 46.
    Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180(8):741–50.PubMedCrossRefGoogle Scholar
  47. 47.
    Topsakal R, Kalay N, Ozdogru I, Cetinkaya Y, Oymak S, Kaya MG, et al. Effects of chronic obstructive pulmonary disease on coronary atherosclerosis. Heart Vessels. 2009;24(3):164–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Hawkins NM, Jhund PS, Simpson CR, Petrie MC, Macdonald MR, Dunn FG, et al. Primary care burden and treatment of patients with heart failure and chronic obstructive pulmonary disease in Scotland. Eur J Heart Fail. 2010;12(1):17–24.PubMedCrossRefGoogle Scholar
  49. 49.
    Rutten FH, Moons KG, Cramer MJ, Grobbee DE, Zuithoff NP, Lammers JW, et al. Recognising heart failure in elderly patients with stable chronic obstructive pulmonary disease in primary care: cross sectional diagnostic study. BMJ. 2005;331(7529):1379.PubMedCrossRefGoogle Scholar
  50. 50.
    Mascarenhas J, Lourenco P, Lopes R, Azevedo A, Bettencourt P. Chronic obstructive pulmonary disease in heart failure. Prevalence, therapeutic and prognostic implications. Am Heart J. 2008;155(3):521–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Curkendall SM, DeLuise C, Jones JK, Lanes S, Stang MR, Goehring Jr E, et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol. 2006;16(1):63–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Lavie CJ, Milani RV, Verma A, O’Keefe JH. C-reactive protein and cardiovascular diseases – is it ready for primetime? Am J Med Sci. 2009;338(6):486–92.PubMedCrossRefGoogle Scholar
  53. 53.
    Willerson JT. Systemic and local inflammation in patients with unstable atherosclerotic plaques. Prog Cardiovasc Dis. 2002;44(6):469–78.PubMedCrossRefGoogle Scholar
  54. 54.
    Wisniacki N, Taylor W, Lye M, Wilding JP. Insulin resistance and inflammatory activation in older patients with systolic and diastolic heart failure. Heart. 2005;91(1):32–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Torre-Amione G. Immune activation in chronic heart failure. Am J Cardiol. 2005;95(11A): 3C–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, Duran-Tauleria E, Sanchez G, et al. Systemic inflammation in chronic obstructive pulmonary disease: a population-based study. Respir Res. 2010;11(1):63.PubMedGoogle Scholar
  57. 57.
    Higashimoto Y, Iwata T, Okada M, Satoh H, Fukuda K, Tohda Y. Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease. Respir Med. 2009;103(8):1231–8.PubMedCrossRefGoogle Scholar
  58. 58.
    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(11):1514–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Hole DJ, Watt GC, Davey-Smith G, Hart CL, Gillis CR, Hawthorne VM. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ. 1996;313(7059):711–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Sin DD, Man SF. Chronic obstructive pulmonary disease as a risk factor for cardiovascular morbidity and mortality. Proc Am Thorac Soc. 2005;2(1):8–11.PubMedCrossRefGoogle Scholar
  61. 61.
    Boudestein LC, Rutten FH, Cramer MJ, Lammers JW, Hoes AW. The impact of concurrent heart failure on prognosis in patients with chronic obstructive pulmonary disease. Eur J Heart Fail. 2009;11(12):1182–8.PubMedCrossRefGoogle Scholar
  62. 62.
    De Blois J, Simard S, Atar D, Agewall S. COPD predicts mortality in HF: the Norwegian Heart Failure Registry. J Card Fail. 2010;16(3):225–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Macchia A, Monte S, Romero M, D’Ettorre A, Tognoni G. The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure. Eur J Heart Fail. 2007;9(9):942–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Dunlay SM, Redfield MM, Weston SA, Therneau TM, Hall LK, Shah ND, et al. Hospitalizations after heart failure diagnosis a community perspective. J Am Coll Cardiol. 2009;54(18): 1695–702.PubMedCrossRefGoogle Scholar
  65. 65.
    Staszewsky L, Wong M, Masson S, Barlera S, Carretta E, Maggioni AP, et al. Clinical, neurohormonal, and inflammatory markers and overall prognostic role of chronic obstructive pulmonary disease in patients with heart failure: data from the Val-HeFT heart failure trial. J Card Fail. 2007;13(10):797–804.PubMedCrossRefGoogle Scholar
  66. 66.
    Sirak TE, Jelic S, Le Jemtel TH. Therapeutic update: non-selective beta- and alpha-adrenergic blockade in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure. J Am Coll Cardiol. 2004;44(3):497–502.PubMedCrossRefGoogle Scholar
  67. 67.
    Le Jemtel TH, Padeletti M, Jelic S. Diagnostic and therapeutic challenges in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure. J Am Coll Cardiol. 2007;49(2):171–80.PubMedCrossRefGoogle Scholar
  68. 68.
    Carstairs JR, Nimmo AJ, Barnes PJ. Autoradiographic visualization of beta-adrenoceptor subtypes in human lung. Am Rev Respir Dis. 1985;132(3):541–7.PubMedGoogle Scholar
  69. 69.
    Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, et al. Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res. 1986;59(3):297–309.PubMedGoogle Scholar
  70. 70.
    Brodde OE. Beta-1 and beta-2 adrenoceptor polymorphisms: functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther. 2008;117(1):1–29.PubMedCrossRefGoogle Scholar
  71. 71.
    Nguyen LP, Omoluabi O, Parra S, Frieske JM, Clement C, Ammar-Aouchiche Z, et al. Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model. Am J Respir Cell Mol Biol. 2008;38(3):256–62.PubMedCrossRefGoogle Scholar
  72. 72.
    Currie GP, Lee DK, Lipworth BJ. Long-acting beta2-agonists in asthma: not so SMART? Drug Saf. 2006;29(8):647–56.PubMedCrossRefGoogle Scholar
  73. 73.
    Wijesinghe M, Perrin K, Harwood M, Weatherall M, Beasley R. The risk of asthma mortality with inhaled long acting beta-agonists. Postgrad Med J. 2008;84(995):467–72.PubMedCrossRefGoogle Scholar
  74. 74.
    Liao MM, Ginde AA, Clark S, Camargo Jr CA. Salmeterol use and risk of hospitalization among emergency department patients with acute asthma. Ann Allergy Asthma Immunol. 2010;104(6):478–84.PubMedCrossRefGoogle Scholar
  75. 75.
    Weatherall M, Wijesinghe M, Perrin K, Harwood M, Beasley R. Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy. Thorax. 2010;65(1):39–43.PubMedCrossRefGoogle Scholar
  76. 76.
    Taylor DR. Pharmacogenetics of beta2-agonist drugs in asthma. Clin Rev Allergy Immunol. 2006;31(2–3):247–58.PubMedCrossRefGoogle Scholar
  77. 77.
    Sandilands A, Yeo G, Brown MJ, O’Shaughnessy KM. Functional responses of human beta1 adrenoceptors with defined haplotypes for the common 389R>G and 49S>G polymorphisms. Pharmacogenetics. 2004;14(6):343–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Kaye DM, Smirk B, Williams C, Jennings G, Esler M, Holst D. Beta-adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogenetics. 2003;13(7):379–82.PubMedCrossRefGoogle Scholar
  79. 79.
    Au DH, Curtis JR, Every NR, McDonell MB, Fihn SD. Association between inhaled beta-agonists and the risk of unstable angina and myocardial infarction. Chest. 2002;121(3):846–51.PubMedCrossRefGoogle Scholar
  80. 80.
    Macie C, Wooldrage K, Manfreda J, Anthonisen N. Cardiovascular morbidity and the use of inhaled bronchodilators. Int J Chron Obstruct Pulmon Dis. 2008;3(1):163–9.PubMedGoogle Scholar
  81. 81.
    Anthonisen NR, Connett JE, Enright PL, Manfreda J. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med. 2002;166(3):333–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB. Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med. 2008;149(6): 380–90.PubMedGoogle Scholar
  83. 83.
    Ogale SS, Lee TA, Au DH, Boudreau DM, Sullivan SD. Cardiovascular events associated with ipratropium bromide in COPD. Chest. 2010;137(1):13–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2008;300(12):1439–50.PubMedCrossRefGoogle Scholar
  85. 85.
    Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA. 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.PubMedCrossRefGoogle Scholar
  86. 86.
    Rodrigo GJ, Castro-Rodriguez JA, Nannini LJ, Plaza MV, Schiavi EA. Tiotropium and risk for fatal and nonfatal cardiovascular events in patients with chronic obstructive pulmonary disease: systematic review with meta-analysis. Respir Med. 2009;103(10):1421–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Hilleman DE, Malesker MA, Morrow LE, Schuller D. A systematic review of the cardiovascular risk of inhaled anticholinergics in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2009;4:253–63.PubMedGoogle Scholar
  88. 88.
    Grosso A, Douglas I, Hingorani AD, MacAllister R, Hubbard R, Smeeth L. Inhaled tiotropium bromide and risk of stroke. Br J Clin Pharmacol. 2009;68(5):731–6.PubMedCrossRefGoogle Scholar
  89. 89.
    Celli B, Decramer M, Leimer I, Vogel U, Kesten S, Tashkin DP. Cardiovascular safety of tiotropium in patients with COPD. Chest. 2010;137(1):20–30.PubMedCrossRefGoogle Scholar
  90. 90.
    Macie C, Wooldrage K, Manfreda J, Anthonisen NR. Inhaled corticosteroids and mortality in COPD. Chest. 2006;130(3):640–6.PubMedCrossRefGoogle Scholar
  91. 91.
    Sin DD, Wu L, Anderson JA, Anthonisen NR, Buist AS, Burge PS, et al. Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease. Thorax. 2005;60(12):992–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Huiart L, Ernst P, Ranouil X, Suissa S. Low-dose inhaled corticosteroids and the risk of acute myocardial infarction in COPD. Eur Respir J. 2005;25(4):634–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Qing F, Rahman SU, Hayes MJ, Rhodes CG, Ind PW, Jones T, et al. Effect of long-term beta2-agonist dosing on human cardiac beta-adrenoceptor expression in vivo: comparison with changes in lung and mononuclear leukocyte beta-receptors. J Nucl Cardiol. 1997;4(6):532–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sageman WS, Lurie K, et al. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982;307(4):205–11.PubMedCrossRefGoogle Scholar
  95. 95.
    Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14): e391–479.PubMedCrossRefGoogle Scholar
  96. 96.
    Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008;29(19):2388–442.PubMedCrossRefGoogle Scholar
  97. 97.
    Hawkins NM, Wang D, Petrie MC, Pfeffer MA, Swedberg K, Granger CB, et al. Baseline characteristics and outcomes of patients with heart failure receiving bronchodilators in the CHARM programme. Eur J Heart Fail. 2010;12(6):557–65.PubMedCrossRefGoogle Scholar
  98. 98.
    Au DH, Udris EM, Fan VS, Curtis JR, McDonell MB, Fihn SD. Risk of mortality and heart failure exacerbations associated with inhaled beta-adrenoceptor agonists among patients with known left ventricular systolic dysfunction. Chest. 2003;123(6):1964–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Cruickshank JM, McAinsh J. Atenolol and ischaemic heart disease: an overview. Curr Med Res Opin. 1991;12(8):485–96.PubMedCrossRefGoogle Scholar
  100. 100.
    Leren P. Ischaemic heart disease: how well are the risk profiles modulated by current beta blockers? Cardiology. 1993;82 Suppl 3:8–12.PubMedCrossRefGoogle Scholar
  101. 101.
    Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA. 2000;283(10):1295–302.PubMedCrossRefGoogle Scholar
  102. 102.
    Eichhorn EJ, Bristow MR. The carvedilol prospective randomized cumulative survival (COPERNICUS) trial. Curr Control Trials Cardiovasc Med. 2001;2(1):20–3.PubMedCrossRefGoogle Scholar
  103. 103.
    The Cardiac Insufficiency Bisoprolol Study II(CIBIS-II): a randomised trial. Lancet 1999; 353(9146):9–13.Google Scholar
  104. 104.
    Tattersfield AE. Beta adrenoceptor antagonists and respiratory disease. J Cardiovasc Pharmacol. 1986;8 Suppl 4:S35–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Fogari R, Zoppi A, Tettamanti F, Poletti L, Rizzardi G, Fiocchi G. Comparative effects of celiprolol, propranolol, oxprenolol, and atenolol on respiratory function in hypertensive patients with chronic obstructive lung disease. Cardiovasc Drugs Ther. 1990;4(4):1145–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Dorow P, Bethge H, Tonnesmann U. Effects of single oral doses of bisoprolol and atenolol on airway function in nonasthmatic chronic obstructive lung disease and angina pectoris. Eur J Clin Pharmacol. 1986;31(2):143–7.PubMedCrossRefGoogle Scholar
  107. 107.
    Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005;(4):CD003566.Google Scholar
  108. 108.
    Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for reversible airway ­disease. Cochrane Database Syst Rev 2002;(4):CD002992.Google Scholar
  109. 109.
    Olenchock BA, Fonarow GG, Pan W, Hernandez A, Cannon CP. Current use of beta blockers in patients with reactive airway disease who are hospitalized with acute coronary syndromes. Am J Cardiol. 2009;103(3):295–300.PubMedCrossRefGoogle Scholar
  110. 110.
    Matera MG, Martuscelli E, Cazzola M. Pharmacological modulation of beta-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure. Pulm Pharmacol Ther. 2010;23(1):1–8.PubMedCrossRefGoogle Scholar
  111. 111.
    Jabbour A, Macdonald PS, Keogh AM, Kotlyar E, Mellemkjaer S, Coleman CF, et al. Differences between beta-blockers in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized crossover trial. J Am Coll Cardiol. 2010;55(17):1780–7.PubMedCrossRefGoogle Scholar
  112. 112.
    Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med. 2010;170(10):880–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Andreas S, Anker SD, Scanlon PD, Somers VK. Neurohumoral activation as a link to systemic manifestations of chronic lung disease. Chest. 2005;128(5):3618–24.PubMedCrossRefGoogle Scholar
  114. 114.
    Leuchte HH, Baumgartner RA, Nounou ME, Vogeser M, Neurohr C, Trautnitz M, et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med. 2006;173(7):744–50.PubMedCrossRefGoogle Scholar
  115. 115.
    Callaerts-Vegh Z, Evans KL, Dudekula N, Cuba D, Knoll BJ, Callaerts PF, et al. Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma. Proc Natl Acad Sci USA. 2004;101(14):4948–53.PubMedCrossRefGoogle Scholar
  116. 116.
    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(7):661–2.PubMedCrossRefGoogle Scholar
  117. 117.
    Mancini GB, Etminan M, Zhang B, Levesque LE, FitzGerald JM, Brophy JM. 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(12):2554–60.PubMedCrossRefGoogle Scholar
  118. 118.
    Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009;33(5):1165–85.PubMedCrossRefGoogle Scholar
  119. 119.
    Soyseth V, Brekke PH, Smith P, Omland T. Statin use is associated with reduced mortality in COPD. Eur Respir J. 2007;29(2):279–83.PubMedCrossRefGoogle Scholar
  120. 120.
    Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977–2016.PubMedCrossRefGoogle Scholar
  121. 121.
    Anker SD, Negassa A, Coats AJ, Afzal R, Poole-Wilson PA, Cohn JN, et al. Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study. Lancet. 2003;361(9363):1077–83.PubMedCrossRefGoogle Scholar
  122. 122.
    Springer J, Filippatos G, Akashi YJ, Anker SD. Prognosis and therapy approaches of cardiac cachexia. Curr Opin Cardiol. 2006;21(3):229–33.PubMedCrossRefGoogle Scholar
  123. 123.
    Song YH, Li Y, Du J, Mitch WE, Rosenthal N, Delafontaine P. Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting. J Clin Invest. 2005;115(2): 451–8.PubMedGoogle Scholar
  124. 124.
    Mancini GB. Clarion call for trials assessing “cardiopulmonary” agents to reduce morbidity and mortality in inflammatory lung diseases. Chest. 2007;131(4):950–1.PubMedCrossRefGoogle Scholar
  125. 125.
    WHO Scientific Group on the Prevention and Management of Osteoporosis. Prevention and management of osteoporosis: report of a WHO scientific group. Geneva: World Health Organisation; 2000.Google Scholar
  126. 126.
    Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993; 94(6):646–50Google Scholar
  127. 127.
    Melton III LJ. Who has osteoporosis? A conflict between clinical and public health perspectives. J Bone Miner Res. 2000;15(12):2309–14.PubMedCrossRefGoogle Scholar
  128. 128.
    LaVelle DG. Fractures and dislocations of the hip. In: Canale ST, Beaty JH, editors. Campbell’s Operative Orthopaedics. Philadelphia, PA: Mosby Elsevier; 2008. p. 3237–308.Google Scholar
  129. 129.
    Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, et al. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med. 1998;128(10):793–800.PubMedGoogle Scholar
  130. 130.
    Schlaich C, Minne HW, Bruckner T, Wagner G, Gebest HJ, Grunze M, et al. Reduced pulmonary function in patients with spinal osteoporotic fractures. Osteoporos Int. 1998;8(3):261–7.PubMedCrossRefGoogle Scholar
  131. 131.
    Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA. 2002;288(15):1889–97.PubMedCrossRefGoogle Scholar
  132. 132.
    Graat-Verboom L, Wouters EF, Smeenk FW, van den Borne BE, Lunde R, Spruit MA. Current status of research on osteoporosis in COPD: a systematic review. Eur Respir J. 2009;34(1): 209–18.PubMedCrossRefGoogle Scholar
  133. 133.
    Biskobing DM. COPD and osteoporosis. Chest. 2002;121(2):609–20.PubMedCrossRefGoogle Scholar
  134. 134.
    Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19(4):385–97.PubMedCrossRefGoogle Scholar
  135. 135.
    National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation; 2010.Google Scholar
  136. 136.
    Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF. Systemic effects of smoking. Chest. 2007;131(5):1557–66.PubMedCrossRefGoogle Scholar
  137. 137.
    Bauer DC, Browner WS, Cauley JA, Orwoll ES, Scott JC, Black DM, et al. Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1993;118(9):657–65.PubMedGoogle Scholar
  138. 138.
    Hollenbach KA, Barrett-Connor E, Edelstein SL, Holbrook T. Cigarette smoking and bone mineral density in older men and women. Am J Public Health. 1993;83(9):1265–70.PubMedCrossRefGoogle Scholar
  139. 139.
    Oncken C, Prestwood K, Kleppinger A, Wang Y, Cooney J, Raisz L. Impact of smoking cessation on bone mineral density in postmenopausal women. J Womens Health (Larchmt). 2006;15(10):1141–50.CrossRefGoogle Scholar
  140. 140.
    Cornuz J, Feskanich D, Willett WC, Colditz GA. Smoking, smoking cessation, and risk of hip fracture in women. Am J Med. 1999;106(3):311–4.PubMedCrossRefGoogle Scholar
  141. 141.
    Ries AL, Bauldoff GS, Carlin BW, Casaburi R, Emery CF, Mahler DA, et al. Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based clinical practice guidelines. Chest. 2007;131(5 Suppl):4S–2.PubMedCrossRefGoogle Scholar
  142. 142.
    Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2009;(2):CD007146.Google Scholar
  143. 143.
    Feskanich D, Willett W, Colditz G. Walking and leisure-time activity and risk of hip fracture in postmenopausal women. JAMA. 2002;288(18):2300–6.PubMedCrossRefGoogle Scholar
  144. 144.
    Braith RW, Conner JA, Fulton MN, Lisor CF, Casey DP, Howe KS, et al. Comparison of alendronate vs alendronate plus mechanical loading as prophylaxis for osteoporosis in lung transplant recipients: a pilot study. J Heart Lung Transplant. 2007;26(2):132–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Mitchell MJ, Baz MA, Fulton MN, Lisor CF, Braith RW. Resistance training prevents vertebral osteoporosis in lung transplant recipients. Transplantation. 2003;76(3):557–62.PubMedCrossRefGoogle Scholar
  146. 146.
    Wang WQ, Ip MS, Tsang KW, Lam KS. Antiresorptive therapy in asthmatic patients receiving high-dose inhaled steroids: a prospective study for 18 months. J Allergy Clin Immunol. 1998;101(4 Pt 1):445–50.PubMedCrossRefGoogle Scholar
  147. 147.
    Reid DM, Nicoll JJ, Smith MA, Higgins B, Tothill P, Nuki G. Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica. Br Med J (Clin Res Ed). 1986;293(6560):1463–6.CrossRefGoogle Scholar
  148. 148.
    Kanis JA, Johansson H, Oden A, Johnell O, de Laet C, Melton III LJ, et al. A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res. 2004;19(6):893–9.PubMedCrossRefGoogle Scholar
  149. 149.
    Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med. 1998;339(5):292–9.PubMedCrossRefGoogle Scholar
  150. 150.
    Shane E, Rivas M, McMahon DJ, Staron RB, Silverberg SJ, Seibel MJ, et al. Bone loss and turnover after cardiac transplantation. J Clin Endocrinol Metab. 1997;82(5):1497–506.PubMedCrossRefGoogle Scholar
  151. 151.
    Reid IR, Heap SW. Determinants of vertebral mineral density in patients receiving long-term glucocorticoid therapy. Arch Intern Med. 1990;150(12):2545–8.PubMedCrossRefGoogle Scholar
  152. 152.
    Brown JP, Josse RG. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ. 2002;167(10 Suppl):S1–34.PubMedGoogle Scholar
  153. 153.
    Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001; 44(7):1496–503.Google Scholar
  154. 154.
    Frediani B, Falsetti P, Bisogno S, Baldi F, Acciai C, Filippou G, et al. Effects of high dose methylprednisolone pulse therapy on bone mass and biochemical markers of bone metabolism in patients with active rheumatoid arthritis: a 12-month randomized prospective controlled study. J Rheumatol. 2004;31(6):1083–7.PubMedGoogle Scholar
  155. 155.
    Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res. 2000;15(6):993–1000.PubMedCrossRefGoogle Scholar
  156. 156.
    Hubbard R, Tattersfield A, Smith C, West J, Smeeth L, Fletcher A. Use of inhaled corticosteroids and the risk of fracture. Chest. 2006;130(4):1082–8.PubMedCrossRefGoogle Scholar
  157. 157.
    Lee TA, Weiss KB. Fracture risk associated with inhaled corticosteroid use in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;169(7):855–9.PubMedCrossRefGoogle Scholar
  158. 158.
    Suissa S, Baltzan M, Kremer R, Ernst P. Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med. 2004;169(1):83–8.PubMedCrossRefGoogle Scholar
  159. 159.
    Scanlon PD, Connett JE, Wise RA, Tashkin DP, Madhok T, Skeans M, et al. Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am J Respir Crit Care Med. 2004;170(12):1302–9.PubMedCrossRefGoogle Scholar
  160. 160.
    Lung Health Study Research Group. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med. 2000;343(26): 1902–9.CrossRefGoogle Scholar
  161. 161.
    Ferguson GT, Calverley PM, Anderson JA, Jenkins CR, Jones PW, Willits LR, et al. Prevalence and progression of osteoporosis in patients with COPD: results from the TOwards a Revolution in COPD Health study. Chest. 2009;136(6):1456–65.PubMedCrossRefGoogle Scholar
  162. 162.
    de Vries F, Pouwels S, Lammers JW, Leufkens HG, Bracke M, Cooper C, et al. Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study. J Intern Med. 2007;261(2):170–7.PubMedGoogle Scholar
  163. 163.
    Johannes CB, Schneider GA, Dube TJ, Alfredson TD, Davis KJ, Walker AM. The risk of nonvertebral fracture related to inhaled corticosteroid exposure among adults with chronic respiratory disease. Chest. 2005;127(1):89–97.PubMedCrossRefGoogle Scholar
  164. 164.
    Pauwels RA, Lofdahl CG, Laitinen LA, Schouten JP, Postma DS, Pride NB, et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med. 1999;340(25):1948–53.PubMedCrossRefGoogle Scholar
  165. 165.
    Heaney RP, Recker RR, Saville PD. Menopausal changes in calcium balance performance. J Lab Clin Med. 1978;92(6):953–63.PubMedGoogle Scholar
  166. 166.
    Ensrud KE, Taylor BC, Paudel ML, Cauley JA, Cawthon PM, Cummings SR, et al. Serum 25-hydroxyvitamin D levels and rate of hip bone loss in older men. J Clin Endocrinol Metab. 2009;94(8):2773–80.PubMedCrossRefGoogle Scholar
  167. 167.
    Cauley JA, Lacroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med. 2008;149(4): 242–50.PubMedGoogle Scholar
  168. 168.
    Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med. 2004;116(9):634–9.PubMedCrossRefGoogle Scholar
  169. 169.
    Pasco JA, Henry MJ, Kotowicz MA, Sanders KM, Seeman E, Pasco JR, et al. Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures: the Geelong Osteoporosis Study. J Bone Miner Res. 2004;19(5):752–8.PubMedCrossRefGoogle Scholar
  170. 170.
    Avenell A, Gillespie WJ, Gillespie LD, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009;(2):CD000227.Google Scholar
  171. 171.
    Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1996;125(12):961–8.PubMedGoogle Scholar
  172. 172.
    Sambrook P, Birmingham J, Kelly P, Kempler S, Nguyen T, Pocock N, et al. Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin. N Engl J Med. 1993;328(24):1747–52.PubMedCrossRefGoogle Scholar
  173. 173.
    Friedman PA. Agents affecting mineral ion homeostasis and bone turnover. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. New York, NY: McGraw-Hill; 2006. p. 1647–78.Google Scholar
  174. 174.
    Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348(9041):1535–41.PubMedCrossRefGoogle Scholar
  175. 175.
    Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999;282(14):1344–52.PubMedCrossRefGoogle Scholar
  176. 176.
    Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008;(1):CD004523.Google Scholar
  177. 177.
    Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008;(1):CD001155.Google Scholar
  178. 178.
    Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296(24):2927–38.PubMedCrossRefGoogle Scholar
  179. 179.
    Sawka AM, Papaioannou A, Adachi JD, Gafni A, Hanley DA, Thabane L. Does alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women. BMC Musculoskelet Disord. 2005;6:39.PubMedCrossRefGoogle Scholar
  180. 180.
    Homik J, Cranney A, Shea B, Tugwell P, Wells G, Adachi R, et al. Bisphosphonates for steroid induced osteoporosis. Cochrane Database Syst Rev 2000;(2):CD001347.Google Scholar
  181. 181.
    Reginster JY, Lecart MP. Efficacy and safety of drugs for Paget’s disease of bone. Bone. 1995;17(5 Suppl):485S–8.PubMedCrossRefGoogle Scholar
  182. 182.
    Cardwell CR, Abnet CC, Cantwell MM, Murray LJ. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA. 2010;304(6):657–63.PubMedCrossRefGoogle Scholar
  183. 183.
    Loke YK, Jeevanantham V, Singh S. Bisphosphonates and atrial fibrillation: systematic review and meta-analysis. Drug Saf. 2009;32(3):219–28.PubMedCrossRefGoogle Scholar
  184. 184.
    Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22(10):1479–91.PubMedCrossRefGoogle Scholar
  185. 185.
    Rossouw JE, Anderson GL, Prentice RL, Lacroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.PubMedCrossRefGoogle Scholar
  186. 186.
    Schneider DL, Barrett-Connor EL, Morton DJ. Timing of postmenopausal estrogen for optimal bone mineral density. The Rancho Bernardo Study. JAMA. 1997;277(7):543–7.PubMedCrossRefGoogle Scholar
  187. 187.
    Greenspan SL, Emkey RD, Bone HG, Weiss SR, Bell NH, Downs RW, et al. Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002;137(11):875–83.PubMedGoogle Scholar
  188. 188.
    Lindsay R, Cosman F, Lobo RA, Walsh BW, Harris ST, Reagan JE, et al. Addition of ­alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a ­randomized, controlled clinical trial. J Clin Endocrinol Metab. 1999;84(9):3076–81.PubMedCrossRefGoogle Scholar
  189. 189.
    Wimalawansa SJ. A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis. Am J Med. 1998;104(3):219–26.PubMedCrossRefGoogle Scholar
  190. 190.
    Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355(2):125–37.PubMedCrossRefGoogle Scholar
  191. 191.
    Riggs BL, Hartmann LC. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med. 2003;348(7):618–29.PubMedCrossRefGoogle Scholar
  192. 192.
    Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997;337(23):1641–7.PubMedCrossRefGoogle Scholar
  193. 193.
    Luckey M, Kagan R, Greenspan S, Bone H, Kiel RD, Simon J, et al. Once-weekly alendronate 70 mg and raloxifene 60 mg daily in the treatment of postmenopausal osteoporosis. Menopause. 2004;11(4):405–15.PubMedCrossRefGoogle Scholar
  194. 194.
    Kamischke A, Kemper DE, Castel MA, Luthke M, Rolf C, Behre HM, et al. Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy. Eur Respir J. 1998;11(1):41–5.PubMedCrossRefGoogle Scholar
  195. 195.
    Riggs BL, Wahner HW, Seeman E, Offord KP, Dunn WL, Mazess RB, et al. Changes in bone mineral density of the proximal femur and spine with aging. Differences between the postmenopausal and senile osteoporosis syndromes. J Clin Invest. 1982;70(4):716–23.PubMedCrossRefGoogle Scholar
  196. 196.
    Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000;85(8):2670–7.PubMedCrossRefGoogle Scholar
  197. 197.
    Amory JK, Watts NB, Easley KA, Sutton PR, Anawalt BD, Matsumoto AM, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab. 2004;89(2):503–10.PubMedCrossRefGoogle Scholar
  198. 198.
    Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci. 2001;56(5):M266–72.PubMedCrossRefGoogle Scholar
  199. 199.
    Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab. 1999;84(6):1966–72.PubMedCrossRefGoogle Scholar
  200. 200.
    Snyder PJ. Androgens. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. New York, NY: McGraw-Hill; 2006. p. 1573–86.Google Scholar
  201. 201.
    Bringhurst FR, Demay MB, Kronenberg HM. Hormones and disorders of mineral metabolism. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. Philadelphia, PA: Saunders Elsevier; 2008. p. 1203–68.Google Scholar
  202. 202.
    Cranney A, Welch V, Adachi JD, Homik J, Shea B, Suarez-Almazor ME, et al. Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis. Cochrane Database Syst Rev 2000;(2):CD001983.Google Scholar
  203. 203.
    Downs Jr RW, Bell NH, Ettinger MP, Walsh BW, Favus MJ, Mako B, et al. Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab. 2000;85(5):1783–8.PubMedCrossRefGoogle Scholar
  204. 204.
    Knopp JA, Diner BM, Blitz M, Lyritis GP, Rowe BH. Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomized, controlled trials. Osteoporos Int. 2005;16(10):1281–90.PubMedCrossRefGoogle Scholar
  205. 205.
    Reginster JY, Franchimont P. Side effects of synthetic salmon calcitonin given by intranasal spray compared with intramuscular injection. Clin Exp Rheumatol. 1985;3(2):155–7.PubMedGoogle Scholar
  206. 206.
    Antonelli Incalzi R, Fuso L, De Rosa M, Forastiere F, Rapiti E, Nardecchia B, et al. Co-morbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. Eur Respir J. 1997;10(12):2794–800.PubMedCrossRefGoogle Scholar
  207. 207.
    Crisafulli E, Costi S, Luppi F, Cirelli G, Cilione C, Coletti O, et al. Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation. Thorax. 2008;63(6): 487–92.PubMedCrossRefGoogle Scholar
  208. 208.
    Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J. 2008;32(4):962–9.PubMedCrossRefGoogle Scholar
  209. 209.
    Gudmundsson G, Gislason T, Lindberg E, Hallin R, Ulrik CS, Brondum E, et al. Mortality in COPD patients discharged from hospital: the role of treatment and co-morbidity. Respir Res. 2006;7:109.PubMedCrossRefGoogle Scholar
  210. 210.
    Parappil A, Depczynski B, Collett P, Marks GB. Effect of comorbid diabetes on length of stay and risk of death in patients admitted with acute exacerbations of COPD. Respirology. 2010;15(6):918–22.PubMedCrossRefGoogle Scholar
  211. 211.
    van den Borst B, Gosker HR, Zeegers MP, Schols AM. Pulmonary function in diabetes: a metaanalysis. Chest. 2010;138(2):393–406.PubMedCrossRefGoogle Scholar
  212. 212.
    Walter RE, Beiser A, Givelber RJ, O’Connor GT, Gottlieb DJ. Association between glycemic state and lung function: the Framingham Heart Study. Am J Respir Crit Care Med. 2003;167(6):911–6.PubMedCrossRefGoogle Scholar
  213. 213.
    Slatore CG, Bryson CL, Au DH. The association of inhaled corticosteroid use with serum glucose concentration in a large cohort. Am J Med. 2009;122(5):472–8.PubMedCrossRefGoogle Scholar
  214. 214.
    Faul JL, Wilson SR, Chu JW, Canfield J, Kuschner WG. The effect of an inhaled corticosteroid on glucose control in type 2 diabetes. Clin Med Res. 2009;7(1–2):14–20.PubMedCrossRefGoogle Scholar
  215. 215.
    Walters JA, Walters EH, Wood-Baker R. Oral corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005;20(3):CD005374.Google Scholar
  216. 216.
    Goel A, Suri JC, Aggarwal K. Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response. Indian J Chest Dis Allied Sci. 1992;34(1): 11–7.PubMedGoogle Scholar
  217. 217.
    Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. 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(5):1256–76.PubMedGoogle Scholar
  218. 218.
    Walters JA, Gibson PG, Wood-Baker R, Hannay M, Walters EH. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2009;(1):CD001288.Google Scholar
  219. 219.
    Baker EH, Janaway CH, Philips BJ, Brennan AL, Baines DL, Wood DM, et al. Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax. 2006;61(4):284–9.PubMedCrossRefGoogle Scholar
  220. 220.
    Chakrabarti B, Angus RM, Agarwal S, Lane S, Calverley PM. Hyperglycaemia as a predictor of outcome during non-invasive ventilation in decompensated COPD. Thorax. 2009;64(10): 857–62.PubMedCrossRefGoogle Scholar
  221. 221.
    Ceglia L, Lau J, Pittas AG. Meta-analysis: efficacy and safety of inhaled insulin therapy in adults with diabetes mellitus. Ann Intern Med. 2006;145(9):665–75.PubMedGoogle Scholar
  222. 222.
    Petersen AH, Korsatko S, Kohler G, Wutte A, Olschewski H, Sparre T, et al. The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma. Br J Clin Pharmacol. 2010;69(3):271–8.PubMedCrossRefGoogle Scholar
  223. 223.
    Mudaliar S, Henry RR. Inhaled insulin in patients with asthma and chronic obstructive ­pulmonary disease. Diabetes Technol Ther. 2007;9 Suppl 1:S83–92.PubMedGoogle Scholar
  224. 224.
    Rosenstock J, Cefalu WT, Hollander PA, Klioze SS, Reis J, Duggan WT. Safety and efficacy of inhaled human insulin (exubera) during discontinuation and readministration of therapy in adults with type 2 diabetes: a 3-year randomized controlled trial. Diabetes Technol Ther. 2009;11(11):697–705.PubMedCrossRefGoogle Scholar
  225. 225.
    Ang E, Lawrence MK, Heilmann CR, Ferguson JA, Tobian JA, Webb DM, et al. Safety and efficacy of AIR inhaled insulin compared with subcutaneous insulin in patients having diabetes and asthma: a 12-month, randomized, noninferiority trial. Diabetes Technol Ther. 2009;11 Suppl 2:S35–44.PubMedGoogle Scholar
  226. 226.
    Shapiro H, Kagan I, Shalita-Chesner M, Singer J, Singer P. Inhaled aerosolized insulin: a “topical” anti-inflammatory treatment for acute lung injury and respiratory distress syndrome? Inflammation. 2010;33(5):315–29.PubMedCrossRefGoogle Scholar
  227. 227.
    Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. J Urol. 1984;132(3):474–9.PubMedGoogle Scholar
  228. 228.
    Miyazaki H, Suda T, Otsuka A, Nagata M, Ozono S, Hashimoto D, et al. Tiotropium does not affect lower urinary tract functions in COPD patients with benign prostatic hyperplasia. Pulm Pharmacol Ther. 2008;21(6):879–83.PubMedCrossRefGoogle Scholar
  229. 229.
    Gudmundsson G, Gislason T, Janson C, Lindberg E, Suppli UC, Brondum E, et al. Depression, anxiety and health status after hospitalisation for COPD: a multicentre study in the Nordic countries. Respir Med. 2006;100(1):87–93.PubMedCrossRefGoogle Scholar
  230. 230.
    Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.PubMedCrossRefGoogle Scholar
  231. 231.
    Eisner MD, Blanc PD, Yelin EH, Katz PP, Sanchez G, Iribarren C, et al. Influence of anxiety on health outcomes in COPD. Thorax. 2010;65(3):229–34.PubMedCrossRefGoogle Scholar
  232. 232.
    Lacasse Y, Beaudoin L, Rousseau L, Maltais F. Randomized trial of paroxetine in end-stage COPD. Monaldi Arch Chest Dis. 2004;61(3):140–7.PubMedGoogle Scholar
  233. 233.
    Omachi TA, Katz PP, Yelin EH, Gregorich SE, Iribarren C, Blanc PD, et al. Depression and health-related quality of life in chronic obstructive pulmonary disease. Am J Med. 2009;122(8):778. e9–15.PubMedCrossRefGoogle Scholar
  234. 234.
    Ng TP, Niti M, Tan WC, Cao Z, Ong KC, Eng P. Depressive symptoms and chronic obstructive pulmonary disease: effect on mortality, hospital readmission, symptom burden, functional status, and quality of life. Arch Intern Med. 2007;167(1):60–7.PubMedCrossRefGoogle Scholar
  235. 235.
    Argyropoulou P, Patakas D, Koukou A, Vasiliadis P, Georgopoulos D. Buspirone effect on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease. Respiration. 1993;60(4):216–20.PubMedCrossRefGoogle Scholar
  236. 236.
    Singh NP, Despars JA, Stansbury DW, Avalos K, Light RW. Effects of buspirone on anxiety levels and exercise tolerance in patients with chronic airflow obstruction and mild anxiety. Chest. 1993;103(3):800–4.PubMedCrossRefGoogle Scholar
  237. 237.
    Silvertooth EJ, Doraiswamy PM, Clary GL, Babyak MA, Wilkerson N, Hellegars C, et al. Citalopram and quality of life in lung transplant recipients. Psychosomatics. 2004;45(3): 271–2.PubMedCrossRefGoogle Scholar
  238. 238.
    Borson S, McDonald GJ, Gayle T, Deffebach M, Lakshminarayan S, VanTuinen C. Improvement in mood, physical symptoms, and function with nortriptyline for depression in patients with chronic obstructive pulmonary disease. Psychosomatics. 1992;33(2):190–201.PubMedGoogle Scholar
  239. 239.
    Gordon GH, Michiels TM, Mahutte CK, Light RW. Effect of desipramine on control of ventilation and depression scores in patients with severe chronic obstructive pulmonary disease. Psychiatry Res. 1985;15(1):25–32.PubMedCrossRefGoogle Scholar
  240. 240.
    Light RW, Merrill EJ, Despars J, Gordon GH, Mutalipassi LR. Doxepin treatment of depressed patients with chronic obstructive pulmonary disease. Arch Intern Med. 1986;146(7):1377–80.PubMedCrossRefGoogle Scholar
  241. 241.
    Strom K, Boman G, Pehrsson K, Alton M, Singer J, Rydstrom PO, et al. Effect of protriptyline, 10 mg daily, on chronic hypoxaemia in chronic obstructive pulmonary disease. Eur Respir J. 1995;8(3):425–9.PubMedCrossRefGoogle Scholar
  242. 242.
    Eisner MD, Trupin L, Katz PP, Yelin EH, Earnest G, Balmes J, et al. Development and validation of a survey-based COPD severity score. Chest. 2005;127(6):1890–7.PubMedCrossRefGoogle Scholar
  243. 243.
    Smoller JW, Pollack MH, Systrom D, Kradin RL. Sertraline effects on dyspnea in patients with obstructive airways disease. Psychosomatics. 1998;39(1):24–9.PubMedGoogle Scholar
  244. 244.
    Cantor L, Jacobson R. COPD: How to manage comorbid depression and anxiety. J Fam Pract 2003; 2(11). http://www.jfponline.com/Pages.asp?AID=691. Accessed Oct 2011.
  245. 245.
    Brenes GA. Anxiety and chronic obstructive pulmonary disease: prevalence, impact, and treatment. Psychosom Med. 2003;65(6):963–70.PubMedCrossRefGoogle Scholar
  246. 246.
    Mikkelsen RL, Middelboe T, Pisinger C, Stage KB. Anxiety and depression in patients with chronic obstructive pulmonary disease (COPD). A review. Nord J Psychiatry. 2004;58(1): 65–70.PubMedCrossRefGoogle Scholar
  247. 247.
    Dunlop BW, Davis PG. Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review. Prim Care Companion J Clin Psychiatry. 2008;10(3): 222–8.PubMedCrossRefGoogle Scholar
  248. 248.
    Lam RW, Kennedy SH, Grigoriadis S, McIntyre RS, Milev R, Ramasubbu R, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009;117 Suppl 1:S26–43.PubMedCrossRefGoogle Scholar
  249. 249.
    Goddard AW, Brouette T, Almai A, Jetty P, Woods SW, Charney D. Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry. 2001;58(7):681–6.PubMedCrossRefGoogle Scholar
  250. 250.
    Yagan MB, White D, Staab J. Sedation of the mechanically ventilated patient. Crit Care Nurs Q. 2000;22(4):90–100.PubMedGoogle Scholar
  251. 251.
    Cox CE, Reed SD, Govert JA, Rodgers JE, Campbell-Bright S, Kress JP, et al. Economic evaluation of propofol and lorazepam for critically ill patients undergoing mechanical ventilation. Crit Care Med. 2008;36(3):706–14.PubMedCrossRefGoogle Scholar
  252. 252.
    Spiegel DR, Ramdath N. A failed case of weaning from a mechanical ventilator with lorazepam successfully accomplished by ziprasidone. Gen Hosp Psychiatry. 2009;31(5):494–6.PubMedCrossRefGoogle Scholar
  253. 253.
    Katon WJ. The comorbidity of diabetes mellitus and depression. Am J Med. 2008;121 (11 Suppl 2):S8–15.PubMedCrossRefGoogle Scholar
  254. 254.
    Ghaeli P, Shahsavand E, Mesbahi M, Kamkar MZ, Sadeghi M, Dashti-Khavidaki S. Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder. J Clin Psychopharmacol. 2004;24(4):386–8.PubMedCrossRefGoogle Scholar
  255. 255.
    Goodnick PJ. Use of antidepressants in treatment of comorbid diabetes mellitus and depression as well as in diabetic neuropathy. Ann Clin Psychiatry. 2001;13(1):31–41.PubMedGoogle Scholar
  256. 256.
    Knol MJ, Derijks HJ, Geerlings MI, Heerdink ER, Souverein PC, Gorter KJ, et al. Influence of antidepressants on glycaemic control in patients with diabetes mellitus. Pharmacoepidemiol Drug Saf. 2008;17(6):577–86.PubMedCrossRefGoogle Scholar
  257. 257.
    Boyer W. Serotonin uptake inhibitors are superior to imipramine in alleviating panic attacks: a meta-analysis. In: Darcourt G, editor. Current therapeutic approaches to panic and other anxiety disorders. New York, NY: Karger; 1994.Google Scholar
  258. 258.
    Glassman AH, O’Connor CM, Califf RM, Swedberg K, Schwartz P, Bigger Jr JT, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288(6):701–9.PubMedCrossRefGoogle Scholar
  259. 259.
    Alvarez M, Malecot CO, Gannier F, Lignon JM. Antimony-induced cardiomyopathy in guinea-pig and protection by l-carnitine. Br J Pharmacol. 2005;144(1):17–27.PubMedCrossRefGoogle Scholar
  260. 260.
    Emery CF, Schein RL, Hauck ER, MacIntyre NR. Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease. Health Psychol. 1998;17(3):232–40.PubMedCrossRefGoogle Scholar
  261. 261.
    de Godoy DV, de Godoy RF. A randomized controlled trial of the effect of psychotherapy on anxiety and depression in chronic obstructive pulmonary disease. Arch Phys Med Rehabil. 2003;84(8):1154–7.PubMedCrossRefGoogle Scholar
  262. 262.
    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):178–86.PubMedCrossRefGoogle Scholar
  263. 263.
    Remels AH, Gosker HR, van der Velden J, Langen RC, Schols AM. Systemic inflammation and skeletal muscle dysfunction in chronic obstructive pulmonary disease: state of the art and novel insights in regulation of muscle plasticity. Clin Chest Med. 2007;28(3):537–52. vi.PubMedCrossRefGoogle Scholar
  264. 264.
    Remels AH, Schrauwen P, Broekhuizen R, Willems J, Kersten S, Gosker HR, et al. Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD. Eur Respir J. 2007;30(2):245–52.PubMedCrossRefGoogle Scholar
  265. 265.
    Patel HJ, Belvisi MG, Bishop-Bailey D, Yacoub MH, Mitchell JA. Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol. 2003;170(5):2663–9.PubMedGoogle Scholar
  266. 266.
    Matera MG, Calzetta L, Cazzola M. TNF-alpha inhibitors in asthma and COPD: we must not throw the baby out with the bath water. Pulm Pharmacol Ther. 2010;23(2):121–8.PubMedCrossRefGoogle Scholar
  267. 267.
    Rabe KF, Bateman ED, O’Donnell D, Witte S, Bredenbroker D, Bethke TD. Roflumilast – an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2005;366(9485):563–71.PubMedCrossRefGoogle Scholar
  268. 268.
    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. 2007;176(2):154–61.PubMedCrossRefGoogle Scholar
  269. 269.
    Cazzola M, Picciolo S, Matera MG. Roflumilast in chronic obstructive pulmonary disease: evidence from large trials. Expert Opin Pharmacother. 2010;11(3):441–9.PubMedCrossRefGoogle Scholar
  270. 270.
    Giamarellos-Bourboulis EJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents. 2008;31(1):12–20.PubMedCrossRefGoogle Scholar
  271. 271.
    Seemungal TA, Wilkinson TM, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;178(11):1139–47.PubMedCrossRefGoogle Scholar
  272. 272.
    Cazzola M, Ciaprini C, Page CP, Matera MG. Targeting systemic inflammation: novel therapies for the treatment of chronic obstructive pulmonary disease. Expert Opin Ther Targets. 2007;11(10):1273–86.PubMedCrossRefGoogle Scholar
  273. 273.
    Barnes PJ. Future treatments for chronic obstructive pulmonary disease and its comorbidities. Proc Am Thorac Soc. 2008;5(8):857–64.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Rachael A. Evans
    • 1
  • Robert G. Varadi
    • 1
  • Kambiz Mirzaei
    • 2
  • Roger S. Goldstein
    • 1
  1. 1.Department of Respiratory MedicineWest Park Healthcare CentreTorontoCanada
  2. 2.Department of PharmacyWest Park Healthcare CentreTorontoCanada

Personalised recommendations