- Email: [email protected]
Chronic obstructive pulmonary disease status 2011: long walk home
Respiratory Medicine (2011) 105 S1, S4–S6
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/rmed
Chronic obstructive pulmonary disease status 2011: long walk home Stanislav Suskovica, *, Dragan Keserb a b
University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia Policlinic for Pulmonary Diseases, Medical Centre of Tuzla, Bosnia and Herzegovina
Chronic obstructive pulmonary disease (COPD) is characterized by chronic and progressive airflow limitation that is practically irreversible. COPD typically progresses over time, with ever increasing symptom burden. Typically, patients will experience breathlessness during normal daily activities or even at rest, increased production and purulence of sputum, overall health decline, and episodes of prognostically grim exacerbations that require medical intervention and sometimes hospitalizations.1–3 Worldwide, COPD is one of the leading causes of morbidity and mortality.1 Prevalence and incidence of COPD is, at least in some countries, exceptionally high, which makes proper and comprehensive management of disease even more important.3 It is projected that COPD will become the third leading cause of death worldwide by 2020 so studies of prevalence, pathophysiology, and management of this disease are needed and in fact fully justified. But are they properly valued? And even more important, are physicians interpreting the obtained information in a proper manner? Pathogenesis of COPD is far from being completely elucidated, with many still poorly recognized pathophysiological mechanisms and pathways.4–9 It is a multifaceted syndrome with much clinical, cellular, and molecular diversity.5,6,8,9 Paradoxically, its diagnosis, assessment of severity, and currently available therapeutic options are based primarily on the degree of airflow obstruction.1 COPD also is a disease with chronic airway inflammation, which is resistant to all known anti-inflammatory drugs with possible exception of anti-inflammatory action of new PD4 antagonist roflumilast.10 Inflammatory cells produce diverse mediators, which can be occasionally detected in exhaled air of patients with COPD. In last years many such biomarkers were identified and their utility partially tested. Assessing the value of specific biomarker is not an easy task.11 Among other prerequisites there should be reproducible association between the biomarker and the outcome of COPD management (diagnosis, risk stratification; selection * Corresponding author. Prof. Stanislav Suskovic, MD, PhD, FCCP. University Clinic of Respiratory and Allergic Diseases Golnik, Golnik 36, 4204 Golnik, Slovenia. Tel.: +386 4 2569 390; fax: +386 4 2569 117. E-mail: [email protected] (S. Suskovic).
of therapy; monitoring disease progression, disease activity, or response to therapy) confirmed in multiple studies. In recently published study,12 Stanojkovic with her team examined markers of oxidative stress (malondialdehyde and others) in 74 patients with severe COPD exacerbation and in 41 healthy subjects. In patients all parameters were assessed at two time points. Lucidly enough patients were divided in two groups according the presence or absence of ischemic heart disease. They found, that malondialdehyde (MDA), advanced oxidation protein products (AOPP) and total oxidant status (TOS) were increased and were higher at discharge compared with admission and the control group. Increased oxidative stress, elevated systemic inflammation and decreased antioxidant defense were common in endstage disease and particularly in patients with concomitant ischemic heart disease. Authors thus confirmed results of Bartoli et al., who demonstrated significant inverse correlation between MDA concentrations and FEV1.13 It has to be admitted, that so far no single biomarker has been able to gain wide acceptance, but some provide clinically useful information. The evaluation of such biomarkers in large studies would to become an object of intensive investigation in the future14 and should maybe include standard and routine laboratory biomarkers, like it was done in heart failure (HF).15 Results of this study again speaks in favor of complex inflammatory and pathophysiologically interactions between COPD and HF and possibly, as stressed in recently published paper, between COPD and other comorbidities as ischemic stroke or endocrinological disorders as diabetes.16 This is an important message especially as inhaled glucocorticoids accelerate the natural course of diabetes.17 COPD frequently walks hand in hand with complex comorbidity. In fact, HF, bronchial carcinoma or pneumonia are the cause of many deaths in COPD patients, particularly in those with mild or moderate disease.18 Although a prevalent and deadly combination, concomitant COPD and HF19–23 frequently remain unrecognized. Such a reluctance, unfortunately, is not limited to daily practice but is evident in international COPD guidelines, where comorbidites are largely neglected.1 This translates back to clinical practice, where beta blockers are withheld in many COPD patients
0954-6111$ – see front matter © 2011 Elsevier Ltd. All rights reserved.
Chronic obstructive pulmonary disease status 2011: long walk home
with known cardiovascular disease. From analysis in the journal24 and previous studies we can conclude that benefits of beta blockers outweigh any potential risk thus COPD should not be regarded as contraindication for beta blocker use any more.25–28 Management of COPD patients is a very complex task indeed. Adherence to treatment is not optimal,29 but is crucial for obtaining best management outcomes.30 Lately it become clear, that for successful management to avoid potential problems that may occur after discharge they should be identified during the discharge planning process.31,32 Standardized, early screening to accurately identify patients at risk for unmet needs after discharge is critical to the development and implementation of a quality discharge plan. The lack of time available to hospital clinicians to assemble and interpret extensive and complex information calls for improved methods to support identifying patients at risk for poor outcomes, engaging discharge planners efficiently and accurately, providing a standardized assessment to identify and address continuing care needs, and identifying patients who would benefit from post-acute care. This complex management process was addressed also in the study of Farkas et al.,33 in which investigators search for the evidence on the effectiveness of a discharge coordinator in patients hospitalized due to acute exacerbation of COPD. First information from this study is already available and elegantly demonstrates the prognostic importance of nutritional risk assessment.34 Further results, primarily about main hypothesis, are eagerly awaited. The quest for adequate management of COPD is far from being complete. Answers to many questions are admittedly not known; yet many were already quite properly answered. Whether knowledge is translated into everyday routine is another issue.
Conflict of interest statement The authors declare that they have no competing interest.
References 1. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management and prevention of chronic pulmonary disease (GOLD): NHLBI/WHO workshop report. Bethesda, MD: National Institutes of Health, 2010. Last view: 1.8.2011: http://www.goldcopd.org/. 2. Lainscak M, von Haehling S, Doehner W, Sarc I, Jeric T, Ziherl K, et al. Body mass index and prognosis in patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease. J Cachexia Sarcopenia Muscle 2011;2:81–6. 3. Afonso AS, Verhamme KM, Sturkenboom MC, Brusselle GG. COPD in the general population: Prevalence, incidence and survival. Respir Med 2011. doi: 10.1016/j.rmed.2011.06.012. 4. Fischer BM, Pavlisko E, Voynow JA. Pathogenic triad in COPD: oxidative stress, protease–antiprotease imbalance, and inflammation. Int J Chron Obstruct Pulmon Dis 2011;6:413–21. 5. Rijavec M, Volarevic S, Osolnik K, Kosnik M, Korosec P. Natural killer T cells in pulmonary disorders. Respir Med 2011;105(Suppl 1):S20–5. 6. Marc MM, Korosec P, Kosnik M, Kern I, Flezar M, Suskovic S, et al. Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma. Am J Respir Cell Mol Biol 2004; 31:216–9.
S5
7. Suskovic S. COPD is not COPD is not allergy. Wien Klin Wochenschr 2009;121:289–92. 8. Doehner W, von Haehling S, Anker SD, Lainscak M. Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review. Wien Klin Wochenschr 2009;121:293–6. 9. Stefanska AM, Walsh PT. Chronic obstructive pulmonary disease: evidence for an autoimmune component. Cell Mol Immunol 2009;6:81–6. 10. Ulrik CS, Calverley PM. Roflumilast: clinical benefit in patients suffering from COPD. Clin Respir J 2010;4:197–201. 11. Agusti A, Sobradillo P, Celli B. Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine. Am J Respir Crit Care Med 2011;183:1129–37. 12. Stanojkovic I, Kotur-Stevuljevic J, Milenkovic B, Spasic S, Vujic T, Stefanovic A, et al. Pulmonary function, oxidative stress and inflammatory markers in severe COPD exacerbation. Respir Med 2011;105(Suppl 1):S31–7. 13. Bartoli ML, Novelli F, Costa F, Malagrino L, Melosini L, Bacci E, et al. Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases. Mediators Inflamm 2011;2011:891752. 14. Koutsokera A, Stolz D, Loukides S, Kostikas K. Systemic biomarkers in exacerbations of COPD: the evolving clinical challenge. Chest 2011. doi: 10.1378/chest.11-0495. 15. Lainscak M, von Haehling S, Anker SD. Natriuretic peptides and other biomarkers in chronic heart failure: From BNP, NT-proBNP, and MR-proANP to routine biochemical markers. Int J Cardiol 2009;132:303–11. 16. Doehner W, Haeusler KG, Endres M, Anker SD, MacNee W, Lainscak M. Neurological and endocrinological disorders: orphans in chronic obstructive pulmonary disease. Respir Med 2011;105(Suppl 1):S12–9. 17. Suissa S, McGhan R, Niewoehner D, Make B. Inhaled corticosteroids in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2007;4:535–42. 18. Rodríguez LA, Wallander MA, Martín-Merino E, Johansson S. Heart failure, myocardial infarction, lung cancer and death in COPD patients: A UK primary care study. Respir Med 2010;104:1691–9. 19. Cazzola M, Calzetta L, Bettoncelli G, Cricelli C, Romeo F, Matera MG, et al. Cardiovascular disease in asthma and COPD: A population-based retrospective cross-sectional study. Respir Med 2011. doi: 10.1016-j.rmed.2011.06.012. 20. Padeletti M, Jelic S, LeJemtel TH. Coexistent chronic obstructive pulmonary disease and heart failure in the elderly. Int J Cardiol 2008;125:209–15. 21. Mascarenhas J, Azevedo A, Bettencourt P. Coexisting chronic obstructive pulmonary disease and heart failure: implications for treatment, course and mortality. Curr Opin Pulm Med 2010; 16:106–11. 22. Lainscak M, Hodoscek LM, Dungen HD, Rauchhaus M, Doehner W, Anker SD, et al. The burden of chronic obstructive pulmonary disease in patients hospitalized with heart failure. Wien Klin Wochenschr 2009;121:309–13. 23. Iversen KK, Kjaergaard J, Akkan D, Kober L, Torp-Pedersen C, Hassager C, et al. Chronic obstructive pulmonary disease in patients admitted with heart failure. J Intern Med 2008;264: 361–9. 24. Lainscak M, Podbregar M, Kovacic D, Rozman J, von Haehling S. Differences between bisoprolol and carvedilol in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized trial. Respir Med 2011;105(Suppl 1):S44–9. 25. Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta-blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ 2011;342:d2549.
S6
26. van Gestel YR, Hoeks SE, Sin DD, Welten GM, Schouten O, Witteveen HJ, 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. 27. Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW. Betablockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med 2010;170:880–7. 28. Lainscak M, Keber I. Patients’ knowledge and beta blocker treatment improve prognosis of patients from a heart failure clinic. Eur J Heart Fail 2006;8:187–90. 29. Sarc I, Jeric T, Ziherl K, Suskovic S, Kosnik M, Anker SD, et al. Adherence to treatment guidelines and long-term survival in hospitalized patients with chronic obstructive pulmonary disease. J Eval Clin Pract 2011;17:737–43. 30. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and
S. Suskovic, D. Keser
31.
32.
33.
34.
survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775–89. Gardiner C, Gott M, Payne S, Small N, Barnes S, Halpin D, et al. Exploring the care needs of patients with advanced COPD: an overview of the literature. Respir Med 2010;104:159–65. O’Leary KJ, Lindquist LA, Colone MA, Haviley C, Thompson JA, Baker DW. Effect of a hospitalist-care coordinator team on a nonteaching hospitalist service. J Hosp Med 2008;3:103–9. Farkas J, Kadivec S, Kosnik M, Lainscak M. Effectiveness of discharge-coordinator intervention in patients with chronic obstructive pulmonary disease: study protocol of a randomized controlled clinical trial. Respir Med 2011; 105(Suppl 1):S26–30. Benedik B, Farkas J, Kosnik M, Kadivec S, Lainscak M. Mini nutritional assessment, body composition, and hospitalisations in patients with chronic obstructive pulmonary disease. Respir Med 2011;105(Suppl 1):S38–43.
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/rmed
Chronic obstructive pulmonary disease status 2011: long walk home Stanislav Suskovica, *, Dragan Keserb a b
University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia Policlinic for Pulmonary Diseases, Medical Centre of Tuzla, Bosnia and Herzegovina
Chronic obstructive pulmonary disease (COPD) is characterized by chronic and progressive airflow limitation that is practically irreversible. COPD typically progresses over time, with ever increasing symptom burden. Typically, patients will experience breathlessness during normal daily activities or even at rest, increased production and purulence of sputum, overall health decline, and episodes of prognostically grim exacerbations that require medical intervention and sometimes hospitalizations.1–3 Worldwide, COPD is one of the leading causes of morbidity and mortality.1 Prevalence and incidence of COPD is, at least in some countries, exceptionally high, which makes proper and comprehensive management of disease even more important.3 It is projected that COPD will become the third leading cause of death worldwide by 2020 so studies of prevalence, pathophysiology, and management of this disease are needed and in fact fully justified. But are they properly valued? And even more important, are physicians interpreting the obtained information in a proper manner? Pathogenesis of COPD is far from being completely elucidated, with many still poorly recognized pathophysiological mechanisms and pathways.4–9 It is a multifaceted syndrome with much clinical, cellular, and molecular diversity.5,6,8,9 Paradoxically, its diagnosis, assessment of severity, and currently available therapeutic options are based primarily on the degree of airflow obstruction.1 COPD also is a disease with chronic airway inflammation, which is resistant to all known anti-inflammatory drugs with possible exception of anti-inflammatory action of new PD4 antagonist roflumilast.10 Inflammatory cells produce diverse mediators, which can be occasionally detected in exhaled air of patients with COPD. In last years many such biomarkers were identified and their utility partially tested. Assessing the value of specific biomarker is not an easy task.11 Among other prerequisites there should be reproducible association between the biomarker and the outcome of COPD management (diagnosis, risk stratification; selection * Corresponding author. Prof. Stanislav Suskovic, MD, PhD, FCCP. University Clinic of Respiratory and Allergic Diseases Golnik, Golnik 36, 4204 Golnik, Slovenia. Tel.: +386 4 2569 390; fax: +386 4 2569 117. E-mail: [email protected] (S. Suskovic).
of therapy; monitoring disease progression, disease activity, or response to therapy) confirmed in multiple studies. In recently published study,12 Stanojkovic with her team examined markers of oxidative stress (malondialdehyde and others) in 74 patients with severe COPD exacerbation and in 41 healthy subjects. In patients all parameters were assessed at two time points. Lucidly enough patients were divided in two groups according the presence or absence of ischemic heart disease. They found, that malondialdehyde (MDA), advanced oxidation protein products (AOPP) and total oxidant status (TOS) were increased and were higher at discharge compared with admission and the control group. Increased oxidative stress, elevated systemic inflammation and decreased antioxidant defense were common in endstage disease and particularly in patients with concomitant ischemic heart disease. Authors thus confirmed results of Bartoli et al., who demonstrated significant inverse correlation between MDA concentrations and FEV1.13 It has to be admitted, that so far no single biomarker has been able to gain wide acceptance, but some provide clinically useful information. The evaluation of such biomarkers in large studies would to become an object of intensive investigation in the future14 and should maybe include standard and routine laboratory biomarkers, like it was done in heart failure (HF).15 Results of this study again speaks in favor of complex inflammatory and pathophysiologically interactions between COPD and HF and possibly, as stressed in recently published paper, between COPD and other comorbidities as ischemic stroke or endocrinological disorders as diabetes.16 This is an important message especially as inhaled glucocorticoids accelerate the natural course of diabetes.17 COPD frequently walks hand in hand with complex comorbidity. In fact, HF, bronchial carcinoma or pneumonia are the cause of many deaths in COPD patients, particularly in those with mild or moderate disease.18 Although a prevalent and deadly combination, concomitant COPD and HF19–23 frequently remain unrecognized. Such a reluctance, unfortunately, is not limited to daily practice but is evident in international COPD guidelines, where comorbidites are largely neglected.1 This translates back to clinical practice, where beta blockers are withheld in many COPD patients
0954-6111$ – see front matter © 2011 Elsevier Ltd. All rights reserved.
Chronic obstructive pulmonary disease status 2011: long walk home
with known cardiovascular disease. From analysis in the journal24 and previous studies we can conclude that benefits of beta blockers outweigh any potential risk thus COPD should not be regarded as contraindication for beta blocker use any more.25–28 Management of COPD patients is a very complex task indeed. Adherence to treatment is not optimal,29 but is crucial for obtaining best management outcomes.30 Lately it become clear, that for successful management to avoid potential problems that may occur after discharge they should be identified during the discharge planning process.31,32 Standardized, early screening to accurately identify patients at risk for unmet needs after discharge is critical to the development and implementation of a quality discharge plan. The lack of time available to hospital clinicians to assemble and interpret extensive and complex information calls for improved methods to support identifying patients at risk for poor outcomes, engaging discharge planners efficiently and accurately, providing a standardized assessment to identify and address continuing care needs, and identifying patients who would benefit from post-acute care. This complex management process was addressed also in the study of Farkas et al.,33 in which investigators search for the evidence on the effectiveness of a discharge coordinator in patients hospitalized due to acute exacerbation of COPD. First information from this study is already available and elegantly demonstrates the prognostic importance of nutritional risk assessment.34 Further results, primarily about main hypothesis, are eagerly awaited. The quest for adequate management of COPD is far from being complete. Answers to many questions are admittedly not known; yet many were already quite properly answered. Whether knowledge is translated into everyday routine is another issue.
Conflict of interest statement The authors declare that they have no competing interest.
References 1. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management and prevention of chronic pulmonary disease (GOLD): NHLBI/WHO workshop report. Bethesda, MD: National Institutes of Health, 2010. Last view: 1.8.2011: http://www.goldcopd.org/. 2. Lainscak M, von Haehling S, Doehner W, Sarc I, Jeric T, Ziherl K, et al. Body mass index and prognosis in patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease. J Cachexia Sarcopenia Muscle 2011;2:81–6. 3. Afonso AS, Verhamme KM, Sturkenboom MC, Brusselle GG. COPD in the general population: Prevalence, incidence and survival. Respir Med 2011. doi: 10.1016/j.rmed.2011.06.012. 4. Fischer BM, Pavlisko E, Voynow JA. Pathogenic triad in COPD: oxidative stress, protease–antiprotease imbalance, and inflammation. Int J Chron Obstruct Pulmon Dis 2011;6:413–21. 5. Rijavec M, Volarevic S, Osolnik K, Kosnik M, Korosec P. Natural killer T cells in pulmonary disorders. Respir Med 2011;105(Suppl 1):S20–5. 6. Marc MM, Korosec P, Kosnik M, Kern I, Flezar M, Suskovic S, et al. Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma. Am J Respir Cell Mol Biol 2004; 31:216–9.
S5
7. Suskovic S. COPD is not COPD is not allergy. Wien Klin Wochenschr 2009;121:289–92. 8. Doehner W, von Haehling S, Anker SD, Lainscak M. Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review. Wien Klin Wochenschr 2009;121:293–6. 9. Stefanska AM, Walsh PT. Chronic obstructive pulmonary disease: evidence for an autoimmune component. Cell Mol Immunol 2009;6:81–6. 10. Ulrik CS, Calverley PM. Roflumilast: clinical benefit in patients suffering from COPD. Clin Respir J 2010;4:197–201. 11. Agusti A, Sobradillo P, Celli B. Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine. Am J Respir Crit Care Med 2011;183:1129–37. 12. Stanojkovic I, Kotur-Stevuljevic J, Milenkovic B, Spasic S, Vujic T, Stefanovic A, et al. Pulmonary function, oxidative stress and inflammatory markers in severe COPD exacerbation. Respir Med 2011;105(Suppl 1):S31–7. 13. Bartoli ML, Novelli F, Costa F, Malagrino L, Melosini L, Bacci E, et al. Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases. Mediators Inflamm 2011;2011:891752. 14. Koutsokera A, Stolz D, Loukides S, Kostikas K. Systemic biomarkers in exacerbations of COPD: the evolving clinical challenge. Chest 2011. doi: 10.1378/chest.11-0495. 15. Lainscak M, von Haehling S, Anker SD. Natriuretic peptides and other biomarkers in chronic heart failure: From BNP, NT-proBNP, and MR-proANP to routine biochemical markers. Int J Cardiol 2009;132:303–11. 16. Doehner W, Haeusler KG, Endres M, Anker SD, MacNee W, Lainscak M. Neurological and endocrinological disorders: orphans in chronic obstructive pulmonary disease. Respir Med 2011;105(Suppl 1):S12–9. 17. Suissa S, McGhan R, Niewoehner D, Make B. Inhaled corticosteroids in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2007;4:535–42. 18. Rodríguez LA, Wallander MA, Martín-Merino E, Johansson S. Heart failure, myocardial infarction, lung cancer and death in COPD patients: A UK primary care study. Respir Med 2010;104:1691–9. 19. Cazzola M, Calzetta L, Bettoncelli G, Cricelli C, Romeo F, Matera MG, et al. Cardiovascular disease in asthma and COPD: A population-based retrospective cross-sectional study. Respir Med 2011. doi: 10.1016-j.rmed.2011.06.012. 20. Padeletti M, Jelic S, LeJemtel TH. Coexistent chronic obstructive pulmonary disease and heart failure in the elderly. Int J Cardiol 2008;125:209–15. 21. Mascarenhas J, Azevedo A, Bettencourt P. Coexisting chronic obstructive pulmonary disease and heart failure: implications for treatment, course and mortality. Curr Opin Pulm Med 2010; 16:106–11. 22. Lainscak M, Hodoscek LM, Dungen HD, Rauchhaus M, Doehner W, Anker SD, et al. The burden of chronic obstructive pulmonary disease in patients hospitalized with heart failure. Wien Klin Wochenschr 2009;121:309–13. 23. Iversen KK, Kjaergaard J, Akkan D, Kober L, Torp-Pedersen C, Hassager C, et al. Chronic obstructive pulmonary disease in patients admitted with heart failure. J Intern Med 2008;264: 361–9. 24. Lainscak M, Podbregar M, Kovacic D, Rozman J, von Haehling S. Differences between bisoprolol and carvedilol in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized trial. Respir Med 2011;105(Suppl 1):S44–9. 25. Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta-blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ 2011;342:d2549.
S6
26. van Gestel YR, Hoeks SE, Sin DD, Welten GM, Schouten O, Witteveen HJ, 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. 27. Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW. Betablockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med 2010;170:880–7. 28. Lainscak M, Keber I. Patients’ knowledge and beta blocker treatment improve prognosis of patients from a heart failure clinic. Eur J Heart Fail 2006;8:187–90. 29. Sarc I, Jeric T, Ziherl K, Suskovic S, Kosnik M, Anker SD, et al. Adherence to treatment guidelines and long-term survival in hospitalized patients with chronic obstructive pulmonary disease. J Eval Clin Pract 2011;17:737–43. 30. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and
S. Suskovic, D. Keser
31.
32.
33.
34.
survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775–89. Gardiner C, Gott M, Payne S, Small N, Barnes S, Halpin D, et al. Exploring the care needs of patients with advanced COPD: an overview of the literature. Respir Med 2010;104:159–65. O’Leary KJ, Lindquist LA, Colone MA, Haviley C, Thompson JA, Baker DW. Effect of a hospitalist-care coordinator team on a nonteaching hospitalist service. J Hosp Med 2008;3:103–9. Farkas J, Kadivec S, Kosnik M, Lainscak M. Effectiveness of discharge-coordinator intervention in patients with chronic obstructive pulmonary disease: study protocol of a randomized controlled clinical trial. Respir Med 2011; 105(Suppl 1):S26–30. Benedik B, Farkas J, Kosnik M, Kadivec S, Lainscak M. Mini nutritional assessment, body composition, and hospitalisations in patients with chronic obstructive pulmonary disease. Respir Med 2011;105(Suppl 1):S38–43.