, Volume 188, Issue 4, pp 321–329 | Cite as

Comorbidity, Hospitalization, and Mortality in COPD: Results from a Longitudinal Study

  • Claudio TerzanoEmail author
  • Vittoria Conti
  • Fabio Di Stefano
  • Angelo Petroianni
  • Daniela Ceccarelli
  • Elda Graziani
  • Salvatore Mariotta
  • Alberto Ricci
  • Antonio Vitarelli
  • Giovanni Puglisi
  • Corrado De Vito
  • Paolo Villari
  • Luigi Allegra


We evaluated comorbidity, hospitalization, and mortality in chronic obstructive pulmonary disease (COPD), with special attention to risk factors for frequent hospitalizations (more than three during the follow-up period), and prognostic factors for death. Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospective longitudinal study, and followed up until December 2007. The Charlson index without age was used to quantify comorbidity. Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization. FEV1, RV, PaO2, and PaCO2 were used to develop an index of respiratory functional impairment (REFI index). Hypertension was the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), and cardiac diseases (22.1%). Main causes of hospitalization were exacerbation of COPD (41.2%) and cardiovascular disease (34.4%). Most of the 56 deaths (19.4%) were due to cardiovascular disease (67.8%). Mortality risk depended on age, current smoking, FEV1, PaO2, the REFI index, the presence of cor pulmonale, ischemic heart disease, and lung cancer. Number and length of hospital admissions depended on the degree of dyspnea and REFI index. The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients.


Chronic obstructive pulmonary disease Comorbidity Hospitalization Long-term prognosis Mortality 


  1. 1.
    Siafakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, Yernault JC, Decramer M, Higenbottam T, Postma DS, Rees J (1995) Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 8:1398–1420CrossRefPubMedGoogle Scholar
  2. 2.
    Antonelli Incalzi R, Fuso L, De Rosa M, Forastiere F, Rapiti E, Nardecchia B, Pistelli R (1997) Co-morbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. Eur Respir J 10:2794–2800CrossRefPubMedGoogle Scholar
  3. 3.
    Nocturnal Oxygen Therapy Trial Group (1980) Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive pulmonary disease: a clinical trial. Ann Intern Med 93:391–398Google Scholar
  4. 4.
    Gerardi DA, Lovett L, Benoit-Connors ML, Reardon JZ, ZuWallack RL (1996) Variables related to increased mortality following out-patient pulmonary rehabilitation. Eur Respir J 9:431–435CrossRefPubMedGoogle Scholar
  5. 5.
    Nishimura K, Izumi T, Tsukino M, Oga T (2002) Dyspnea is a better predictor of 5 year survival than airway obstruction in patients with COPD. Chest 121:1434–1440CrossRefPubMedGoogle Scholar
  6. 6.
    Landbo C, Prescott E, Lange P, Vestbo J, Almdal TP (1999) Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 160:1856–1861PubMedGoogle Scholar
  7. 7.
    Holguin F, Folch E, Redd SC, Mannino DM (2005) Comorbidity and mortality in COPD related hospitalizations in the United States, 1979 to 2001. Chest 128:2005–2011CrossRefPubMedGoogle Scholar
  8. 8.
    Huiart L, Ernst P, Suissa S (2005) Cardiovascular morbidity and mortality in COPD. Chest 128:2640–2646CrossRefPubMedGoogle Scholar
  9. 9.
    Sidney S, Sorel M, Quesenberry CP, DeLuise C, Lanes S, Eisner MD (2005) COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program. Chest 128:2068–2075CrossRefPubMedGoogle Scholar
  10. 10.
    Ridker PM, Rifai N, Rose L, Buring JE, Cook NR (2002) Comparison of C-reactive protein and low density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347:1557–1565CrossRefPubMedGoogle Scholar
  11. 11.
    Peng RD, Chang HH, Bell ML, McDermott A, Zeger SL, Samet JM, Dominici F (2008) Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory diseases among medicare patients. JAMA 299:2172–2179CrossRefPubMedGoogle Scholar
  12. 12.
    Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, Samet JM (2006) Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 295:1127–1134CrossRefPubMedGoogle Scholar
  13. 13.
    Jennings JH, Digiovine B, Obeid D, Frank C (2009) The association between depressive symptoms and acute exacerbations of COPD. Lung 187:128–135CrossRefPubMedGoogle Scholar
  14. 14.
    COPD Guideline Group of the Standards of Care Committee of the BTS (1997) BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax 52(Suppl 5):S1–S28Google Scholar
  15. 15.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 40:373–383CrossRefPubMedGoogle Scholar
  16. 16.
    Charlson ME, Szatrowski TP, Peterson J, Gold J (1994) Validation of a combined comorbidity index. J Clin Epidemiol 47:1245–1251CrossRefPubMedGoogle Scholar
  17. 17.
    Newth CJ, Enright P, Johnson RL Jr (1997) Multiple breath nitrogen washout techniques: including measurements with patients on ventilators. Eur Respir J 10:2174–2185CrossRefPubMedGoogle Scholar
  18. 18.
    Mahler D, Wells C (1988) Evaluation of clinical methods for rating dyspnea. Chest 93:580–586CrossRefPubMedGoogle Scholar
  19. 19.
    Redelmeier DA, Bayoumi AM, Goldstein RS, Guyatt GH (1997) Interpreting small differences in functional status: the six minute walk test in chronic lung disease patients. Am J Respir Crit Care Med 155:1278–1282PubMedGoogle Scholar
  20. 20.
    Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847PubMedGoogle Scholar
  21. 21.
    Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH Jr, Heimovitz H, Cohen HJ, Wallace R (1999) Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 106:506–512CrossRefPubMedGoogle Scholar
  22. 22.
    Thogersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, Hallmans G (1998) High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation 98:2241–2247PubMedGoogle Scholar
  23. 23.
    Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Rumley A, Lowe GD (2001) Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis. Circulation 103:2323–2327PubMedGoogle Scholar
  24. 24.
    Newman AB, Shemanski L, Manolio TA, Cushman M, Mittelmark M, Polak JF, Powe NR, Siscovick D (1999) Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 19:538–545PubMedGoogle Scholar
  25. 25.
    Dewan NA, Rafique S, Kanwar B, Satpathy H, Ryschon K, Tillotson GS, Niederman MS (2000) Acute exacerbation of COPD: factors associated with poor treatment outcome. Chest 117:662–671CrossRefPubMedGoogle Scholar
  26. 26.
    Ferrer M, Alonso J, Morera J, Marrades RM, Khalaf A, Aguar MC, Plaza V, Prieto L, Antò JM (1997) Chronic obstructive pulmonary disease stage and health related quality of life. Ann Intern Med 127:1072–1079PubMedGoogle Scholar
  27. 27.
    Anthonisen NR, Wright EC, Hodgkin JE (1986) Prognosis in chronic obstructive pulmonary disease. Am Rev Respir Dis 133:14–20PubMedGoogle Scholar
  28. 28.
    Burrows B (1991) Predictors of loss of lung function and mortality in obstructive lung diseases. Eur Respir Rev 1:340–345Google Scholar
  29. 29.
    Dykstra BJ, Scanlon PD, Kester MM, Beck KC, Enright PL (1999) Lung volumes in 4, 774 patients with obstructive lung disease. Chest 115:68–74CrossRefPubMedGoogle Scholar
  30. 30.
    Hosmer DW, Lemeshow S (2000) Applied logistic regression, 2nd edn. Wiley, New YorkGoogle Scholar
  31. 31.
    Fuso L, Antonelli Incalzi R, Pistelli R, Muzzolon R, Valente S, Pagliari G, Ghiozzi F, Ciappi G (1995) Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease. Am J Med 98:272–277CrossRefPubMedGoogle Scholar
  32. 32.
    Buch P, Friberg J, Scharling H, Lange P, Prescott E (2003) Reduced lung function and risk of atrial fibrillation in the Copenhagen City Heart Study. Eur Respir J 21:1012–1016CrossRefPubMedGoogle Scholar
  33. 33.
    Christensen S, Thomsen RW, Tørring ML, Riis A, Nørgaard M, Sørensen HT (2008) Impact of COPD on outcome among patients with complicated peptic ulcer. Chest 133:1360–1366CrossRefPubMedGoogle Scholar
  34. 34.
    MacNee W (1994) Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part two. Am J Respir Crit Care Med 150:1158–1168PubMedGoogle Scholar
  35. 35.
    Dubois P, Jamart J, Machiels J, Smeets F, Lulling J (1994) Prognosis of severely hypoxemic patients receiving long term oxygen therapy. Chest 105:469–474CrossRefPubMedGoogle Scholar
  36. 36.
    Ashutosh K, Dunsky M (1987) Non invasive test for responsiveness of pulmonary hypertension to oxygen. Prediction of survival in patients with chronic obstructive lung disease and cor pulmonale. Chest 92:392–399CrossRefGoogle Scholar
  37. 37.
    Skawarski K, MacNee W, Wraith PK, Sliwinski P, Zielinski J (1991) Predictors of survival in patients with chronic obstructive pulmonary disease treated with long term oxygen therapy. Chest 100:1522–1527CrossRefGoogle Scholar
  38. 38.
    Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE (2005) The effects of a smoking cessation intervention on 14.5-year mortality. A randomized clinical trial. Ann Intern Med 142:233–239PubMedGoogle Scholar
  39. 39.
    Resnick HE, Lindsay RS, McDermott M, Devereux RB, Jones KL, Fabsitz R, Howard BW (2004) Relationship of high and low ankle brachial index to all cause and cardiovascular disease mortality. The strong heart study. Circulation 109:733–739CrossRefPubMedGoogle Scholar
  40. 40.
    Hole DJ, Watt GC, Davey-Smith G, Hart CL, Gillis CR, Hawthorne VM (1996) Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ 313:711–715PubMedGoogle Scholar
  41. 41.
    Leith DE, Mead J (1967) Mechanisms determining residual volume of the lungs in normal subjects. J Appl Physiol 23:221–227PubMedGoogle Scholar
  42. 42.
    Gibson GJ (1996) Pulmonary hyperinflation: a clinical overview. Eur Respir J 9:2640–2649CrossRefPubMedGoogle Scholar
  43. 43.
    Marin JM, Carrizo SJ, Casanova C, Martinez-Camblor P, Soriano JB, Agusti AG, Celli BR (2009) Prediction of risk of COPD exacerbations by the BODE index. Respir Med 103:373–378CrossRefPubMedGoogle Scholar
  44. 44.
    Baker EH, Janaway CH, Philips BJ, Brennan AL, Baines DL, Wood DM, Jones PW (2006) Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax 61:284–289CrossRefPubMedGoogle Scholar
  45. 45.
    McCullough PA, Li S, Jurkovitz CT, Stevens L, Collins AJ, Chen SC, Norris KC, McFarlane S, Johnson B, Shlipak MG, Obialo CI, Brown WW, Vassaloti J, Whaley-Connell AT, Brenner RM, Bakris GL (2008) KEEP Investigators (2008) Chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality. Am Heart J 156:277–283CrossRefPubMedGoogle Scholar
  46. 46.
    Thomas F, Blacher J, Benetos A, Safar ME, Pannier B (2008) Cardiovascular risk as defined in the 2003 European blood pressure classification: the assessment of an additional predictive value of pulse pressure on mortality. J Hypertens 26:1072–1077CrossRefPubMedGoogle Scholar
  47. 47.
    Golomb BA, Dang TT, Criqui MH (2006) Peripheral arterial disease: morbidity and mortality implications. Circulation 114:688–699CrossRefPubMedGoogle Scholar
  48. 48.
    Menon B, Gurnani M, Aggarwal B (2008) Comparison of outpatient visits and hospitalisations, in patients with chronic obstructive pulmonary disease, before and after influenza vaccination. Int J Clin Pract 62:593–598CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Claudio Terzano
    • 1
    Email author
  • Vittoria Conti
    • 1
  • Fabio Di Stefano
    • 1
  • Angelo Petroianni
    • 1
  • Daniela Ceccarelli
    • 1
  • Elda Graziani
    • 1
  • Salvatore Mariotta
    • 2
  • Alberto Ricci
    • 2
  • Antonio Vitarelli
    • 3
  • Giovanni Puglisi
    • 4
  • Corrado De Vito
    • 5
  • Paolo Villari
    • 5
  • Luigi Allegra
    • 6
  1. 1.Respiratory Diseases Unit, Department of Cardiovascular and Respiratory Sciences‘Sapienza’ University of Rome, Fondazione E. Lorillard Spencer CenciRomeItaly
  2. 2.Respiratory Diseases Unit, Department of Cardiovascular and Respiratory Sciences‘Sapienza’ University of Rome, Sant’Andrea HospitalRomeItaly
  3. 3.Echocardiology Unit, Department of Cardiovascular and Respiratory Sciences‘Sapienza’ University of RomeRomeItaly
  4. 4.Department of Respiratory DiseasesSan Camillo-Forlanini HospitalRomeItaly
  5. 5.Department of Experimental Medicine and Pathology‘Sapienza’ University of RomeRomeItaly
  6. 6.Institute of Respiratory DiseasesUniversity of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico- Mangiagalli-Regina ElenaMilanItaly

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