Change in the BODE Index Reflects Disease Modification in COPD: Lessons From Lung Volume Reduction Surgery

Abstract

Since the studies of Fletcher and colleagues,1Fletcher CM Tinker CM Peto R et al.The natural history of chronic bronchitis and emphysema. Oxford University Press, Oxford, UK1976Google Scholar the natural history of COPD has been associated with the accelerated progressive decline of FEV1. FEV1 became the defining feature of the disease, and because it predicted mortality, health costs, and exacerbations,2Anthonisen NR Wright EC Hodgkin JE the IPPB Trial Group. Prognosis in chronic obstructive pulmonary disease.Am Rev Respir Dis. 1986; 133: 14-20Crossref PubMed Scopus (492) Google Scholar, 3Ferrer M Alonso J Morera J et al.Chronic obstructive pulmonary disease and health related quality of life.Ann Intern Med. 1997; 127: 1072-1079Crossref PubMed Scopus (352) Google Scholar, 4Friedman M Serby C Menjoge S et al.Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD.Chest. 1999; 115: 635-641Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar it constituted the logical target for disease-modifying interventions. Unfortunately, the diagnosis of COPD mandates that there be minimal FEV1 response to bronchodilators, thus making changes in FEV1 very difficult to achieve. It is time to change the way in which we define disease modification in COPD. Indeed, COPD is associated with clinical manifestations not closely related to the FEV1, such as worsened dyspnea, reduction in exercise capacity, pulmonary hypertension, peripheral muscle weakness, and malnutrition.5Agusti AG Noguera A Sauleda J et al.Systemic effects of chronic obstructive pulmonary disease.Eur Respir J. 2003; 21: 347-360Crossref PubMed Scopus (661) Google Scholar Furthermore, all of these factors appear to be more important predictors of mortality than FEV1.6Schols AM Slangen J Volovics L et al.Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 1998; 157: 1791-1797Crossref PubMed Scopus (876) Google Scholar7Decramer M Gosselink R Troosters T et al.Muscle weakness is related to utilization of health care resources in COPD patients.Eur Respir J. 1997; 10: 417-423Crossref PubMed Scopus (343) Google Scholar8Nishimura K Izumi T Tsukino M et al.Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD.Chest. 2002; 121: 1434-1440Abstract Full Text Full Text PDF PubMed Scopus (722) Google Scholar9Pinto-Plata VM Cote C Cabral H et al.The 6-min walk distance: change over time and value as a predictor of survival in severe COPD.Eur Respir J. 2004; 23: 28-33Crossref PubMed Scopus (446) Google Scholar Therefore, defining disease modification solely on the improvement on the FEV1 does not reflect the clinical manifestations of the disease and its ultimate prognosis. Borrowing from the experience of other medical fields, disease modification in COPD can be defined as any of the changes in a patient with COPD that are caused by an intervention. The changes should be maintained over time. If we accept certain patient-centered outcomes as important, changes in any of them should be conceived as disease modifying. One such intervention, lung volume reduction surgery (LVRS), was popularized by Cooper et al10Cooper JD Patterson GA Sundaresan RS et al.Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema.J Thorac Cardiovasc Surg. 1996; 112 (discussion 1329–1330): 1319-1329Abstract Full Text Full Text PDF PubMed Scopus (467) Google Scholar as a therapy for COPD patients with primarily upper-lobe emphysema. Although the National Emphysema Treatment Trial11National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.N Engl J Med. 2003; 348: 2059-2073Crossref PubMed Scopus (1630) Google Scholar did not confer survival advantage to the surgical group as a whole, it resulted in differences in health status and exercise capacity in favor of LVRS and, at least in patients with upper-lobe emphysema and poor exercise capacity, a difference in survival after 3 years. It would be extremely useful if there were “surrogate” markers that could detect changes in a relatively short period of time, and that were accurate in predicting patient outcome. In this sense that marker could become a tool in monitoring disease modification. The multidimensional index BODE that includes the body mass index (B), percentage of predicted FEV1 (O), dyspnea (D), and the 6-min walk distance (E) is such a tool,12Celli BR Cote CG Marin JM et al.The body mass index, airflow obstruction, dyspnea and exercise capacity index in chronic obstructive pulmonary disease.N Engl J Med. 2004; 350: 1005-1012Crossref PubMed Scopus (2945) Google Scholar as it predicts mortality better than FEV1. Furthermore, the variables that contribute to the index are amenable to change by interventions and thus make the BODE a potential tool to use in the evaluation of disease-modifying interventions. In this issue of CHEST (see page 873), Imfeld and coworkers13Imfeld S Block K Weder W et al.The BODE index after lung volume reduction surgery correlates with survival.Chest. 2006; 129: 873-878Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar evaluated the power of short-term (3 months) changes in the BODE index in predicting survival in 186 patients undergoing LVRS. Using C statistics, the postoperative BODE index was a better predictor of survival than FEV1, dyspnea score, or 6-min walk distance. These results are in line with those reported by Cote and Celli,14Cote CG Celli BR Pulmonary rehabilitation and the BODE index in COPD.Eur Respir J. 2005; 26: 630-636Crossref PubMed Scopus (253) Google Scholar who showed that the BODE index can improve after pulmonary rehabilitation and that the magnitude of the change was predictive of survival. In the last few years, there have been important changes in the way we view COPD. Unfortunately, the regulatory agencies, the medical public at large, and many in our midst still cling to the old concept that it is only by changing FEV1 that we modify the course of the disease. Imfeld and coworkers are to be praised for helping show that there are disease-modifying interventions and that tools such as the BODE index can be used as markers defining ulterior outcome.