A Multidimensional Grading System (BODE Index) as Predictor of Hospitalization for COPD*

Kian-Chung Ong, FRCP (Edin); Arul Earnest, MSc; and Suat-Jin Lu, MBBS

Study objectives: We hypothesized that the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index would better predict hospitalization for COPD than FEV1 alone, and the purpose of this study was to test this hypothesis in a cohort of patients with COPD. Design: Historical cohort study. Setting: University-affiliated hospital. Patients: One hundred twenty-seven patients with COPD recruited from the outpatient clinic of a single institution were followed up for a mean period of 16.2 months. Measurements: The BODE index was calculated for each patient using variables obtained within 4 weeks of enrollment. The main outcome measure was the number of hospital admissions for COPD during follow-up. We used the Poisson regression model to quantify and compare the relationship between FEV1 and BODE scores with the number of hospital admissions. Results: During the follow-up period, 47% of patients required at least one hospital admission and 17% died. Using Poisson regression analysis, a significant effect of BODE score on the number of hospital admissions was found (incidence rate ratio, 1.20; 95% confidence interval [CI], 1.15 to 1.25; p < 0.001). In comparison, there was a significant but smaller effect of the FEV1 percentage of predicted on the number of hospital admissions (incidence rate ratio, 0.08; 95% CI, 0.04 to 0.16; p < 0.001). When categorizing the BODE scores into four quartiles, we found that the BODE index is also a better predictor of hospital admissions than the staging system of COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease. The pseudo r2 using quartiles of the BODE index as the predictor was 0.16, as compared to 0.04 for stages of severity based on FEV1. Conclusions: The BODE staging system, which includes in addition to FEV1 other physiologic and clinical variables, helps to better predict hospitalization for COPD. (CHEST 2005; 128:3810 3816)
Key words: airflow; body mass index; dyspnea; exercise capacity; obstruction; prognosis; risk factors Abbreviations: ATS American Thoracic Society; BODE body mass index, airflow obstruction, dyspnea, and exercise capacity; CI confidence interval; GOLD Global Initiative for Chronic Obstructive Lung Disease; HR hazard ratio; HSDP Health Service Development Program; IRR incidence rate ratio; MRC Medical Research Council

OPD is slowly C ized by aairflow progressive disorder characterobstruction that is not fully reversible.1 Although the progression of COPD is usually gradual, the disease is often associated with exacerbations of respiratory symptoms. Such exacer*From the Department of Respiratory Medicine (Dr. Ong and Mr. Earnest) and Clinical Research Unit (Dr. Lu), Tan Tock Seng Hospital, Singapore, Tan Tock Seng Hospital, Singapore. Manuscript received March 28, 2005; revision accepted June 1, 2005. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Kian-Chung Ong, FRCP (Edin), Department of Respiratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433; e-mail: kian_chung_ong@ttsh. com.sg
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bations of symptoms requiring medical intervention are important clinical events in COPD, and they place a heavy burden on health-care resources. In many countries, exacerbations of COPD are a leading cause of hospital admissions among men, and expenditures for hospitalizations represent the bulk of all COPD-related medical-care costs.2 The association between potential risk factors and hospitalization for exacerbation of COPD has been assessed. A large number of potentially modifiable risk factors of COPD exacerbation could be found among a large group of patients hospitalized for COPD.3 In a case-control study4 of a wide range of potential risk factors, lower FEV1 was one of several factors found to be independently associated with a
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higher risk of admission for a COPD exacerbation. In a subsequent prospective study,5 after adjusting for sociodemographic and clinical factors, physical activity was identified to show a strong association with reduced risk of COPD readmission. These studies suggest that factors other than the degree of airflow obstruction may influence the frequency of hospitalization for COPD, and a multidimensional grading system that assesses the respiratory and systemic manifestations of COPD would thus categorize and predict this outcome better than a classification of disease severity based on FEV1 alone. Recently, the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, a multidimensional grading system, was shown to be better than FEV1 in predicting the risk of death among patients with COPD.6 This multistage scoring system that incorporates an assessment of symptoms, nutritional state, and exercise capacity together with the spirometric measure of airflow (FEV1) can provide useful prognostic information in patients with COPD. Although the BODE index has been shown to be a predictor of the risk of death, it is not known whether this index is a useful indicator of the degree of utilization of health-care resources. We hypothesized that the BODE index would better predict hospitalization for COPD than FEV1 alone, and the purpose of this study is to test this hypothesis in a cohort of patients with hospitalization for COPD as the primary outcome variable. Materials and Methods
Patient Recruitment Between October 2002 and April 2004, patients with a wide range of severity of COPD, regardless of whether they had previous COPD hospital admissions or not, were recruited from a single institution and enrolled in the Health Service Development Program (HSDP) for COPD funded by the Ministry of Health, Singapore. This pilot service project provided several interventions optimal medication, patient education, home care, and telephone supportand is aimed at reducing hospitalization for COPD. The main outcome measure monitored in this project was the frequency of hospital admissions for COPD. Patients were recruited from the outpatient clinic. A diagnosis of COPD was established by a pulmonologist based on medical history, current symptoms, and available pulmonary function tests following Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.1 An exacerbation was defined as an increase in dyspnea, sputum production, or sputum purulence.7 At enrollment, all patients were in clinically stable condition and receiving appropriate therapy. The exclusion criteria were an illness other than COPD that was likely to result in death within 2 years; bronchial asthma, defined as an increase in the FEV1 15% above the baseline value or 200 mL after the administration of a bronchodilator; an inability to perform the lung function and 6-min walk tests; myocardial infarction within the preceding 4 months; unstable angina; or congestive heart failure (New York Heart Association class III or IV).
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The BODE index was calculated for each patient using variables obtained within 4 weeks of enrollment. For calculation of the BODE index, we used the empirical model as previously described6: for each threshold value of FEV1, distance walked in 6 min, and score on the modified Medical Research Council (MRC) dyspnea scale,8 the patients received points ranging from 0 (lowest value) to 3 (maximal value). For body mass index the values were 0 or 1. The points for each variable were added, so that the BODE index ranged from 0 to 10 points in each patient. The postbronchodilator FEV1 as a percentage of the predicted value9 was used and classified according to the three stages identified by the American Thoracic Society (ATS).10 The best of two 6-min walk tests performed at least 30-min apart11 was used for scoring. This study involved the retrospective analysis of baseline variables on entry as well as outcomes during follow-up in the HSDP project for COPD. The study protocol was approved by the institutional ethics committee. Follow-up Information on admissions and readmissions during the follow-up period was obtained from the hospital database as well as the Electronic Medical Records Exchange, a national administrative database that monitors and records admissions to all major public hospitals in Singapore. All admissions with a main and/or secondary diagnosis fulfilling any of the following code combinations (according to the International Classification of Diseases, Ninth Revision) were recorded as hospital admissions for COPD: (1) 490 496 (COPD group), 480 486 (pneumonia), 487 (influenza), or 518.81 (respiratory failure) as the main diagnosis; (2) 428 (cardiac failure) as the main diagnosis if 518.81 (respiratory failure) or 491.21 (acute exacerbation of chronic bronchitis) were the secondary diagnosis; and (3) any other respiratory problems [011 (tuberculosis), 466 (acute bronchitis), 500 505 (pneumoconiosis), 277.6 (deficit 1-antitrypsin)] as the main diagnosis if 518.81 or 491.21 were the secondary diagnosis. Criteria of the expert consensus of the ATS were used to define such combinations.5,10 At enrollment, a respiratory nurse gave all patients brief education about their disease and treatment. They were also encouraged to call the HSDP office if they were in need of assistance for a worsening of respiratory symptoms, and they would normally have called their general practitioner or specialist or have come to the emergency department instead. At the HSDP office, case managers answered all telephone calls and, in consultation with a pulmonologist, offered treatment advice by telephone or invited the patient to come to the hospital for consultation. When deemed necessary, a respiratory nurse conducted home visits to assess their condition. Pharmacologic treatment of exacerbations was not standardized. Other than these services, patients received usual care from their pulmonologist or internal medicine specialist during follow-up. Patients were seen at least once every 3 months during the follow-up period or until death. The patient and family were contacted if the patient failed to return for appointments. There were no losses to follow-up, as all patients were contacted for telephone interview, registered as dead in the mortality registry, visited in the outpatient clinics, or hospitalized during the follow-up period. Death from any cause and from specific respiratory causes was recorded. The cause of death was determined after reviewing the medical record and death certificate. Statistical Analysis The main outcome measure was the number of hospital admissions for COPD (according to the above code combinaCHEST / 128 / 6 / DECEMBER, 2005

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tions) during follow-up. We used the Poisson regression model12 to quantify and compare the relationship between FEV1 and BODE scores with the number of hospital admissions. To correct for the difference in the follow-up period between patients, we adjusted for this in the Poisson model. The incidence rate ratios (IRRs) and the corresponding 95% confidence intervals (CIs) are presented as a measure of the effect size. Furthermore, we also used the Kruskal-Wallis test to compare the geometric mean rate of hospitalization between groups with higher and lower BODE index scores. Geometric means of the rate of hospitalization were used so that patients with no hospital admissions were excluded from analysis. In addition to the primary outcome, we also studied the effect of the two measures on mortality. For this purpose, we used the Cox regression model.13 Survival time was defined as the interval between date of enrollment and date of final follow-up (October 30, 2004) or the date of death instead for those who died while during follow-up. The hazard ratios (HRs) and their corresponding 95% CIs are presented as a measure of the effect size. The Mann-Whitney U test was used to compare the median BODE scores between those who died and those who survived. Data analysis was performed using statistical software (Stata V7.0; StataCorp; College Station, TX), and all tests were done at the 5% level of significance.

Table 2Classification of Patients in the Cohort According to Airflow Obstruction With the Median BODE Index Scores in Each Category (n 127)
Patients, No. 10 31 60 26 BODE Index Median 1 2 5 7.5 Range 03 06 210 310

Severity of COPD* Stage I (FEV1 80 % predicted) Stage II (50% FEV1 80% predicted) Stage III (30% FEV1 50% predicted) Stage IV (FEV1 30% predicted or FEV1 50% predicted plus chronic respiratory failure)

*Stage I to IV of COPD were defined by the GOLD.1 Respiratory failure: Pao2 60 mm Hg with or without Paco2 mm Hg while breathing air at sea level.

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Results One hundred twenty-seven patients were followed up. The baseline characteristics of these patients are shown in Table 1. The mean age SD was 70.9 8.2 years, and mean FEV1 was 43.7% of predicted. The number of patients in stages I to IV of COPD severity as defined by GOLD and the median BODE scores of the patients in each category are shown in Table 2. The vast majority of patients had moderate-to-very severe COPD (stages II to IV). The median BODE scores were progressively higher from stage I to stage IV. Table 3 shows the classification of patients according to BODE index score and individual variable scores. Patients in the cohort generally fared worse in airflow obstruction score

than dyspnea and exercise capacity scores. Ten percent of patients had at least one significant comorbid condition. The mean duration of follow-up in the cohort was 16.2 6.2 months (range, 6 to 24 months). There

Table 3Classification of Patients in the Cohort According to BODE Index Score and Individual Variable Scores (n 127)
Characteristics BODE index score 0 1 2 3 4 5 6 7 8 9 10 Body mass index score 0 1 Airflow obstruction score 0 1 2 3 Dyspnea score 0 1 2 3 Exercise capacity score 0 1 2 3 Patients, No. (%) 4 (3) 17 (13) 13 (10) 20 (16) 14 (11) 14 (11) 13 (10) 11 (9) 10 (8) 7 (6) 4 (3) 60 (47) 67 (53) 21 (16) 20 (16) 35 (28) 51 (40) 54 (43) 36 (28) 20 (16) 17 (13) 58 (46) 21 (16) 35 (28) 13 (10)

Table 1Baseline Characteristics of Patients in the Cohort (n 127)*

Characteristics Male/female gender, No. Age, yr Body mass index, kg/m2 FEV1, L FEV1, % predicted FVC, L Modified MRC dyspnea scale Six-minute walk distance, m BODE index score Data 116/11 70.9 8.2 20.8 3.9 1.04 0.44 43.7 19.8 1.89 0.63 1.9 1.2 323.3 141.8 4.5 2.7

*Values are presented as mean SD unless otherwise indicated. Scores on the modified MRC dyspnea scale can range from 0 to 4, with a score of 4 indicating that the patient is too breathless to leave the house or becomes breathless when dressing or undressing. 3812

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were 60 patients (47%) who required at least one hospital admission for COPD during the follow-up period. The mean number of admissions for COPD was 2.5 4.9 during follow-up. The mean duration of hospital stay per admission was 6.3 5.7 days. Patients with higher BODE scores had higher rates of hospitalization. The geometric mean number of hospitalizations per month for patients with BODE scores ranging from 0 to 5 was 0.32, and the corresponding number for patients with BODE scores ranging from 6 to 10 was 0.42 (p 0.001). Using Poisson regression analysis, a significant effect of BODE score on the number of hospital admissions (IRR, 1.20; 95% CI, 1.15 to 1.25; p 0.001) was found (Table 4). In comparison, there was also a significant but smaller effect of the FEV1 percentage of predicted on the number of hospital admissions (IRR, 0.08; 95% CI, 0.04 to 0.16; p 0.001). All the individual components of the BODE index are significantly associated with hospitalization (Table 4). When categorizing the BODE scores into four quartiles6 (quartile 1, score of 0 to 2; quartile 2, score of 3 to 4; quartile 3, score of 5 to 6; and quartile 4, a score of 7 to 10), we found that the BODE index is also a better predictor of hospital admissions than the staging system of COPD as defined by GOLD (Table 5). The pseudo r2 using quartiles of the BODE index as the predictor was 0.16, as compared to 0.04 for stages of severity based on FEV1. The IRR is essentially the ratio of the rates of hospitalization of two groups. When comparing patients with BODE scores of 3 or 4 vs those with scores of 0 to 2 in Table 5, the ratio of the incidence rates between the two groups was 1.94, ie, the latter group was about twice as likely to be admitted to hospital. It is unclear why patients with BODE scores of 5 or 6 were less likely to require hospitalization than those with BODE scores of 0 to 2. Perhaps differences in

patient characteristics or other unmeasured confounders have contributed to this finding. It could also be that, as the patients with BODE scores 5 or 6 were at higher risk of death than patients of any other BODE quartile (Table 6 and described below), their hospitalization rates were lower than patients of other BODE quartiles. There were 22 deaths (17%), and all of the deaths were due to respiratory insufficiency. The median BODE score was lower among survivors than among those who died (4 vs 6, respectively; p 0.003). There was a significant effect of BODE score on mortality (HR, 1.30; 95% CI, 1.08 to 1.56; p 0.006), but no significant effect of the FEV1 percentage of predicted on mortality was observed (Table 4). Among the individual components of the BODE index, only dyspnea score and exercise capacity are associated with mortality. The HR of mortality for the patients with BODE scores of 5 to 6 was 9.41 (95% CI, 1.16 to 76.49; p 0.036) as compared to those with BODE scores of 0 to 2 (Table 6). As the HR models the time until death, the patients with BODE scores of 5 or 6 would be approximately nine times more likely to die during follow-up compared to those with BODE scores of 0 to 2. Similarly, the HR of mortality for those with BODE scores of 7 to 10 was also higher than in patients with BODE scores of 0 to 2, although this difference only tended toward statistical significance (p 0.062). In comparison, none of the FEV1 categories was significantly associated with mortality (Table 6).

Discussion The main finding of this study is that the BODE staging system,6 which includes in addition to FEV1

Table 4 Predicting Hospital Admissions and Mortality Using the BODE Index Score, Individual Variable Scores, and FEV1
Variables Risk of hospitalization BODE index Body mass index score Airflow obstruction score Dyspnea score Exercise capacity score FEV1 % predicted Risk of death from all causes BODE index Body mass index score Airflow obstruction score Dyspnea score Exercise capacity score FEV1 % predicted IRR for Hospital Admissions 1.20 1.96 1.50 1.38 1.33 0.08 1.30 1.67 1.21 1.58 2.36 0.41 HR for Mortality 95% CI 1.151.25 1.552.49 1.321.69 1.251.52 1.201.47 0.040.16 1.081.56 0.624.52 0.761.92 1.052.38 1.443.87 0.035.57 z Value 8.44 5.53 6.56 6.58 5.43 6.91 2.75 1.01 0.81 2.20 3.41 0.67 p Value 0.001 0.001 0.001 0.001 0.001 0.001 0.006 0.312 0.419 0.027 0.001 0.503

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Table 5Predicting Hospital Admissions Using Quartiles of the BODE Index and the Four Stages of COPD Severity
Covariates BODE index 02 34 56 710 COPD severity* Stage I Stage II Stage III Stage IV *Defined by GOLD.1 IRR for Hospital Admissions 1 1.94 0.3 4.18 1 7.09 10.78 11.47 95% CI z Value p Value Pseudo r2 0.16 1.342.81 0.150.60 3.005.83 3.53 3.43 8.42 0.001 0.001 0.001

2.2122.68 3.4433.77 3.6336.25

3.30 4.08 4.16

0.001 0.001 0.001

other physiologic and clinical variables, helps to better predict hospitalization in patients with COPD. COPD is a complex multidimensional disease, and classification schemes that incorporate more parameters than the degree of airflow obstruction are likely to predict outcomes more accurately.14 FEV1 is known to correlate poorly with symptoms,15 quality of life,16 exacerbation frequency,17 and exercise intolerance.18 Hence, newer approaches to disease assessment are required and may even supercede the current FEV1-based system of classification of disease severity.19 The multistage scoring system used in this study incorporates variables that can be easily evaluated in any office setting, and the BODE index has potential widespread applicability, just like the FEV1. Important to the acceptance for use of this new classification system is the evidence to support that it provides more useful prognostic information than FEV1 alone. The multidimensional staging system of the BODE index has already been shown to be a superior predictor of the risk of death in COPD patients compared to the FEV1-based staging system by the ATS.6 In this study, we were able to replicate the finding of the BODE index being a better predictor of mortality than the FEV1 and, furthermore, a staging system utilizing the BODE index was

Table 6 Predicting Mortality Using Quartiles of the BODE Index and the Four Stages of COPD Severity
Covariates BODE index 02 34 56 710 COPD severity* Stage I Stage II Stage III Stage IV *Defined by GOLD.1 3814 HR for Mortality 1 2.1 9.41 7.37 1 0.82 1.91 1.56 95% CI z Value p Value

0.1923.21 1.1676.49 0.9159.91

0.61 2.1 1.87

0.543 0.036 0.062

0.079.02 0.2414.94 0.1713.92

0.17 0.62 0.40

0.868 0.538 0.693

found to have superior predictive power for this outcome compared to the GOLD classification1 of disease severity. The latter classification of severity was based, in part, on previous recommendations of both the ATS and European Respiratory Society using spirometry as a pragmatic surrogate for disease severity. In its current form, the GOLD classification identifies five stages of COPD, although stage 0, the presence of symptoms without airflow limitation, was conceived of as an opportunity for early identification of the disease rather than a precursor of illness in all cases. The other major difference between GOLD and previous classification schemes is that individuals with respiratory failure or cor pulmonale are assigned to stage 4 irrespective of their FEV1. It is possible that the GOLD classification may have different prognostic value compared to previous classifications of severity, even though the cut points chosen by GOLD may not have been clinically validated. At present, the criteria directed by GOLD have now been adopted by both national and international guidelines for stratifying disease severity.20 Hence, it is important that we attempt to compare the predictive value of new approaches to disease assessment with these currently established and widely used criteria. To our knowledge, this is the first study to show that the BODE staging system better predicts hospitalization for COPD than the current COPD classification based on FEV1. Whether FEV1 can predict hospitalization for COPD is debatable; FEV1 was found to be a predictor of COPD hospital admissions in two studies,4,21 whereas others2224 did not find this association. A multiple component staging system combining FEV1, 6-min walking distance, dyspnea scored with the MRC scale, and Pao2 was reported to better describe health-care resources utilization among COPD patients in different geographic areas when compared to international COPD classifications (ATS, British Thoracic Society, and GOLD).25 The BODE index was also reported
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to be a much better predictor of the severity in COPD acute exacerbations than FEV1.26 Additionally, the BODE index is also responsive to changes resulting from exacerbations and may capture the impact of exacerbations in patients with COPD.27 Our findings of the usefulness of the BODE index in predicting hospitalization for COPD are also supported by the findings of a prospective study5 of risk factors of hospital readmissions for COPD exacerbation. In that study, a strong association between usual physical activity and reduced risk of COPD readmission was demonstrated. Patients with COPD who reported an activity equivalent to walking 60 min/d had a reduction in risk of readmission to hospital of almost 50%.5 Moreover, the association did not change when adjusted for FEV1 or nutritional status. These results are in agreement with the increased risk of COPD hospital admission associated with a limited 6-min walking test reported by another group of investigators.23 Therefore, it may be speculated that the superior value of the BODE index compared to FEV1 in predicting hospital admissions for COPD that we have observed is accounted for by the evaluation of physical performance status among the individual components of the BODE scoring system. Admission to the hospital and heavy use of healthcare resources is a common feature of COPD. A clinical implication of the present study is that the BODE scoring system may prove to be helpful in health-care resource allocation and in guiding therapy for individual patients in the future. This multistage scoring system, which incorporates variables that can be evaluated easily in any office setting, should not be difficult or costly to implement routinely. As the BODE index can provide useful prognostic information of survival and hospitalization, the findings of the present study are in support of the utility of the BODE index as an assessment tool for COPD patients.14 Limitations of this study that the authors would like to acknowledge are that a relatively small number of patients were evaluated and that the number of patients required to detect a significant difference in the predictive power of the BODE index and FEV1 were not been prospectively determined. Nonetheless, we managed to detect significant differences between the predictors of hospitalization and mortality despite these limitations. In addition, we acknowledge that large differences in health-care resource utilization may exist in different countries and cultures. Hence, not all the findings of this study performed in a single institution may be generalized to other countries or health-care systems. Preliminary results of the health service program in which the patients in this study participated showed a
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significant reduction in hospital admissions and total hospitalization days.28 Although this program conducted in our institution may have affected the overall hospitalization rates of these patients, it is unlikely to affect the conclusions of the present study, as the interventions and follow-up provided in addition to usual patient care in the program are irrespective of the baseline status of patients. In summary the BODE scoring system is a better predictor of hospitalization for COPD than the GOLD staging criteria based largely on FEV1. These findings are in support of the use of the BODE scoring system as a practical instrument for outcomes assessment in COPD.

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