Health-related quality of life is associated with COPD severity: a comparison between the GOLD staging and the BODE index

Chronic Respiratory Disease 2009; 6: 75 80 http://crd.sagepub.com ORIGINAL PAPER Health-related quality of life is associated with COPD severity: a comparison between the GOLD staging and the BODE index M Medinas Amorós 1, C Mas-Tous 2, F Renom-Sotorra 1, M Rubí-Ponseti 1, MJ Centeno-Flores 1 and MT Gorriz-Dolz 1 1 Department of Respiratory Medicine, Joan March Hospital, Bunyola, Baleares, Spain; and 2 Psychology Department, University of Balearic Islands, Baleares, Spain Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease. Currently, severity Global initiative for chronic Obstructive Lung Disease (GOLD) criteria are used to diagnose the severity of COPD, but a new grading system, the body mass index, bronchial obstruction, dyspnea, exercise (BODE) index, was recently proposed to provide useful prognostic information. The objective of this study is to evaluate the association between health-related quality of life (HRQOL) and COPD severity assessed by two criteria: the GOLD classification and the BODE index. Sixty-four patients with COPD were examined with lung function tests and specific and generic HRQOL questionnaires (St. George s Respiratory Questionnaire [SGRQ], Nottingham Health Profile [NHP]). Participants were divided into four severity groups using the GOLD guidelines and the BODE index quartiles. The association between NHP and SGRQ subscales, and the BODE index was significant (P < 0.01). However, the GOLD classification shows a correlation only with SGRQ total score (P < 0.05) but not with NHP or SGRQ subscales. There was an association of the SGRQ total score between the severity groups of BODE (P = 0.0001), but there was no difference in the SGRQ total score between the severity groups of GOLD classification (P = 0.244). The present study suggests that COPD severity assessed by the BODE index can be more directly related with HRQOL. Chronic Respiratory Disease 2009; 6: 75 80 Key words: COPD; dyspnea; Nottingham Health Profile; quality of life; St. George s Respiratory Questionnaire; walking test Introduction Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, and it is estimated that 7 10% of the adult population may be affected. 1 COPD is a slow, progressive, and largely irreversible airways disease that encompasses the old terms emphysema and chronic bronchitis, resulting in breathlessness, cough, and sputum production. Smoking and other air pollutants, as well as a number of other exposures and conditions are wellestablished risk factors for COPD. 2 In 2001 (revised in 2004 3 ) the U.S. National Heart, Lung and Blood Institute and the World Health Organization published guidelines for the diagnosis, management, and treatment of COPD. The Global initiative for chronic Obstructive Lung Correspondence to: Magdalena Medinas Amorós, Department of Respiratory Medicine, Joan March Hospital, Bunyola, Mallorca, Baleares, Spain. Email: mmapsi1@gmail.com Disease (GOLD) criteria were launched with the aim of increasing awareness of COPD and of decreasing morbidity and mortality from the disease. One key aspect of these guidelines is that COPD is classified by severity into four stages; this constitutes the basis of treatment recommendations. However, over the last decade, more research on the development of utility instruments has been undertaken to quantify the impact of disease on daily life and general well-being from the COPD patient s point of view. As the disease progresses, patients with COPD experience a worsening in their quality of life. The concept of health-related quality of life (HRQOL) combines some of the main aspects of health, disease, and adaptation that take an integral part of the patient and his or her treatment. The measurement of HRQOL in these patients mainly covers the following dimensions related to their subjective experience: difficulties in physical mobility, psychological SAGE Publications 2009 Los Angeles, London, New Delhi and Singapore 10.1177/1479972308101551

76 Quality of life associated with COPD severity and social status, and general perception of health and well-being in relation to the disease. HRQOL has become an important outcome in respiratory patients as proved by the development of several respiratory disease-specific questionnaires like the St. George s Respiratory disease Questionnaire (SGRQ) or the Chronic Respiratory Disease Questionnaire. Currently, severity GOLD criteria were used to diagnose the severity of COPD and to predict COPD mortality. 4 The forced expiratory volume in the first second (FEV 1 ) is the single best variable to stratify for COPD severity; however, it does not accurately predict dyspnea symptoms, fatigue, or exercise tolerance. 5 This is because COPD is a multisystemic disease, and the airflow limitation alone does not capture all aspects of disease severity and their consequences. 6 Recently, a new multidimensional grading system, the body mass index, Bronchial Obstruction, Dyspnea, Exercise (BODE) index, was proposed to provide useful prognostic information of COPD patients. This multidimensional grading system incorporates four parameters: assessment of symptoms, nutritional state, exercise capacity, and spirometric measures such as FEV 1, all aimed to include both respiratory and systemic manifestations of COPD. BODE was reported to be better than FEV 1 alone in predicting the risk of death in COPD. 7 Recently, Cote and Celli 8 have reported the utility of the BODE index in the evaluation of pulmonary rehabilitation programs, and Ong, et al. 9 also reported the capacity of BODE to predict hospitalizations in COPD patients. Frequent exacerbations and hospitalizations in patients with COPD, mainly in advanced stages, represents a challenge for studies that try to validate the effectiveness of the BODE index on the staging, prognosis, and results of therapeutic interventions in COPD. The objective of this study is to evaluate the association between HRQOL and level of COPD severity when assessed by two criteria: the GOLD classification and the BODE index classification. Methods Study design A cross-sectional sample of patients with COPD was selected and examined comprehensively with lung function tests and a battery of specific and generic HRQOL questionnaires. All patients were included in a Continued Attention Programme for COPD patients (called the RESC program in Spain) approved by the Hospital Medical Ethical Committee at the Department of Respiratory Medicine of the Joan March Hospital in Baleares, Spain. Patients The 64 consecutive outpatients with a diagnosis of COPD who agreed to participate in the RESC program and who met the inclusion criteria were included in our study. Inclusion criteria are as follows: COPD with a ratio FEV 1 /forced vital capacity (FVC) < 0.7, an FEV 1 < 80% of predicted, age 50 90 years, and smokers or former smokers with a smoking history of 10 pack-years or more. Exclusion criteria were other disabling or severe disease and/or coexistence of other causes of impaired pulmonary function. Patients with a history indicative of asthma were excluded. None of them were in acute COPD exacerbation at the time of investigation. Measures Clinical data and lung-function tests All participants were administered a structured clinical interview to obtain the following clinical, social and demographic parameters: age, gender, weight, height, diagnosis of COPD, number of hospitalizations in the last year; and presence of comorbidities (Charlson Index). 10 Assessment of lung function (FEV 1, FVC, absolute and reference values) was based on the reference values from American Thoracic Society/European Respiratory Society guidelines. Levels of FVC% predicted were also used in the analysis instead of COPD severity stages. The definition and severity criteria for GOLD and BODE index are described in Table 1. Exercise performance and breathlessness The 6-min walking test (6WT): Patients were instructed to walk as far as possible for 6 min, taking Table 1 Severity criteria of COPD (GOLD and BODE index) Global initiative for chronic Obstructive Lung Disease, GOLD classification BODE index quartile classification. Celli, et al. 7 ImildCOPDFEV 1 80% predicted Q1: 0 2 II moderate COPD FEV 1 50 < 80% predicted Q2: 3 4 III severe COPD FEV 1 30 < 50% predicted Q3: 5 6 IV very severe COPD FEV 1 < 30% predicted Q4: 7 10 Chronic Respiratory Disease

Quality of life associated with COPD severity 77 rest periods if necessary. Before each test, the patient s resting heart rate, blood pressure, and arterial oxygen saturation level were monitored at rest in a sitting position. These measurements were taken primarily for patient monitoring and safety purposes and were not formally collected or analyzed. The total distance walked was measured to the nearest meter and recorded. All patients, who were tested by the same technician, performed the 6WT after the first training session, 11 but only the results of the second test have been analyzed in this study. The Modified Medical Research Council (MMRC) dyspnea scale: the MMRC dyspnea scale has been used extensively for grading breathlessness on daily activities. This scale measures perceived respiratory disability. Patients were asked about their perceived breathlessness and were then classified into the MMRC five dyspnea grades (0 minimal to 4 maximum) according to how they perceived their disability. 12 Quality of life measures The Nottingham Health Profile (NHP): The NHP was developed to be used in epidemiological studies of health and disease. It consists of two parts. Part I contains 38 yes/no items in six dimensions: pain, physical mobility, emotional reactions, energy, social isolation, and sleep. Part II contains seven general yes/no questions on daily living problems. The two parts may be used independently, and part II is not analyzed in this study. The NHP questionnaire has an adapted and validated Spanish version, which is used in our study. 13 The higher the NHP score the lower the general quality of life. The SGRQ: The SGRQ is a standardized selfadministered airways disease-specific questionnaire developed by Jones, et al. 14 This questionnaire has an adapted and validated Spanish version used in our study. 15 It contains 50 items divided into three subscales: symptoms (8 items), including several respiratory symptoms, their frequency, and severity; activity (16 items), on activities that cause or are limited by breathlessness; and impact (26 items), which covers a wide range of aspects related with social functioning and psychological disturbances resulting from airways disease. The higher the SGRQ score the lower the general quality of life. Design All patients underwent clinical examination, lungfunction tests, and questionnaires on the same day. Sequentially, all clinical, social and demographic data were collected; then, the lung function and the 6WTs were conducted. Brief instructions from the administrator, an appointed psychologist, were given to all subjects before completing the questionnaires. All questionnaires were completed in the same order: first the HRQOL questionnaires (NHP and SGRQ) and then the dyspnea scale (MRC). Finally, the body mass index and the BODE index were calculated. Statistical analysis Descriptive statistics were computed for each of the analyzed variables. All measures had a normal distribution. Participants were divided into four severity groups according to FEV 1 % predicted (prebronchodilator) using the GOLD guidelines and the BODE Index quartiles. Nonparametric Spearman correlation coefficient analysis were calculated to study the relationships between the HRQOL measures, GOLD classification, and the BODE index. Statistical analysis of covariance was performed with HRQOL scores as dependent variable. The BODE index and the GOLD classification were used as factors in the analysis. Variables like age, gender, smoking status, and comorbility were used as covariates. All variables with a P-value <0.05 were entered in the model and changes were considered to be statistically significant at the 0.05 level of significance. Data was analyzed by the statistical program SPSS version 12, for Windows. Results Subjects characteristics Participants were 64 patients (59 men and 5 women), aged 51 90 years (mean = 69.7; SD = 8.9) with a diagnosis of COPD from the Joan March Hospital in Baleares (Spain). The 52.3% of the sample presented comorbidity measured by the Charlson Index. The baseline demographic and clinical characteristics of our sample are shown in Table 2. Correlation between HRQOL measures and the BODE index/gold classification Table 3 shows the Spearman correlation coefficients between the generic (NHP total score) and SGRQ scores adjusted to GOLD criteria and BODE index. The association between SGRQ subscales and http://crd.sagepub.com

78 Quality of life associated with COPD severity Table 2 Subjects characteristics (n = 64) 100 Mean SD Mín Max Age 70.062 8.984 51.00 90.00 FEV 1 (L) 0.943 0.393 0.34 1.91 FEV 1% Predicted 38.234 16.616 12.00 77.00 FEV 1 /FVC 45.952 14.639 12.00 83.00 6-min walking test (m) 258.953 119.330 30.00 500.00 BMI 27.864 4.846 16.26 41.72 MMRC 2.515 0.890 0.00 4.00 SGRQ symptoms 50.269 19.620 8.60 86.12 SGRQ activity 62.283 20.884 9.56 100.00 SGRQ impact 37.145 18.550 0.00 78.37 SGRQ total score 48.261 16.843 10.89 80.90 NHP total store 30.256 17.298 0.00 73.68 BODE index 5.218 2.491 0.00 9.00 the BODE index (P < 0.0001) was statistically significant. The NHP total score also shows a statistical correlation with the BODE index (P < 0.01). However, the GOLD classification shows a statistically significant correlation only with SGRQ total score (P < 0.05) but not with all SGRQ subscales or the NHP total score. HRQOL (SGRQ and NHP) in relation to COPD severity according to BODE index There was a statistically significant association of the SGRQ total score between the severity groups of BODE (P for trend = 0.0001) (Figure 1). The mean SGRQ total score by BODE quartile are as follows: quartile I (0 2), 34.17; quartile II (3 4), 41.26; quartile III (5 6), 46.98; and quartile IV (7 10), 61.06. The scores for SGRQ symptoms were 44.51 in Q1 and 61.06 in Q4 (P for trend = 0.001); for SGRQ activity were 47.16 in Q1 and 76.41 in Q4 (P for trend = 0.001); and for SGRQ impact were 21.17 in Q1 and 49.91 in Q4 (P for trend = 0.001). However, the scores for NHP total score were 19.51 in the group labeled Q1 and 36.24 in Q4 (P = 0.060). St. George's total score 80 60 40 20 0 N = HRQOL (SGRQ and NHP) in relation to COPD severity according to GOLD classification There was no difference in the SGRQ total score between the severity groups of GOLD classification (P = 0.244) (Figure 2). The severity affected the level of SGRQ total score as follows: stage I (>80), no sample; stage II (79 50), 44.06; stage III (49 30), 46.68; and stage IV (<30), 53.37. The scores for NHP total score were 29.74 in the group labeled stage II and 29.34 in stage IV (P = 0.341). Discussion 12 1,00 13 2,00 BODE index quartiles 17 3,00 22 4,00 Figure 1 Box plot for SGRQ total scores by BODE quartiles. Error bars show standard deviation and horizontal lines within boxes show the mean for SGRQ total scores. The present study confirms that COPD severity, based on the BODE index, influenced HRQOL. In Table 3 Spearman correlation analysis of the BODE index and GOLD classification Variable BODE index (correlation coefficients) Significance GOLD classification (correlation coefficients) Significance SGRQ symptoms 0.404 P = 0.0001* 0.094 P =0.230 SGRQ activity 0.538 P = 0.0001* 0.099 P =0.219 SGRQ impact 0.556 P = 0.0001* 0.202 P =0.055 SGRQ total score 0.613 P = 0.0001* 0.237 P = 0.030* NHP total score 0.631 P = 0.002* 0.062 P =0.314 *Significant differences (P < 0.05). Chronic Respiratory Disease

Quality of life associated with COPD severity 79 St. George's total score 100 80 60 40 20 19 22 0 N = 18 stage II FEV1gold 20 stage III 26 stage IV Figure 2 Box plot for SGRQ total scores by GOLD classification (FEV 1 % predicted). Error bars show standard deviation and horizontal lines within boxes show the mean for SGRQ total scores. our study, HRQOL was strongly related to the impaired BODE index. Once COPD has been diagnosed, neither age, gender, smoking status, nor comorbility predicted the level of HRQOL, in our study. We conclude that COPD severity assessed by the BODE index is associated with HRQOL, particularly with SGRQ total and subscales scores. One of the most important implications of a nonlinear relationship is that similar changes in pulmonary function may have a different effect on measured HRQOL. In previous studies 16 it has been suggested that FEV 1 is one of the most important factors to measure the level of severity in COPD patients. Contrary to a classification system based only on FEV 1, COPD severity assessed by the BODE index can be more directly related with self-perceived symptoms, difficulties with daily life activities, and physical mobility. To date, only a few studies have highlighted a relationship between disease severity measured by the BODE index and HRQOL in COPD patients. Ong, et al. 17 and Medinas-Amorós, et al., 18 in the same line of results, have carried out a study to verify to what extent the BODE index correlates with a diseasespecific index of health status in patients with COPD. They concluded that the BODE index scoring system corresponds to important differences in health status of patients with COPD, and this grading system is better correlated to the health status indexes of the SGRQ than the GOLD staging criteria. However, in another recent study, Nquyen, et al., 19 in an attempt to identify the main factors of the global perception of self-rated health in patients with COPD, reported that only disease severity as measured by the BODE index was associated with global self-rated health. On the other hand, Huijsmans, et al. 20 had showed that the BODE index displayed slightly better discriminatory capacity for quality of life and the GOLD classification, and it does not seem adequate as a basis for individual management plans in rehabilitation. While additional work is needed to better understand this systemic respiratory disease, the application of the BODE index, as a multidimensional assessment, produces a broader picture of the reality of COPD patients, incorporating a subjective dyspnea scale (MMRC) in addition to the tests of lung function and exercise capacity. Quality of life, as a measurement of disease, broadens and enriches any severity staging of COPD patients, adding data about the level of psychosocial adaptation and wellbeing of COPD, particularly in the severe stages. 21 However, a large variation in deterioration was observed within each stage of severity, indicating that both multidimensional and HRQL measures should be considered in the assessment of these patients. Acknowledgements We would like to thank Dr. Joan B. Soriano, MD, PhD, head of Program of Epidemiology and Clinical Research of the Caubet-Cimera Foundation (Balearic Islands) for his assistance in the review of this manuscript, and to express our gratitude to Prof. Bernard Davis from Eckersley School of Oxford, England, for his help in the translation of this manuscript. References 1. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease and asthma. Am Rev Respir Dis 1987; 136: 225 244. 2. BTS. BTS guidelines for the management of chronic obstructive pulmonary disease. The COPD Guidelines Group of the Standards of Care Committee of the BTS. Thorax 1997; 52: S1 S28. 3. The GOLD expert panel. Global strategy for the diagnosis, management and prevention of COPD. Available at: http://www.goldcopd.com [accessed January 2008]. 4. Mannino, DM, Buist, AS, Petty, TL, Enright, PL, Redd, SC. Lung function and mortality in the United States: data from the First National Health and Nutrition Examination Survey follow up study. Thorax 2003; 58: 388 393. 5. Jones, PW. St. George s Respiratory Questionnaire: MCID. COPD 2005; 2: 75 79. http://crd.sagepub.com

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