Lung DOI 10.1007/s00408-013-9547-4
Association of Depression with Disease Severity in Patients with Chronic Obstructive Pulmonary Disease Ki Uk Kim • Hye-Kyung Park • Hee Young Jung • Jong-Joon Ahn • Eunsoo Moon • Yun Seong Kim • Min Ki Lee • Haejung Lee
Received: 21 February 2013 / Accepted: 14 December 2013 Ó Springer Science+Business Media New York 2014
Abstract Purpose Patients with chronic obstructive pulmonary disease (COPD), which is predicted to be the third most common cause of death worldwide by 2020, often suffer from depression, one of the most common and modifiable comorbidities of COPD. This study assessed the prevalence of depression in patients with COPD and the association of depression with disease severity. Methods This was a multicenter, prospective cross-sectional study of 245 patients with stable COPD. Disease severity was assessed using two scales: the global initiative for chronic obstructive lung disease (GOLD) stage and BODE index. Depression was measured using the Centers for Epidemiologic Studies Depression (CES-D) scales. Data were analyzed using descriptive statistics, Spearman correlation, and multivariate logistic regression.
K. U. Kim H.-K. Park (&) Y. S. Kim M. K. Lee Department of Internal Medicine, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea e-mail: [email protected] K. U. Kim H.-K. Park Y. S. Kim M. K. Lee Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea H. Y. Jung H. Lee Department of Nursing, Pusan National University College of Nursing, Yangsan-si, Gyeongsangnam-do, Republic of Korea J.-J. Ahn Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan, Republic of Korea E. Moon Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea
Results Depression defined as a CES-D score of 24 and higher was observed in 17.6 % of patients with COPD. The prevalence of depression increased with disease severity based on the BODE quartile (r = 0.16; P = 0.014). By contrast, no difference was observed in the prevalence of depression among the severity groups using the GOLD staging system (r = - 0.01; P = 0.898). Elementary school graduates were more likely to experience depression than graduates of high school and above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) 1.37–9.85] and patients in BODE quartile II were more likely to experience depression than those with BODE quartile I (OR = 2.5; 95 % CI 1.04–6.06). Conclusions Depression was associated with disease severity according to the BODE quartile in patients with COPD. BODE quartile II was a significant predictor of depression. Screening patients with a high risk of depression and proactive intervention for those patients are needed. Keywords Airflow Depression Dyspnea Exercise Obstruction
Introduction Noncommunicable diseases (NCDs), including chronic respiratory diseases, cardiovascular diseases, cancer, and diabetes, are major health problems worldwide. By 2020, these diseases are predicted to cause seven of every ten deaths in developing countries. Chronic obstructive pulmonary disease (COPD) is a major respiratory NCD that affects approximately 10 % of the adult population [1–3]. COPD is characterized by persistent airflow limitation, an enhanced chronic inflammatory response in the airways, and systemic comorbidities including depression.
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Depression frequently affects subjects with COPD and impairs quality of life due to its effect on emotional, social, and physical functioning [4–7]. Moreover, depression is a risk factor for increased COPD exacerbation, hospitalization, and mortality [8–10]. The prevalence of clinical depression ranges from 10 to 42 % in patients with stable COPD [5, 11, 12] and is generally higher than that reported in some other advanced chronic diseases [13]. However, depression often is undetected and untreated or undertreated in patients with COPD [14, 15]. According to Jordan and his colleagues [16], only one-third of patients with COPD who suffered from depressive symptoms received proper treatment for their condition. To better cope with its impact on health-related quality of life, disease outcome, and the cost of healthcare, several aspects of depression in COPD need to be better understood, including its relationship with disease severity. Traditional assessment of disease severity relies heavily on measuring lung function in patients with COPD, specifically the forced expiratory volume in the first second (FEV1). However, FEV1, a measurement of the degree of airflow obstruction, shows poor correlation with symptoms [17], quality of life [18], exacerbation frequency [19], and exercise capacity [20]. COPD is a multidimensional disease, and airflow obstruction alone does not capture all aspects of disease severity and their consequences [21]. Currently, the BODE index (B body mass index, O obstruction of airways as measured by FEV1, D dyspnea as measured by modified Medical Research Council scale, E exercise capacity as measured by a 6-min walk test) is widely accepted as a multidimensional assessment tool in patients with COPD [22]. The BODE index has been shown to be superior to the FEV1-based Global initiative for chronic obstructive lung disease (GOLD) stage for predicting the risk of death, hospitalization, and quality of life in patients with COPD [22–24]. Little is known concerning the association between depressive symptoms and the BODE index, including all of the quartiles. Furthermore, it is not well established which scale is more consistently related to the depressive symptoms between the BODE index or GOLD staging system. To our knowledge, this is the first study to investigate the association between depression and disease severity according to all of the quartiles of the BODE index and GOLD staging system among Asians. We examined the prevalence of depression in Korean patients with COPD and its association with disease severity. We also assessed related characteristics to identify patients at risk of depression.
Methods Subjects and Study Design This was a prospective, cross-sectional study conducted between March 2010 and November 2010. Patients with a
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wide range of severity of COPD were recruited from six institutions. Patients were recruited consecutively from the outpatient clinic. A diagnosis of COPD was established based on medical history, current symptoms, and available pulmonary function tests following GOLD guidelines [25]. Exclusion criteria included an illness other than COPD that was likely to result in death within 6 months, an inability to perform the lung function and 6-min walk test (6MWT); myocardial infarction within the preceding 4 months, unstable angina, or congestive heart failure (New York Heart Association class III or IV). Patients not considered clinically stable (i.e., with changes in medication dose or frequency, disease exacerbation, or hospital admissions in the preceding 6 weeks) also were excluded. General characteristics, including age, sex, education level, marital status, smoking status (current-, ex-, or never-smoker), and cumulative smoking (pack-years) were assessed based on patient reports. Patients’ weight and height were measured before the lung function test, and body mass index (BMI) was obtained by the equation of BMI = weight/height2. The study protocol was approved by the institutional ethics committee, and written, informed consent was obtained from all patients. Classification of COPD Severity The BODE index was calculated for each patient using variables obtained on enrollment. For calculation of the BODE index, we used the empirical model [22]. The modified Medical Research Council (MMRC) scale is the most commonly used validated scale to assess dyspnea in daily living in chronic lung disease and consists of five statements that describe a range of dyspnea [26]. Scores on MMRC dyspnea scale can range from 0 to 4; 0—‘‘Not troubled with breathlessness except with strenuous exercise’’; 1—‘‘Troubled by shortness of breath when hurrying on the level or walking up a slight hill’’; 2—‘‘Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level’’; 3—‘‘Stops for breath after walking about 100 yards or after a few minutes on the level’’; 4—‘‘Too breathless to leave the house or breathless when dressing or undressing.’’ The values for MMRC were 0 (Grade 0–1), 1 (Grade 2), 2 (Grade 3), and 3 (Grade 4). Spirometry was performed according to ATS/ERS recommendations using a standard PFT unit (SensorMedics Vmax 22, Viasys Healthcare) [27]. For FEV1, the values were 0 (C65 % predicted), 1 (50–64 % predicted), 2 (36–49 % predicted), and 3 (B35 % predicted). The 6MWT was conducted in an enclosed corridor on a measured course that was 30 m in length. The course was marked every 5 m, and subjects were instructed to walk from one end to the other end, covering as much distance as possible during the 6 min. Patients were
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verbally encouraged and remaining time was called out after every elapsed minute. Patients were allowed to rest if needed. For 6-min walk distance (6MWD), the values were 0 (C350 m), 1 (250–349 m), 2 (150–249 m), and 3 (B149 m). For BMI, the values were 0 ([21 kg/m2) or 1 (B21 kg/m2). Points for each variable were added so that the total score of BODE index ranged from 0 to 10 points. The BODE index can be divided into four quartiles based on the total score: quartile I is scored 0–2; quartile II is scored 3–4; quartile III is scored 5–6; and quartile IV is scored 7–10 [22]. GOLD stage is a simple spirometric classification of disease severity. The spirometric values are based on the postbronchodilator measurements. GOLD stages were classified according to the guidelines of GOLD (Stage I: mild, FEV1 C 80 % predicted; Stage II: moderate, 50 B FEV1 \ 80 % predicted; Stage III: severe, 30 B FEV1 \ 50 % predicted; Stage IV: very severe, FEV1 \ 30 % predicted or FEV1 \ 50 % predicted plus chronic respiratory failure) [25]. Assessment of Depression The Korean version of the Center for Epidemiologic Studies-Depression scale (CES-D) was used for measurement of depression. The CES-D scale is a general measure of depressive symptoms that has been used extensively in epidemiologic studies [28, 29]. CES-D is a self-report questionnaire for screening clinically significant depression, but not confirming diagnosis of depression. The CESD scale has been found to have high internal consistency and test–retest reliability, and it is highly correlated with other standardized depression scales [30]. According to a recent validation study of CES-D using Diagnostic Interview Schedule (DIS), this scale has good sensitivity (r = 0.84) and specificity (r = 0.82) [31]. In a study using Korean version of CES-D, this scale has good split-half reliability (r = 0.84) and good internal consistency reliability (Cronbach’s alpha 0.8) [32]. The scale includes 20 items and taps dimensions of depressed mood, feelings of guilt and worthlessness, appetite loss, sleep disturbance, and energy level. These items are assumed to represent the major components of depressive symptoms. In order to avoid patterned responses, 16 of the symptoms are worded negatively and 4 are worded positively. Patients are asked to report how often they experienced a particular symptom during the past week on a fourpoint scale ranging from 0 to 3 (0 = rarely or none of the time—less than 1 day; 1 = some or a small amount of the time—1 to 2 days; 2 = occasionally or a moderate amount of time—3 to 4 days; and 3 = most or all of the time—5 to 7 days). Responses to the four positive items are reverse scored, and the total sum of the responses is calculated. Scores on the CES-D scale can range from 0 to 60. The cutpoint of 24 distinguished Koreans with clinical depression
from Koreans with nondepression, indicating Kappa values of 0.92 [32]. Differently from the cut-point of 16 suggested by previous studies, the cut-point of 24 was suggested as a useful and validated scale for detecting the clinically significant depression among Koreans [32]. Therefore, we considered a score of 24 and higher to indicate clinically significant probable depression. Statistical Analysis Data are expressed as frequency (n, %) for categorical variables and mean ± standard deviation (SD) for continuous variables. The relationship of the BODE quartile and GOLD stage to the prevalence of depression was tested by Spearman’s rank correlation test. Differences in depression proportion between BODE quartile and GOLD stage were compared using the v2 test for trend. For the multivariate logistic regression, we included variables that were significant from the previous bivariate analysis, which showed P value \ 0.05. The computer-based analysis program Statistical Package for Social Science (SPSS) version 14.0 was used for all calculations. The level of significance was set at P \ 0.05.
Results Characteristics of the Subjects A total of 245 patients were included in the study; 226 (92 %) were males, and the mean age was 66.91 ± 8.16 years. The patients showed a mean FEV1 of 1.58 L (SD, 0.65 L), a mean BMI of 22.25 kg/m2 (SD, 3.34 kg/m2), and a mean 6MWD of 345.9 m (SD, 84.2 m). Disease severity according to GOLD stage showed the following distribution: 53 (21.6 %) mild, 107 (43.7 %) moderate, 72 (29.4 %) severe, and 13 (5.3 %) very severe. When the disease severity were classified by BODE quartile, participants were distributed into quartile I of 125 (51 %), quartile II of 60 (24.5 %), quartile III of 41 (16.7 %), and quartile IV of 19 (7.8 %). Prevalence of Depressive Symptoms in Patients with COPD Sociodemographic and baseline characteristics of these patients with and without probable depression are shown in Table 1. Among the subject population, 43 patients (17.6 %) were found to be depressed (CES-D score C24). Compared with nondepressed patients, more depressed patients, to a statistically significant degree (P \ 0.05), were single, divorced, or widowed, and uneducated. Patients with probable depression had a significantly increased dyspnea (MMRC
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2.26 ± 1.18 vs. 1.58 ± 1.12; P = 0.001) and decreased exercise capacity (6MWD 320.77 ± 85.74 m vs. 352.43 ± 79.48; P = 0.02) compared with those without depression. Indices of lung function, including FEV1, did not show any significant differences between those with or without depression.
The prevalences of depression in BODE quartiles I, II, III, and IV were 11.2, 23.3, 24.4, and 26.3 %, respectively, and showed a weak correlation between the BODE quartile and prevalence of depression (r = 0.16; P = 0.014). The prevalences of depression in GOLD stages I, II, III, and IV were 20.8, 15, 19.4, and 15.4 %, respectively, and showed no correlation with the GOLD severity groups (r = - 0.01; P = 0.898). For the determination of the predictors of depression, we used a multivariate logistic regression model. Based on the Table 1 Baseline characteristics of the patients with no depression or probable depression (n = 245) No depression (n = 202)
Probable depression (n = 43)
P value
Sex Male
189 (83.6)
37 (16.4)
Female
13 (68.4)
6 (31.6)
0.092
Age (years) \65
73 (85.9)
12 (14.1)
C65
129 (80.6)
31 (19.4)
Currently married
176 (85.4)
30 (14.6)
Single, divorced, widowed
26 (66.7)
13 (33.3)
Uneducated
16 (72.7)
6 (27.3)
Elementary school
46 (74.2)
16 (25.8)
0.198
Marital status (n, %) 0.007
Educational level
Middle school
55 (80.9)
13 (19.1)
High school and above
85 (91.4)
8 (8.6)
0.022
Very low (\1,000)
111 (76.6)
34 (23.4)
Low (1,000 to \ 2,000)
39 (92.9)
3 (7.1)
Middle (2,000 to \ 3,000)
17 (94.4)
1 (5.6)
High ([3,000)
35 (87.5)
5 (12.5)
Probable depression (n = 43)
Former
145 (85.3)
25 (14.7)
Current
41 (78.8)
11 (21.2)
P value
FVC (L) FEV1 (L)
2.9 ± 0.92 1.59 ± 0.62
2.83 ± 0.93 1.52 ± 0.61
0.653 0.558
FEV1 % predicted
60.57 ± 22.48
60.37 ± 23.65
0.959
FEV1/FVC
55.17 ± 13.73
55.02 ± 14.72
0.95
BMI index (kg/m2)
22.34 ± 3.35
21.75 ± 3.13
0.289
Dyspnea (MMRC scale)
1.58 ± 1.12
2.26 ± 1.18
0.001
6MWD (m)
352.43 ± 79.48
320.77 ± 85.74
0.02
BODE index score
2.75 ± 2.28
3.72 ± 2.23
0.011
Data are presented as mean ± SD or numbers with percentages in parentheses unless otherwise indicated 6MWD 6-min walk distance; BMI body mass index; BODE body mass index, degree of airway obstruction, dyspnea, and exercise capacity; CES-D Centers for Epidemiologic Studies Depression score; MMRC Modified Medical Research Council
previous analysis, the marital status, educational level, monthly income, and BODE quartile were included in the model. Dyspnea status (MMRC) and exercise capacity (6MWD) were not included in the regression model separately to avoid redundancy because those factors were considered in the BODE index. Participants who had an elementary school education tended to suffer from depression 3.67-fold more frequently than those with a high school education or above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) = 1.37–9.85]. Participants with BODE quartile II were 2.5-fold more likely to report depressive symptoms than those with BODE quartile I (OR = 2.5; 95 % CI 1.04–6.06; Table 2). In the present study, 84.5 % of the participants were correctly classified as no depression and probable depression groups using the suggested regression model.
16 (69.6)
7 (30.4)
0.028
Smoking
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No depression (n = 202)
Discussion
Monthly income (US$)
Never
Characteristics
Spirometry values (post-bronchodilator)
Depression in Relation to COPD Severity
Characteristics
Table 1 continued
0.132
We identified an association of depression with disease severity according to the BODE quartile in outpatients with COPD. A few studies have verified the relationship between the BODE index and depressive symptoms among patients with COPD [33–35]. Al-shair et al. [35] showed that patients with the greatest severity of disease (BODE quartile III/IV) were more likely to suffer from depression than those with milder disease (BODE quartile I/II).
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However, they did not specify an association of depression with disease severity according to each quartile of the BODE. In a study of 256 patients with stable COPD, An et al. [34] found that the prevalence of depressive symptoms increased with increasing BODE quartile. However, due to the absence of subjects with BODE quartile IV, they could not draw conclusions with respect to BODE quartile IV. In our study, patients with BODE quartile II were 2.5fold more likely to experience depressive symptoms than those with BODE quartile I. Although the tendency of depressive symptoms increased with the increase in BODE quartile, no significant distinction existed between the groups, a finding that could be related to the low numbers of patients in BODE quartiles III and IV. Thus far, one study assessed the association between depressive symptoms and the BODE index, compared with GOLD stage, including all the quartiles of BODE in patients with COPD. Funk et al. [33] suggested that the BODE quartile is superior to GOLD stage for explaining depressive symptoms, although the prevalence of depression increased with both increasing GOLD stage and BODE quartile in 122 stable patients with COPD. However, our data of 245 patients revealed no association of depression with GOLD stage, in concordance with previous research [34, 35]. Although the association of depression with GOLD stage is not clear, it seems evident that the
Table 2 Multivariate logistic regression: predictors of probable depression in patients with COPD (n = 245) Parameters
OR
95 % CI
P value
0.47 1.0
0.2–1.1
0.083
Marital status Currently married Single, divorced, widowed Educational level Uneducated
3.52
0.97–12.79
0.056
Elementary school
3.67
1.37–9.85
0.01
Middle school
2.24
0.82–6.07
0.114
High school and above
1.0
Monthly income (US$) Very low (\1,000)
1.08
0.36–3.28
0.887
Low (1,000 to \ 2,000)
0.35
0.07–1.68
0.188
Middle (2,000 to \ 3,000)
0.25
0.02–2.52
0.238
High ([3,000)
1.0
BODE Quartile I
1.0
Quartile II
2.5
1.04–6.06
0.042
Quartile III Quartile IV
2.24 2.85
0.86–5.87 0.81–9.98
0.101 0.102
BODE body mass index, degree of airway obstruction, dyspnea, and exercise capacity; OR odds ratio; CI confidence interval
BODE is better correlated to depressive symptoms than GOLD stage in patients with COPD. In general, patients with COPD have a higher prevalence of depression. In studies by van Manen et al. [5] and Hanania et al. [29], the prevalences of depression were 21.6 and 26 %, respectively, using CES-D as a screening tool, as in our study. Our data showed a lower prevalence of depression (17.6 %), possibly because our study included subjects with GOLD stages I–IV, whereas previous studies enrolled subjects with GOLD stages II–IV. However, our data revealed a similar prevalence of depression (16.7 %) among patients with GOLD stages II–IV. This result may be due to a higher cutoff value of CES-D score. In previous studies, patients with a score of 16 and higher were considered to have depression. In the present study, we considered a score of 24 and higher on the CES-D to indicate clinically significant depression, according to Shin et al. [32]. They suggested 24 to best correspond to the clinical diagnosis of depression in the Korean population. We used the CES-D instrument to evaluate the presence of depressive symptoms among various screening questionnaires, including the CES-D, the Patient Health Questionnaire-9, the 15-item Geriatric Depression Scale, and the Hospital Anxiety and Depression Scale [29, 36–38]. Although CESD was not designed to be diagnostic and cannot be used to differentiate primary depression from secondary depression, it is a versatile and well-established tool for epidemiological studies [29]. Another reason for the lower prevalence of depression in our study could be the lower proportion of females than in previous studies. Prior research has suggested that depression is more common in females with COPD than in males with COPD [29, 39, 40]. Our study included a lower proportion of females (8 %) compared with the report by van Manen et al. (28 %) [5] and that by Hanania et al. (35 %) [29]. Our study has clinical implications. We found an association of depression with the level of education as well as disease severity. Patients who graduated from elementary school tended to experience depressive symptoms 3.67fold more frequently than those who graduated from high school or above. Increased dyspnea and poor exercise capacity also were significantly correlated with depression. Dyspnea has been reported to correlate with depression in patients with COPD [41]. In a study by van Manen et al. [5], patients with severe COPD had a 2.5-fold greater risk of depression than controls. Poor exercise capacity also was shown to be significantly associated with depression in a study of 122 stable COPD patients [35]. Given the association of depression with poorer treatment adherence [42], greater disability [15], and increased mortality [43] in COPD, screening and early intervention for depression in those with these characteristics would enhance the clinical
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outcomes of COPD. In addition, clinical strategies need to be developed to reduce depression in patients with COPD. In this respect, pulmonary rehabilitation [44], long-term oxygen therapy [45], and COPD self-management programs [46] have demonstrated significant and specific benefits for depression in COPD patients. There were several limitations to our study. First, the present study comprised a small number of females, which might explain the lack of a difference in the prevalence of depression between males and females in our data. Second, our definition of depression was based on the score of a well-validated instrument (CES-D), and we did not seek an objective, physician-based diagnosis of depression. Some further information, such as regarding comorbidities and history of exacerbation, would help to characterize the subjects. Finally, we could not assess any possible etiologic or causal links between COPD and depression due to the cross-sectional nature of this analysis. Nevertheless, the large population, which included a wide range of disease severity in subjects of a single ethnicity, is a strength of the present study. In conclusion, depression was associated with disease severity according to the BODE quartile and educational level in patients with COPD. More attention should be paid to patients with BODE quartile II and those with an elementary school education. Further investigation with patients evenly distributed among the BODE quartiles would provide greater insight into the association between COPD severity and depression. Acknowledgments This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0088833) and Pusan National University Research Grant, 2013. Conflict of interest
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Association of Depression with Disease Severity in Patients with Chronic Obstructive Pulmonary Disease Ki Uk Kim • Hye-Kyung Park • Hee Young Jung • Jong-Joon Ahn • Eunsoo Moon • Yun Seong Kim • Min Ki Lee • Haejung Lee
Received: 21 February 2013 / Accepted: 14 December 2013 Ó Springer Science+Business Media New York 2014
Abstract Purpose Patients with chronic obstructive pulmonary disease (COPD), which is predicted to be the third most common cause of death worldwide by 2020, often suffer from depression, one of the most common and modifiable comorbidities of COPD. This study assessed the prevalence of depression in patients with COPD and the association of depression with disease severity. Methods This was a multicenter, prospective cross-sectional study of 245 patients with stable COPD. Disease severity was assessed using two scales: the global initiative for chronic obstructive lung disease (GOLD) stage and BODE index. Depression was measured using the Centers for Epidemiologic Studies Depression (CES-D) scales. Data were analyzed using descriptive statistics, Spearman correlation, and multivariate logistic regression.
K. U. Kim H.-K. Park (&) Y. S. Kim M. K. Lee Department of Internal Medicine, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea e-mail: [email protected] K. U. Kim H.-K. Park Y. S. Kim M. K. Lee Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea H. Y. Jung H. Lee Department of Nursing, Pusan National University College of Nursing, Yangsan-si, Gyeongsangnam-do, Republic of Korea J.-J. Ahn Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan, Republic of Korea E. Moon Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea
Results Depression defined as a CES-D score of 24 and higher was observed in 17.6 % of patients with COPD. The prevalence of depression increased with disease severity based on the BODE quartile (r = 0.16; P = 0.014). By contrast, no difference was observed in the prevalence of depression among the severity groups using the GOLD staging system (r = - 0.01; P = 0.898). Elementary school graduates were more likely to experience depression than graduates of high school and above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) 1.37–9.85] and patients in BODE quartile II were more likely to experience depression than those with BODE quartile I (OR = 2.5; 95 % CI 1.04–6.06). Conclusions Depression was associated with disease severity according to the BODE quartile in patients with COPD. BODE quartile II was a significant predictor of depression. Screening patients with a high risk of depression and proactive intervention for those patients are needed. Keywords Airflow Depression Dyspnea Exercise Obstruction
Introduction Noncommunicable diseases (NCDs), including chronic respiratory diseases, cardiovascular diseases, cancer, and diabetes, are major health problems worldwide. By 2020, these diseases are predicted to cause seven of every ten deaths in developing countries. Chronic obstructive pulmonary disease (COPD) is a major respiratory NCD that affects approximately 10 % of the adult population [1–3]. COPD is characterized by persistent airflow limitation, an enhanced chronic inflammatory response in the airways, and systemic comorbidities including depression.
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Depression frequently affects subjects with COPD and impairs quality of life due to its effect on emotional, social, and physical functioning [4–7]. Moreover, depression is a risk factor for increased COPD exacerbation, hospitalization, and mortality [8–10]. The prevalence of clinical depression ranges from 10 to 42 % in patients with stable COPD [5, 11, 12] and is generally higher than that reported in some other advanced chronic diseases [13]. However, depression often is undetected and untreated or undertreated in patients with COPD [14, 15]. According to Jordan and his colleagues [16], only one-third of patients with COPD who suffered from depressive symptoms received proper treatment for their condition. To better cope with its impact on health-related quality of life, disease outcome, and the cost of healthcare, several aspects of depression in COPD need to be better understood, including its relationship with disease severity. Traditional assessment of disease severity relies heavily on measuring lung function in patients with COPD, specifically the forced expiratory volume in the first second (FEV1). However, FEV1, a measurement of the degree of airflow obstruction, shows poor correlation with symptoms [17], quality of life [18], exacerbation frequency [19], and exercise capacity [20]. COPD is a multidimensional disease, and airflow obstruction alone does not capture all aspects of disease severity and their consequences [21]. Currently, the BODE index (B body mass index, O obstruction of airways as measured by FEV1, D dyspnea as measured by modified Medical Research Council scale, E exercise capacity as measured by a 6-min walk test) is widely accepted as a multidimensional assessment tool in patients with COPD [22]. The BODE index has been shown to be superior to the FEV1-based Global initiative for chronic obstructive lung disease (GOLD) stage for predicting the risk of death, hospitalization, and quality of life in patients with COPD [22–24]. Little is known concerning the association between depressive symptoms and the BODE index, including all of the quartiles. Furthermore, it is not well established which scale is more consistently related to the depressive symptoms between the BODE index or GOLD staging system. To our knowledge, this is the first study to investigate the association between depression and disease severity according to all of the quartiles of the BODE index and GOLD staging system among Asians. We examined the prevalence of depression in Korean patients with COPD and its association with disease severity. We also assessed related characteristics to identify patients at risk of depression.
Methods Subjects and Study Design This was a prospective, cross-sectional study conducted between March 2010 and November 2010. Patients with a
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wide range of severity of COPD were recruited from six institutions. Patients were recruited consecutively from the outpatient clinic. A diagnosis of COPD was established based on medical history, current symptoms, and available pulmonary function tests following GOLD guidelines [25]. Exclusion criteria included an illness other than COPD that was likely to result in death within 6 months, an inability to perform the lung function and 6-min walk test (6MWT); myocardial infarction within the preceding 4 months, unstable angina, or congestive heart failure (New York Heart Association class III or IV). Patients not considered clinically stable (i.e., with changes in medication dose or frequency, disease exacerbation, or hospital admissions in the preceding 6 weeks) also were excluded. General characteristics, including age, sex, education level, marital status, smoking status (current-, ex-, or never-smoker), and cumulative smoking (pack-years) were assessed based on patient reports. Patients’ weight and height were measured before the lung function test, and body mass index (BMI) was obtained by the equation of BMI = weight/height2. The study protocol was approved by the institutional ethics committee, and written, informed consent was obtained from all patients. Classification of COPD Severity The BODE index was calculated for each patient using variables obtained on enrollment. For calculation of the BODE index, we used the empirical model [22]. The modified Medical Research Council (MMRC) scale is the most commonly used validated scale to assess dyspnea in daily living in chronic lung disease and consists of five statements that describe a range of dyspnea [26]. Scores on MMRC dyspnea scale can range from 0 to 4; 0—‘‘Not troubled with breathlessness except with strenuous exercise’’; 1—‘‘Troubled by shortness of breath when hurrying on the level or walking up a slight hill’’; 2—‘‘Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level’’; 3—‘‘Stops for breath after walking about 100 yards or after a few minutes on the level’’; 4—‘‘Too breathless to leave the house or breathless when dressing or undressing.’’ The values for MMRC were 0 (Grade 0–1), 1 (Grade 2), 2 (Grade 3), and 3 (Grade 4). Spirometry was performed according to ATS/ERS recommendations using a standard PFT unit (SensorMedics Vmax 22, Viasys Healthcare) [27]. For FEV1, the values were 0 (C65 % predicted), 1 (50–64 % predicted), 2 (36–49 % predicted), and 3 (B35 % predicted). The 6MWT was conducted in an enclosed corridor on a measured course that was 30 m in length. The course was marked every 5 m, and subjects were instructed to walk from one end to the other end, covering as much distance as possible during the 6 min. Patients were
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verbally encouraged and remaining time was called out after every elapsed minute. Patients were allowed to rest if needed. For 6-min walk distance (6MWD), the values were 0 (C350 m), 1 (250–349 m), 2 (150–249 m), and 3 (B149 m). For BMI, the values were 0 ([21 kg/m2) or 1 (B21 kg/m2). Points for each variable were added so that the total score of BODE index ranged from 0 to 10 points. The BODE index can be divided into four quartiles based on the total score: quartile I is scored 0–2; quartile II is scored 3–4; quartile III is scored 5–6; and quartile IV is scored 7–10 [22]. GOLD stage is a simple spirometric classification of disease severity. The spirometric values are based on the postbronchodilator measurements. GOLD stages were classified according to the guidelines of GOLD (Stage I: mild, FEV1 C 80 % predicted; Stage II: moderate, 50 B FEV1 \ 80 % predicted; Stage III: severe, 30 B FEV1 \ 50 % predicted; Stage IV: very severe, FEV1 \ 30 % predicted or FEV1 \ 50 % predicted plus chronic respiratory failure) [25]. Assessment of Depression The Korean version of the Center for Epidemiologic Studies-Depression scale (CES-D) was used for measurement of depression. The CES-D scale is a general measure of depressive symptoms that has been used extensively in epidemiologic studies [28, 29]. CES-D is a self-report questionnaire for screening clinically significant depression, but not confirming diagnosis of depression. The CESD scale has been found to have high internal consistency and test–retest reliability, and it is highly correlated with other standardized depression scales [30]. According to a recent validation study of CES-D using Diagnostic Interview Schedule (DIS), this scale has good sensitivity (r = 0.84) and specificity (r = 0.82) [31]. In a study using Korean version of CES-D, this scale has good split-half reliability (r = 0.84) and good internal consistency reliability (Cronbach’s alpha 0.8) [32]. The scale includes 20 items and taps dimensions of depressed mood, feelings of guilt and worthlessness, appetite loss, sleep disturbance, and energy level. These items are assumed to represent the major components of depressive symptoms. In order to avoid patterned responses, 16 of the symptoms are worded negatively and 4 are worded positively. Patients are asked to report how often they experienced a particular symptom during the past week on a fourpoint scale ranging from 0 to 3 (0 = rarely or none of the time—less than 1 day; 1 = some or a small amount of the time—1 to 2 days; 2 = occasionally or a moderate amount of time—3 to 4 days; and 3 = most or all of the time—5 to 7 days). Responses to the four positive items are reverse scored, and the total sum of the responses is calculated. Scores on the CES-D scale can range from 0 to 60. The cutpoint of 24 distinguished Koreans with clinical depression
from Koreans with nondepression, indicating Kappa values of 0.92 [32]. Differently from the cut-point of 16 suggested by previous studies, the cut-point of 24 was suggested as a useful and validated scale for detecting the clinically significant depression among Koreans [32]. Therefore, we considered a score of 24 and higher to indicate clinically significant probable depression. Statistical Analysis Data are expressed as frequency (n, %) for categorical variables and mean ± standard deviation (SD) for continuous variables. The relationship of the BODE quartile and GOLD stage to the prevalence of depression was tested by Spearman’s rank correlation test. Differences in depression proportion between BODE quartile and GOLD stage were compared using the v2 test for trend. For the multivariate logistic regression, we included variables that were significant from the previous bivariate analysis, which showed P value \ 0.05. The computer-based analysis program Statistical Package for Social Science (SPSS) version 14.0 was used for all calculations. The level of significance was set at P \ 0.05.
Results Characteristics of the Subjects A total of 245 patients were included in the study; 226 (92 %) were males, and the mean age was 66.91 ± 8.16 years. The patients showed a mean FEV1 of 1.58 L (SD, 0.65 L), a mean BMI of 22.25 kg/m2 (SD, 3.34 kg/m2), and a mean 6MWD of 345.9 m (SD, 84.2 m). Disease severity according to GOLD stage showed the following distribution: 53 (21.6 %) mild, 107 (43.7 %) moderate, 72 (29.4 %) severe, and 13 (5.3 %) very severe. When the disease severity were classified by BODE quartile, participants were distributed into quartile I of 125 (51 %), quartile II of 60 (24.5 %), quartile III of 41 (16.7 %), and quartile IV of 19 (7.8 %). Prevalence of Depressive Symptoms in Patients with COPD Sociodemographic and baseline characteristics of these patients with and without probable depression are shown in Table 1. Among the subject population, 43 patients (17.6 %) were found to be depressed (CES-D score C24). Compared with nondepressed patients, more depressed patients, to a statistically significant degree (P \ 0.05), were single, divorced, or widowed, and uneducated. Patients with probable depression had a significantly increased dyspnea (MMRC
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2.26 ± 1.18 vs. 1.58 ± 1.12; P = 0.001) and decreased exercise capacity (6MWD 320.77 ± 85.74 m vs. 352.43 ± 79.48; P = 0.02) compared with those without depression. Indices of lung function, including FEV1, did not show any significant differences between those with or without depression.
The prevalences of depression in BODE quartiles I, II, III, and IV were 11.2, 23.3, 24.4, and 26.3 %, respectively, and showed a weak correlation between the BODE quartile and prevalence of depression (r = 0.16; P = 0.014). The prevalences of depression in GOLD stages I, II, III, and IV were 20.8, 15, 19.4, and 15.4 %, respectively, and showed no correlation with the GOLD severity groups (r = - 0.01; P = 0.898). For the determination of the predictors of depression, we used a multivariate logistic regression model. Based on the Table 1 Baseline characteristics of the patients with no depression or probable depression (n = 245) No depression (n = 202)
Probable depression (n = 43)
P value
Sex Male
189 (83.6)
37 (16.4)
Female
13 (68.4)
6 (31.6)
0.092
Age (years) \65
73 (85.9)
12 (14.1)
C65
129 (80.6)
31 (19.4)
Currently married
176 (85.4)
30 (14.6)
Single, divorced, widowed
26 (66.7)
13 (33.3)
Uneducated
16 (72.7)
6 (27.3)
Elementary school
46 (74.2)
16 (25.8)
0.198
Marital status (n, %) 0.007
Educational level
Middle school
55 (80.9)
13 (19.1)
High school and above
85 (91.4)
8 (8.6)
0.022
Very low (\1,000)
111 (76.6)
34 (23.4)
Low (1,000 to \ 2,000)
39 (92.9)
3 (7.1)
Middle (2,000 to \ 3,000)
17 (94.4)
1 (5.6)
High ([3,000)
35 (87.5)
5 (12.5)
Probable depression (n = 43)
Former
145 (85.3)
25 (14.7)
Current
41 (78.8)
11 (21.2)
P value
FVC (L) FEV1 (L)
2.9 ± 0.92 1.59 ± 0.62
2.83 ± 0.93 1.52 ± 0.61
0.653 0.558
FEV1 % predicted
60.57 ± 22.48
60.37 ± 23.65
0.959
FEV1/FVC
55.17 ± 13.73
55.02 ± 14.72
0.95
BMI index (kg/m2)
22.34 ± 3.35
21.75 ± 3.13
0.289
Dyspnea (MMRC scale)
1.58 ± 1.12
2.26 ± 1.18
0.001
6MWD (m)
352.43 ± 79.48
320.77 ± 85.74
0.02
BODE index score
2.75 ± 2.28
3.72 ± 2.23
0.011
Data are presented as mean ± SD or numbers with percentages in parentheses unless otherwise indicated 6MWD 6-min walk distance; BMI body mass index; BODE body mass index, degree of airway obstruction, dyspnea, and exercise capacity; CES-D Centers for Epidemiologic Studies Depression score; MMRC Modified Medical Research Council
previous analysis, the marital status, educational level, monthly income, and BODE quartile were included in the model. Dyspnea status (MMRC) and exercise capacity (6MWD) were not included in the regression model separately to avoid redundancy because those factors were considered in the BODE index. Participants who had an elementary school education tended to suffer from depression 3.67-fold more frequently than those with a high school education or above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) = 1.37–9.85]. Participants with BODE quartile II were 2.5-fold more likely to report depressive symptoms than those with BODE quartile I (OR = 2.5; 95 % CI 1.04–6.06; Table 2). In the present study, 84.5 % of the participants were correctly classified as no depression and probable depression groups using the suggested regression model.
16 (69.6)
7 (30.4)
0.028
Smoking
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No depression (n = 202)
Discussion
Monthly income (US$)
Never
Characteristics
Spirometry values (post-bronchodilator)
Depression in Relation to COPD Severity
Characteristics
Table 1 continued
0.132
We identified an association of depression with disease severity according to the BODE quartile in outpatients with COPD. A few studies have verified the relationship between the BODE index and depressive symptoms among patients with COPD [33–35]. Al-shair et al. [35] showed that patients with the greatest severity of disease (BODE quartile III/IV) were more likely to suffer from depression than those with milder disease (BODE quartile I/II).
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However, they did not specify an association of depression with disease severity according to each quartile of the BODE. In a study of 256 patients with stable COPD, An et al. [34] found that the prevalence of depressive symptoms increased with increasing BODE quartile. However, due to the absence of subjects with BODE quartile IV, they could not draw conclusions with respect to BODE quartile IV. In our study, patients with BODE quartile II were 2.5fold more likely to experience depressive symptoms than those with BODE quartile I. Although the tendency of depressive symptoms increased with the increase in BODE quartile, no significant distinction existed between the groups, a finding that could be related to the low numbers of patients in BODE quartiles III and IV. Thus far, one study assessed the association between depressive symptoms and the BODE index, compared with GOLD stage, including all the quartiles of BODE in patients with COPD. Funk et al. [33] suggested that the BODE quartile is superior to GOLD stage for explaining depressive symptoms, although the prevalence of depression increased with both increasing GOLD stage and BODE quartile in 122 stable patients with COPD. However, our data of 245 patients revealed no association of depression with GOLD stage, in concordance with previous research [34, 35]. Although the association of depression with GOLD stage is not clear, it seems evident that the
Table 2 Multivariate logistic regression: predictors of probable depression in patients with COPD (n = 245) Parameters
OR
95 % CI
P value
0.47 1.0
0.2–1.1
0.083
Marital status Currently married Single, divorced, widowed Educational level Uneducated
3.52
0.97–12.79
0.056
Elementary school
3.67
1.37–9.85
0.01
Middle school
2.24
0.82–6.07
0.114
High school and above
1.0
Monthly income (US$) Very low (\1,000)
1.08
0.36–3.28
0.887
Low (1,000 to \ 2,000)
0.35
0.07–1.68
0.188
Middle (2,000 to \ 3,000)
0.25
0.02–2.52
0.238
High ([3,000)
1.0
BODE Quartile I
1.0
Quartile II
2.5
1.04–6.06
0.042
Quartile III Quartile IV
2.24 2.85
0.86–5.87 0.81–9.98
0.101 0.102
BODE body mass index, degree of airway obstruction, dyspnea, and exercise capacity; OR odds ratio; CI confidence interval
BODE is better correlated to depressive symptoms than GOLD stage in patients with COPD. In general, patients with COPD have a higher prevalence of depression. In studies by van Manen et al. [5] and Hanania et al. [29], the prevalences of depression were 21.6 and 26 %, respectively, using CES-D as a screening tool, as in our study. Our data showed a lower prevalence of depression (17.6 %), possibly because our study included subjects with GOLD stages I–IV, whereas previous studies enrolled subjects with GOLD stages II–IV. However, our data revealed a similar prevalence of depression (16.7 %) among patients with GOLD stages II–IV. This result may be due to a higher cutoff value of CES-D score. In previous studies, patients with a score of 16 and higher were considered to have depression. In the present study, we considered a score of 24 and higher on the CES-D to indicate clinically significant depression, according to Shin et al. [32]. They suggested 24 to best correspond to the clinical diagnosis of depression in the Korean population. We used the CES-D instrument to evaluate the presence of depressive symptoms among various screening questionnaires, including the CES-D, the Patient Health Questionnaire-9, the 15-item Geriatric Depression Scale, and the Hospital Anxiety and Depression Scale [29, 36–38]. Although CESD was not designed to be diagnostic and cannot be used to differentiate primary depression from secondary depression, it is a versatile and well-established tool for epidemiological studies [29]. Another reason for the lower prevalence of depression in our study could be the lower proportion of females than in previous studies. Prior research has suggested that depression is more common in females with COPD than in males with COPD [29, 39, 40]. Our study included a lower proportion of females (8 %) compared with the report by van Manen et al. (28 %) [5] and that by Hanania et al. (35 %) [29]. Our study has clinical implications. We found an association of depression with the level of education as well as disease severity. Patients who graduated from elementary school tended to experience depressive symptoms 3.67fold more frequently than those who graduated from high school or above. Increased dyspnea and poor exercise capacity also were significantly correlated with depression. Dyspnea has been reported to correlate with depression in patients with COPD [41]. In a study by van Manen et al. [5], patients with severe COPD had a 2.5-fold greater risk of depression than controls. Poor exercise capacity also was shown to be significantly associated with depression in a study of 122 stable COPD patients [35]. Given the association of depression with poorer treatment adherence [42], greater disability [15], and increased mortality [43] in COPD, screening and early intervention for depression in those with these characteristics would enhance the clinical
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outcomes of COPD. In addition, clinical strategies need to be developed to reduce depression in patients with COPD. In this respect, pulmonary rehabilitation [44], long-term oxygen therapy [45], and COPD self-management programs [46] have demonstrated significant and specific benefits for depression in COPD patients. There were several limitations to our study. First, the present study comprised a small number of females, which might explain the lack of a difference in the prevalence of depression between males and females in our data. Second, our definition of depression was based on the score of a well-validated instrument (CES-D), and we did not seek an objective, physician-based diagnosis of depression. Some further information, such as regarding comorbidities and history of exacerbation, would help to characterize the subjects. Finally, we could not assess any possible etiologic or causal links between COPD and depression due to the cross-sectional nature of this analysis. Nevertheless, the large population, which included a wide range of disease severity in subjects of a single ethnicity, is a strength of the present study. In conclusion, depression was associated with disease severity according to the BODE quartile and educational level in patients with COPD. More attention should be paid to patients with BODE quartile II and those with an elementary school education. Further investigation with patients evenly distributed among the BODE quartiles would provide greater insight into the association between COPD severity and depression. Acknowledgments This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0088833) and Pusan National University Research Grant, 2013. Conflict of interest
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12.
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15.
16.
None. 17.
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