Symptom Distress and Quality of Life in Patients with Advanced Chronic Obstructive Pulmonary Disease

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1 Vol. 38 No. 1 July 2009 Journal of Pain and Symptom Management 115 Original Article Symptom Distress and Quality of Life in Patients with Advanced Chronic Obstructive Pulmonary Disease Craig D. Blinderman, MD, MA, Peter Homel, PhD, J. Andrew Billings, MD, Sharon Tennstedt, PhD, and Russell K. Portenoy, MD Palliative Care Service (C.D.B., J.A.B.), Massachusetts General Hospital and the Harvard Medical School Center for Palliative Care, Boston, Massachusetts; Department of Pain Medicine and Palliative Care (P.H., R.K.P.), Beth Israel Medical Center, New York, New York; and New England Research Institutes (S.T.), Watertown, Massachusetts, USA Abstract Although chronic obstructive pulmonary disease (COPD) is a highly prevalent and disabling illness, few empirical studies have evaluated the impact of the disease on symptom distress, functional status, and quality of life. These outcomes were explored in a prospective survey of 100 patients with advanced COPD. Patients were recruited from two academic centers. The mean forced expiratory volume in 1 second (FEV1) was 24.4% (standard deviation ¼ 3.9). Validated instruments were used to assess symptom distress (Memorial Symptom Assessment Scale [MSAS]), mental health (Mental Health Inventory [MHI]-5), functional status (Sickness Impact Profile [SIP]), quality of life (Multidimensional Index of Life Quality [MILQ]), spirituality (Functional Assessment of Chronic Illness Therapy [FACIT] Spirituality Scale), and comorbid conditions (Charlson Comorbidity Index). The most prevalent symptoms were dyspnea (94%), fatigue (71%), xerostomia (60%), coughing (56%), and anxiety (51%). Other symptoms with high prevalence were drowsiness (47%), irritability (42%), feeling nervous (40%), and wheezing (40%). Significant pain was reported in about one-third of patients. Patients reported relatively high levels of overall functional impairment (SIP median ¼ 24.0) and modest impairment in overall quality of life (MILQ median ¼ 52). Overall, psychological well-being was relatively unimpaired (median ¼ 24.5), and the comfort derived from faith was intact (FACIT median ¼ 2.5). Impairment in quality of life was strongly associated with symptom distress (MSAS-GDI; r ¼ 0.74, P < 0.001), functional impairment (SIP total; r ¼ 0.59, P < 0.001), female sex (r ¼ 0.26, P ¼ 0.01), and poor psychological well-being (MHI-5; r ¼ 0.68, P < 0.001). In multivariate analyses, poor quality of life was strongly correlated with higher total symptom distress, sickness-related dysfunction, and lower levels of psychological wellbeing (R 2 ¼ 0.66). In addition, two specific psychological symptomsdworrying and feeling irritabledwere independently predictive of poor quality of life. Patients with advanced COPD have multiple distressing symptoms and a high prevalence of disturbances in mood, This study was supported by grant #NR05154 from the National Institute of Nursing Research, National Institutes of Health to Dr. Sharon Tennstedt. Address correspondence to: Craig D. Blinderman, MD, MA, Palliative Care Service, Massachusetts General Ó 2009 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved. Hospital, Founders 600, 55 Fruit Street, Boston, MA 02114, USA. cblinderman@partners.org Accepted for publication: August 8, /09/$esee front matter doi: /j.jpainsymman

2 116 Blinderman et al. Vol. 38 No. 1 July 2009 functional status, and quality of life. A focus on ameliorating prevalent physical symptoms and psychological distress may lead to an improvement in the overall quality of life in this patient population. J Pain Symptom Manage 2009;38:115e123. Ó 2009 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Chronic obstructive pulmonary disease, symptom distress, quality of life, MSAS Introduction Chronic obstructive pulmonary disease (COPD) is a highly prevalent, usually progressive illness associated with disability and early death. According to the World Health Organization, 80 million people worldwide have moderate to severe COPD. More than 3 million people died of COPD in 2005, which is approximately 5% of all deaths worldwide. 1 In the United States, COPD is the fourth leading cause of death. The prevalence of COPD in the United States in 2000e2001 was more than 12 million, and accounted for 1.5 million emergency department visits and 726,000 hospitalizations. 2 COPD prevalence has been steadily increasing over the past 25 years in the United States, and is projected to become the third leading source of mortality by Although COPD is commonly perceived to be associated with symptom distress and impaired functional status, few empirical studies have profiled this population. The first study to describe symptom burden specifically was the Confronting COPD Survey, a multinational study of 3265 patients with a diagnosis of COPD or symptoms that matched a strict definition of chronic bronchitis. 3 Of the 573 patients from the United States, moderate to severe disease was reported by 61%; 34% were unable to work, 31% had difficulty making plans, 32% felt that they were not in control of their breathing, 37% said that they panicked when they could not get their breath; and 41% expected their condition to get worse. 3 Two mixed cohort studies that included patients with COPD demonstrated a high prevalence of symptoms. 4,5 A study that compared patients with COPD, congestive heart failure, and advanced cancer noted that the most common moderate-to-severe symptoms among those with COPD were shortness of breath (65%), limited activity (61%), fatigue (49%), and physical discomfort (44%); COPD patients were more symptomatic overall than those with heart failure, and specifically experienced more anxiety, shortness of breath, and physical discomfort than the latter group. 6 Another recent study observed that symptom burden increased significantly over time in patients with COPD, with fatigue showing the greatest increase in severity. 7 To better understand the burden of illness associated with COPD, the symptoms and various other factors related to quality of life should be evaluated concurrently. We conducted a prospective observational study of patients with advanced COPD to evaluate the pattern of symptom distress and investigate the relationships among symptoms and measures of comorbidity, physical and mental functioning, and quality of life. Results from a similarly studied cohort with congestive heart failure have been reported previously. 8 Methods Data were obtained from a longitudinal observational study of patients with advanced COPD or congestive heart failure. Only the baseline data for COPD patients were used for this analysis. The Institutional Review Boards at Beth Israel Medical Center in New York, the Massachusetts General Hospital, Boston, and the New England Research Institute approved the original study protocol. Written informed consent was obtained from all patients before participation. Patient Selection and Procedures Data were collected between 2000 and Potentially eligible patients were identified by review of medical records in outpatient practices. Criteria for eligibility included:

3 Vol. 38 No. 1 July 2009 Symptom Distress and QoL in Patients with Advanced COPD 117 a diagnosis of COPD with documented forced expiratory volume in 1 second (FEV1) < 30%; estimated life expectancy more than three months; noninstitutional (i.e., community) residence; English speaking; and no evidence of any cognitive or psychiatric disorder sufficient to preclude adequacy of response. Patients with comorbid conditions for which survival was less than six months were excluded. Once a patient met eligibility criteria from chart review, the treating physicians were contacted to verify eligibility and to obtain consent to contact the patient. The patient was then contacted and asked to provide consent for participation in the study, whereupon eligibility was reconfirmed. Measures Demographic, disease-related, and treatment-related data were obtained from medical records and the patient. Patients also completed a packet of questionnaires. The following measures were collected for all patients. Charlson Comorbidity Index. The Charlson Comorbidity Index was based on information from the medical records and was used to characterize the degree to which patients were affected by comorbid factors. The Charlson Comorbidity Index encompasses 19 categories of comorbid conditions, primarily defined using ICD-9-CM diagnoses codes. 9 Each category is weighted based on estimated risk for oneyear mortality, and the overall Charlson score reflects the cumulative likelihood of one-year mortality. Charlson scores range between 0 and 35, and higher scores indicate greater comorbid burden. Short Portable Mental Status Questionnaire. The 10-item Short Portable Mental Status Questionnaire (SPMSQ) assesses cognitive status, 10 and was used to screen for subtle impairment. An SPMSQ score of 0e2 ¼ normal mental functioning; 3e4 ¼ mild cognitive impairment; 5e7 ¼ moderate cognitive impairment; and eight or more ¼ severe cognitive impairment. Memorial Symptom Assessment Scale. The MSAS is a patient-report instrument for the assessment of prevalence, characteristics, and degree of symptom distress. 11 For this study, an additional symptom dealing with pain localized in the chest area was added to the usual pain items. The MSAS yields four basic symptom distress scores: overall physical symptom distress (MSAS-PHYS), overall psychological symptom distress (MSAS-PSYCH), global symptom distress (MSAS-GDI), 11,12 and total symptom distress (MSAS-Total). The MSAS-GDI includes four psychological symptoms (e.g., feeling sad, worrying, feeling irritable, and feeling nervous) and six physical symptoms (e.g., lack of appetite, lack of energy, pain, feeling drowsy, constipation, and dry mouth). All distress scores for individual symptoms, and for indices such as the MSAS-GDI, range from 0 (not at all) to 4 (very much). Mental Health Inventory-5. The Mental Health Inventory-5 (MHI-5) consists of five patientrated items measuring psychological state and psychological well-being. The range of possible scores is 0e30, with higher scores indicating greater psychological well-being. Scores less than or equal to 18 indicate severe depression. 13 Sickness Impact Profile. The Sickness Impact Profile (SIP) consists of 68 items that assess sickness-related impairment in terms of somatic autonomy, mobility control, psychological autonomy and communication, social behavior, feelings, and mobility. 14 The SIP also yields overall measures of physical and psychological dysfunction, and a total dysfunction score. Subscores and total score range from 0 to 100, with higher scores indicating greater impairment. For example, a score of 20 indicates the need for substantial daily care. A score of 30 indicates the need for almost complete care. The SIP for the general population is 5. Multidimensional Index of Life Quality. The 35- item Multidimensional Index of Life Quality (MILQ) is a patient-rated measure of healthrelated quality of life. 15 In addition to an overall composite score that measures global quality of life, there are nine subscales dealing with physical health, physical functioning, mental health, cognitive functioning, social functioning, intimacy, productivity, financial status, and relationship with health professionals. Each item consists of a Likert scale

4 118 Blinderman et al. Vol. 38 No. 1 July 2009 ranging from 1 (very dissatisfied) to 7 (very satisfied). The MILQ composite score ranges from 12 to 84. Functional Assessment of Chronic Illness Therapy- Spirituality Scale. The Functional Assessment of Chronic Illness Therapy-Spirituality Scale (FACIT-Spirituality) consists of four-items, which ask about the degree to which patients derive comfort and strength from their faith. 16 The single score is the average of the four items, and it ranges from 0 to 4, with higher scores indicating greater spirituality. Statistical Methods Data are described as frequency (percent) for categorical variables, mean standard deviation (SD) for normally distributed variables, and as median (minimum, maximum) for skewed variables. Although they tend to be skewed, MSAS scores are presented as mean SD for the sake of historical comparison. The MILQ composite score was the primary outcome for univariate correlation and for multivariate regression analyses. Pearson correlations were first calculated between the MILQ and all other measures. Categorical variables were dummy coded to facilitate the calculation of correlations. Based on these univariate correlations, a potential pool of predictors was selected for multivariate analysis, with MILQ composite score as the dependent variable. Several multiple regression models with stepwise entry were first analyzed to select the best set of nonredundant variables for predicting the MILQ composite score. All measures showing a correlation with P < 0.05 with MILQ composite score were included for multivariate modeling. Interim stepwise analyses were done on subscales from the same measure to minimize the number of predictors entering the final multivariate model. For the sake of comparison, standardized regression coefficients (beta coefficients) are presented, because these give the magnitude of importance of each predictor in the regression model. A significance level of P ¼ 0.05 was used for all statistical tests. SPSS 15.0 (SPSS Inc., Chicago, IL, USA) was used to calculate all statistical test and P values. Results Patient Characteristics One hundred and three COPD patients were enrolled in the study. Three patients had a confirmed diagnosis of advanced heart failure and were excluded from the present analysis. Table 1 presents the demographics and baseline characteristics of the population studied. The mean age of the sample was 62.2 years (SD ¼ 10.5). Most of the patients were white (81%) and female (53%), whereas 44% were married. The patients had a mean FEV1 of 24.4% (SD ¼ 3.9). Table 1 also lists some of the primary diagnoses and comorbid conditions of these patients. Most patients primary pulmonary diseases were chronic bronchitis, followed by asthma, emphysema, sarcoidosis, and fibrosis. There were relatively low levels of comorbidity (Charlson Comorbidity Index median ¼ 1). The most prevalent comorbid conditions were cardiovascular disease, cancer, stroke, and diabetes. Cognitive Table 1 Demographics and Related Characteristics (n ¼ 100) Female 53 a Age (mean SD) Marital status Married 44 Lives alone 31 Race/ethnicity White 81 Black 10 Hispanic 6 Other 3 FEV1 (mean SD%) Charlson Comorbidity Index 1 (1, 9) Cognitive status (SPMSQ) 0 (0, 2) b (mean [min, max]) Comorbidities Bronchitis 72 Asthma 41 Emphysema 24 Sarcoidosis 4 Fibrosis 2 Cancer 14 Myocardial infarction 15 Neoplasms 14 Ulcer disease 9 Stroke 7 Diabetes 6 Kidney disease 3 Peripheral vascular disease 2 Connective tissue disease 2 a Descriptives presented as percent unless otherwise noted. b 0e2 indicates normal mental functioning.

5 Vol. 38 No. 1 July 2009 Symptom Distress and QoL in Patients with Advanced COPD 119 functioning was relatively unimpaired (SPMSQ median ¼ 0). Symptom Prevalence and Characteristics Table 2 lists symptom prevalence and the percentage of patients reporting higher scores (3 or 4 on a scale of 0e4) for frequency, severity, and degree of distress. Symptoms with the highest prevalence were shortness of breath (94%), lack of energy (71%), dry mouth (60%), cough (56%), and worrying (51%). Other symptoms with high prevalence were drowsiness (47%), irritability (42%), non-chest pain (41%), feeling nervous (40%), and wheezing (40%). Chest pain was reported in 37% of patients. The median number of symptoms for each patient was 10.5 (0e25). Apart from the prevalence of symptoms, the MSAS symptom descriptors for frequency, severity, and distress give a comprehensive picture of symptom burden. Half of all patients rated shortness of breath and lack of energy as being particularly distressful. Symptom distress indices revealed mild distress in the sample overall, with substantial variation in each index. These scores varied between 0 and 4. The medians (ranges) for the MSAS-GDI (global symptom distress), MSAS-PHYS (physical distress), MSAS-PSYCH (psychological distress), and MSAS-Total (totalc distress) were 0.68 (0e1.90), 0.78 (0e2.97), 0.56 (0e2.02), and 0.75 (0e2.80), respectively. Patients reported relatively high levels of overall functional impairment (SIP median ¼ 24.0) and modest impairment in overall quality of life (MILQ median ¼ 52) (Table 3). Table 2 Prevalence and Characteristics of Symptoms and Total MSAS Score (n ¼ 100) Symptoms Prevalence (%) Frequency (%) a Severity (%) b Distress (%) c MSAS Score d Shortness of breath Lack of energy Dry mouth Cough Worrying Feeling drowsy Feeling irritable Other pain (non-chest) Feeling nervous Wheezing Feeling sad Chest pain or pressure Difficulty sleeping I don t look like myself 31 N/A Problems with sexual interest/activity Numbness/tingling hands/feet Swelling of arms or legs 27 N/A Difficulty concentrating Sweats Feeling bloated Headaches Feeling fearful Itching Change in skin 22 N/A Problems with urination Lack of appetite Nausea Constipation 15 N/A Dizziness Hair loss 12 N/A Weight loss 12 N/A Difficulty in swallowing Mouth sores 11 N/A Change in the way food tastes 10 N/A Diarrhea Vomiting a Percentage of patients with symptom describing the frequency of the symptom as frequently or almost constantly. b Percentage of patients with symptom describing the severity of the symptoms as severe or very severe. c Percentage of patients with symptom describing the distress associated with the symptom as quite a bit or very much. d Mean SD provided for historical comparison. MSAS score ranges from 0 to 4.

6 120 Blinderman et al. Vol. 38 No. 1 July 2009 However, psychological and spiritual well-being was relatively preserved (MHI median ¼ 24.5; FACIT-Spirituality median ¼ 2.5). Quality of Life: Univariate Relationships Quality of life, as measured by the MILQ composite score, showed a strong negative association with all indices of symptom distress (Table 4). The strongest association between global symptom distress and impaired quality of life was seen with the MSAS-GDI (r ¼ 0.74, P < 0.001). Impairment in quality of life also was strongly associated with female sex (r ¼ 0.26, P ¼ 0.01) and functional impairment, as indicated by the SIP total score (r ¼ 0.59, P < 0.001) and subtest scores. Higher ratings of quality of life were correlated with psychological well-being, as measured by the MHI-5 (r ¼ 0.68, P < 0.001). The burden of comorbid diseases, cognitive status, and spirituality, as measured by the Charlson Comorbidity Index, SPMSQ, and FACIT-Spirituality, respectively, were not significantly related Measure Table 3 Descriptive Statistics for Quality of Life and Other Measures Sample Size Median (min, max) Possible Range Number of MSAS (0, 25) 0e36 symptoms per patient MSAS-PHYS (0, 2.97) 0e4 MSAS-PSYCH (0, 2.02) 0e4 MSAS-Total (0, 2.80) 0e4 MSAS-GDI (0, 1.90) 0e4 MHI (9, 30) 5e30 SIP Somatic autonomy (0, 63) 0e100 Mobility control (0, 100) 0e100 Psychological autonomy (0, 90) 0e100 Social behavior (0, 100) 0e100 Feelings (0, 100) 0e100 Mobility (0, 100) 0e100 Overall physical (0, 74) 0e100 Overall psychological (0, 83) 0e100 Total score (0, 76) 0e100 MILQ Mental health (5, 28) 4e28 Physical health (4, 28) 4e28 Physical function (4, 28) 4e28 Social function (5, 28) 4e28 Partner intimacy (4, 28) 4e28 Cognitive function 99 24(5, 28) 4e28 Financial status (4, 28) 4e28 Health professionals (2, 28) 4e28 Work/productivity (4, 28) 4e28 Composite score (14, 84) 12e84 FACIT-Spirituality (0, 4) 0e4 to quality of life. No association with quality of life was observed with any of the other baseline patient characteristics, including age, race, marital status, living alone, and the severity of COPD, as measured by FEV1. Quality of Life: Multivariate Relationships For multivariate analyses, an interim stepwise approach was used to reduce the number of potential predictor variables from the SIP and the MSAS. The MILQ composite score was regressed onto all the SIP scores shown in Table 4. This yielded two SIP predictors: SIP social behavior (beta ¼ 0.40, P ¼ 0.001); and total SIP (beta ¼ 0.28, P ¼ 0.02). In the case of the MSAS, the MILQ composite score was regressed onto the number of MSAS symptoms reported by each patient, namely MSAS- PSYCH, MSAS-PHYS, MSAS-Total, and MSAS- GDI. This yielded only the GDI as the best predictor of MILQ composite score (beta ¼ 0.74, P < 0.001). The results of these interim regressions were then entered into a stepwise regression model Measure Table 4 Univariate Correlations with MILQ Composite Score MILQ Composite Score Correlation r P-value Age Female Separated, divorced, widowed Lives alone White FEV Charlson Comorbidity Index SPMSQ MHI <0.001 SIP somatic autonomy 0.36 <0.001 SIP mobility control 0.48 <0.001 SIP psychological 0.39 <0.001 autonomy SIP social behavior 0.62 <0.001 SIP feelings 0.39 <0.001 SIP mobility 0.47 <0.001 SIP overall physical 0.53 <0.001 SIP overall psychological 0.58 <0.001 SIP total score 0.59 <0.001 FACIT-Spirituality Number of MSAS 0.56 <0.001 symptoms MSAS-PHYS score 0.55 <0.001 MSAS-PSYCH score 0.66 <0.001 MSAS-Total score 0.67 <0.001 MSAS-GDI 0.74 <0.001

7 Vol. 38 No. 1 July 2009 Symptom Distress and QoL in Patients with Advanced COPD 121 along with the variables that were significantly associated with the MILQ composite score in univariate analysis (Table 4), specifically female sex and MHI-5 score (Model 1). Three predictors were selected: MSAS-GDI (beta ¼ 0.40, P < 0.001); MHI-5 (beta ¼ 0.28, P ¼ 0.001); and SIP social behavior (beta ¼ 0.28, P < 0.001). The R 2 for this model was 0.66, indicating that 66% of the variance of the MILQ was explained by these three predictors (Table 5). To determine which symptoms of the MSAS- GDI were most important in determining its association with the MILQ composite score, the MILQ was regressed onto the 10 individual symptom distress scores comprising the GDI along with the MHI-5 and SIP social behavior. Two symptoms were chosen by backward selection: worrying (beta ¼ 0.23, P ¼ 0.001) and feeling irritable (beta ¼ 0.13, P ¼ 0.07). The R 2 for this model was 0.63, indicating that 63% of the variance of the MILQ was explained by the four predictors selected by Model 2. Discussion This cohort of patients with advanced COPD lived at home, was not cognitively impaired, and had a relatively low burden of comorbid conditions. Findings, therefore, should be interpreted as profiling those with this illness who may be disabled by the disease but are not imminently dying. Nonetheless, the findings demonstrate high symptom burden, high functional impairment, and moderate impairment in overall quality of life. Table 5 Factors Associated with Quality of Life: Results of Multivariate Regression Models Regression Coefficients Predictor Unstandardized (Beta) Standardized (Beta) P-value Model 1 (R 2 ¼ 0.66) MSAS-GDI <0.001 MHI SIP social <0.001 behavior Model 2 (R 2 ¼ 0.63) MHI <0.001 SIP social <0.001 behavior Worrying Feeling irritable The most prevalent symptoms included those typically associated with COPD: shortness of breath, fatigue, dry mouth, cough, and anxiety. These findings are consistent with previous studies of symptom prevalence in COPD, 6,7 in which, shortness of breath, physical discomfort, fatigue, lack of appetite, and anxiety were found to be the primary symptoms. Other common symptoms included drowsiness, irritability, nervousness, and wheezing. Chest pain occurred in over a third of patients, and more than half of the sample reported pain of some type. The prevalence of these symptoms and the level of distress associated with them were comparable in magnitude to other chronically ill populations, including ambulatory patients with cancer, 17,18 and communitydwelling patients with advanced congestive heart failure. 8 This indicates that there is a striking similarity in terms of symptom clustering among patients with chronic illness despite distinct differences in disease etiology. Previous studies that have looked at quality of life in COPD patients have either focused only on the association of quality of life with symptoms 19,20 or were less detailed in terms of choice of potential predictors. 21 The multivariate analyses in the present study were based on a comprehensive collection of measures and instruments, which yielded a model in which two-thirds of the variance in quality-oflife scores was predicted by a combination of global symptom distress, psychological wellbeing, and degree of impairment in social behavior. In addition, two specific psychological symptomsdworrying and feeling irritabled were independently predictive of poor quality of life. Significant correlations between psychological symptoms and quality of life are consistent with previous findings. 20 The relationship between symptom distress and quality of life is likely to be complex; additional studies are needed to clarify the extent to which other factors, such as coping or support from family or health professionals, may influence outcomes. For example, a previous study of 4418 COPD patients suggested that the relationship between symptom severity and patient satisfaction with the primary care provider might be attenuated by the patient s ability to cope with dyspnea. 22 This complexity notwithstanding, the associations revealed in this cohort of patients with

8 122 Blinderman et al. Vol. 38 No. 1 July 2009 advanced COPD underscore the need for effective symptom control and other interventions associated with optimal palliative care. Given the high prevalence and distress associated with dyspnea, fatigue, xerostomia, and pain among COPD patients, treatment focused on these symptoms is important. The data also suggest that addressing psychological distress and assisting in the effort to maintain social functioning also may improve quality of life. The interpretation of these data should consider several potential limitations. The associations are correlational and do not indicate causality. The clinical implication that quality of life may be improved by effective management of distressing symptoms or other factors identified in these analyses requires confirmation through clinical trials in patients with COPD, although there are several studies in the literature suggesting that palliative care interventions in patients with advanced disease improves well-being and quality of life. 23e25 The present study also focused on a relatively small sample recruited from two academic urban medical centers. The findings, therefore, may not be representative of the total population with COPD residing in community settings. Moreover, interpretation of the data may be compromised by elements that were not assessed, including information about treatment of the disease itself and symptoms, caregiver characteristics, and psychological resilience. All these factors should be further explored in future studies. Despite these limitations, the data acquired from this cohort of patients with advanced COPD suggest that symptom distress remains a significant clinical problem in this population and that quality of life potentially could be improved if symptoms were more effectively managed and if psychosocial concerns were better addressed. A focus on palliative care in this population may yield substantial benefits. References 1. World Health Organization. Burden, Avaliable at burden/en/print.html. Accessed January 8, Centers for Disease Control and Prevention. Available at tion/copd/copdfag.htm. Accessed January 12, Rennard S, Decramer M, Calverley PM, et al. Impact of COPD in North America and Europe in 2000: subjects perspective of Confronting COPD International Survey. Eur Respir J 2002;20(4): 799e Tranmer JE, Heyland D, Dudgeon D, et al. Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the Memorial Symptom Assessment Scale. J Pain Symptom Manage 2003;25(5): 420e Rabow MW, Dibble SL. Ethnic differences in pain among outpatients with terminal and end-stage chronic illness. Pain Med 2005;6(3):235e Walke LM, Gallo WT, Tinetti ME, Fried TR. The burden of symptoms among community-dwelling older persons with advanced chronic disease. Arch Intern Med 2004;164(21):2321e Walke LM, Byers AL, Tinetti ME, et al. Range and severity of symptoms over time among older adults with chronic obstructive pulmonary disease and heart failure. Arch Intern Med 2007;167(22): 2503e Blinderman CD, Homel P, Billings JA, Portenoy RK, Tennstedt SL. Symptom distress and quality of life in patients with advanced congestive heart failure. J Pain Symptom Manage 2008;35(6): 594e603. Epub January 22, Charlson ME, Pompei P, Ales KL, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40(5): 373e Pfeiffer E. A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J Am Geriatric Soc 1975;23: 433e Portenoy RK, Thaler HT, Kornblith AB, et al. The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer 1994;30A: 1226e Chang VT, Hwang SS, Thaler HT, Kasimis BS, Portenoy RK. Memorial Symptom Assessment Scale. Expert Rev Pharmacoeconomics Outcomes Res 2004;4:171e Veit CT, Ware JE. The structure of psychological distress and well-being in general populations. J Consult Clin Psychol 1983;51(5):730e Bergner M, Bobbitt RA, Carter WB, Gilson BS. The Sickness Impact Profile: development and final revision of a health status measure. Med Care 1981; 19:787e Avis NE, Smith KW, Hambleton RK, et al. Development of the Multidimensional Index of Life

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