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(Chest. 2005;127:328-334.)
© 2005 American College of Chest Physicians

Association of Depression and Life-Sustaining Treatment Preferences in Patients With COPD*

Renee D. Stapleton, MD; Elizabeth L. Nielsen, MPH; Ruth A. Engelberg, PhD; Donald L. Patrick, PhD, MSPH and J. Randall Curtis, MD, MPH, FCCP

* From the Division of Pulmonary and Critical Care Medicine (Drs. Stapleton, Nielsen, Engelberg, and Curtis), Department of Medicine, School of Medicine; and Program in Social and Behavioral Sciences (Dr. Patrick), Department of Health Services, School of Public Health, University of Washington, Seattle, WA.

Correspondence to: Renee D. Stapleton, MD, Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box 359762, 325 Ninth Ave, Seattle, WA 98104-2499; e-mail: rstaplet{at}u.washington.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: Depressive symptoms and reduced health-related quality of life are common in patients with severe COPD. Therefore, understanding the association between preferences for life-sustaining treatment and depression or quality of life is important in providing care. No prior studies have examined the effects of depression and quality of life on treatment preferences in this population.

Design and patients: Cross-sectional study of 101 patients with oxygen-prescribed COPD.

Methods: Patients completed the St. George’s Respiratory Questionnaire, Center for Epidemiologic Studies–Depression survey, and questions regarding their preferences for mechanical ventilation and cardiopulmonary resuscitation if needed to sustain life.

Results: Median age was 67.4 years, and median FEV1 was 26.3% predicted. Depression was significantly associated with preferences for resuscitation (50% of depressed patients and 23% of patients without depression refused resuscitation; p = 0.007), but was not associated with preferences for mechanical ventilation. Health-related quality of life was not associated with preferences for either resuscitation or mechanical ventilation.

Conclusions: Clinicians caring for patients with oxygen-prescribed COPD should understand that health-related quality of life does not predict treatment preferences and should not influence clinicians’ views of patients’ treatment preferences. However, depression does appear to influence patients’ treatment decisions for cardiopulmonary resuscitation, and improvement in depressive symptoms should trigger a reassessment of these preferences.

Key Words: COPD • depression • end of life • quality of life • treatment preferences


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
COPD is a chronic progressive illness that affects 6% of the general population, and is the fourth leading cause of death in the United States.12 Patients with COPD and hypoxemia have a 2-year survival of only 50%.3 Exacerbations and episodes of respiratory failure are common in these patients. Therefore, it is important that patients, caregivers, and physicians discuss treatment preferences and make decisions regarding life-sustaining treatments. Although it is known that patients with COPD have a reduced health-related quality of life456 and a high prevalence of depressive symptoms,789101112 previous studies have not examined the influence of reduced quality of life and increased depressive symptoms on these patients’ treatment preferences for life-sustaining treatments.

Previous investigations have examined the influence of health-related quality of life and depressive symptoms on treatment preferences for patients with other diseases. Studies131415 investigating the association between health-related quality of life and treatment preferences have reported preferences for less aggressive life-sustaining treatments when respondents have been questioned about future, hypothetical, and very poor health states. In contrast, studies131416 that have measured current self-reported health-related quality of life have found no association between treatment preferences and health-related quality of life. Studies investigating the association of depressive symptoms with desire for life-sustaining treatments have also reported conflicting results. Rosenfeld and colleagues, in the Study To Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT),17 examined 1,590 seriously ill hospitalized patients and found that preferences for do-not-resuscitate status were significantly associated with increased depressive symptoms. They also noted that a reduction in depressive symptoms after a 2-month follow-up resulted in a fivefold increase in the likelihood of patients changing preferences to wanting full cardiopulmonary resuscitation (CPR). Similarly, Blank and colleagues18 studied 150 hospitalized patients ≥ 60 years old and reported that increased depressive symptoms were significantly associated with refusal of life-sustaining treatments. However, Garrett and colleagues16 examined 2,536 ambulatory Medicare patients and found that higher depression scores were associated with the desire for more life-sustaining treatment at the end of life. These contradictory results may be due to variations in patients’ underlying diseases or severity of illness or due to regional differences. In this study, we examined the effects of depressive symptoms and health-related quality of life on preferences for life-sustaining treatments, specifically mechanical ventilation and CPR, in patients with oxygen-prescribed COPD. Some of the results in this article have been previously reported in the form of an abstract.19


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Recruitment and Enrollment
This study was conducted in Seattle, WA, between July 1999 and June 2002. Methods have been described previously in a report of the quality of communication about end-of-life care.20 Eligibility criteria included age > 18 years, English-speaking, diagnosis of COPD with evidence of airflow obstruction, and prescription for 24-h home oxygen. Exclusion criteria were temporary oxygen use or mental status that precluded participation. Patients were identified through ambulatory pulmonary clinics in three hospitals (university, county, and Veterans Affairs Medical Center) and through an oxygen delivery company. We used two enrollment methods. At the county and university hospital, a clinician familiar with the patient asked the patient if he or she was willing to talk with study staff. At the Veterans Affairs Medical Center and oxygen delivery company, a letter was mailed to all patients receiving oxygen asking them to call a toll-free telephone number if they were unwilling to participate; if they did not leave a message declining participation, they received a phone call from the study staff. The Human Subjects Committee at the University of Washington approved all study procedures.

Interviews and Questionnaires
Patients were interviewed in person by a trained study interviewer, during which patients self-reported demographic information, duration of oxygen therapy, and current coexisting illnesses. Each patient’s FEV1 was either obtained with portable spirometry according to American Thoracic Society standards,21 or from the medical record if the patient consented to medical record review. Patients also completed the St. George Respiratory Questionnaire (SGRQ) and the Center for Epidemiologic Study–Depression (CES-D) survey, validated instruments for assessing health-related quality of life and depressive symptoms, respectively.2223 During the interview, patients were asked two previously validated questions about their treatment preferences for mechanical ventilation or CPR given their current health status (Table 1 ).24


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  		Table 1. Questions Asked to Patients About Their Treatment Preferences

 
The SGRQ and CES-D for each patient were scored according to standard methods.2223 As previously validated, a CES-D score of 16 was used as the dichotomous cutoff point, with higher and lower scores indicating presence or absence of depression, respectively.25 We used the dichotomous assessment of depression because we believed it to be more clinically relevant than an absolute CES-D score.

Statistical Analyses
The primary dependent (outcome) variables for these analyses were the patients’ treatment preferences for CPR and mechanical ventilation. Analyses were performed to identify association between these preferences and the following patient characteristics: (1) age, (2) number of coexisting illnesses, (3) FEV1, (4) presence/absence of depression as measured by the CES-D, and (5) health-related quality of life as measured by the SGRQ total and subscale scores. Differences in treatment preferences were examined using t tests for continuous variables and {chi}2 analyses for dichotomous variables. In order to evaluate potential confounding effects of the above patient characteristics, multivariate analyses were performed using logistic regression with the dichotomous treatment preferences as the outcome variables and the characteristics as predictors. Predictors were entered using a backward stepwise procedure with a p value of 0.10 to enter and 0.05 to be retained in the model. A p value ≤ 0.05 was considered significant. SPSS software (SPSS; Chicago, IL) was used for all statistical analyses.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
At the two study sites where patients were contacted by clinicians familiar to the patient, 78 eligible patients were identified and 50 patients were enrolled, for a participation rate of 64%. At the two study sites where patients were sent a mailing describing participation and then telephoned by study staff, 217 eligible patients were identified and 68 patients were enrolled, for a participation rate of 31%. Overall, of the 295 eligible patients contacted and asked to participate in a 1-h in-person interview, 118 patients were enrolled for 40% participation. Of the 118 enrolled patients, 115 patients completed the interviews, and 3 patients were unable due to fatigue. Of the 115 interviews, 14 interviews were completed prior to inclusion of the CES-D questionnaire, and therefore are excluded from analyses in this article. The SGRQ and CES-D were self-administered for 79 patients (78.2%), and interviewer administered for 22 patients (21.8%) who required assistance because of poor health or visual impairment.

Table 2 describes the study sample of 101 patients who completed all study instruments. Median patient age was 67.4 years, men comprised 77% of the sample, and 84% were white. Coexisting chronic medical conditions were common, with back pain and arthritis most frequently cited (47%). Median FEV1 (available in 83 patients because 18 patients refused spirometry) was 26.3% of the predicted value, and the patients had spent a median of 25.5 months receiving oxygen. None of the patients was receiving noninvasive ventilation during the daytime.


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  		Table 2. Characteristics of 101 Patients With Oxygen-Prescribed COPD*

 
A majority of the patients surveyed reported they would want mechanical ventilation (62.2%) and CPR (63.6%). Older age was significantly associated with refusal of both treatments. Patients who indicated that they would refuse mechanical ventilation had a mean age of 69.4 years, while those who desired mechanical ventilation were a mean age of 65.1 years (p = 0.022). Those who refused CPR had a mean age of 69.2 years, and those who desired CPR had a mean age of 65.3 years (p = 0.049). FEV1 and gender were not associated with preferences for either life-sustaining treatment. Increasing numbers of coexisting illnesses were associated with increased likelihood of wanting mechanical ventilation (p = 0.033), but not CPR (p = 0.370).

CES-D scores (n = 97) had a mean of 16.4 with a SD of 10.6, and 45.4% of subjects had a CES-D score ≥ 16, suggesting presence of depression. SGRQ domain and total scores of our patients (n = 100) were as follows: symptom domain, 62.78 ± 22.19; activity domain, 74.05 ± 22.84; impact domain, 44.79 ± 18.56; and total, 56.96 ± 15.45 (± SD).

The presence of depression, as measured by a score of ≥ 16 on the CES-D, was significantly associated with a preference against CPR, as shown in Figure 1 . Of patients who had evidence of depression, 50% declined CPR, while only 23% of patients without evidence of depression declined CPR (p = 0.007). However, evidence of depression was not significantly associated with preferences for mechanical ventilation, also shown in Figure 1. Finally, as shown in Table 3 , treatment preferences for mechanical ventilation and CPR were not associated with health-related quality of life as measured by the SGRQ total score or any of the three domain subscores.



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  		Figure 1. Depression, as defined by a CES-D score ≥ 16, is associated with a preference against CPR but not associated with preferences regarding mechanical ventilation among patients with oxygen-prescribed COPD.

 

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  		Table 3. Absence of an Association Between Health Status as Measured by the SGRQ and Preferences for Life-Sustaining Treatments for Patients With Oxygen-Prescribed COPD*

 
Multivariate analyses using logistic regression found that none of the potentially confounding patient characteristics, including patient age and number of comorbid illnesses, predicted treatment preferences. Only absence of depression was an independent significant predictor of preference for CPR (p = 0.047).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study of patients with oxygen-prescribed COPD resulted in three central findings. First, in univariate analysis, older age is associated with a preference against CPR and mechanical ventilation. This result extends the findings of a prior survey13 of elderly outpatients, as well as the SUPPORT study,26 to patients with oxygen-prescribed COPD. In our study, 44% of patients > 65 years old preferred not to receive either CPR or mechanical ventilation or both, a percentage similar to the 42% of patients aged 60 to 69 years found in SUPPORT to refuse CPR. These results suggest that older patients with oxygen-prescribed COPD are similar to other chronically ill patients in this respect.

A second finding from our study was that health status as measured by the SGRQ was not associated with end-of-life treatment preferences in this population of patients with severe COPD. These data confirm and extend the results of two prior studies done in elderly outpatients without severe comorbidity13 and in seriously ill, hospitalized patients with several different primary diagnoses.14 This finding suggests that physicians and other health-care providers caring for patients with severe COPD should not assume that poorer health status is associated with a higher likelihood of refusing life-sustaining treatment. Since physicians consistently underestimate patients’ quality of life compared to the patients’ own assessments,2728 and since there is evidence that physicians’ estimates of patients’ treatment preferences are influenced by the physicians’ estimates of patients’ quality of life,13 it is important that physicians caring for patients with severe COPD examine their own assumptions and directly obtain treatment preferences from patients.

A third finding from our study was that a higher burden of depressive symptoms was significantly associated with a preference against CPR, but was not statistically associated with preferences for mechanical ventilation among patients with oxygen-prescribed COPD. The fact that depression is associated with refusal of life-sustaining treatment in our study is similar to the findings of two prior investigations1718 that assessed preferences for CPR but not specifically for mechanical ventilation. However, these results are quite different from the results of Garrett and colleagues,16 who found that patients with higher depression scores were significantly more likely to desire more life-sustaining treatments. This discrepancy may be explained by the difference in samples of the three studies. Patients in the SUPPORT study17 were seriously ill, hospitalized, and had at least one illness which carried a 50% 6-month mortality. In the study by Blank and colleagues,18 patients were also medically ill and hospitalized. Although our study participants were outpatients, they had quite severe illness as defined by the entry criterion of oxygen-prescribed COPD. The study by Garrett et al,16 however, consisted of elderly outpatients without serious illness. Therefore, these differences in the role of depression on treatment preferences may be accounted for by severity of illness.

A prior report20 from this study showed that patients with depression rate the quality of patient-physician communication about end-of-life care significantly lower than those without depression. It is not clear whether this finding reflects an effect of depression on patients’ ratings of the quality of communication or whether the quality of patient-physician communication is negatively influenced by depression. Further study is needed to determine whether depression or depressive symptoms directly affects the quality of patient-clinician communication about end-of-life care and whether this may influence patients’ treatment preferences.

The fact that depressed patients with COPD appear to have a preference against CPR more often than patients without depression implies that treatment of depression might change end-of-life treatment preferences for these patients. Several studies have examined this hypothesis in patients with different diseases. SUPPORT17 found that among patients who initially preferred do-not-resuscitate status, those whose depression score improved substantially at 2-month follow-up were five times more likely to change treatment preferences to wanting CPR than those patients whose depression scores did not improve. Ganzini and colleagues29 examined the treatment preferences of 43 elderly depressed patients before and after treatment of the depression, finding that there was not a significant change in preferences in the majority of patients. However, there was a clinically evident change in the preferences of the 11 patients who had initially been rated as more severely depressed. Similarly, Eggar and colleagues30 investigated the CPR preferences of 49 elderly depressed patients before and after treatment for depression, finding that 16 of 17 patients who initially declined CPR accepted CPR after treatment for depression. Since prior research31 suggests that clinical depression among patients with severe COPD responds to antidepressant therapy, our findings have implications for clinicians caring for patients with coexisting oxygen-prescribed COPD and depression.

Although we found that patients with evidence of depression, defined by the CES-D score, would refuse CPR significantly more often than patients without evidence of depression, we did not find that patients with depression made significantly different decisions about mechanical ventilation. There are two potential explanations for this discrepancy. First, it is possible that patients with depression view CPR in the event of cardiac arrest differently than they view mechanical ventilation in the event of respiratory failure. This difference in attitude toward CPR could be affected by the depressed patients’ views of the likelihood of success of CPR or the potential harm or discomfort invoked by CPR. Alternatively, it is also possible that depressed patients are less likely to prefer mechanical ventilation, but perhaps the effect size is smaller and we were unable to detect it with our sample size of 101 patients. This is an area that should be explored in future studies if we are to fully understand the effect of depression on patients’ treatment preferences.

Strengths of this investigation are several. It is the first study to examine the associations between depression, health status, and end-of-life treatment preferences specifically in a population of outpatients with severe COPD. Additionally, the patients were recruited from a variety of outpatient settings, thus increasing the generalizability of the results to a broader COPD population. In addition, we believe that it is important to discuss end-of-life preferences with patients in an outpatient setting when they are relatively well and able to engage in these types of conversations. Since the patients in this investigation are all outpatients, these data may be particularly useful to clinicians providing care to such patients.

Several limitations to this study are noteworthy. First, the sample size is relatively small, with only 101 patients, and therefore we may not be able to detect small but important associations with treatment preferences. In addition, our sample was largely white, male, and receiving care in the Pacific Northwest. All of these factors may limit the generalizability of the results. Second, the overall response rate was approximately 40% and was different with two different recruitment methods. We have no way of knowing how this response rate and the potential selection bias may affect the results. However, the fact that our patients report similar health-related quality of life to previous studies532 and similar treatment preferences to that found in SUPPORT26 suggests the results may be generalizable to these populations. Prior research has also found relatively low participation rates for interviews or surveys regarding end-of-life care.33 Since there is no ethical alternative to only studying those willing to participate, future studies should identify ways to improve the participation rates without coercion. Additionally, our study suggests that the more time-intensive method of having patients approached by clinicians with whom they are familiar to ask permission for study staff to explain the study provides a significantly higher response rate for this kind of investigation. Third, we did not assess whether any of these patients had experienced CPR or mechanical ventilation in the past, an event that could have influenced their preferences for life-sustaining therapies. We also did not collect data on patients’ level of oxygen or carbon dioxide during the study interview, which may affect responses. Fourth, the results of this study are limited by the specific phrasing of the questions regarding treatment preferences themselves. We did not specify in the questions to which state of health the patient would be likely to return if he/she survived resuscitation. However, a prior investigation18 has shown that treatment preferences are quite different when the hypothetical outcome was specified as "restored to current condition" as opposed to "restored to coma." The likelihood of a good outcome after CPR in any patient is low34 and is likely extremely small in a patient with severe COPD. Although it is possible that bias was introduced if patients with depression are fundamentally different than those without depression in their understanding of this prognosis, we believe this "bias" likely reflects the way most of these discussions occur in the outpatient setting. Finally, subjects were asked to answer questions about their preferences for end-of-life care in the context of hypothetical situations (critical illness requiring mechanical ventilation or CPR) and we do not know how well their responses would correlate to their true preferences if critical illness did occur. Nonetheless, since clinicians may wish to discuss such hypothetical treatment preferences with patients when they are clinically stable, our results will apply to these discussions.

In conclusion, clinicians caring for patients with oxygen-prescribed COPD should understand that patients’ current health-related quality of life is not a reliable predictor of their treatment preferences. Furthermore, clinicians should recognize that coexistence of depression in these patients may influence patients’ decisions regarding treatment preferences for life-sustaining therapies and that spontaneous or therapy-induced improvement in depressive symptoms might warrant a reassessment of patients’ treatment preferences.


   Footnotes
 
Abbreviations: CES-D = Center for Epidemiologic Studies–Depression; CPR = cardiopulmonary resuscitation; SGRQ = St. George Respiratory Questionnaire; SUPPORT = Study To Understand Prognoses and Preferences for Outcomes and Risks of Treatment

Grant support was provided by a Career Investigator Award from the American Lung Association and the American Lung Association of Washington (Dr. Curtis).

Received for publication March 3, 2004. Accepted for publication June 30, 2004.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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