Emphysema

Study objectives: The goal of this study was to evaluate the neuropsychological and psychological functioning of emphysema patients following lung volume reduction surgery (LVRS) compared with patients receiving only medical therapy (MT).

Design: Patients with moderate-to-severe emphysema who were enrolled in the National Emphysema Treatment Trial at two sites (National Jewish Medical and Research Center and Ohio State University) were given a neuropsychological battery at baseline, 6 to 10 weeks later (following participation in pulmonary rehabilitation), and at 6 months following randomization to either LVRS or MT treatment.

Subjects and measurements: Twenty patients randomized to MT, 19 patients randomized to LVRS, and 39 matched, healthy control subjects completed a battery of tests that measured cognitive functioning, depression, anxiety, and quality of life (QoL).

Results: Controlling for practice, patients in the LVRS treatment arm at the 6-month follow-up demonstrated significant improvement compared with MT patients in cognitive tasks involving sequential skills and verbal memory. The LVRS patients also showed significant reductions in depression compared with the MT patients, as well as improved physical and psychosocial QoL. Correlational analysis indicated that improved immediate verbal memory in the LVRS group was related to improved QoL. No associations were found between changes in cognitive function and changes in depression, exercise performance, or pulmonary functioning.

Conclusion: Patients who received LVRS demonstrated improvement in specific neuropsychological functions, depression, anxiety, and QoL scores compared with patients with continued MT treatment 6 months following randomization. However, mechanisms for these neurobehavioral changes are unclear. Improved verbal memory and sequential skills following LVRS were not directly associated with depression or exercise capacity. Nonetheless, LVRS led to a strong and likely clinically significant improvement in neuropsychological functioning over and above that explained by practice effects or MT. This finding adds to the growing list of clinical benefits of LVRS over MT, and supports additional research into the underlying mechanisms of this therapeutic effect.

Key words: cognition; emphysema; psychology; quality of life; surgery

Abbreviations: ANOVA = analysis of variance; BDI = Beck depression inventory; DRS = Delirium Rating Scale; LVRS = lung volume reduction surgery; NETT = National Emphysema Treatment Trial; QoL = quality of life; WPNS = Western Perioperative Neurologic Scale

**********

Emphysema is associated with significant physical, cognitive, and psychological sequelae. (1) Common medical treatment modalities in emphysema, such as oxygen therapy and physical rehabilitation, improve neurobehavioral functions, (2,3) yet no studies to date have examined these changes following lung volume reduction surgery (LVRS). Published results from the National Emphysema Treatment Trial (NETT) (4) indicate that non-high-risk patients who were randomized to surgery had notable improvement in disease-specific quality of life (QoL) and physical function. Neuropsychological and psychological changes following LVRS have not yet been investigated.

It has been known for some time that patients with mild-to-severe COPD exhibit cognitive deficits in visual-motor skills, reasoning, visual and auditory attention, visual and verbal learning and memory, and language skills. (5-8) Additionally, psychological difficulties, such as depression and anxiety, are common in COPD patients. (3,9-11) Patients with emphysema constitute a subset of the COPD group, and most data pertaining to COPD are highly relevant for patients with emphysema.

Two medical treatment approaches have demonstrated a positive impact on cognitive and psychological functioning in patients with COPD. Evidence exists that long-term (ie, >6 months) use of oxygen therapy improves cognitive performance in COPD patients and may be attributable to the direct effects of improved oxygen delivery to the CNS. (3,12-14) Improved cognition and reduced depression in COPD patients have also been reported, (2,15-18) following multidisciplinary rehabilitation. The mechanisms associated with cognitive improvement in these COPD patients have included better physical endurance and improved psychological functioning. Another proposed mechanism suggests that an improved exercise capacity contributes to the enhanced utilization of oxygen in the brain and improved neurotransmitter function. Extrapolating from these results, a procedure such as LVRS that enhances exercise capacity and oxygenation would be expected to contribute to enhanced neuropsychological performance.

This longitudinal study included neuropsychological evaluations at the following three time points: baseline; after 6 to 10 weeks of rehabilitation (just prior to randomization); and 6 months postrandomization into the LVRS and MT groups. We hypothesized that patients who were assigned to the LVRS group would experience improvements in cognitive performance over and above those observed in the MT-only group, as demonstrated by improvement between the postrehabilitation assessment and the 6-month follow-up examination. Second, it was expected that changes in cognitive function would exceed those expected by a learning effect as quantified with an age-matched, but healthy, control group. Third, we expected that the incidence of neurologic events and delirium would be low in the LVRS group and would not account for group changes in cognitive performance. Fourth, we hypothesized that improved exercise and oxygenation, but not psychological status, would be mechanisms associated with neuropsychological improvement.

MATERIALS AND METHODS

Subjects

All of the patients in the NETT at the National Jewish Medical and Research Center (Denver, CO) and at the Ohio State University (Columbus, OH) were invited to join this ancillary study. Fifty-six patients from both sites completed baseline (time 1) and postrehabilitation (time 2) testing. As indicated in Figure 1, subjects withdrew prior to and following randomization to both the LVRS and MT groups. A total of three deaths occurred, one prior to randomization and two following LVRS. Data from the two patients who died following LVRS are reported at the end of this section. In addition, a sample of 39 healthy subjects matched by age, education, gender, and physical activity level were recruited as a control group and were used to quantify the learning effects on this battery of neuropsychological tests.

[FIGURE 1 OMITTED]

The following three groups of subjects completed this study: 39 NETT patients (19 randomized to LVRS and 20 randomized to MT) and 39 matched healthy control subjects. As shown in Table 1, the groups were primarily older white men with a high-school education. All of the MT and LVRS subjects were enrolled as participants in the NETT protocol (19) with moderate-to-severe emphysema. All of the NETT subjects participated in an exercise rehabilitation program for 6 to 10 weeks (including physician visits, exercise training, and educational and psychosocial sessions). Those who completed the required rehabilitation, met inclusion criteria following rehabilitation, and consented to randomization were randomized to either the MT or the LVRS group. All of the patients in the LVRS group received a median sternotomy procedure, as described previously. (19)

Measures and Procedures

If patients agreed to participate, they signed a consent form and continued with the neuropsychological battery of tests described below (the time to completion of the tests was approximately 90 min), which was administered by trained neuropsychological personnel. All of the enrolled subjects completed the Beck depression inventory (BDI), (20) The State Trait Anxiety Inventory, (21)and the Trail Making Test (22) as a part of the initial assessment for the general NETT study. To assure proper oxygenation throughout the neuropsychological testing period, oximetry readings were taken before and after testing (model 3800 oximeter; Datex-Ohmeda; Madison, WI). Only one patient showed a slight drop in saturation levels during the neuropsychological evaluation (to 86%).

Neuropsychological Tests: The battery was developed to evaluate cognitive dysfunction across a variety of areas, including intelligence, reasoning, attention, memory, language, and visuo-spatial functions, all of which have been found to be impaired in patients with moderate-to-severe emphysema. The tests included four subtests from the Wechsler Adult Intelligence Scale-Revised to estimate intelligence quotient (23); the Logical Memory, Verbal Paired Associates, and Faces subtests from the Wechsler Memory Scales-third edition, as measures of immediate and delayed recall for verbal and nonverbal information (24); the revised Wechsler Adult Intelligence Scale Digit Span and Arithmetic subtests as measures of immediate auditory attention (25); the Digit Vigilance test as a measure of sustained visual attention (26); the Trail Making Test, forms A and B, as a measure of efficiency in completing sequential tasks (22); the Complex Ideational Material subtest from the Boston Diagnostic Aphasia Examination as a measure of verbal comprehension (27); the Controlled Oral Word Association Test and the Animal Naming Test as measures of oral verbal fluency to letter and semantic cues (27,28); a 15-item version of the Boston Naming Test as a measure of naming to confrontation (27,29); and Clock Drawing to command as a measure of visuospatial and graphomotor constructional processes. (27,30)

Neuromedical Interview: At baseline, the patients completed a brief (10 to 15 min) structured interview regarding their current status and medical, neurologic, and psychiatric histories. Any changes in this background information were recorded at the follow-up time points.

Psychological Functioning and QoL Measures: The BDI (20) is a 21-item scale with well-established reliability and validity (31) that measures symptoms of depression. The scores for each item can range from 3 (the most severe) to 0 (absence). A total score of 63 is possible, and the higher the score, the greater the level of depressive symptoms. Subscales of cognitive-affective and somatic symptoms were also derived according to the BDI procedures, The State Trait Anxiety Inventory (21) is a 40-item self-report questionnaire that examines both the state (acute) and trait (chronic) symptoms of anxiety. It has been used extensively in prior clinical studies, and the reliability and validity are well-established. (32-34) The first 20 items are summed to create a state anxiety score (range, 20 to 80), and the latter 20 items form the trait anxiety score (range, 20 to 80). The Medical Outcomes Study 36-item short form (35,36) examines the functional status and well-being in a self-administered format using Likert-type scales. It provides eight subscale scores, as well as a total score. The subscales include physical functioning, social functioning, role limitations due to physical problems, bodily pain, general mental health, role limitations due to emotional problems, vitality, and general health perceptions. Reliability and validity are well-established, and it has been found (37) to provide a valid indicator of change in health status.

Neurologic and Delirium Evaluation: Tests were administered to subjects in the LVRS group using the Western Perioperative Neurologic Scale (WPNS) and the Delirium Rating Scale (DRS) by a technician who was trained by a neurologist in the administration and scoring of this procedure at times 2 (ie, after randomization and prior to surgery) and 7 days following LVRS. The WPNS (38) was designed to detect and quantify discrete neurologic abnormalities across surgical procedures and has demonstrated reliability and validity. The examination assessesmentation, cranial nerve function, motor power, reflexes, sensation/cerebellar function, and gait. The DRS (39,40) was designed to assess delirium using a 10-item, clinician-rated scale. High internal consistency, validity, specificity, and interrater reliability have been reported. (40)

Exercise Measures: The maximal workload measures the exercise capacity (ie, the maximal workload that the subject achieves during an incremental cycle exercise test) and was a primary outcome measure in the NETT. Testing was performed using 30% inspired oxygen in 'all of the subjects and included 3 min of unloaded pedaling. The 6-min walk test is a measure of a subject's exercise capacity and is calculated as the maximum distance walked in 6 min. (41)

Statistical Analysis

The data are presented as the mean ([+ or -] SD) for continuous data (unless otherwise specified) and the percentage of the whole for dichotomous data. To compare the demographic and health characteristic variables at baseline among the groups, the [chi square] test or Fisher exact test is used for the dichotomous variables, and analysis of variance (ANOVA) is used for the continuous variables. To correct for practice effects in evaluating neuropsychological tests, a regression approach is used. (42) Control group data are used to generate the formulae for predicting time 2 scores from time 1 scores, and time 3 scores from time 1 and time 2 scores. The differences between the observed and predicted scores are calculated within each experimental group and are compared between groups at time 3 and between time 2 and time 3 within groups via ANOVA. For psychological functioning and QoL, repeated-measures ANOVA is used with each group (LVRS vs MT) as a between-subjects variable and time as a within-subject variable. To examine the potential mediators of cognitive improvements in the LVRS group, Spearman rank correlation coefficients are computed for neuropsychological variables with health characteristics, psychological functioning, and QoL. To test for the change after LVRS in pulmonary functions and exercise testing, repeated-measures ANOVA is utilized with each group (LVRS vs MT) as a between-subjects variable. All of the data analyses were conducted using a statistical software package (SAS; SAS Institute; Cary, NC), with statistical significance determined by a two-tailed p value of < 0.05.

RESULTS

Descriptive Analysis

No demographic differences (ie, gender, age, educational level, ethnicity, or marital status) were observed across the LVRS, MT, and control groups (Table 1). In comparing the health characteristics of the LVRS and MT groups (Table 2), there were no significant differences regarding the length of diagnosis, medication use, [FEV.sub.1] percent predicted, arterial oxygen saturation, Pa[O.sub.2], or maximum workload. The LVRS patients had a shorter 6-min walk distance and higher PaC[O.sub.2] than the MT patients. Sixty-nine percent of the NETT patients (27 of 39 patients) were receiving oxygen therapy at baseline (12 were randomized to LVRS and 15 were randomized to MT), and 26 patients continued to receive oxygen therapy at time 2 (one patient in the MT group stopped receiving oxygen therapy) and at time 3 (one patient in the MT group was receiving oxygen therapy and two patients in the LVRS group stopped receiving oxygen therapy). Across groups, 20% of the NETT patients and 10% of the control subjects had a history of mild neurologic disorders; 18% of NETT and 10% of control subjects had a history of moderate-to-severe neurologic disorders; 18% of the NETT patients and 5% of the control subjects were currently receiving psychological treatment; 58% of the patients in both groups had received psychological treatment in the past; 15% of NETT patients and 8% of control subjects had a history of alcohol abuse; 23% of NETT patients and 10% of control subjects self-reported some visual problems; and 46% of NETT patients and 35% of control subjects self-reported hearing problems.

No changes in medication percentages were noted from baseline to follow-up. Following surgery, there was no evidence of a decline on the WPNS or a change in the DRS.

Neuropsychological Functioning

As noted in Tables 3 and 4, 20 individual test scores and a summary cognitive impairment index were derived from the neuropsychological battery. Using statistical methods that control for practice effects across the three time points described above, the LVRS group showed significant improvement compared with the MT group at 6 months on measures of psychomotor speed (Trails A in Table 3) and delayed recall for verbal information (Verbal pairs II in Table 4). Trends toward improved performance on sequential thinking and psychomotor speed (Trails B) and the measure of naming to confrontation (Boston Naming Test) were noted, as is shown in Table 3. The examination of individual tests in Tables 3 and 4 indicates the overall improved cognitive performance within the LVRS group, with relatively stability or notable decline observed in test scores from the MT group.

Psychological Functioning and QoL

As indicated in Table 5 and Figure 2, the LVRS group showed significant improvement compared with the MT group across the three time points on the BDI (total score and cognitive-affective subscores) using repeated-measures ANOVA. A trend was noted in the BDI somatic subscore. There was no difference among the groups on the acute or chronic anxiety subscores from the State Trait Anxiety Inventory.

[FIGURE 2 OMITTED]

As shown in Table 6, the Medical Outcomes Study 36-item short-form QoL subscores are significantly improved in the LVRS group compared with those in the MT group across the 6-month time span. The results indicate significant improvement in the following scores for the LVRS group compared with the MT group in the subscores of physical functioning, role-physical, and change in health. Trends were apparent in the subscores for role emotional, social functioning, and vitality.

Pulmonary Function, Oxygenation, and Exercise Capacity

The LVRS group showed significant improvement compared with the MT group from time 2 to time 3 in workload (p < 0.001), [FEV.sub.1] percent predicted (p = 0.003), Pa[O.sub.2] (p = 0.005), and PaC[O.sub.2] (p = 0.007) as illustrated in Figure 3. No significant differences occurred between the groups on the 6-rain walk test.

[FIGURE 3 OMITTED]

Mediators of Cognitive Change in the LVRS Group

Correlation analyses were performed to examine the potential mediators of cognitive improvement in the LVRS group between time 2 (postrehabilitation) and time 3 (6 months following randomization) on the measures identified above. There were no associations among the improved neuropsychological tests in the LVRS group (Verbal Pairs II and Trail Making Test A) and changes in depression (BDI scores), exercise tests (6-min walk test and workload), pulmonary function, oxygenation, or QoL scores. The improved delayed recall for verbal information (Wechsler Memory Scale-third edition and Verbal Pairs II) was not associated with depression, exercise tests, or pulmonary functions but was associated with improved role emotional score (r = 0.55; p = 0.02), vitality score (r = -0.69; p = 0.002), and change in health score (r = -0.53; p = 0.024).

Analysis of Deceased LVRS Patients

It is possible that the exclusion of the two deceased LVRS patients may have affected our results. Therefore, we imputed data from time 2 to time 3 for these two patients and re-ran all of the analyses. Because we expected improvement on the cognitive test scores due to these practice effects, over time we believed that using the time 2 data points at time 3 for the deceased subjects was appropriate. In terms of neuropsychological analyses over time, adding values for the deceased patients at time 3 did not change any of the results between LVRS and MT. In terms of psychological findings, there was one slight change in the data reported: the BDI somatic subscale was significantly improved in the LVRS patient group compared with the MT from time 2 to time 3 (p = 0.045) when the deceased LVRS patient data were added. Our initial results without the two deceased patients indicated a trend p value of 0.058. Finally, in terms of pulmonary function, if we assumed that the LVRS patients remain the same at time 3, there was no longer a significant improvement in [FEV.sub.1] percent predicted between times 2 and 3 in the LVRS patients compared with the MT patients (p = 0.136). Our original results indicated a p value of 0.0024 when the two deceased patients were not included.

DISCUSSION

LVRS improves exercise capacity, dyspnea, and QoL in selected patients. (4) The current study suggests that additional improvement in a variety of neuropsychological and behavioral functions occurs in emphysema patients at 6 months after LVRS. LVRS is associated with improvements in delayed verbal memory and sequential psychomotor skills, and there was a trend toward improved naming to confrontation. Given the conservative nature of the control for practice effects in this analysis and the relatively poor health of the subjects prior to LVRS, these findings are substantial and very likely reflect clinically meaningful improvements post-LVRS.

The results additionally demonstrate significantly less depression in LVRS patients compared with MT patients at 6 months. The findings specifically showed lowered total depression scores, as well as improved subtest scores involving cognitive-affective components and somatic components. Consistent with data from the full NETT sample, (4) improvement in LVRS patients compared with MT patients at 6 months in QoL scores was also noted (ie, increased participation in vigorous activities, amount of time spent on accomplishing activities, decreased health problems interfering with social activities, increased energy, and improved health).

In contrast with improvements noted within the LVRS patients, the MT group showed improvement in only one cognitive area, accuracy in visual attention. None of the other tests showed significant improvement over time, and some tests showed a slight decline (ie, verbal abstract reasoning and sequential psychomotor skills). Additionally, no specific improvements in psychological functioning (anxiety and depression) or QoL measures were noted in the MT patients. In fact, the MT patients showed more depressive symptoms from time 2 (6 to 10 weeks of initial rehabilitation) to times 3 (6 months following randomization) in cognitive-affective items as well as in somatic items. Although these findings appear to be inconsistent with those of prior studies (2,15-17) of improved neuropsychological performance and psychological status following multidisciplinary treatment, most of the past studies examined cognition only at the 6-week to 10-week points, and data (18) suggest that ongoing exercise rehabilitation may be necessary to sustain this improvement. Overall, the current study suggests no significant changes in the MT patients at 6 months when controlling for practice effects. Future studies may find it useful to examine the difference between high and low exercise adherence in order to examine the degree to which exercise behavior directly influences neurobehavioral symptoms at 6 months.

The mechanisms underlying the neurobehavioral improvements in LVRS compared with MT were less clear. As expected, our findings indicate a minimal occurrence of neurologic events after LVRS. Two of the LVRS patients died following surgery, and we considered whether the data lost from these subjects influenced our results. In fact, post hoc analysis in which we added the values for these two patients from time 2 to time 3 showed no significant change in the original neuropsychological or psychological outcomes. None of the other improved cognitive scores in the LVRS group showed significant associations with depression or anxiety. Additionally, there was no difference in medication use or antidepressant use from baseline to follow-up in either the LVRS or MT groups. As expected, the LVRS patients demonstrated significant improvements in pulmonary and physical capacity compared with the MT group. In contrast with our expectations, there was no direct evidence that improved cognition in LVRS was strongly related to improved physical capacity (workload and 6-min walk) or pulmonary function. Thus, improvement in the LVRS group on measures of verbal memory, visual-spatial function, and sequential ability cannot be accounted for by psychological changes, medications, or pulmonary/exercise measures. Our results do suggest that overall improvement in QoL played a role in the improved cognitive function for LVRS. It was noted that the LVRS patients had more severe disease at baseline compared with the MT group (ie, lower workload, lower 6-min walk time, higher PC[O.sub.2], and more respiratory medication). The fact that this group was more ill at baseline, underwent a major thoracic surgery procedure, and had better cognitive function at follow-up is striking and lends additional support to the unity of LVRS regarding neurobehavioral improvement in this population.

The lack of an association between improved neuropsychological function and improved oxygenation or exercise may result from a number of factors. First, our overall sample size was quite small. Because of the multiple analyses conducted across the neurobehavioral measures, there is the potential for type 1 error and an overinterpretation of the neurobehavioral improvement. Alternatively, although we found significant improvement in the LVRS group on several cognitive test results, there were many results that did not reach statistical improvement, and a larger sample size may be necessary to control for multiple comparisons, to detect subtle cognitive changes, and to find associations with our measures. Second, although we included several widely used measures of exercise capacity, it may be that a more comprehensive assessment of exercise performance and daily activities, such as adaptive living skills or overall level of daily activity, is required to uncover key and/or subtle factors underlying the observed cognitive improvement. It is also possible that confounding factors that we controlled for, such as practice effects, as well as oxygen saturation across neuropsychological testing, may have contributed to the positive results in prior studies. Few relationships were found among the improved neuropsychological scores and exercise, oxygenation, and psychological variables, making it difficult to fully account for the mechanisms underlying our results.

In summary, LVRS led to a strong and likely clinically significant improvement in neuropsychological functioning over and above that explained by practice effects or MT. This adds to the growing list of clinical benefits of LVRS.

ACKNOWLEDGMENT: We would like to sincerely thank all of the patients/subjects and the diverse staff who participated in this project. We specifically acknowledge the research assistants, NETT coordinators, surgeons, and office assistants at National Jewish Medical and Research Center (Jennifer M. Keith, PsyD; Amy Lukowski, MA; Jolene Gregg; Mary Gilmartin RN RRT; Marvin Pomerantz, MD; and Tilli Urban) and Ohio State University (Meghan Fondow, MA; Karen Wilson, MA; Ronda Cress; Amanda Dillard; Marquisha Green, MA; Michelle Huffman; Tina Bees; and Pat Ross, MD).

This study was supported by grants RO1-HL63761-01, M01RR00051, and M01-RR00034 from the National Institutes of Health.

Manuscript received July 23, 2004; revision accepted April 15, 2005.

REFERENCES

(1) Make B. Pulmonary rehabilitation. In: Crapo JD, Glassroth JK, Karlinsky J, et al, eds. Baum's textbook of pulmonary diseases. Philadelphia, PA: Lippincott Williams and Wilkins, 2004; 289-307

(2) Emery CF, Schein RL, Hauck ER, et al. Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease. Health Psychol 1998; 17:232-240

(3) Heaton RK, Grant I, McSweeny AJ, et al. Psychologic effects of continuous and nocturnal oxygen therapy in hypoxemic chronic obstructive pulmonary disease. Arch Intern Med 1983; 143:1941-1947

(4) National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003; 348:2059-2073

(5) Grant I, Prigatano GP, Heaton RK, et al. Progressive neuropsychologic impairment and hypoxemia: relationship in chronic obstructive pulmonary disease. Arch Gen Psychiatry 1987; 44:999-1006

(6) Prigatano GP, Parsons O, Wright E, et al. Neuropsychological test performance in mildly hypoxemic patients with chronic obstructive pulmonary disease. J Consult Clin Psychol 1983; 51:108-116

(7) Stuss DT, Peterkin I, Guzman DA, et al. Chronic obstructive pulmonary disease: effects of hypoxia on neurological and neuropsychological measures. J Clin Exp Neuropsychol 1997; 19:515-524

(8) Kozora E, Filley CM, Julian LJ, et al. Cognitive functioning in patients with chronic obstructive pulmonary disease and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls. Neuropsychiatry Neuropsychol Behav Neurol 1999; 12:178-183

(9) McSweeny AJ, Grant I, Heaton RK, et al. Life quality of patients with chronic obstructive pulmonary disease. Arch Intern Med 1982; 142:473-478

(10) Prigatano GP, Wright EC, Levin D. Quality of life and its predictors in patients with mild hypoxemia and chronic obstructive pulmonary disease. Arch Intern Med 1984; 144: 1613-1619

(11) Ries AL, Kaplan RM, Limberg TM, et al. Effects of pulmonary rehabilitation on physiologic and psychosocial outcomes in patients with COPD. Ann Intern Med 1995; 122:823-832

(12) Wilson DK, Kaplan RM, Timms RM, et al. Acute effects of oxygen treatment upon information processing in hypoxemic COPD patients. Chest 1985; 64:317-322

(13) Borak J, Sliwinski P, Tobiasz M, et al. Psychological status of COPD patients before and after one year of long-term oxygen therapy. Monaldi Arch Chest Dis 1996; 51:7-11

(14) Krop HD, Block AJ, Cohen E. Neuropsychological effects of continuous oxygen therapy in COPD. Chest 1973; 64:317-322

(15) de Godoy DV, de Godoy RF. A randomized controlled trial of the effect of psychotherapy on anxiety and depression in chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2003; 84:1154-1157

(16) Kozora E, Tran Z, Make B. Neurobehavioral improvement following brief rehabilitation in patients with chronic obstructive pulmonary diseases. J Cardiopulm Rehabil 2002; 22:426-430

(17) Garuti G, Cilione C, Dell'Orso D, et al. Impact of comprehensive pulmonary rehabilitation on anxiety and depression in hospitalized COPD patients. Monaldi Arch Chest Dis 2003; 59:56-61

(18) Emery CF, Shermer RL, Hauck ER, et al. Cognitive and psychological outcomes of exercise in a 1 year follow-up study of patients with COPD. Health Psychol 2003; 22:598-604

(19) National Emphysema Treatment Trial Research Group. Rationale and design of the National Emphysema Treatment Trial. Chest 1999; 116:1750-1761

(20) Beck AT, Steer RA. Beck depression inventory manual. San Antonio, TX: Psychological Corporation, 1987

(21) Spielberger CD. State-trait anxiety inventory. Palo Alto, CA: Mind Garden, 1983

(22) Reitan RM, Wolfson D. The Halstead-Reitan neuropsychological test battery. Tucson, AZ: Neuropsychological Press, 1985

(23) Kaufman A. Assessing adolescents and adult intelligence. Boston, MA: Allyn and Bacon, 1990

(24) Wechsler D. Wechsler adult intelligence scale-third addition. San Antonio, TX: Psychological Corporation, 1997

(25) Wechsler D. Wechsler memory scale: revised manual. San Antonio, TX: Psychological Corporation, 1987

(26) Lewis R, Kupke T. The Lafayette clinical repeatable neuropsychological test battery: its development and research applications. Paper presented at: meeting of the Southeastern Psychological Association; 1977; Hollywood, IL

(27) Goodglass H, Kaplan E. The assessment of aphasia and related disorders. Philadelphia, PA: Lea and Febiger, 1983

(28) Borkowski JG, Benton AL, Spreen O. Word fluency and brain damage. Neuropsychologia 1967; 5:135-140

(29) Lansing AE, Ivnik RJ, Cullum CM, et al. An empirically derived short form of the Boston Naming Test. Arch Clin Neuropsychol 1999; 14:481-487

(30) Kozora E, Cullum CM. Qualitative features of clock drawings in normal aging and Alzheimer's disease. Assessment 1994; 1:179-188

(31) Beck AT, Steer RA, Garbin MG. Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev 1988; 8:77-100

(32) Stanley MA, Beck JG, Zebb BJ. Psychometric properties of four anxiety measures in older adults. Behav Res Ther 1996; 34:827-838

(33) Iwamoto I, Dodo H, Yoneda J, et al. A study of the State-Trait Anxiety Inventory (STAI) and its application to noise stress. Jpn J Hygiene 1989; 43:1116-1123

(34) Ramanaiah NV, Franzen M, Schill T. A psychometric study of the State-Trait Anxiety Inventory. J Pers Assess 1983; 47:531-535

(35) Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992; 30:473-483

(36) Hays RD, Sherbourne CD, Mazel RM. The RAND 36-item health survey 1.0. health economics. Health Econ 1993; 2:217-227

(37) Kopjar B. The SF-36 health survey: a valid measure of changes in health status after injury. Inj Prev 1996; 2:135-139

(38) Murkin JM, Martzke JS, Buchan AM, et al. A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery: II. Neurologic and cognitive outcomes. J Thorac Cardiovasc Surg 1995; 110:349-362

(39) Trzepacz PT, Baker RW, Greenhouse J. A symptom rating scale for delirium. Psychiatry Res 1988; 23:89-97

(40) Trzepacz PT. The delirium rating scale: its use in consultation-liaison research. Psychosomatics 1999; 40:193-204

(41) Steele B. Timed walking tests of exercise capacity in chronic cardiopulmonary illness. J Cardpulm Rehabil 1996; 16:24-33

(42) McSweeny AJ, Naugle RI, Chelune GJ, et al. T-scores for change: an illustration of a regression approach to depicting change in clinical neuropsychology. Clin Neuropsychol 1993; 7:300-312

Elizabeth Kozora, PhD; Charles F. Emery, PhD; Misoo C. Ellison, PhD; Frederick S. Wamboldt, MD; Philip T. Diaz, MD; and Barry Make, MD, FCCP

* From the National Jewish Medical and Research Center (Drs. Kozora, Ellison, Wamboldt, and Make), Denver, CO; and Ohio State University (Drs. Emery and Diaz), Columbus, OH.

Correspondence to: Elizabeth Kozora, PhD, ABPP/CN, National Jewish Medical and Research Center, 1400 Jackson St, A111, Denver, CO 80206; e-mail: kozorae@njc.org

COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group