• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Thorax. Author manuscript; available in PMC Jun 9, 2011.
Published in final edited form as:
PMCID: PMC3111227
NIHMSID: NIHMS250258

The influence of anxiety on health outcomes in COPD

Mark D. Eisner, MD, MPH,1,2 Paul D. Blanc, MD, MSPH,1,2 Edward H. Yelin, PhD,3 Patricia P. Katz, PhD, Gabriela Sanchez, BA,4 Carlos Iribarren, MD, MPH, PhD, and Theodore A. Omachi, MD, MBA

Abstract

Background

Psychological functioning is an important determinant of health outcomes in chronic lung disease. To better define the role of anxiety in COPD, we studied the inter-relations between anxiety and COPD in a large cohort of COPD subjects and a matched control group.

Methods

We used data from the FLOW (Function, Living, Outcomes, and Work) cohort (n=1,202) of COPD and matched controls (n=302) without COPD. Anxiety was measured using the Anxiety subscale of the Hospital Anxiety and Depression Scale.

Results

COPD was associated with a greater risk of anxiety in multivariable analysis (OR 1.85; 95% CI 1.072 to 3.18). Among patients with COPD, anxiety was related to poorer health outcomes including worse submaximal exercise performance (less distance walked during the Six Minute Walk Test: -66.3 feet for anxious vs. non-anxious groups; 95% CI -127.3 to -5.36 feet) and a greater risk of self-reported functional limitations (OR 2.41; 95% CI 1.71 to 3.41). COPD subjects with anxiety had a higher longitudinal risk of COPD exacerbation in Cox proportional hazards analysis after controlling for covariates (HR 1.39; 95% CI 1.007 to 1.90).

Conclusion

COPD is associated with a higher risk of anxiety. Once anxiety develops among COPD patients, it is related to poorer health outcomes. Further research is needed to determine whether systematic screening and treatment of anxiety in COPD will improve health outcomes and prevent functional decline and disability.

Chronic obstructive pulmonary disease (COPD) is an important cause of respiratory symptoms, disability, and other poor health outcomes. Recent clinical trials have advanced the treatment of COPD by establishing a beneficial effect of inhaled medications on longer term health outcomes.1-4 Nonetheless, many patients continue to suffer from marked respiratory symptoms and activity limitation despite optimal medical management.

A conundrum of COPD treatment is that patients with a given level of lung function may differ substantively in their symptom burden and activity limitation. Other factors, beyond the respiratory system, must exert important impacts on clinical outcomes.5 Psychological functioning, in particular, may influence why two patients with the same degree of lung function impairment have different health outcomes.6

Anxiety is likely to be a problem for many patients with COPD. The symptom of dyspnea, which is a cardinal manifestation of COPD, can be a potent stimulus for anxiety.7 Inability to perform daily activities or fulfill expected social roles may also lead to anxiety. Cigarette smoking, which is the primary cause of COPD, has also been strongly linked to anxiety symptoms.8 Furthermore, some therapies for COPD, such as beta agonists and theophylline-containing medications, may increase symptoms of anxiety and panic.

There remain significant unanswered questions about the prevalence and impact of anxiety among patients with COPD. Although the prevalence of anxiety is likely high in COPD, most studies have not included an adequate control group to estimate the relative risk.9 A recent workshop conducted by the American College of Chest Physicians concluded that further research was needed to assess the impact of anxiety on health outcomes.9 In particular, the influence of COPD severity on the risk of anxiety has not been adequately characterized. Moreover, the impact of anxiety on the risk of COPD exacerbations is not clear.10

To evaluate these issues, we studied the inter-relations between anxiety and COPD in a large cohort of COPD subjects and a matched control group. We theorized that COPD increases the risk of anxiety and that, among patients with the established disease, greater disease severity increases the likelihood of anxiety, which, in turn leads to poorer health outcomes. The FLOW study, which was designed to evaluate the development of disability in COPD, pre-specified this analysis of anxiety and COPD.

Methods

The FLOW (Function, Living, Outcomes, and Work) study of COPD is an ongoing prospective cohort study of adult members of an integrated health care delivery system with a physician's diagnosis of COPD with an accompanying matched control group. Recruitment methods have been previously reported in detail (see online supplement).5 6 11 12 We recruited a cohort of 1,202 Kaiser Permanente Medical Care Program (KPMCP) members who were recently treated for COPD using a validated algorithm based both on health care utilization and pharmacy dispensing for COPD.13 A control group of 302 subjects without COPD were recruited who were matched by age, sex, and race to the cohort members. At baseline assessment, we conducted structured telephone interviews that ascertained sociodemographic characteristics, COPD clinical history, and health status.5 11 12 Research clinic visits included spirometry and other physical assessments. The study was approved both by the University of California, San Francisco Committee on Human Research and the Kaiser Foundation Research Institute's institutional review board and all participants provided written informed consent.

Measurement of anxiety

We used a concept of anxiety based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a state characterized by cognitive features (fearful thoughts, difficulty concentrating), emotional response (apprehension, nervousness), behavioral symptoms (agitated movements, hand wringing, pacing), and physiologic arousal (sweating, palpitations, muscle tension).14 Anxiety was measured using the 7-item anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), which is a widely used validated instrument designed to detect clinically significant anxiety among patients who attend outpatient medical clinics.15 16 The anxiety scale score ranges from 0 to 21, with higher scores reflecting more severe anxiety. We used the recommended optimal cutting point of 8/9 points to identify subjects with significant anxiety.17 In secondary analysis, we also used the suggested score ranges to define moderate (11-14 points) and severe anxiety (15-21 points). The scale has been previously used to measure anxiety in COPD.10 18 19 We have previously reported our findings for depression in COPD.6

Assessment of COPD severity

We used a combined approach to measure COPD severity. We used a disease-specific COPD Severity Score that we had previously developed and validated for use in epidemiologic and outcomes research.20 Based on survey responses, the COPD Severity Score is comprised of five overall aspects of COPD severity: respiratory symptoms, systemic corticosteroid use, other COPD medication use, previous hospitalization or intubation for respiratory disease, and home oxygen use. Each item was weighted based on clinical aspects of the disease and its expected contribution to overall COPD severity. Possible total scores range from 0 to 35, with higher scores reflecting more severe COPD.

We also used the validated BODE Index, which is a multi-modal measure of disease severity.21 The BODE Index is based on the body-mass index (B), the degree of airflow obstruction (O) measured by Forced Expiratory Volume in one second (FEV1), grade of dyspnea (D) assessed by the modified Medical Research Council (MRC) Dyspnea Scale,22 and exercise capacity (E) measured by the Six Minute Walk Test. Each component is assigned a specific Index and the total score ranges from 0 to 10 points (higher scores indicate greater severity). The BODE index predicts death and other poor outcomes in COPD.21 23 24 We have reported elsewhere that the BODE and COPD severity instruments provide independent explanatory power in relation to disease status.25 Because we posited that dyspnea may be an important cause of anxiety, the MRC Dyspnea Scale score was also evaluated as a separate measure.

Pulmonary function impairment

To assess respiratory impairment, we conducted spirometry according to American Thoracic Society (ATS) Guidelines.26 27 We used the EasyOne™ Frontline spirometer (ndd Medical Technologies, Chelmsford, MA), which is known for its reliability, accuracy, and durability.28 29 The Easyone spirometer has been used by large scale multicenter international epidemiologic studies of COPD.29 30 Because research clinic examinations were conducted by trained non-medical personnel, we did not administer bronchodilators for study purposes. However, 90% of subjects had taken their own short-acting bronchodilator within 4 hours of spirometry or had taken a long-acting bronchodilator earlier in the same day.

Patient-centered health outcomes

At the time of telephone interview, generic physical health status was measured with the Short Form (SF)-12 Physical Component Summary (PCS) score. The SF-12 is derived from the Medical Outcomes Study SF-36 instrument, which is the most widely used measure of generic health status. Defined from the eight SF-36 subscales by factor analysis, the PCS score reflects an underlying physical dimension of physical HRQL.31 Higher scores reflect more favorable health states. We also used the Airways Questionnaire 20 revised (AQ-20R) to measure disease specific health-related quality of life (HRQL).32 33 This validated instrument has excellent psychometric properties for assessing HRQL in persons with airway disease, including COPD. Higher scores correspond to poorer HRQL.32 34

Submaximal exercise performance was measured using the Six Minute Walk Test, which has been widely used in studies of COPD.35 36 We used a standardized flat, straight course of 30 meters in accordance with American Thoracic Society (ATS) Guidelines.37 Subjects who routinely used home oxygen or who had a resting oxygen saturation < 90% were supplied with supplemental oxygen during the test. Every two minutes, the technician used standardized phrases to encourage effort, as recommended by the ATS guidelines. The primary outcome measured was the total distance walked in 6 minutes.

Self-reported functional limitation was measured using a previously validated approach. 38 The scale is comprised of 10 questions that assess the degree of difficulty in multiple domains of basic physical functioning such as pushing, stooping, kneeling, getting up from a standing position, lifting lighter or heavier objects, standing, sitting, standing from a seated position, walking up stairs, and walking in the neighborhood. Subjects who indicate “a lot of difficulty” with one or more functions or not doing a function because they were unable or they were told by a doctor not to do so are defined by this measure as having a self-reported functional limitation.38

Longitudinal COPD outcomes: COPD exacerbations

We used emergency department (ED) visits and hospitalization for COPD as proxy measures of severe disease exacerbation. ED visits and hospitalizations were ascertained from Kaiser Permanente computerized health care databases that capture complete health care utilization at its facilities. These outcomes were measured from the time of completion of the baseline interviews up until the time of data acquisition. The median duration of follow-up was 2.1 years (25th-75th interquartile range 1.7 to 2.6 years). During the follow-up period, there were 76 hospitalizations and 244 ED visits for COPD.

COPD-related hospitalization was defined as those with a principal ICD-9 discharge diagnosis code for COPD (491,492, or 496). COPD-related emergency department (ED) visits were identified as those with an ICD-9 code for COPD. A composite outcome for hospital-based care was defined as either an ED visit or hospitalization for COPD.

Covariates

We selected covariates that may be related to anxiety. These included sociodemographic characteristics such as age, sex, educational attainment, and income, which were measured as previously described.5 6 11 12 Cigarette smoking was assessed using questions developed for the National Health Interview Survey.39 Because cardiovascular conditions may be associated with anxiety, we assessed comorbid cardiovascular conditions using survey items modified from the National Health Interview Survey.40 These include a reported physician's diagnosis of coronary artery disease, congestive heart failure, and hypertension.

Statistical analysis

Statistical analysis was conducted using SAS software, version 9.1 (SAS Institute, Inc, Cary, NC). Bivariate analysis was conducted with the t-test for continuous variables and chi-square test for dichotomous variables. Multivariable logistic regression analysis was used to examine the impact of COPD on the risk of anxiety compared to controls without COPD after controlling for potential confounders.

In our theoretical model of anxiety and COPD, we posit that greater disease severity increases the risk of anxiety, which, in turn leads to poorer health outcomes. Moreover, anxiety may also feedback to increase disease severity and indirectly affect health outcomes. To assess the impact of COPD severity on the risk of anxiety, we used logistic regression analysis. Multivariable analysis was performed to control for the potential confounding effects of age, sex, race, educational attainment, income, and smoking history. Continuous predictor variables were scaled by dividing by one-half standard deviation which corresponds approximately to the minimal clinically important difference.41

We then examined the impact of anxiety on patient-centered outcomes using multivariable linear regression for continuous outcome variables (PCS-12 scores, AQ-20R scores, and SMWT distance) and logistic regression for binary outcome variables (functional limitations). Cox proportional hazards analysis was used to evaluate the longitudinal relationship between baseline anxiety and the subsequent risk of COPD exacerbation. Schoenfeld residuals were used to evaluate the proportional hazards assumption; no evidence of violation was found.42 Kaplan-Meier curves were also generated to display the risk of COPD exacerbation for COPD subjects with and without anxiety.

To test for an exposure-response relationship between degree of anxiety and the risk of COPD exacerbation, we defined an ordinal variable based on the total anxiety score (no anxiety = 0, mild = 1, moderate =2, severe = 3). Consequently, the hazard ratio is expressed for a one-category increase in anxiety level.

We evaluated the impact of concurrent depression, as measured by the Geriatric Depression Scale short-form, on the results for anxiety. The impact of depression on COPD-related health outcomes in the FLOW cohort has been previously reported in detail.6 Substantive depressive symptoms occurred in less than half of COPD subjects with anxiety (44%). To examine the effect of depression, we repeated the analysis of anxiety and health outcomes (both patient centered outcomes and longitudinal risk of COPD exacerbations) with inclusion of an interaction term for anxiety and depression (in the respective linear regression and Cox proportional hazards analysis).43 The Wald chi-square test was used to test the statistical significance of interaction terms. There was no statistical evidence for interaction in any case (p>0.20) indicating that depression did not modify the impact of anxiety on health outcomes. Consequently, depression was not further considered in the analysis.

Results

COPD and the risk of anxiety

The unadjusted prevalence of anxiety was higher among those with COPD (15%) than in controls (6%; p<0.0001) (Table 1). As shown in the table, anxiety was associated with several demographic and other personal factors including younger age, female sex, non-white race, lower socioeconomic status, current smoking (see Table 1). The pattern of results was similar for control subjects without COPD, although only age was statistically significant due to the smaller size of the control group. Figure 1 shows the prevalence of mild, moderate, and severe anxiety among those with and without COPD.

Figure 1
Prevalence of mild, moderate, and severe anxiety in COPD and referents. The overall prevalence of anxiety is 15% and 6% among persons COPD and referents. The bars show the proportion of anxious patients in the mild (8-10 points), moderate (11-14 points), ...
Table 1
Baseline characteristics and anxiety

COPD was associated with a greater risk of anxiety in both unadjusted (OR 2.64; 95% CI 1.62 to 4.31) and multivariable analysis (OR 1.85; 95% CI 1.072 to 3.18) (Table 2). When FEV1 was additionally added to the multivariable model to account for lung function differences among COPD subjects and controls, COPD remained related to a higher risk of anxiety (OR 2.23; 95% CI 1.26 to 3.96) (data not shown in table).

Table 2
COPD and the risk of anxiety

COPD severity and the risk of anxiety

Higher COPD severity, as measured by the COPD Severity Score and BODE Index, was associated with a greater risk of anxiety among persons with COPD (Table 3). A higher degree of dyspnea was also related to a greater risk of anxiety. Lung function impairment was not clearly related to anxiety (p=0.13).

Table 3
Disease severity and the risk of anxiety among 1,202 subjects with COPD

Impact of anxiety on patient-centered health outcomes in COPD

Anxiety was associated with poorer patient-centered outcomes, including physical health status and disease specific HRQL (Table 4). It was also related to poorer distance walked during the Six Minute Walk Test (-66.3 feet for anxious vs. non-anxious groups; 95% CI -127.3 to -5.36 feet) and a greater risk of self-reported functional limitations (OR 2.41; 95% CI 1.71 to 3.41).

Table 4
The impact of anxiety on patient-centered outcomes in COPD

Anxiety and the prospective risk of COPD exacerbation

Kaplan-Meier analysis indicated that COPD subjects with baseline anxiety had a greater risk of COPD exacerbation than those without anxiety (log-rank test p=0.017) (Figure 2). COPD subjects with baseline anxiety had a higher longitudinal risk of COPD exacerbation in Cox proportional hazards analysis after controlling for covariates (HR 1.39; 95% CI 1.007 to 1.90) (Table 5).

Figure 2
Anxiety and the risk of COPD exacerbation requiring emergency health care utilization. Red line = subjects with anxiety. Blue line = subjects without anxiety. Log-rank test p=0.017 for difference between the two groups.
Table 5
Anxiety and the longitudinal risk of COPD exacerbation

There was evidence of an exposure-response relationship between severity of anxiety and the risk of COPD exacerbation. For each increment of anxiety category (i.e., mild vs. none, moderate vs. mild, and severe vs. moderate), the risk of COPD exacerbation increased (HR 1.27; 95% CI 1.09 to 1.49). The overall p value for exposure-response trend was 0.0025.

Anxiety and COPD-related outcomes: COPD severity as a potential mediator

To examine whether the impact of anxiety on COPD-related health outcomes was mediated by COPD severity, we repeated the multivariable analyses after adding the COPD Severity Score and BODE Index as disease-specific severity measures (Table 6). The impact of anxiety on distance walked in 6 minutes and risk of COPD exacerbations appeared to be mediated completely by COPD severity, in that the effect estimates decreased markedly and became statistically non-significant. The association between anxiety and physical health status, disease specific quality of life, and risk of self-reported physical limitations was partly, but not completely, mediated by COPD severity (i.e., effect estimates were reduced but not eliminated).

Table 6
Anxiety and COPD-related health outcomes: potential mediation by disease severity

Discussion

Study findings and integration with prior literature

COPD was associated with a higher risk of anxiety compared to a matched control group without the condition. Among a large cohort of COPD patients, disease severity, as measured by the COPD Severity Score and BODE Index, increased the risk of anxiety. Dyspnea, in particular, had the strongest association with the risk of anxiety. Anxiety, in turn, had a negative impact on the patient centered outcomes of physical health status, disease specific HRQL, submaximal exercise performance, and functional limitations. It also increased the prospective risk of COPD exacerbations requiring hospital based care. The relation between anxiety and COPD-related health outcomes was mediated by COPD severity for some outcomes (submaximal exercise performance and COPD exacerbation) and partially mediated for others (physical health status, disease specific HRQL, and self-reported functional limitations). In sum, COPD appears to increase the likelihood of anxiety, especially as the disease becomes more severe; once established, anxiety exerts a negative impact on health outcomes.

Several studies have found a high prevalence of anxiety among persons with COPD.9 44 These estimates have been limited by small sample size, inclusion of patients with advanced or end staged disease, and the lack of a control group. Our paper advances the field by establishing that COPD is associated with a higher risk of anxiety compared to a matched control group in a large study with a broad range of disease severity.

Although COPD severity increased the risk of anxiety, there was no clear impact of physiologic impairment of lung function. This observation extends those from a small study of 122 COPD patients in which the BODE Index, and not the GOLD stage based on lung function, was related to anxiety.18 A larger Nordic study also found no relationship between GOLD stage and anxiety among patients with severe COPD.45 Our findings reinforce the concept that a comprehensive measure of disease severity, and not just physiologic impairment, is required to study the impact of psychosocial factors in COPD.

Our analysis clarifies the impact of anxiety on COPD exacerbation. Although depression has been established as a risk factor for COPD exacerbation, the role of anxiety has been less clear.6 10 46 47 In the FLOW cohort study, which has more statistical power than previous investigations, anxiety was a prospective risk factor for COPD exacerbation requiring emergency health care utilization. This effect was, however, entirely explained by the impact of anxiety on greater COPD severity.

Anxiety has a broad negative impact on patient-centered health outcomes in COPD. We theorize that the cognitive aspects of anxiety, which includes concentration difficulty and fearful thoughts, will have a major impact on HRQL and exacerbations, whereas the symptoms of physiologic arousal such as sweating and muscle tension may greatly affect physical health status, exercise performance, and functional limitations. We expect that the emotional and behavioral correlates of anxiety to have a more global impact on health outcomes. Future work is needed to parse out these specific effects of anxiety on health outcomes.

Implications for treatment of COPD

The mediation analysis has implications for treatment. For some health outcomes (submaximal exercise capacity and COPD exacerbation), the impact of anxiety appeared to be mediated entirely by COPD severity. In our theoretical framework, higher levels of anxiety lead to increased COPD severity, which, in turn adversely affect health outcomes. Consequently, comprehensive treatment of COPD, with the aim of decreasing its severity, should be the initial goal to improve exercise performance and reduce exacerbations. If response to treatment is partial or inadequate, then treatment of anxiety may be indicated. For physical health status, disease specific HRQL, and functional limitations, treatment of anxiety may improve outcomes even after maximizing treatments aimed at reducing COPD severity.

Study limitations

Our study has several limitations. Although we used a reliable and valid measure of anxiety, it is not a clinical diagnosis of generalized anxiety disorder or any other specific DSM-IV diagnosis. We were also not able to evaluate change in anxiety over time. In addition, there is some possibility of misclassification of COPD, although we took rigorous steps to avoid this. The inclusion criteria required a physician diagnosis of COPD, health care utilization for COPD, and dispending of COPD medications, which was designed to increase the accuracy of case ascertainment. We also previously demonstrated the validity of our approach using medical record review.13 Nonetheless, we acknowledge this potential limitation.

In addition, we acknowledge that the causal pathway between anxiety and COPD is complex. We theorized that the most important pathway is that greater COPD symptoms and disease severity increase the risk of anxiety, which then leads to poorer health outcomes; anxiety also feeds back to increase disease severity and affect health outcomes. Alternatively, it is possible that the primary mechanism could be anxiety increasing disease severity and, consequently, poorer health outcomes. COPD exacerbations may also mimic anxiety which further increases the complexity. Our results must be interpreted in light of the theoretical framework upon which they are based.

Conclusions

COPD is associated with a higher risk of anxiety; once anxiety develops, it is related to poorer health outcomes, some of which are mediated by disease severity. Further research is needed to determine whether systematic screening and treatment of anxiety in COPD will improve health outcomes and prevent functional decline and disability.

Supplementary Material

supplement

Acknowledgments

Funded by: National Heart, Lung, and Blood Institute / National Institutes of Health R01HL077618 and K24 HL 097245

Footnotes

The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd, and its Licensees to permit this article (if accepted) to be published in Thorax and any other BMJPGL products and to exploit all subsidiary rights, as set out in our licence.

Competing Interest: none to declare

References

1. Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–54. [PubMed]
2. Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177(1):19–26. [PubMed]
3. Singh D, Brooks J, Hagan G, Cahn A, O'Connor BJ. Superiority of “triple” therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax. 2008;63(7):592–8. [PubMed]
4. Celli BR, Thomas NE, Anderson JA, Ferguson GT, Jenkins CR, Jones PW, et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med. 2008;178(4):332–8. [PubMed]
5. Eisner MD, Blanc PD, Yelin EH, Sidney S, Katz PP, Ackerson L, et al. COPD as a systemic disease: impact on physical functional limitations. Am J Med. 2008;121(9):789–96. [PMC free article] [PubMed]
6. Omachi TA, Katz PP, Yelin EH, Gregorich SE, Iribarren C, Blanc PD, et al. Depression and health-related quality of life in chronic obstructive pulmonary disease. Am J Med. 2009;122(8):778 e9–15. [PMC free article] [PubMed]
7. Hill K, Geist R, Goldstein RS, Lacasse Y. Anxiety and depression in end-stage COPD. Eur Respir J. 2008;31(3):667–77. [PubMed]
8. Goodwin RD, Zvolensky MJ, Keyes KM. Nicotine dependence and mental disorders among adults in the USA: evaluating the role of the mode of administration. Psychol Med. 2008;38(9):1277–86. [PubMed]
9. Maurer J, Rebbapragada V, Borson S, Goldstein R, Kunik ME, Yohannes AM, et al. Anxiety and depression in COPD: current understanding, unanswered questions, and research needs. Chest. 2008;134(4 Suppl):43S–56S. [PMC free article] [PubMed]
10. Xu W, Collet JP, Shapiro S, Lin Y, Yang T, Platt RW, et al. Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations. Am J Respir Crit Care Med. 2008;178(9):913–20. [PubMed]
11. Eisner MD, Iribarren C, Yelin EH, Sidney S, Katz PP, Ackerson L, et al. Pulmonary function and the risk of functional limitation in chronic obstructive pulmonary disease. Am J Epidemiol. 2008;167(9):1090–101. [PMC free article] [PubMed]
12. Blanc PD, Iribarren C, Trupin L, Earnest G, Katz PP, Balmes J, et al. Occupational exposures and the risk of COPD: dusty trades revisited. Thorax. 2009;64(1):6–12. [PMC free article] [PubMed]
13. Sidney S, Sorel M, Quesenberry CP, Jr, DeLuise C, Lanes S, Eisner MD. COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program. Chest. 2005;128(4):2068–75. [PubMed]
14. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders DSM IV. Arlington, VA: American Psychiatric Publishing; 1994.
15. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70. [PubMed]
16. Mykletun A, Stordal E, Dahl AA. Hospital Anxiety and Depression (HAD) scale: factor structure, item analyses and internal consistency in a large population. Br J Psychiatry. 2001;179:540–4. [PubMed]
17. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002;52(2):69–77. [PubMed]
18. Funk GC, Kirchheiner K, Burghuber OC, Hartl S. BODE index versus GOLD classification for explaining anxious and depressive symptoms in patients with COPD - a cross-sectional study. Respir Res. 2009;10:1. [PMC free article] [PubMed]
19. Puhan MA, Frey M, Buchi S, Schunemann HJ. The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease. Health Qual Life Outcomes. 2008;6:46. [PMC free article] [PubMed]
20. Eisner MD, Trupin L, Katz PP, Yelin EH, Earnest G, Balmes J, et al. Development and validation of a survey-based COPD severity score. Chest. 2005;127(6):1890–7. [PubMed]
21. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–12. [PubMed]
22. Hajiro T, Nishimura K, Tsukino M, Ikeda A, Koyama H, Izumi T. Analysis of clinical methods used to evaluate dyspnea in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;158(4):1185–9. [PubMed]
23. Martinez FJ, Han MK, Andrei AC, Wise R, Murray S, Curtis JL, et al. Longitudinal change in the BODE index predicts mortality in severe emphysema. Am J Respir Crit Care Med. 2008;178(5):491–9. [PMC free article] [PubMed]
24. Ong KC, Lu SJ, Soh CS. Does the multidimensional grading system (BODE) correspond to differences in health status of patients with COPD? Int J Chron Obstruct Pulmon Dis. 2006;1(1):91–6. [PMC free article] [PubMed]
25. Eisner MD, Iribarren C, Yelin E, Sidney S, Katz PP, Ackerson L, et al. The BODE index and COPD severity score offer complementary assessment of COPD status. 2008;177:A399.
26. American Thoracic Society Standardization of spirometry--1987 update. Statement of the American Thoracic Society. American Review of Respiratory Disease. 1987;136(5):1285–98. [PubMed]
27. Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995;152(3):1107–36. [PubMed]
28. Walters JA, Wood-Baker R, Walls J, Johns DP. Stability of the EasyOne ultrasonic spirometer for use in general practice. Respirology. 2006;11(3):306–10. [PubMed]
29. Perez-Padilla R, Vazquez-Garcia JC, Marquez MN, Jardim JR, Pertuze J, Lisboa C, et al. The long-term stability of portable spirometers used in a multinational study of the prevalence of chronic obstructive pulmonary disease. Respir Care. 2006;51(10):1167–71. [PubMed]
30. Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet. 2007;370(9589):741–50. [PubMed]
31. Ware J, Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Medical Care. 1996;34(3):220–33. [PubMed]
32. Hajiro T, Nishimura K, Jones PW, Tsukino M, Ikeda A, Koyama H, et al. A novel, short, and simple questionnaire to measure health-related quality of life in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 1999;159(6):1874–8. [PubMed]
33. Chen H, Eisner MD, Katz PP, Yelin EH, Blanc PD. Measuring disease-specific quality of life in obstructive airway disease: validation of a modified version of the airways questionnaire 20. Chest. 2006;129(6):1644–52. [PubMed]
34. Alemayehu B, Aubert RE, Feifer RA, Paul LD. Comparative analysis of two quality-of-life instruments for patients with chronic obstructive pulmonary disease. Value Health. 2002;5(5):436–41. [PubMed]
35. Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO, Taylor DW, et al. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Canadian Medical Association Journal. 1985;132(8):919–23. [PMC free article] [PubMed]
36. Sciurba F, Criner GJ, Lee SM, Mohsenifar Z, Shade D, Slivka W, et al. Six-minute walk distance in chronic obstructive pulmonary disease: reproducibility and effect of walking course layout and length. Am J Respir Crit Care Med. 2003;167(11):1522–7. [PubMed]
37. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111–7. [PubMed]
38. Sternfeld B, Ngo L, Satariano WA, Tager IB. Associations of body composition with physical performance and self-reported functional limitation in elderly men and women. Am J Epidemiol. 2002;156(2):110–21. [PubMed]
39. Cigarette smoking among adults - United States, 1997. Mmwr Morbidity and Mortality Weekly Report. 1999;48(43):993–996. [PubMed]
40. National Center for Health Statistics . National Health Interview Survey.
41. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003;41(5):582–92. [PubMed]
42. Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika. 1982;69:239–241.
43. Rothman KJ, Greenland S. Modern Epidemiology. Philadelphia: Lippincott-Raven Publishers; 1998.
44. Putman-Casdorph H, McCrone S. Chronic obstructive pulmonary disease, anxiety, and depression: state of the science. Heart Lung. 2009;38(1):34–47. [PubMed]
45. Gudmundsson G, Gislason T, Janson C, Lindberg E, Suppli Ulrik C, Brondum E, et al. Depression, anxiety and health status after hospitalisation for COPD: a multicentre study in the Nordic countries. Respir Med. 2006;100(1):87–93. [PubMed]
46. Gudmundsson G, Gislason T, Janson C, Lindberg E, Hallin R, Ulrik CS, et al. Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression. Eur Respir J. 2005;26(3):414–9. [PubMed]
47. Kim HF, Kunik ME, Molinari VA, Hillman SL, Lalani S, Orengo CA, et al. Functional impairment in COPD patients: the impact of anxiety and depression. Psychosomatics. 2000;41(6):465–71. [PubMed]

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...