Depression, anxiety and health status after hospitalisation for COPD: A multicentre study in the Nordic countries

Respiratory Medicine (2006) 100, 87 93 Depression, anxiety and health status after hospitalisation for COPD: A multicentre study in the Nordic countries Gunnar Gudmundsson a,, Thorarinn Gislason a, Christer Janson b, Eva Lindberg b, Charlotte Suppli Ulrik c, Eva Brøndum c, Markku M. Nieminen d, Tiina Aine d, Runa Hallin b, Per Bakke e a Department of Respiratory Medicine and Allergology, Landspitali University Hospital, E-7 Fossvogur, IS-108 Reykjavik, Iceland b Department of Medical Sciences: Respiratory Medicine and Allergology, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden c Department of Respiratory Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark d Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland e Haukeland University Hospital, Bergen, Norway Received 15 May 2004; accepted 31 March 2005 KEYWORDS COPD; Health status; Depression; Anxiety; Hospitalisation Summary Patients with chronic obstructive pulmonary disease (COPD) often report anxiety, depression and poor health status, not least if they experience repeated hospitalisations due to acute exacerbations. The aim of this study was to analyse the interrelationships between health status, anxiety, depression and physical status in COPD patients being discharged after hospitalisation. This was a prospective study of 416 patients in five university hospitals in each of the Nordic countries. Data included demographic information, lung function and co-morbidity. The Hospital Anxiety and Depression Scale and St. George s Respiratory Questionnaire (SGRQ) were applied to all patients. Both anxiety and depression were common among these patients. Anxiety was more common in women than in men (47% vs. 34%, P ¼ 0:009) and current smokers had a higher prevalence of both anxiety (54% vs. 37%) and depression (43% vs. 23%) than non-smokers (Po0:01). In general, the studied COPD patients had poor health status, especially those with anxiety, depression or both. Psychological status was independently related to all dimensions of SGRQ. Higher GOLD stages were significantly associated with increasing impairment in health status. In conclusion this multicentre study showed that anxiety and depression are common in patients with COPD, and, furthermore, that patients with psychological disorders have poor health status. Screening for Corresponding author. Tel.: +354 5436876; fax: +354 5436568. E-mail address: ggudmund@landspitali.is (G. Gudmundsson). 0954-6111/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2005.04.003

88 G. Gudmundsson et al. depression and anxiety may help to identify patients with poor quality of life and an urgent need for intervention in order to improve their health status. & 2005 Elsevier Ltd. All rights reserved. Introduction Chronic obstructive pulmonary disease (COPD) is associated with intermittent exacerbations characterised by acute deterioration in the symptoms of chronic dyspnoea, cough and sputum production. These acute exacerbations are the main cause for hospitalisation in COPD patients and they are also associated with deterioration in health status and lung function. 1,2 Health status is a very important outcome variable. To evaluate health status valuable questionnaires have been developed that are used mainly for research purposes on groups. 3 This has been done in epidemiological studies and in studies on medications and in evaluating the efficacy of new drugs 4 6 including large trials with inhaled corticosteroids and long-acting anticholinergic medications. 6 8 Other factors are also important for the well-being of the COPD patient, including psychological status. Depression has been described with increased frequency in patients with COPD. 9 Anxiety is also important in patients with chronic diseases, especially if the disease can be life threatening as is COPD. 10 Anxiety and depression can be evaluated with a questionnaire that is short and easy to administer. 11 A study on patients with obstructive lung diseases receiving emergency care found that those with anxiety and depression were at much higher risk of hospitalisation or relapse 1 month later. 12 There is limited information on the interrelationships between the measures of health status, anxiety and depression, and physical status. Such knowledge could potentially enable better individual care for patients with COPD. The aim of this study was to analyse simultaneously in a large prospective Nordic multicentre setting health status, anxiety, depression, physical status and their interrelationships before discharge after hospitalisation for COPD exacerbation. Materials and methods This is a prospective study of patients hospitalised with acute exacerbations of obstructive airway disease in five university hospitals in the Nordic countries. The departments included were: The Department of Respiratory Medicine and Allergology, Akademiska sjukhuset, Uppsala, Sweden; The Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; The Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland; The Department of Respiratory Medicine, Vifilstadir University Hospital, Gardabaer, Iceland and The Department of Respiratory Medicine, Hvidovre Hospital, Copenhagen Denmark. Consecutive patients from each of the participating hospitals were included provided that they had been admitted with acute exacerbations of obstructive lung disease (asthma, chronic bronchitis, chronic obstructive bronchitis or emphysema) during the year 2000 2001. In the following analysis all patients with asthma were excluded and reported are only data from those fulfilling criteria for COPD according to the Global Initiative for Chronic Obstructive Pulmonary Disease (www.goldcopd.com) stage 1 or higher. 2 The following data were collected at discharge from the respective pulmonary departments: 1. Questionnaire that included information on smoking history, type of living and family situation (living at home, assisted at home, nursing home, with spouse, alone or with others) in addition to educational level. 2. Spirometry, body weight and height. Predicted values for forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were calculated based on the European Coal and Steel Union reference values. 13 3. Health status was assessed using the diseasespecific St. George s Respiratory Questionnaire (SGRQ). It has three components: symptoms, activity and impact, in addition to the total score. 8 The symptoms score measures distress caused by respiratory symptoms, activity measures the effect of disturbance on the mobility and physical activity and impact quantifies the psycho-social impact of the disease. Higher scores indicate worse health status. Anxiety and depression were evaluated with the Hospital Anxiety and Depression Scale (HADS). 11 It is self-reported and has been used extensively to screen psychiatric morbidity and has high validity when it is used as a screening instrument for psychiatric morbidity in outpatients. 14 16 It is composed of two parts, one with seven questions that are related to anxiety and another

Depression, anxiety and health status in COPD 89 with seven questions that are related to depression. A score of 8 or greater on either part was used as the cut-off point for diagnosing anxiety and depression, respectively. 11 4. From the patient records, information was collected on treatment during the hospitalisation and at discharge, including long-term oxygen therapy. Assessment of co-morbidity was based on the diagnosis used by the treating physician. Diabetes mellitus was considered to be present if medications were used for diabetes. Hypertension, ischemic heart disease or atrial fibrillation were considered to be present when diagnosed by the attending physican and when the patient was using appropriate medications. Statistics Analysis was carried out using Stata 8.0 (Stata Corporation, College Station, Texas). The w 2 -test, t-test and one-way analysis of variation were used in the univariable analyses, whilst multiple linear regression was used in the multiple variable analyses. SGRQ scores were analysed as a continuous variable and then checked for normality. In order to detect heterogeneity between the hospitals the regression estimates were also calculated by hospital and then combined, using random effect meta-analysis. A P-value of o0.05 was considered statistically significant. Results A total of 416 consecutive patients with COPD were enrolled in the study. The demographics of the study patients are shown in Table 1. Of those admitted, one-fourth were current smokers but most of the patients in the study had an extensive smoking history in the past. Women had significantly lower life-time tobacco exposure compared with men. Furthermore, women were more likely to be living alone than men. Lung function, oxygen use and co-morbid conditions Spirometry at discharge was performed in 386 of the patients. The mean FEV 1 was low (38.5% of predicted value) suggesting significant disease. Figure 1 shows the distribution of the patients according to the GOLD classification. Most of the patients were in stages III and IV. There was a nonsignificant trend that the men had more severe COPD than women (P ¼ 0:07). The use of long-term % of patients 60 50 40 30 20 10 0 men women I II III IV GOLD stages Figure 1 Staging of COPD in men and women according to GOLD criteria. Table 1 Characteristics of patients included in the study (mean71 SD, or as %). All Males Females P-value Number 416 205 211 Age (years) 69.4710.4 71.079.4 67.8711.2 0.001 Smokers (%) 25.8 23.6 28.0 0.32 Pack years smoking 33.7723.9 38.9727.0 28.8719.2 o0.0001 College education (%) 30.7 33.3 28.1 0.25 Living alone (%) 52.1 37.6 66.2 o0.0001 FEV 1 (% of predicted) 38.5718.2 36.4716.2 40.5719.7 0.01 FVC (% of predicted) 61.7720.3 58.7717.8 64.5722.1 0.002 LTOT (%) 23.6 24.4 22.8 0.69 Cardiovascular diseases (%) 45.0 48.3 41.7 0.17 Diabetes (%) 10.6 10.2 10.9 0.82 FEV 1 : forced expiratory volume in 1 s; FVC: forced vital capacity; LTOT: long-term oxygen therapy.

90 oxygen therapy was relatively high (23.6%) and comorbidities were common, with nearly half of the patients being diagnosed with cardiovascular disease and 10% having diabetes mellitus. Further details of the study patients are given in Table 1. Anxiety, depression and relationship with demographic factors Almost half of the study population suffered from anxiety and/or depression as measured by the HAD scale. Anxiety was significantly more common in women than in men (Fig. 2). Both anxiety and depression were more common in current smokers compared with non-smokers (Po0:001) while no significant relationship was found between psychological status and age, education, living conditions, lung function, LTOT or somatic co-morbidity (Table 2). % of patients 30 25 20 15 10 5 0 men women Anxiety Depression Anxiety and depression Figure 2 Psychological co-morbidity in men and women. Health status G. Gudmundsson et al. The mean total score on the SGRQ was 58, suggesting overall poor health among these severely affected COPD patients in the study. COPD patients with anxiety, depression or both had significantly higher scores in all domains and the total score of the SGRQ, suggesting a worse health status than those who did not suffer from psychiatric co-morbidity (Table 3). Effects of psychological condition on health condition Lung function and psychological status both have a large impact on health status as measured by the SGRQ (Table 4). A significant impairment in health status was seen with decreasing FEV 1 for all domains except symptoms. Depression alone or anxiety with depression had clinically significant effects on all domains and anxiety alone had effects on all domains except symptoms. The effects were substantial, i.e. up to 14.8 points. More severe COPD, as indicated by higher GOLD stages, was significantly associated with increasing impairment in health status. In contrast, anxiety and depression were reported in similar frequency regardless of the severity of COPD (Table 5). There was no significant difference between the study centres in the association between psychological status and health status (P for heterogeneity ¼ 0.88, 0.83, 0.93 and 0.98 for symptom, activity, impact and total score, respectively). Table 2 Demographics and psychological disorders (mean and 1 SD or %). None Anxiety only Depression only Anxiety and depression Number 202 81 31 79 Women (%) 47.0 56.8 38.7 62.0 Age (years) 70.0710.7 67.979.4 72.376.6 67.9711.3 Smokers (%) 19.4 23.5 23.3 43.0 Pack years smoking 33.3723.4 34.9721.4 38.0735.1 31.4722.9 College education (%) 31.8 35.8 12.9 31.6 Living alone (%) 49.2 56.8 50.0 48.7 FEV 1 (% of predicted) 39.6718.4 38.4719.0 36.6715.9 39.2716.9 FVC (% of predicted) 61.1720.5 64.1720.0 59.5713.1 62.1721.1 LTOT (%) 21.3 23.5 35.5 27.8 CV diseases (%) 41.1 49.4 48.4 53.2 Diabetes (%) 10.4 8.6 16.1 10.1 FEV 1 : forced expiratory volume in 1 s; FVC: forced vital capacity; LTOT: long-term oxygen therapy; CV: cardiovascular.

Depression, anxiety and health status in COPD 91 Table 3 Health status and psychological condition. All None Anxiety Depression Anxiety and depression Number 383 199 78 30 76 SGRQ points Symptoms 61.1720.2 68.0716.0 69.7717.4 69.0717.2 Activity 62.7723.6 69.3718.8 70.9719.3 74.7716.8 Impact 40.3719.1 52.1718.5 55.9717.8 53.6717.9 Total 58 52.3717.8 61.8715.0 64.1714.0 64.2714.6 Table 4 Relationship between lung function and psychological and health status. SGRQ components Symptoms estimate* (95% CI) Activity estimate (95% CI) Impact estimate (95% CI) Total estimate (95% CI) FEV 1 (% pred)** 0.59 ( 1.74, 0.57) 4.10 ( 5.33, 2.87) 2.29 ( 3.42, 1.16) 2.59 ( 3.56, 1.62) Anxiety 3.32 ( 1.89, 8.53) 5.77 (0.26, 11.3) 9.49 (4.37, 14.6) 7.09 (2.68, 11.5) Depression 6.04 ( 1.71, 13.8) 5.06 ( 3.21, 13.3) 14.8 (7.24, 22.4) 10.3 (3.83, 16.8) Anxiety and Depression 6.02 (0.68, 11.4) 12.0 (6.25, 17.7) 13.2 (8.02, 18.5) 11.9 (7.39, 16.33) *Estimates are regression coefficients derived from multiple linear regression. **Calculated per 10% unit. Adjusted for country, smoking, educational level, living partner and co-morbidity (cardiovascular disease and diabetes). Table 5 Health and psychological status in different GOLD stages. GOLD stages Stage I and II mild and moderate Stage III severe Stage IV very severe P-value Number 95 120 180 Psychological status (%) Anxiety 42.4 39.6 41.3 0.92 Depression 31.5 25.0 30.8 0.50 Anxiety and/or depression 48.9 46.8 50.6 0.83 Health status SGRQ points Symptoms 61.9719.6 62.6719.7 68.0717.8 0.01 Activity 58.0724.0 64.1721.8 74.5717.5 o0.001 Impact 41.7721.3 43.2719.2 51.6718.1 o0.001 Total 51.4718.6 54.7717.2 63.0714.9 o0.001 Discussion The main findings of our prospective multicentre study of a large group of COPD patients were that patients being discharged after hospitalisation for acute exacerbation had a high prevalence of anxiety and depression and also a poor health status. Women and current smokers were more likely to suffer from more significant anxiety or depression. There was a close relation between health status and psychological condition among these severely affected COPD patients who were close to being discharged from the hospital. Their health status may be expected to improve with increasing time from recovery after their exacerbation 17 but we are not aware of studies on the

92 time course on the interrelationship between health status and psychological condition. The prevalence of poor health status, anxiety and depression found are in accordance with those of some other studies. In a recent study by van Manen it was shown that the risk for depression in stable COPD patients from general practice was 2.5 times greater in patients with severe COPD (FEV 1 o50% of predicted) compared to controls. 18 Living alone, respiratory symptoms and physical impairment were also significantly associated with the risk for depression. In the COPD group, as a whole, 21.6% were depressed compared to 17.5% in the control group. In another study by the same author, where the prevalence of co-morbidity in patients with chronic airway obstruction was studied, depression was found to be more common in the study group than among the controls. 9 Heart disease and diabetes were not more common in the patients with chronic airway obstruction than in the control group. A study from Japan on 218 male patients with COPD of differing severity showed higher scores on SGRQ (worse health status) with increasing severity of disease 19 ; and also a correlation between the HAD scale and SGRQ. In another study, patients with COPD reported anxiety with increased frequency and this correlated with severity of disease. 20 In a recent study, GOLD stages II and higher, marked a dramatic worsening of health status as measured by SGRQ, but psychological status was not analysed simultaneously. 21 Multiple studies have shown how various interventions such as medications can improve health status. 3 7,22 In such studies the change in the SGRQ score of 4 units is regarded as clinically significant. 3 In our study the effects that anxiety and depression have on the SGRQ scores were striking or up to 12 units. This is a figure that is much higher than most medications have. 5,7 Based on our descriptive epidemiological study we are tempted to speculate whether improving psychological status can by itself lead to improved health status, even independent of changes in pulmonary status. Vice versa would be equally interesting. In future studies it could be valuable to include both measures of psychological status as well as health status when evaluating different treatment outcomes. Studies are lacking regarding the primary effect of medications such as anxiolytics, antidepressants and inhaled corticosteroids on both health status and psychological status among patients with COPD. 23 From a clinical point of view, our study underlines how important it is to identify those COPD patients who suffer anxiety and depression at discharge after an acute exacerbation and to pay attention to these commonly encountered complaints. This study shows that special attention needs to be put on females with COPD and current smokers. The HAD scale is a simple and effective way to screen patients for anxiety and depression. It requires only a short time to apply and analyse and is well standardised, all of which makes it attractive for this purpose. 11,14 16 Further studies should be conducted evaluating the effect of treatment of anxiety and depression and also to analyse whether simple screening tests such as the HAD scale can be used to select those that could benefit from specific therapy based on future randomised trials. Acknowledgements The authors wish to thank all the participants in the study, and also Boehringer Ingelheim Denmark, Norway, Sweden and Finland, as well as the Swedish Heart and Lung Association and the Swedish Heart Lung Foundation for financial support. References G. Gudmundsson et al. 1. Siafakes NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, et al. ERS-consensus statement: optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 1995;8:1398 420. 2. Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001; 163:1256 76. 3. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A selfcomplete measure of health status for chronic airflow limitation. The St. George 0 s Respiratory Questionnaire. Am Rev Respir Dis 1992;145:1321 7. 4. Bestall JC, Paul EA, Garrod R, Garnham R, Jones RW, Wedzicha AJ. Longitudinal trends in exercise capacity and health status after pulmonary rehabilitation in patients with COPD. Respir Med 2003;97:173 80. 5. Spencer S, Calverley PM, Sherwood Burge P, Jones PW, ISOLDE Study Group. Inhaled steroids in obstructive lung disease: health status deterioration in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163:122 8. 6. Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson J, Maden C. Trial of inhaled steroids and longacting beta2 agonists study group. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003; 36:449 56. 7. Tashkin D, Kesten S. Long-term treatment benefits with tiotropium in COPD patients with and without short-term bronchodilator responses. Chest 2003;123:1441 9. 8. Donohue JF, van Noord JA, Bateman ED, Langley SJ, Lee A, Witek Jr TJ, Kesten S, Towse L. A 6-month,

Depression, anxiety and health status in COPD 93 placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest 2002;122:47 55. 9. van Manen JG, Bindels PJE, Ijzermans CJ, van der Zee JS, Bottema BJAM, Schade E. Prevalence of comorbidity in patients with a chronic airway obstruction and controls over the age of 40. J Clin Epidemiol 2001;54:287 93. 10. Janson C, Björnsson E, Hetta J, et al. Anxiety and depression in relation to respiratory symptoms and asthma. Am J Respir Crit Care Med 1994;149:930 4. 11. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psyciat Scand 1983;67:361 70. 12. Dahlén I, Jansson C. Anxiety and depression are related to the outcome of emergency treatment in patients with obstructive pulmonary disease. Chest 2002;122:1633 7. 13. European Community for Coal and Steel. Standardisation of lung function tests. Clin Respir Phys 1983;19(Suppl. 5):22 7. 14. Lewin B, Robertson IH, Cay EL, et al. Effects of self-help post-myocardial-infarction rehabilitation on psychological adjustment and use of health services. Lancet 1992; 339:1036 40. 15. Wilkinson MJ, Barczak P. Psychiatric screening in general practice: comparison of the general health questionnaire and the hospital anxiety depression scale. J R Coll Gen Pract 1988;38:311 3. 16. Moorey S, Greer S, Watson M, et al. The factor structure and factor stability of the hospital anxiety and depression scale in patients with cancer. Br J Psychiatry 1991;158:255 9. 17. Spencer S, Jones PW, GLOBE Study Group. Time course of recovery of health status following an infective exacerbation of chronic bronchitis. Thorax 2003; 58:589 93. 18. van Manen JG, Bindels PJ, Dekker FW, Ijzermans CJ, van der Zee JS, Schade E. Risk of depression in patients with chronic obstructive pulmonary disease and its determinants. Thorax 2002;57:412 6. 19. Hajiro T, Nishimura K, Tsukino M, Ikeda A, Oga T. Stages of disease severity and factors that affect the health status of patients with chronic obstructive pulmonary disease. Respir Med 2000;94:841 6. 20. Dowson C, Laing R, Barraclough R, Town I, Mulder R, Norris K, Drennan C. The use of the Hospital Anxiety and Depression Scale (HADS) in patients with chronic obstructive pulmonary disease: a pilot study. NZ Med J 2001; 114:447 9. 21. Antonelli-Incalzi R, Imperiale C, Bellia V, catalano F, Scichilone N, Pistelli R, Rengo F. Do GOLD stages of COPD severity really correspond to differences in health status? Eur Respir J 2003;22:444 9. 22. Peruzza S, Sergi G, Vianello A, Pisent C, Tiozzo F, Manzan A, et al. Chronic obstructive pulmonary disease (COPD) in elderly subjects: impact on functional status and quality of life. Respir Med 2003;97:612 7. 23. Croxton TL, Weinmann GG, Senior RM, Wise RA, Crapo JD, Buist AS. Clinical research in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167:1142 9.