Acute exacerbations of obstructive pulmonary disease

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1 Anxiety and Depression Are Related to the Outcome of Emergency Treatment in Patients With Obstructive Pulmonary Disease* Inger Dahlén, MD, PhD; and Christer Janson, MD, PhD Study objectives: To investigate whether psychological factors predict outcome after emergency treatment for obstructive pulmonary disease. Setting: Emergency department at a university hospital. Patients: Forty-three patients presenting with exacerbation of asthma or COPD. Intervention: The patients received emergency treatment and were followed up for 4 weeks. Measurement: Spirometry, blood sampling, pulse oximetry, breathing rate, pulse rate, and dyspnea score was measured before and during emergency treatment. The psychological status was assessed using the hospital anxiety and depression (HAD) scale questionnaire at the end of the follow-up period. Results: Anxiety and/or depression was found in 17 patients (40%). Of these patients, nine patients (53%) were admitted to hospital or had a relapse within 1 month, compared with five patients (19%) in the group without anxiety and/or depression (p < 0.05). Among patients who relapsed within 1 month (n 14), the HAD total score was compared with (mean SD) among the patients without a relapse (p < 0.05). After making adjustments for age, gender, atopic status, treatment, and pack-years, the significant association between treatment failure and anxiety and/or depression still remained. Conclusion: Our study indicates that anxiety and depression are related to the outcome of emergency treatment in patients with obstructive pulmonary disease. Further studies should be conducted evaluating the effect of treatment of anxiety and depression in patients with recurrent exacerbations of asthma and COPD. (CHEST 2002; 122: ) Key words: anxiety; asthma; COPD; depression; emergency treatment; relapse Abbreviation: HAD hospital anxiety and depression *From the Department of Medical Sciences, Respiratory Medicine, and Allergology, Uppsala University Hospital, Sweden. This study was supported by the Bror Hjerpstedt Foundation, Sweden, the Swedish Heart and Lung Foundation, and Astra, Sweden. Manuscript received February 13, 2001; revision accepted May 29, Correspondence to: Inger Dahlén, MD, PhD, Department of Lung Medicine and Allergology, Uppsala University Hospital, SE Uppsala, Sweden; inger.dahlen@medsci.uu.se Acute exacerbations of obstructive pulmonary disease are a very common reason for medical emergency treatment. There is a subgroup of patients who repeatedly visit the emergency department. 1 Decompensated COPD has been shown to be one of the most common causes of return visits to an emergency department. 2 Relapses in acute asthma are also common. In one American study, 3 approximately 25% of patients treated for asthma relapsed within 3 weeks of being seen at the emergency department. Baseline disease severity did not account for the relapses. In another study, 4 asthmatic patients with many emergency visits had evidence of greater nonadherence to asthma treatment. Stehr et al 5 found that psychosocial factors, such as being widowed or divorced, were closely correlated to relapses among male patients with COPD. The aim of this study was to investigate whether psychological factors assessed by the hospital anxiety and depression (HAD) questionnaire are correlated to the risk of relapse in consecutive patients with acute exacerbations of obstructive pulmonary disease. Materials and Methods The study comprised adult patients ( 18 years old) with acute exacerbations of obstructive pulmonary disease, both asthma and COPD, presenting during the day at our emergency department. They were all assessed as being in need of emergency treatment. They were excluded if immediate hospital admission was deemed CHEST / 122 / 5/ NOVEMBER,

2 necessary or if they were unable to perform lung function tests. All participation was voluntary, and the study was approved by the Ethics Committee at the Medical Faculty at Uppsala University. The respiratory rate and oxygen saturation (Nellcor N-20P; Nellcor Incorporated; Hayward, CA) were measured on arrival. Patients were then asked to rate their dyspnea according to the Borg modified scale Before treatment, all patients were examined and spirometry (Vitalograph Alfa; Vitalograph Ltd; Buckingham, UK) was performed. The best value from three recordings was chosen. The predicted FEV 1 value was calculated for each patient. 11 Spirometry was repeated after 2 h. Venous blood samples were obtained. Patients were interviewed about their smoking history, and the number of pack-years was calculated. The clinical diagnosis of asthma and COPD was based on previous history, symptoms, and earlier investigations recorded in the case notes. The HAD questionnaire was completed by the patients at the follow-up visit after 4 weeks. All relapses were recorded during the 4 weeks after the emergency visit. A relapse was defined as any hospital contact at which antiobstructive treatment was administered. Patient information was checked against hospital records. All patients were administered 5 to 15 mg of nebulized salbutamol (in one to three doses) via Ventstream with a Porta Neb compressor (Medic Aid Ltd.; West Sussex, UK). If necessary, oxygen was administered. The patients were treated after randomization with 60 mg of oral prednisolone followed by 30 mg/d of prednisolone for 1 week, with 4 mg of budesonide suspension (2 mg/ml), followed by 1,600 g/d of budesonide (via dry-powder inhaler) for 1 week or no steroid treatment in the acute phase but the inhalation of 400 g qid of budesonide immediately after discharge. For the following 3 weeks, all patients were treated with 1,600 g/d of budesonide. 12 Atopic Status Phadiatope (Pharmacia & Upjohn Diagnostics, Uppsala, Sweden) was used to classify patients as atopic or nonatopic. HAD Questionnaire The self-reported HAD questionnaire 13 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. 17 It consists of 14 questions: 7 questions are related to anxiety and 7 questions are related to depression. Each item is rated on a 4-point scale, giving maximum subscale scores of 21 for anxiety and depression, respectively. Zigmond and Snaith 13 recommended that scores of 8 on a subscale should be taken as an indication of possible pathology. Statistical Methods The statistical analyses were performed with StatView 5.0 (SAS Institute; Cary, NC). Comparisons between patients with and without anxiety or depression were performed using the Mann- Whitney U test for continuous variables, while the 2 test was used for comparisons of proportions. The Kaplan-Meier survival analysis was used to study the difference in time to relapse between patients with and without anxiety/depression. Multivariate analysis was performed by multiple logistic regression. A p value 0.05 was regarded as statistically significant. Results Fifty patients were included in the investigation. We obtained full records from 43 patients who were evaluated in this study. The mean age was 65.3 years (range, 22 to 87 years). Nineteen patients were men (mean age, 65.8 years), and 24 were women (mean age, 64.8 years). Sixteen patients (37%) had an anxiety score of 8 (probable anxiety), 5 patients (12%) had a depression score of 8 (probable depression), 4 patients (9%) had both an anxiety and a depression score of 8, and 17 patients (40%) had either probable anxiety and/or depression. The mean HAD total score was 9.8. The characteristics of patients with and without anxiety and/or depression are shown in Table 1. No significant differences between the groups were seen with regard to age, gender, smoking history, or severity of the attack. Of the 43 patients, 28 patients had a clinical diagnosis of asthma and 15 patients had COPD. The emergency treatment was unsuccessful in 14 patients: 3 patients could not be discharged after the emergency treatment, 6 patients relapsed within 1 week, and a further 5 patients relapsed within 1 month. The characteristics of the patients with and without treatment failure are shown in Table 2. The patients who relapsed within 1 month had a significantly lower FEV 1 before treatment than the patients who did not relapse. In the group of patients with probable anxiety and/or depression, nine patients (53%) relapsed within 1 month compared with five patients (19%) in the group without anxiety/depression (p 0.05). The psychological characteristics of patients with and without a relapse within 1 month are shown in Table 3. Patients with treatment failure had a significantly higher HAD total score, and the number of patients with probable anxiety/depression was higher. The Table 1 of Patients With and Without Anxiety and/or Depression* No Anxiety or Depression (n 26) Probable Anxiety and/or Depression (n 17) Age, yr 65.3 (14.8) 64.3 (11.6) Male gender, % Pack-years 19.7 (23.0) 20.0 (15.2) Atopy, % FEV 1, % predicted 50.8 (25.2) 43.0 (22.8) FEV 1 at2h,%of 22.9 (22.2) 31.2 (51.1) baseline FEV 1 at4wk,%of 24.5 (37.7) 43.9 (84.5) baseline Dyspnea, Borg scale 6.2 (1.4) 5.9 (1.6) Sao 2,% 95.2 (2.7) 94.5 (3.0) Breathing rate, min 21 (5) 19 (4) Pulse rate, min 86 (14) 88 (22) *No statistically significant difference. Values shown are mean (SD) unless otherwise indicated. Sao 2 arterial oxygen saturation Clinical Investigations

3 Table 2 of Patients With a Relapse Within 1 Month* Success (n 29) Failure (n 14) Age, yr 62.8 (13.8) 68.6 (13.1) Male gender, % Pack-years 18.4 (21.7) 23.8 (18.7) Atopy, % FEV 1, % predicted 53.4 (24.5) 35.7 (19.0) FEV 1 2 h, % of baseline 24.7 (33.3) 29.3 (41.5) FEV 1 4 wk, % of baseline 33.4 (54.2) 30.0 (75.2) Dyspnea, Borg scale 6.0 (1.6) 5.9 (1.5) Sao 2,% 95.2 (2.5) 94.2 (3.3) Breathing rate, min 20 (4) 20 (5) Pulse rate, min 84 (16) 93 (19) *Values shown are mean (SD) unless otherwise indicated. See Table 1 for expansion of abbreviation. p Figure 1. Kaplan-Meier cumulative survival plot for days until first relapse. Table 3 Psychological of Patients With and Without a Relapse Within 1 Month* Success (n 29) Failure (n 14) HAD anxiety score 5.3 (3.6) 7.1 (3.4) HAD depression score 3.3 (2.2) 5.2 (4.0) HAD total score 8.6 (5.1) 12.4 (5.9) Probable anxiety, % Probable depression, % 3 28 Probable anxiety and/or depression, % *Values shown are mean (SD) unless otherwise indicated. p difference in the time until treatment failure in patients with and without anxiety and/or depression is illustrated in a survival analysis in Figure 1. When the patients were classified according to their clinical diagnosis, a significant relationship was found between treatment failure and the HAD score in the asthmatic group: mean, 13.6 (SD, 4.0) vs mean, 8.9 (SD, 5.3) [p 0.03]. The HAD score was also higher in COPD patients with treatment failure than in the COPD patients with a successful treatment, but this difference was not statistically significant: mean, 11.1 (SD, 7.4) vs mean, 7.8 (SD, 4.6) [p 0.4]. In a multiple logistic regression analysis, the association of different variables with treatment failure was studied with adjustments for age, gender, packyears, emergency treatment, and atopic status. The results are shown in Table 4. A significant correlation between psychological factors and the risk of treatment failure was also found when replacing probable anxiety and/or depression with the HAD total score (odds ratio, 1.18; 95% confidence interval, 1.01 to 1.39). Replacing pack-years with the clinical diagnosis of asthma or COPD did not significantly change our results. The adjusted odds ratio for the relationship between probable anxiety and/or depression and treatment failure was 7.1 (95% confidence interval, 1.1 to 53.4) in this model. Discussion The main finding of this study is that patients who had a relapse after emergency treatment of obstructive pulmonary disease are more likely to report signs of anxiety and/or depression. We have not found similar studies for comparison, but our results are in accordance with those of some other studies. In the study by Stehr et al 5 involving male patients with COPD, psychosocial factors such as experiencing the loss of a first-order relative and being more pessimistic about the prognosis, were more common among the group of relapses. Yohannes et al 18 found that anxiety was a major predicting factor for frequency of hospital admission for acute exacerbations of COPD in elderly patients (aged 60 to 89 years). In Table 4 Association of Variables and Treatment Failure With Adjustments for Age, Gender, Pack-Years, Atopic Status, Treatment Variables Odds Ratio 95% Confidence Interval FEV Dyspnea Breathing rate Oxygen saturation Pulse rate Probable anxiety and/or depression CHEST / 122 / 5/ NOVEMBER,

4 studies of brittle asthma, near-fatal asthma, and asthma deaths, a high prevalence of psychiatric disorders and psychosocial problems has been reported This could mean that there is an association between asthma severity and psychological disability. In the study by Dales et al, 1 however, no association could be found between psychological health and the risk of relapses. The prevalence of anxiety and depression in our patient group was higher than what has been found in the general population in Sweden. Lisspers et al 28 evaluated the HAD scale in a Swedish population sample and found a prevalence of probable anxiety of 12% (in our study, 37%), of probable depression of 9% (in our study, 12%) and a total HAD score of 8.5 (in our study, 9.8). The age group investigated was 30 to 59 years, which makes direct comparisons with our study difficult. Centanni et al 29 studied 80 asthmatic outpatients and found significantly higher levels of depression and anxiety than in the control groups consisting of patients with chronic liver disease and healthy subjects. It has been shown that emotional stimuli induce asthmatic attacks and reductions in FEV 1, but it does not appear that asthmatic patients as a whole have a specific personality profile. 14,33,34 In COPD, several studies have 18,35 38 shown a high prevalence of emotional disturbance, anxiety, and depression, but in one study of unselected, elderly patients with COPD, depressive symptoms were equally common among patients and control subjects. 39 One reason for the high prevalence of psychiatric morbidity in our study might be that the patients in our study were selected because they had visited an emergency department. The HAD questionnaire was administered at the visit at the end of the study period. The reason for this was that we wanted to evaluate the patients in as steady a state as possible, in order to avoid the acute psychological effects of the emergency visit. A drawback with this approach is that the relapse in itself may have negatively affected the patient s psychological well-being. While we cannot exclude this possibility, it should be pointed out that only one of the of the patients had a relapse within the last 10 days preceding the psychological evaluation, and this patient did not have probable anxiety or depression. Our study group comprised both asthma and COPD patients, as it is often difficult, especially in the acute phase, to distinguish asthma from COPD. Looking at the groups separately, asthmatic patients with a relapse had a higher HAD score than the asthmatics with successful emergency treatment. The same trend was also found in the COPD group, although the difference here was not statistically significant. With the limited number of patients included in our study, it is therefore difficult to conclude whether the relationship between psychological factors and the outcome of emergency treatment is different in asthma and COPD. Our study indicates that anxiety and depression are related to the outcome of emergency treatment in patients with obstructive pulmonary disease. Further studies should be conducted evaluating the effect of treatment of anxiety and depression in patients with recurrent exacerbations of asthma and COPD. ACKNOWLEDGMENT: The assistance of Elisabeth Rydéhn, RN, is greatly appreciated. References 1 Dales RE, Schweitzer I, Kerr P, et al. Risk factors for recurrent emergency department visits for asthma. Thorax 1995; 50: Murata GH, Gorby MS, Chick TW, et al. Use of emergency medical services by patients with decompensated obstructive lung disease. Ann Emerg Med 1989; 18: Emerman CL, Cydulka RK. Factors associated with relapse after emergency department treatment for acute asthma. Ann Emerg Med 1995; 26: Schmaling KB, Afari N, Blume AW. Predictors of treatment adherence among asthma patients in the emergency department. J Asthma 1998; 35: Stehr DE, Klein BJ, Murata GH. Emergency department return visits in chronic obstructive pulmonary disease: the importance of psychosocial factors. Ann Emerg Med 1991; 20: Burdon JG, Juniper EF, Killian KJ, et al. The perception of breathlessness in asthma. Am Rev Respir Dis 1982; 126: Yamamoto H, Inaba S, Nishimura M, et al. Relationship between the ability to detect added resistance at rest and breathlessness during bronchoconstriction in asthmatics. Respiration 1987; 52: Mahler DA, Rosiello RA, Harver A, et al. Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease. Am Rev Respir Dis 1987; 135: Silverman M, Barry J, Hellerstein H, et al. Variability of the perceived sense of effort in breathing during exercise in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1988; 137: Wolkove N, Dajczman E, Colacone A, et al. The relationship between pulmonary function and dyspnea in obstructive lung disease. Chest 1989; 96: European Community for Coal and Steel. Standardized lung function testing. Clin Respir Physiol 1983; 19:S22 S27 12 Dahlén I, Janson C, Björnsson E, et al. Inflammatory markers in acute exacerbations of obstructive pulmonary disease: predictive value in relation to smoking history. Respir Med 1999; 93: Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67: 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: Lewin B, Robertson IH, Cay EL, et al. Effects of self-help post-myocardial-infarction rehabilitation on psychological ad Clinical Investigations

5 justment and use of health services. Lancet 1992; 339: 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: 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: Yohannes A, Baldwin R, Connolly M. Depression and anxiety in elderly outpatients with chronic obstructive pulmonary disease: prevalence, and validation of the BASDEC screening questionnaire. Int J Geriatr Psychiatry 2000; 15: Harrison BD. Psychosocial aspects of asthma in adults. Thorax 1998; 53: Miles JF, Garden GM, Tunnicliffe WS, et al. Psychological morbidity and coping skills in patients with brittle and non-brittle asthma: a case-control study. Clin Exp Allergy 1997; 27: Yellowlees PM, Ruffin RE. Psychological defenses and coping styles in patients following a life-threatening attack of asthma. Chest 1989; 95: Campbell DA, Yellowlees PM, McLennan G, et al. Psychiatric and medical features of near fatal asthma. Thorax 1995; 50: Innes NJ, Reid A, Halstead J, et al. Psychosocial risk factors in near-fatal asthma and in asthma deaths. J R Coll Physicians Lond 1998; 32: Joseph KS, Blais L, Ernst P, et al. Increased morbidity and mortality related to asthma among asthmatic patients who use major tranquilisers. BMJ 1996; 312: Ryan G, Musk AW, Perera DM, et al. Risk factors for death in patients admitted to hospital with asthma: a follow-up study. Aust NZJMed1991; 21: Wareham NJ, Harrison BD, Jenkins PF, et al. A district confidential enquiry into deaths due to asthma. Thorax 1993; 48: Picado C, Montserrat J, de Pablo J, et al. Predisposing factors to death after recovery from life-threatening asthmatic attack. J Asthma 1989; 26: Lisspers J, Nygren A, Soderman E. Hospital Anxiety and Depression Scale (HAD): some psychometric data for a Swedish sample. Acta Psychiatr Scand 1997; 96: Centanni S, Di Marco F, Castagna F, et al. Psychological issues in the treatment of asthmatic patients. Respir Med 2000; 94: Masuda M, Notske R, Holmes T. Catecholamine excretion and asthmatic behaviour [abstract]. J Psychosom Res 1966; 10: Tal A, Miklich DR. Emotionally induced decreases in pulmonary flow rates in asthmatic children. Psychosom Med 1976; 38: Deal E, McFadden E, Ingram R, et al. Hyperpnea and heat reflux: initial reaction sequence in exercise-induced asthma. J Appl Physiol 1979; 46: Benjamin S. Is asthma a psychosomatic illness? A retrospective study of mental illness and social adjustment. J Psychosom Res 1977; 21: Chetta A, Gerra G, Foresi A, et al. Personality profiles and breathlessness perception in outpatients with different gradings of asthma. Am J Respir Crit Care Med 1998; 157: Guyatt GH, Townsend M, Berman LB, et al. Quality of life in patients with chronic airflow limitation. Br J Dis Chest 1987; 81: Kellner R, Samet JM, Pathak D. Hypochondriacal concerns and somatic symptoms in patients with chronic airflow obstruction. J Psychosom Res 1987; 31: Yellowlees PM, Alpers JH, Bowden JJ, et al. Psychiatric morbidity in patients with chronic airflow obstruction. Med J Aust 1987; 146: Peach H, Pathy M. Follow-up study of disability among elderly patients discharged from hospital with exacerbations of chronic bronchitis. Thorax 1981; 36: Isoaho R, Keistinen T, Laippala P, et al. Chronic obstructive pulmonary disease and symptoms related to depression in elderly persons. Psychol Rep 1995; 76: CHEST / 122 / 5/ NOVEMBER,

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