Co-morbid association of depression and COPD: A population-based study

  • Tze-Pin Ng
    Correspondence
    Corresponding author. Gerontological Research Programme, National University of Singapore, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. Tel.: +65 67724514; fax: +65 67772191.
    Affiliations
    Gerontological Research Programme, Faculty of Medicine, National University of Singapore (NTP, MN), National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074

    Department of Psychological Medicine, National University of Singapore (NTP, MN), Singapore
    Search for articles by this author
  • Mathew Niti
    Affiliations
    Gerontological Research Programme, Faculty of Medicine, National University of Singapore (NTP, MN), National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074

    Department of Psychological Medicine, National University of Singapore (NTP, MN), Singapore
    Search for articles by this author
  • Calvin Fones
    Affiliations
    Gerontological Research Programme, Faculty of Medicine, National University of Singapore (NTP, MN), National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074

    Department of Psychological Medicine, National University of Singapore (NTP, MN), Singapore
    Search for articles by this author
  • Keng Bee Yap
    Affiliations
    Gerontological Research Programme, Faculty of Medicine, National University of Singapore (NTP, MN), National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074

    Alexandra Hospital (YKB), Singapore
    Search for articles by this author
  • Wan-Cheng Tan
    Affiliations
    University of British Columbia, Vancouver (TWC), Canada
    Search for articles by this author
Open ArchivePublished:January 12, 2009DOI:https://doi.org/10.1016/j.rmed.2008.12.010

      Summary

      Objectives

      Depression occurs commonly among patients with COPD, but the independent association of depression and COPD and the effect of depression on COPD outcomes are not well established.

      Method

      A population sample of 2402 Chinese aged ≥55 with and without COPD (characteristic symptoms of chronic cough, sputum or breathlessness and airflow obstruction and FEV1/FVC<0.70) was assessed on Geriatric Depression Scale (score5), dependence on basic activities of daily living (ADL), SF-12 health status, smoking and medication behaviour.

      Results

      The 189 respondents with COPD showed higher depressive symptoms prevalence (22.8%) than 2213 respondents without COPD (12.4%); multivariate odd ratio (OR) was 1.86; 95% CI, 1.25–2.75 after controlling for confounding risk factors. In multivariate analyses of respondents with COPD, those who were depressed (N=43), compared to those who were not (N=146), were more likely to report ADL disability (OR=2.89, p=0.049) poor or fair self-reported health (OR=3.35, p=0.004), poor SF-12 PCS scores (OR=2.35, p=0.041) and SF-12 MCS scores (OR=4.17, p<0.001).

      Conclusion

      Depressive symptoms were associated with COPD independent of known risk factors. In COPD participants, depressive symptoms were associated with worse health and functional status and self-management.

      Keywords

      Introduction

      Chronic obstructive pulmonary disease (COPD) is a major cause of disability and death worldwide.
      • Murray C.J.
      • Lopez A.D.
      Global mortality, disability, and the contribution of risk factors: global burden of disease study.
      In contrast to the marked morbidity and mortality declines observed with other major chronic diseases, the trends for chronic obstructive pulmonary disease (International Classification of Diseases, Tenth Revision, ICD-10 J40-J47) are continually increasing.
      • Jemal A.
      • Ward E.
      • Hao Y.
      • Thun M.
      Trends in the leading causes of death in the United States, 1970-2002.
      Patients with COPD bear a heavy burden of respiratory distress, physical disability in daily living activities and poor quality of life.
      Depression is commonly observed in patients with COPD. Reports suggest that depressive disorders or depressive symptoms are present in between 16 and 74% of patients with COPD.
      • Coultas D.B.
      • Edwards D.W.
      • Barnett B.
      • Wludyka P.
      Predictors of depressive symptoms in patients with COPD and health impact.
      • Schane R.E.
      • Woodruff P.G.
      • Dinno A.
      • Covinsky K.E.
      • Walter L.C.
      Prevalence and risk factors for depressive symptoms in persons with chronic obstructive pulmonary disease.
      • Ng T.P.
      • Niti M.
      • Tan W.C.
      • Cao Z.
      • Ong K.C.
      • Eng P.
      Depressive symptoms and chronic obstructive pulmonary disease: effect on mortality, hospital readmission, symptom burden, functional status, and quality of life.
      • van Manen J.G.
      • Bindels P.J.E.
      • Dekker F.W.
      • Yzermans C.J.
      • van der Zee J.S.
      • Schadé E.
      Risk of depression in patients with chronic obstructive pulmonary disease and its determinants.
      • Yohannes A.M.
      • Roomi J.
      • Baldwin R.C.
      • Connolly M.J.
      Depression in elderly outpatients with disabling chronic obstructive pulmonary disease.
      However, depression is also present in significant proportions of elderly in the community without COPD, and known risk factors for depression that are common in the elderly such as psychosocial deprivation and loss, multiple chronic illnesses, poor health and functional disability and the use of multiple drugs that potentially can cause depression could all contribute to increase the prevalence of depression in COPD patients. Hence, the primary co-morbid association of depression and COPD resulting uniquely from psychobiological processes specifically related to COPD, without the mediating effects of other risk factors, is debatable. Systematic reviews
      • van Ede L.
      • Yzermans C.J.
      • Brouwer H.J.
      Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.
      have highlighted the major methodological drawbacks in previous studies that investigated this relationship. These included lack of control groups, small sample sizes, highly selective patient samples in clinical settings, failure to take into account important confounding by psychosocial and socio-economic factors, medical co-morbidity, and medications which cause mood alterations.
      Furthermore, few studies have demonstrated whether the presence of depression among the elderly with COPD had a strong adverse effect on COPD-specific outcomes, medication adherence and smoking cessation, poorer functional status and quality of life. The Medical Outcomes Study suggested that patients with chronic respiratory disease (next only to patients with chronic gastro-intestinal disease) appeared worst off on their mental health status than patients with all other chronic diseases.
      • Stewart A.L.
      • Greenfield S.
      • Hays R.D.
      • Wells K.
      • Rogers W.H.
      • Berry S.D.
      • et al.
      Functional status and well being of patients with chronic conditions: results from the medical outcomes study.
      Whereas studies of patients with coronary artery disease, diabetes and hypertension have demonstrated that depression is associated with major adverse impact on specific disease outcomes,
      • Katon W.
      • Sullivan M.D.
      Depression and chronic medical illness.
      • Wells K.B.
      • Rogers W.
      • Burnam M.A.
      • Camp P.
      Course of depression in patients with hypertension, myocardial infarction or insulin-dependent diabetes.
      • Fraser-Smith F.
      • Lesperance F.
      • Talagic M.
      Depression and 18-month prognosis after myocardial infarction.
      • Ciechanowski P.S.
      • Katon W.J.
      • Russo J.E.
      Depression and diabetes: impact of depressive symptoms on adherence, function, and costs.
      very few studies have evaluated the impact of depression on disease specific outcomes in COPD patients.
      In this population-based study of Chinese older adults aged 55 and above, we sought to determine whether depressive symptoms were associated with COPD independent of other known risk factors and health correlates; and among those with COPD, whether depressed respondents were more likely to experience worse health, functional and quality of life status, and performance on self-management tasks related to medication and smoking behavior.

      Method

       Study population

      The study was based on baseline data collected from the Singapore Longitudinal Ageing Study (SLAS) of ageing and health.
      • Niti M.
      • Ng T.P.
      • Kua E.H.
      • Ho R.C.
      • Tan C.H.
      Depression and chronic medical illnesses in Asian older adults: the role of subjective health and functional status.
      The SLAS is an ongoing observational cohort study of a whole population of community-dwelling Singaporean older adults resident in five districts in South East Region of Singapore. Singaporean citizens or permanent residents aged 55 and above were identified by door-to-door census, and invited to participate. Residents who were physically or mentally incapacitated to give informed consent or participate were excluded. A total of 2804 residents participated in the study (estimated response rate 78%). The study was approved by the National University of Singapore Institutional Review Board.

       Spirometry

      Ventilatory function testing was performed using a portable, battery operated, ultrasound transit-time based spirometer (Easy-One; Model 2001 Diagnostic Spirometer, NDD Medical Technologies, Zurich, Switzerland). Calibration was checked daily with a 3-L syringe. Forced expiratory maneuvers were performed with the respondent seated according to American Thoracic Society (ATS) recommended guidelines and standardization of procedures: at least three acceptable maneuvers, with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) reproducible within 200 mL. Chronic airflow obstruction was defined as FEV1/FVC<0.70.
      Height and weight were measured with a portable Seca stadiometer (Model 708 1314004, Vogel & Hake Hamburg, Germany)
      Questions from the British Medical Research Council Questionnaire on chronic respiratory symptoms were used to elicit symptoms characteristic of COPD: chronic cough and/or sputum lasting at least 3 months in the year and/or breathlessness on exertion.

       COPD

      Among the 2478 Chinese respondents in the cohort, 81 respondents who did not perform spirometry, 46 respondents with technically unsatisfactory spirometric performance and 3 with other missing data were excluded. We identified cases of COPD among the participants who had characteristic symptoms of COPD and spirometric evidence of chronic airflow obstruction (FEV1/FVC<0.70), consistent with the definition as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD).

      Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Executive summary. NHLBI/WHO workshop report; 2001.

      Because it is difficult to differentiate COPD and asthma in some individuals, we excluded respondents (N=76) who reported a history of asthma diagnosis and treatment (40 among those with airflow obstruction, and 36 among those without). The final analysis was therefore based on 2402 respondents.
      Among the resulting 189 respondents with COPD, severity of airflow obstruction was assessed using FEV1 percent of predicted values for normal lung function derived from the data from the present study, according to GOLD recommended criteria: mild: FEV180% of predicted, moderate: FEV1 50% or more and less than 80% predicted, severe: FEV1<50% of predicted.

       Depression

      The presence of depressive symptoms was determined by the 15-item Geriatric Depression Scale (GDS-15).
      • Yesavage J.A.
      • Brink T.L.
      Development and validation of a geriatric depression screening scale. A preliminary report.
      • Seikh J.I.
      • Yesavage J.A.
      Geriatric depression scale (GDS): recent evidence and development of a shorter version.
      It is well suited for the study because it is largely free of the measurement artefact due to overlapping somatic symptoms of physical illness(es) and depression. The translated versions of the GDS have been found to have good reliability (coefficient of 0.90), sensitivity (96.3%) and specificity (87.5%) for assessing late-life depression in Chinese subjects.
      • Lim P.P.
      • Ng L.L.
      • Chiam P.C.
      • Ong P.S.
      • Ngui F.T.
      • Sahadevan S.
      Validation and comparison of three brief depression scales in an elderly Chinese population.
      The internal reliability coefficient (Cronbach's α) was 0.84. Scores range from 0 to 15, and scores of 5 or more are indicative of depression. Face-to-face interviews were performed using both English and Chinese versions of the GDS, according to the respondents' language preference.

       Other measurements

       Co-morbid medical illnesses

      Respondents were asked to report whether in the 12 months prior to the interview they were diagnosed and treated by a doctor for any one or more of 16 specific medical conditions, which included asthma, COPD, coronary artery disease, heart failure, hypertension, dyslipidemia, diabetes, stroke, hip fracture, arthritis, asthma, COPD, cataract, and other conditions specified by them. The presence of hypertension was defined by a self-report of high blood pressure, and/or treatment with anti-hypertensive drugs and/or sitting systolic blood pressure ≥140 mm Hg and/or sitting diastolic blood pressure ≥90 mm Hg. The presence of diabetes was defined as self-report of diabetes and/or treatment with oral hypoglycemic agents or insulin, and/or fasting blood glucose >7.0 mmol/L. Hyperlipidemia was defined as self reported hyperlipidemia, and/or total cholesterol ≥6.5 mmol/L and/or LDL-Cholesterol ≥4.1 mmol/L and/or TG ≥2.3 mmol/L and/or HDL-Cholesterol <1.0 mmol/L and/or total cholesterol: HDL-Cholesterol ratio >4.5.

       Potentially depressogenic medications

      For each medical condition reported by the respondent, information on the drugs currently used was ascertained from the drug labels physically produced by the respondents. This included the use of drugs widely reported in the literature to cause depression: corticosteroids (e.g. prednisolone), hormone replacement therapy (e.g. premarin), anti-hypertensives (e.g. methyldopa), beta-blockers (propranolol, atenolol, bisoprolol), cardiovascular drugs (e.g. thiazide diuretics, digoxin), anti-Parkinsonism drugs (e.g. L-dopa, benzhexol), neuroleptics and anti-anxiety drugs (e.g. haloperodiol, risperidone, chloral hydrate, benzodiazepines), NSAIDs (e.g. indomethacine, naproxen, tramodol), anti-neoplastic medications (e.g. tamoxifen, metrothexate), and others (e.g. cimetidine, ranitidine).
      • Patten S.B.
      • Barbui C.
      Drug-induced depression: a systematic review to inform clinical practice.
      Data of socio-demographic characteristics and psycho-social variables included age, gender, ethnicity, education, housing type and size (which has been shown in national census reports and numerous studies to be a more robust indicator of socio-economic status than income), marital status (whether widowed/divorced/separated), living arrangement (whether living alone), whether having a confidante, frequency of visits or telephone calls by family, relatives or friends.

       Self-reported health status

      Self-rated health status was assessed by a question, ‘In general, would you say your health is excellent, very good, good, fair, poor?’, which has been validated in numerous studies to be highly predictive of health, functional and mortality outcomes. The respondents were classified in two categories of self-rated health (‘poor and fair’ or ‘good, very good and excellent’).
      Dyspnoea was assessed by a five-point dyspnoea scale (modified Medical Research Council questionnaire),
      • Warley A.R.
      • Finnegan O.C.
      • Nicholson E.M.
      • Laszlo G.
      Grading of dyspnoea and walking speed in cardiac disease and in chronic airflow obstruction.
      and respondents were classified as having moderate to severe dyspnoea (grade 2 or more) if they were breathless on moderate exertion or worse.
      Functional disability was assessed by the respondent's dependence in performing ten basic activities of daily living (BADLs), including feeding, bathing, dressing, grooming, bladder control, bowel control, toileting, transferring from bed/chair, walking inside house, climbing stairs, derived from the Barthel's scale.
      • Mahoney F.I.
      • Barthel D.W.
      Functional evaluation: the Barthel index.
      Functional disability was defined as needing at least some help in one or more BADLs.
      The respondent's quality of life was measured globally using the Medical Outcomes Study 12-item Short Form (SF-12),
      • Ware J.E.
      • Kosinski M.
      • Keller S.D.
      SF-12: how to score the SF-12 physical and mental health summary scales.
      which provided two weighted summary scores – Mental Health Component Summary (MCS) score for mental health and functional status and Physical Health Component Summary (PCS) score for physical health and functional status. Higher scores on the PCS and MCS indicate better health status and quality of life. Respondents were classified as having worse quality of life by being in the lowest tertile values of SF-12 PCS and MCS scores.
      The respondent's performance on self-management tasks was assessed in relation to smoking and medications. Respondents were classified on their smoking behaviour as never smoking, stopped smoking and currently smoking.

       Statistical analysis

      The prevalence of depression, risk factors and outcomes of respondents with and without COPD were compared by using analysis of variance or chi-squared test, as appropriate. Multivariate binary or multinomial logistic regression analysis was used to estimate odds ratios (ORs) of association, controlling for confounders such as socio-demographic, psychosocial, co-morbidity, mood-altering medications, health and functional status. This was also performed in the subgroup of respondents with COPD to estimate the ORs of association of depression with outcome variables such as dyspnoea, BADL disability and poor or fair self-reported health, and lowest tertiles of SF-12 PCS and MCS scores. Statistical analyses were performed using SPSS statistical software version 14.0 (SPSS Inc, Chicago Il). All reported statistical tests were two-sided. A p value of <0.05 was accepted as statistically significant.

      Results

      The majority of the 189 respondents with COPD had mild obstructive airway disease, the remaining 43.9% having moderate to severe obstruction (FEV1% predicted <80%). Dyspnoea was assessed as moderate or severe in 32.8%. Interestingly, only 25% reported that they were either past or current smokers.
      The 189 respondents with COPD were found to have a higher proportion who were depressed (22.8%) compared to the 2213 respondents without COPD (12.4%, p=0.001), Table 1. The crude OR was 2.08 (95% CI 1.44–2.98). The two groups of respondents with and without COPD differed in proportions of risk factors for depression, notably age, housing size, education, widowed/divorced, number of chronic medical conditions, use of potentially depressogenic drugs, IADL and BADL disability and self-reported health status. The OR of association of depression with COPD remained significantly elevated (OR, 1.86; 95% CI, 1.25–2.75) after controlling for these potential confounding variables (Table 2).
      Table 1Prevalence of depression, risk factors and outcomes in respondents with and without chronic obstructive pulmonary disease (COPD).
      COPD (FEV1/FVC<70%)
      No, N=2213Yes, N=189p
      COPD severity
       FEV180% predictedNA56.1
       FEV1<80%, ≥50% predictedNA34.4
       FEV1<50% predictedNA9.5NA
      Moderate to severe dyspnoea6.432.8<001
      BADL disability5.511.6<0.001
      Self-reported health fair or poor31.843.90.001
      SF-12 PCS scores
       Lowest tertile32.044.4
       Middle tertile33.437.6
       Highest tertile34.618.0<0.001
      SF-12 MS scores
       Lowest tertile32.040.7
       Middle tertile35.129.6
       Highest tertile32.929.6.04
      Depressive symptoms (GDS5)12.422.80.001
      Female gender63.264.60.71
      Age, years
       55–6450.537.6
       65–7537.544.4
       ≥7512.018.0<0.001
      Housing size
       1–3 room27.340.7
       4–5 room42.740.2
       Private apartments and landed housing30.019.1<0.001
      Education: <6 years50.870.9<0.001
      Widowed, Divorced. Separated18.824.90.042
      Lived alone7.65.80.36
      No confidante5.03.70.44
      Infrequent visits or telephone calls14.714.30.88
      Daily alcohol drinking1.92.10.80
      Past or current smoking
       <20 cigarettes daily10.816.9
       ≥20 cigarettes daily4.68.5<0.001
      Medical co-morbidities
      None7.54.2
      1–260.052.9
      3 or more32.542.90.008
      Potentially depressogenic medications35.646.00.004
      NA: Not applicable.
      Figures shown in the table are percentages.
      Table 2Odds ratios of association of depressive symptoms with COPD.
      OR95% CI
      Crude2.081.442.98
      Adjusted for gender, age, housing size, education, being widowed, divorced, separated, living alone, having no confidante, infrequent visits or telephone calls by family or friends, smoking, alcohol, smoking, co-morbidity, potentially depressogenic medications, physical functional disability, poor or fair self-reported health.1.861.252.75
      Among the 189 respondents with COPD (Table 3), those who were depressed (N=43) had significantly greater proportions of individuals who reported poor health and functional status, compared to those who were not depressed (N=146). In multivariate analyses that controlled for COPD severity, gender, age, housing size, education, smoking, co-morbidity, BADL disability and dyspnoea as appropriate, depression was significantly associated with BADL disability (OR=2.89, p=0.049), poor or fair self-reported health (OR=3.35, p=0.004), poor SF-12 PCS scores (OR=2.35, p=0.041) and poor SF-12 MCS scores (OR=4.17, p<0.001). Depressed patients were more likely to report worse dyspnoea (41.9% versus 30.1%) although the association in multivariate analysis was not statistically significant (p=0.13). Depressed respondents also reported significantly no significant differences in smoking status.
      Table 3Association of depressive symptoms with symptoms burden, functional status and self-rated health in respondents with COPD (N=189).
      Not depressed, N=146 % (N)Depressed, N=43 % (N)pAdjusted OR 95% CIpModel
      Stopped smoking15.1 (22)9.3 (4)1.440.37–5.550.60
      Currently smoking11.6 (17)11.6 (5)0.620.890.24–3.320.871
      Moderate to severe dyspnoea30.1 (44)41.9 (18)0.151.800.85–3.830.132
      BADL disability8.9 (13)20.9 (9)0.0312.891.01–8.380.0493
      Fair or poor self-reported health37.7 (55)65.1 (28)<0.0013.251.46–7.200.0044
      SF-12 PCS lowest tertile39.7 (58)60.5 (26)<0.0012.351.04–5.350.0414
      SF-12 MCS lowest tertile33.6 (49)65.1 (28)<0.0014.171.86–9.380.0014
      1. COPD severity, gender, age, education, marital status, co-morbidity, BADL disability.
      2. Adjusted for COPD severity, gender, age, housing size, smoking, co-morbidity, BADL disability.
      3. Adjusted for COPD severity, gender, age, housing size, smoking, co-morbidity and dyspnoea.
      4. Adjusted for COPD severity, gender, age, education, housing size, smoking, co-morbidity, BADL disability, dyspnoea.
      In multivariate analysis that controlled for other covariates, the variables that were significantly associated with depressive symptoms were increasing airflow obstruction (FEV1 50–<80 and <50% versus ≥80 predicted, OR=1.48, 1.64, p for trend=0.028), younger age (<65 and 65–74 versus ≥75, OR=1.40, 0.88, p for trend=0.003), lower-end housing (OR=1.74, p=0.003), living alone (OR=1.75, p=0.019), no confidante (OR=2.31, p=0.001), poor self-rated health (OR=2.39, p=0.001), moderate to severe dyspnoea (OR=1.53, p=0.034), SF-12 PCS lowest tertile (OR=1.79, p<0.001) and SF-12 MCS lowest tertile (OR=5.21, p<0.001).

      Discussion

      Rigorous systemic reviews indicate that the validity and significance of the primary co-morbid association of depression with COPD is unclear. The evidence from our study strongly suggests a primary relationship between COPD and depression that was independent of confounding factors that are known to increase the risk of depression that included psychosocial factors, smoking and alcohol, multiple co-morbid illnesses, poor physical health and functional disability, and medication use. Also our observation that COPD individuals with depression were more likely to experience disability, worse health status and quality of life and poor adherence to medication further support the validity and significance of the co-morbid association of depression with COPD.
      Our results differ in important respects from previous studies. Previous studies mostly controlled for a limited number of confounding factors such as on age and sex,
      • Yohannes A.M.
      • Roomi J.
      • Baldwin R.C.
      • Connolly M.J.
      Depression in elderly outpatients with disabling chronic obstructive pulmonary disease.
      • McSweeny A.J.
      • Grant I.
      • Heaton R.K.
      • et al.
      Life quality of patients with chronic obstructive pulmonary disease.
      • Engström C.
      • Persson L.
      • Larsson S.
      • et al.
      Functional status and well being in chronic obstructive pulmonary disease with regard to clinical parameters and smoking: a descriptive and comparative study.
      • Gordon G.H.
      • Michiels T.M.
      • Mahutte C.K.
      • Light R.W.
      Effect of desipramine on control of ventilation and depression scores in patients with severe chronic obstructive pulmonary disease.
      • Isoaho R.
      • Keistinen T.
      • Laippala P.
      • Kivela S.L.
      Chronic obstructive pulmonary disease and symptoms related to depression in elderly persons.
      or education and social class.
      • McSweeny A.J.
      • Grant I.
      • Heaton R.K.
      • et al.
      Life quality of patients with chronic obstructive pulmonary disease.
      • Prigatano G.P.
      • Wright E.C.
      • Levin D.
      Quality of life and its predictors in patients with mild hypoxemia and chronic obstructive pulmonary disease.
      Also most COPD patients have multiple co-morbid medical illnesses and use multiple medications, and these are not taken into account in previous studies. Our results showed that the presence of multiple chronic illnesses and the use of medications that reportedly could cause depression were not confounding factors in the observed association with depression.
      Previous studies of the relationship between depression and COPD have involved highly selected groups of COPD patients such as those on oxygen therapy or with acute exacerbations.
      • Coultas D.B.
      • Edwards D.W.
      • Barnett B.
      • Wludyka P.
      Predictors of depressive symptoms in patients with COPD and health impact.
      • McSweeny A.J.
      • Grant I.
      • Heaton R.K.
      • et al.
      Life quality of patients with chronic obstructive pulmonary disease.
      Selection bias from sampling subjects in clinical settings and the narrow range of COPD severity thus limit the generalizability of the results. The present study is based on a large population cohort of community-living older adults and included persons with COPD that reflected a broad spectrum of disease severity.
      The present study thus strongly suggests that the co-morbid association of depression and COPD was related uniquely to disease-specific psychobiological responses, without the mediating effects of non-specific factors such as poor physical health and functional status. We had reported in an earlier study
      • Niti M.
      • Ng T.P.
      • Kua E.H.
      • Ho R.C.
      • Tan C.H.
      Depression and chronic medical illnesses in Asian older adults: the role of subjective health and functional status.
      from the same cohort that self-reports of asthma/COPD, next to gastro-intestinal disorders, stood out among other chronic disorders in being associated with depression. The present study supports our earlier findings, but differs in using spirometric measures that objectively identified a homogeneous group of persons with COPD without asthma.
      The case definition of COPD in this study should be discussed. Our criteria are specific for cases with chronic airflow obstruction and were symptomatic, and consistent with generally accepted clinical definitions of COPD. Spirometric indices using pre- and post-bronchodilatation that is now recommended for excluding reversible airways obstruction due to bronchial asthma were not performed. We excluded a large number (76) of symptomatic respondents with a history of asthma diagnosis and anti-asthma medications. As COPD is more often under-diagnosed and mislabeled as asthma in the elderly, it was thus unlikely they would include many asthma cases. Hence, misclassification errors are small, and not likely to substantially bias the results. As expected, COPD showed strong association with current smoking (OR=2.28, 9% CI 1.41–3.70). We further restricted our case definition of COPD to include only those who were ever smokers (N=48), and observed similarly they had a higher prevalence of depressive symptoms than non-COPD respondents (22.9% versus 13.1%, p=0.048), although because of small numbers, the association was of borderline significance in multivariate analysis.
      It may also be noted that apparently only 25% of cases of COPD in our study were ever smokers. Considering that usually at least two thirds of COPD cases are ever smokers in Western population studies, this may be unexpected, but there are plausible reasons for this. Unreported smoking could partly account for this. The low prevalence of smoking in the general population (14% overall, 27% in men and 2.7% in women in 1998) is well documented in Singapore.
      • Ng T.P.
      • Tan W.C.
      • Niti M.
      Trends and ethnic differences in COPD hospitalisation and mortality in Singapore.
      It is also possible that the effect of smoking in increasing the risk and severity of COPD may be less pronounced in Asian populations. Notwithstanding the undisputed contribution of cigarette smoking, its relative contribution to COPD may be reduced by its low prevalence and the contributions of other environmental and infectious causes in Asian populations. Further research is required.
      There are limitations in the study. The Geriatric Depression Scale which we used as a measure for depression is designed to detect the presence of clinically significant depressive symptoms, but is not tantamount to a diagnosis of clinical depression. Among participants with COPD, the estimation of effects was limited by the small and unbalanced number of depressed and non-depressed subjects. Hence, depressed COPD participants were not significantly more likely to report worse dyspnoea. However, we observed that, in agreement with previous studies,
      • van Manen J.G.
      • Bindels P.J.E.
      • Dekker F.W.
      • Yzermans C.J.
      • van der Zee J.S.
      • Schadé E.
      Risk of depression in patients with chronic obstructive pulmonary disease and its determinants.
      • McSweeny A.J.
      • Grant I.
      • Heaton R.K.
      • et al.
      Life quality of patients with chronic obstructive pulmonary disease.
      • Jones P.W.
      • Quirk F.H.
      • Baveystock C.M.
      • Littlejohns P.
      A self-completed measure of health status for chronic airflow limitation: the St George's respiratory questionnaire.
      • Felker B.
      • Katon W.
      • Hedrick S.C.
      • Rasmussen
      • McKnight J.K.
      • McDonnell M.B.
      • et al.
      The association between depressive symptoms and health status in patients with chronic pulmonary disease.
      • 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.
      depressed COPD individuals, compared to non-depressed, were more likely to experience worse physical impairment and quality of life. Other COPD outcomes such as mortality and health resource use are also relevant but were not studied. Finally, because the cross-sectional design of the study precludes making firm conclusions to be drawn about the temporal relationship, further longitudinal studies are required.
      The relationship between depression and COPD is explained through complex causal mechanisms.
      • Borson S.
      • Claypoole K.
      • McDonald G.J.
      Depression and chronic obstructive pulmonary disease: treatment trials.
      Depression may contribute to the etiology and progression of COPD and addictive smoking may be the common link. Mood disorder in early life is a factor contributing to early smoking and failure to quit, and the latter may persist after the development of COPD in later life. Patients with a history of major depression are more likely to fail in smoking cessation programs, and to fall into major depression if they stop. Respiratory insufficiency in patients with COPD is associated with progressive hypoxia that leads to structural brain disease and impairs the function of critical neurotransmitter systems involved in both cognition and mood, resulting in neurocognitive deficits and day-to-day functional impairment. Physical functional disability in COPD patients itself promotes and perpetuates reactive depression which can also be the cause of much problems with medication adherence.
      Depressive symptoms were present in 23% of our COPD participants. The correlates and risk factors of depressive symptoms in COPD subjects share much of the same psychosocial etiology as depression in general, but significantly include increased airflow obstruction and physical health and functional impairment. Our results emphasize the importance of identifying depression which is often under-recognized and under-treated in patients with COPD. Healthcare interventions should aim to improve physician and patient recognition and treatment of depression. Behavioural approaches to prevent, delay and treat patients with COPD to improve patient outcomes merit closer attention.

      Conclusion

      Depressive symptoms were associated with COPD independent of known risk factors. In individuals with COPD, depressive symptoms were associated with worse daily functioning abilities, including medication adherence, and health status and quality of life. Because depression is often under-recognized, our findings underscore the importance of treating depression to improve physical functioning and quality of life in patients with COPD.

      Acknowledgement

      Funding: The study is supported by a research grant (No. 03/1/21/17/214) from the Biomedical Research Council, Agency for Science, Technology and Research (ASTAR).

      Conflict of interest statement

      The authors declare no financial and personal relationships with other people or organisations that could inappropriately influence their work.

      References

        • Murray C.J.
        • Lopez A.D.
        Global mortality, disability, and the contribution of risk factors: global burden of disease study.
        Lancet. 1997; 349 ([PubMed -42]): 1436
        • Jemal A.
        • Ward E.
        • Hao Y.
        • Thun M.
        Trends in the leading causes of death in the United States, 1970-2002.
        JAMA. 2005 Sep 14; 294: 1255-1259
        • Coultas D.B.
        • Edwards D.W.
        • Barnett B.
        • Wludyka P.
        Predictors of depressive symptoms in patients with COPD and health impact.
        COPD. 2007 Mar; 4: 23-28
        • Schane R.E.
        • Woodruff P.G.
        • Dinno A.
        • Covinsky K.E.
        • Walter L.C.
        Prevalence and risk factors for depressive symptoms in persons with chronic obstructive pulmonary disease.
        J Gen Intern Med. 2008 Nov; 23 ([Epub 2008 Aug 9]): 1757-1762
        • Ng T.P.
        • Niti M.
        • Tan W.C.
        • Cao Z.
        • Ong K.C.
        • Eng P.
        Depressive symptoms and chronic obstructive pulmonary disease: effect on mortality, hospital readmission, symptom burden, functional status, and quality of life.
        Arch Intern Med. 2007 Jan 8; 167: 60-67
        • van Manen J.G.
        • Bindels P.J.E.
        • Dekker F.W.
        • Yzermans C.J.
        • van der Zee J.S.
        • Schadé E.
        Risk of depression in patients with chronic obstructive pulmonary disease and its determinants.
        Thorax. 2002; 57: 412-416
        • Yohannes A.M.
        • Roomi J.
        • Baldwin R.C.
        • Connolly M.J.
        Depression in elderly outpatients with disabling chronic obstructive pulmonary disease.
        Age Ageing. 1998; 27: 155-160
        • van Ede L.
        • Yzermans C.J.
        • Brouwer H.J.
        Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.
        Thorax. 1999 Aug; 54: 688-692
        • Stewart A.L.
        • Greenfield S.
        • Hays R.D.
        • Wells K.
        • Rogers W.H.
        • Berry S.D.
        • et al.
        Functional status and well being of patients with chronic conditions: results from the medical outcomes study.
        JAMA. 1989; 262: 207-213
        • Katon W.
        • Sullivan M.D.
        Depression and chronic medical illness.
        J Clin Psychiatry. 1990; 51: 3-11
        • Wells K.B.
        • Rogers W.
        • Burnam M.A.
        • Camp P.
        Course of depression in patients with hypertension, myocardial infarction or insulin-dependent diabetes.
        Am J Psychiatry. 1993; 150 ([PubMed]): 632-638
        • Fraser-Smith F.
        • Lesperance F.
        • Talagic M.
        Depression and 18-month prognosis after myocardial infarction.
        Circulation. 1995; 91 ([PubMed]): 999-1005
        • Ciechanowski P.S.
        • Katon W.J.
        • Russo J.E.
        Depression and diabetes: impact of depressive symptoms on adherence, function, and costs.
        Arch Intern Med. 2000; 160 ([PubMed]): 3278-3285
        • Niti M.
        • Ng T.P.
        • Kua E.H.
        • Ho R.C.
        • Tan C.H.
        Depression and chronic medical illnesses in Asian older adults: the role of subjective health and functional status.
        Int J Geriatr Psychiatry. 2007; 22: 1087-1094
      1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Executive summary. NHLBI/WHO workshop report; 2001.

        • Yesavage J.A.
        • Brink T.L.
        Development and validation of a geriatric depression screening scale. A preliminary report.
        J Psychiatr Res. 1983; 17: 37-49
        • Seikh J.I.
        • Yesavage J.A.
        Geriatric depression scale (GDS): recent evidence and development of a shorter version.
        Clin Gerontol. 1986; 6: 165-173
        • Lim P.P.
        • Ng L.L.
        • Chiam P.C.
        • Ong P.S.
        • Ngui F.T.
        • Sahadevan S.
        Validation and comparison of three brief depression scales in an elderly Chinese population.
        Int J Geriatr Psychiatry. 2000; 15: 824-830
        • Patten S.B.
        • Barbui C.
        Drug-induced depression: a systematic review to inform clinical practice.
        Psychother Psychosom. 2004; 73: 207-215
        • Warley A.R.
        • Finnegan O.C.
        • Nicholson E.M.
        • Laszlo G.
        Grading of dyspnoea and walking speed in cardiac disease and in chronic airflow obstruction.
        Br J Dis Chest. 1987 Oct; 81: 349-355
        • Mahoney F.I.
        • Barthel D.W.
        Functional evaluation: the Barthel index.
        Md State Med J. 1965; 14: 61-65
        • Ware J.E.
        • Kosinski M.
        • Keller S.D.
        SF-12: how to score the SF-12 physical and mental health summary scales.
        3rd ed. QualityMetric Inc., Bostom, Mass: The Health Assessment Lab, Lincoln, Rhode Island1998
        • McSweeny A.J.
        • Grant I.
        • Heaton R.K.
        • et al.
        Life quality of patients with chronic obstructive pulmonary disease.
        Arch Intern Med. 1982; 142: 473-478
        • Engström C.
        • Persson L.
        • Larsson S.
        • et al.
        Functional status and well being in chronic obstructive pulmonary disease with regard to clinical parameters and smoking: a descriptive and comparative study.
        Thorax. 1996; 51: 825-830
        • Gordon G.H.
        • Michiels T.M.
        • Mahutte C.K.
        • Light R.W.
        Effect of desipramine on control of ventilation and depression scores in patients with severe chronic obstructive pulmonary disease.
        Psychiatry Res. 1985; 15: 25-32
        • Isoaho R.
        • Keistinen T.
        • Laippala P.
        • Kivela S.L.
        Chronic obstructive pulmonary disease and symptoms related to depression in elderly persons.
        Psychol Rep. 1995; 76: 287-297
        • Prigatano G.P.
        • Wright E.C.
        • 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
        • Ng T.P.
        • Tan W.C.
        • Niti M.
        Trends and ethnic differences in COPD hospitalisation and mortality in Singapore.
        COPD. 2004; 1: 5-11
        • Jones P.W.
        • Quirk F.H.
        • Baveystock C.M.
        • Littlejohns P.
        A self-completed measure of health status for chronic airflow limitation: the St George's respiratory questionnaire.
        Am Rev Respir Dis. 1992; 145: 1321-1327
        • Felker B.
        • Katon W.
        • Hedrick S.C.
        • Rasmussen
        • McKnight J.K.
        • McDonnell M.B.
        • et al.
        The association between depressive symptoms and health status in patients with chronic pulmonary disease.
        General Hospital Psychiatry. 2001; 23: 56-61
        • 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 Jan; 100: 87-93
        • Borson S.
        • Claypoole K.
        • McDonald G.J.
        Depression and chronic obstructive pulmonary disease: treatment trials.
        Semin Clin Neuropsychiatry. 1998 Apr; 3: 115-130