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Anxiety and depression in COPD patients: The roles of gender and disease severity

Open ArchivePublished:March 15, 2006DOI:https://doi.org/10.1016/j.rmed.2006.01.026

      Summary

      Background

      The aim of our study was to assess the prevalence of anxiety and depression in the whole chronic obstructive pulmonary disease (COPD) population and in subgroups according to sex and severity classification. A secondary objective was to evaluate the possible differences between patients with and without a significant high level of anxiety, depression, or both, and finally to find out a correlation between psychological aspects, symptoms, functional parameters, and quality of life (QoL).

      Methods

      Two hundred and two COPD patients were enrolled. Their levels of anxiety, depression, dyspnea, and QoL were assessed using specific questionnaires. One hundred and fourteen sex- and age-matched healthy subjects were used as the control population.

      Results

      The prevalences of anxiety and depression were high (28.2% and 18.8%) in COPD even when it was of mild degree, compared to the control group, in which the prevalence of anxiety and depression were 6.1% and 3.5%, respectively. Female patients had higher levels of anxiety and depression and worse symptom-related QoL. Female patients reported a higher level of dyspnea than males for the same level of ventilatory impairment. Dyspnea was more strongly correlated with depression in women than in men.

      Conclusions

      Anxiety and depressive symptoms are common in patients affected by COPD, even when their disease is mild in terms of FEV1 and respiratory symptoms. Female patients appear to be more exposed to psychological impairment, which correlates well with some specific symptomatic aspects of the disease, such as dyspnea. Psychological aspects need to be carefully assessed in COPD patients, particularly in females.

      Keywords

      Introduction

      Psychological issues, particularly anxiety and depression, have received growing attention and should not be overlooked when assessing patients’ quality of life (QoL),
      • McCathie H.C.
      • Spence S.H.
      • Tate R.L.
      Adjustment to chronic obstructive pulmonary disease: the importance of psychological factors.
      • Prigatano G.P.
      • Wright E.C.
      • Levin D.
      Quality of life and its predictors in patients with mild hypoxemia and chronic obstructive pulmonary disease.
      which is an important target in the clinical management of a chronic irreversible disease, such as chronic obstructive pulmonary disease (COPD).
      • van Ede L.
      • Yzermans C.J.
      • Brouwer H.J.
      Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.
      To maximize QoL in patients with COPD, psychological factors need to be carefully assessed and addressed.
      • McCathie H.C.
      • Spence S.H.
      • Tate R.L.
      Adjustment to chronic obstructive pulmonary disease: the importance of psychological factors.
      An association between COPD and depression has been proposed but definitive data supporting such a theory have previously not been provided due to the limited number of studies, mainly on stable outpatients also with mild to moderate disease.
      • van Ede L.
      • Yzermans C.J.
      • Brouwer H.J.
      Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.
      • van Manen J.G.
      • Bindels P.J.
      • Dekker F.W.
      • et al.
      Risk of depression in patients with chronic obstructive pulmonary disease and its determinants.
      Some studies evaluated the mood profile of COPD patients, but limited observation either to elderly or hypoxemic patients or they evaluated depression but not anxiety.
      • Prigatano G.P.
      • Wright E.C.
      • Levin D.
      Quality of life and its predictors in patients with mild hypoxemia and chronic obstructive pulmonary disease.
      • van Manen J.G.
      • Bindels P.J.
      • Dekker F.W.
      • et al.
      Risk of depression in patients with chronic obstructive pulmonary disease and its determinants.
      • Antonelli-Incalzi R.A.
      • Bellia V.
      • Catalano F.
      • et al.
      Evaluation of health outcomes in elderly patients with asthma and COPD using disease-specific and generic instruments: the Salute Respiratoria nell’Anziano (Sa.R.A.) Study.
      • Crockett A.J.
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      • Moss J.R.
      • et al.
      The impact of anxiety, depression and living alone in chronic obstructive pulmonary disease.
      • McSweeny A.J.
      • Grant I.
      • Heaton R.K.
      • et al.
      Life quality of patients with chronic obstructive pulmonary disease.
      A recent paper which investigated the level of psychological distress in a heterogeneous group of patients with COPD found that patients with COPD experienced significantly more psychological distress than the general population and significantly less than psychiatric outpatients.
      • Wagena E.J.
      • Arrindell W.A.
      • Wouters E.F.
      • et al.
      Are patients with COPD psychologically distressed?.
      The importance of psychological support as a significant part of successful rehabilitation has increasingly been emphasized.
      • Celli B.R.
      Pulmonary rehabilitation in patients with COPD.
      Many studies have attempted to demonstrate the effects of drugs and psychotherapy on anxiety, depression, and finally physical functioning in COPD, but no definitive data are available.
      • Kunik M.E.
      • Braun U.
      • Stanley M.A.
      • et al.
      One session cognitive behavioural therapy for elderly patients with chronic obstructive pulmonary disease.
      • Yohannes A.M.
      • Connolly M.J.
      • Baldwin R.C.
      A feasibility study of antidepressant drug therapy in depressed elderly patients with chronic obstructive pulmonary disease.
      One study demonstrated the association between low compliance for inhalatory treatment and depression.
      • Bosley C.M.
      • Fosbury J.A.
      • Cochrane G.M.
      The psychological factors associated with poor compliance with treatment in asthma.
      A surprisingly high prevalence of anxiety and depression was reported in one study on patients with chronic breathing disorders, included COPD.
      • Kunik M.E.
      • Roundy K.
      • Veazey C.
      • et al.
      Surprisingly high prevalence of anxiety and depression in chronic breathing disorders.
      However, the patients, all veterans, were pre-screened by telephone and patients lacking any indication of anxiety or depression were not eligible for the study, which would presumably result in the selection of a population with elevated anxiety and depression.
      • Kunik M.E.
      • Roundy K.
      • Veazey C.
      • et al.
      Surprisingly high prevalence of anxiety and depression in chronic breathing disorders.
      The aim of our study was to assess the prevalence of anxiety and depression both in the whole COPD population and in subgroups according to sex and severity classification. A secondary objective was to evaluate the possible differences between patients with and without a significant high level of anxiety, depression, or both, and finally to find out a correlation between psychological aspects, symptoms, functional parameters, and QoL.

      Material and methods

      Study design and population

      In order to be included in the study, patients had to present a well-established diagnosis of COPD according to the American Thoracic Society criteria.
      American Thoracic Society
      Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease.
      Patients treated with long-term oxygen therapy or with a chronic severe disabling non-pulmonary disease that would confound results (e.g. insulin-dependent diabetes, symptomatic cancer, chronic psychiatric illness, or dementia) were excluded. Two hundred and ninety-five consecutive patients attending our Respiratory Unit were screened, 93 met exclusion criteria and the remaining 202 were enrolled (155 males, mean age±sem 68±1, FEV1 54±1% of predicted values) in this prospective study. The levels of anxiety, depression, dyspnea, and health-related QoL were assessed in all cases using specific questionnaires. Moreover, all patients underwent physiological tests (spirometry by Elite DL, Medgraphics, USA and arterial blood gas analysis by Omni S4, Roche Diagnostics, Basel, Switzerland). COPD patients were grouped in four severity subgroups according to the GOLD classification,
      • Pauwels R.A.
      • Buist A.S.
      • Calverley P.M.
      • et al.
      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.
      based on FEV1 values. One hundred and fourteen sex- and age-matched healthy subjects (80 males, mean±sem age 68±1) were used as a control population. The control subjects were selected from subjects who were undergoing a routine annual check-up in our hospital and had normal spirometric values in the absence of clinically significant chronic diseases. The hospital ethics committee approved the protocol, and all patients and controls gave their written consent.

      Physiological measurements and health-related QoL questionnaires

      The variables in the study were as follows:
      Anxiety: The Italian version of the State Trait Anxiety Inventory (STAI) questionnaire contains 20 items equally divided between positive and negative statements regarding anxiety.
      • Spielberger C.D.
      • Gorsuch R.L.
      • Lushene R.E.
      Manual for the state-trait anxiety.
      • Macor A.
      • Pedrabissi L.
      • Santinello M.
      Ansia di stato e di tratto: ulteriore contributo alla verifica della validità psicometrica e teorica dello S.T.A.I. forma Y di Spielberger.
      The range of possible scores varies from a minimum of 20 to a maximum of 80, the higher the score the higher the level of anxiety. A cut-off value of 45 has been used to dichotomize patients into low- and high-anxiety groups.
      • Millar K.
      • Jelicic M.
      • Bonke B.
      • et al.
      Assessment of preoperative anxiety: comparison of measures in patients awaiting surgery for breast cancer.
      The STAI questionnaire was used to evaluate traits of anxiety among healthy, adult subjects, psychiatric patients, and patients suffering from chronic heart failure, asthma, and COPD.
      • McCathie H.C.
      • Spence S.H.
      • Tate R.L.
      Adjustment to chronic obstructive pulmonary disease: the importance of psychological factors.
      • Centanni S.
      • Di Marco F.
      • Castagna F.
      • et al.
      Psychological issues in the treatment of asthmatic patients.
      A high score is associated with higher-anxiety level. Studies carried out on patients with anxiety disorders confirmed the questionnaire's reliability in accurately measuring anxiety level in comparison with the Diagnostic and Statistical Manual of Mental Disorders (DSM) standard.
      • Kvaal K.
      • Ulstein I.
      • Nordhus I.H.
      • et al.
      The Spielberger state-trait anxiety inventory (STAI): the state scale in detecting mental disorders in geriatric patients.
      • Okun A.
      • Stein R.E.
      • Bauman L.J.
      • et al.
      Content validity of the psychiatric symptom index, CES-depression scale, and State-Trait anxiety inventory from the perspective of DSM-IV.
      Depression: The Zung
      • Zung W.W.
      A self-rating depression scale.
      self-rated depression scale (SDS, Italian version) is a questionnaire that presents 20 items with negative and positive contents and evaluates depressive state.

      Conti L. Repertorio delle scale di valutazione in psichiatria. SEE Editrice- Firenze, 2002.

      Possible scores range from 20 to 80: the higher the score, the higher the level of depression. This instrument is of particular relevance in that it has been widely used in normal persons as well as in various patient groups, including patients suffering from chronic respiratory diseases, making considerable validation data available as well as a large number of comparison groups to aid in the interpretation of the results.
      • Centanni S.
      • Di Marco F.
      • Castagna F.
      • et al.
      Psychological issues in the treatment of asthmatic patients.
      • Akashiba T.
      • Kawahara S.
      • Akahoshi T.
      • et al.
      Relationship between quality of life and mood or depression in patients with severe obstructive sleep apnea syndrome.
      • Agrell B.
      • Dehlin O.
      Comparison of six depression rating scales in geriatric stroke patients.
      A cut-off of 50 has been demonstrated to be sensitive in distinguishing patients with and without depression.
      • van Ede L.
      • Yzermans C.J.
      • Brouwer H.J.
      Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.
      • Agrell B.
      • Dehlin O.
      Comparison of six depression rating scales in geriatric stroke patients.
      A study demonstrated that, using the criteria of the DSM as a standard, the SDS questionnaire has a sensitivity of 97% and a specificity of 63%.
      • Zung W.W.
      • Magruder-Habib K.
      • Velez R.
      • et al.
      The comorbidity of anxiety and depression in general medical patients: a longitudinal study.
      QoL: The Italian version of St. George's Respiratory Questionnaire (SGRQ) comprises 50 items and 76 weighted responses divided into three subscales: symptoms, activity, and impact. Scores range from 0% to 100%, with 0 being the best possible score and 100% the worst.
      • Carone M.
      • Bertolotti G.
      • Anchisi F.
      • et al.
      The St. George's Respiratory Questionnaire (SGRQ): Italian version.
      Dyspnea: The Italian version of the modified Medical Resource Council (MRC) dyspnea scale consists of five statements about perceived breathlessness: from grade 1 (I only get breathless with strenuous exercise) up to grade 5 (I’m too breathless to leave the house).
      • Brooks S.
      Surveillance for respiratory hazards.

      Statistical analysis

      Analysis was carried out using the Statistical Package for Social Sciences (SPSS, Chicago, USA). The results are shown as mean±sem unless otherwise stated. Quantitative variables were analysed using analysis of variance (ANOVA) and, if positive, post hoc comparisons were carried out by t-test with Bonferroni adjustment. For qualitative variables, either a χ2 or a Fischer exact test was used. The relationships between variables were evaluated using Pearson product moment correlation coefficients. As there were multiple comparisons, Bonferroni adjustment was used. Stepwise multiple regression was used to identify the factors that were most strongly related to QoL (SGRQ total score) and to both anxiety and depression. All variables with a P-value of <0.05 were entered into the regression model according to stepwise approach, while all variables with a P-value of >0.10 were removed. In order to avoid contamination, the three separate SGRQ subscales (impact, activity, and symptoms) were excluded from the regression analysis regarding SGRQ total score. A P-value <0.05 was the criterion for statistical significance.

      Results

      Baseline characteristics of the COPD patients and control subjects are shown in Table 1. The number of subjects with a significant, high score for depression and anxiety yielded prevalences in the COPD group of 18.8% and 28.2%, respectively, while in the control group the prevalences were 3.5% and 6.1% for depression and anxiety, respectively. The differences in prevalence of both anxiety and depression between the COPD and control groups were statistically significant (P<0.001).
      Table 1Variables studied in COPD and control groups (whole population, males, and females).
      CharacteristicsAllMalesFemalesP-value
      COPD patients
      No. participants20215547
      Age (year)68±168±170±10.135
      BMI (kg/m2)26.3±0.326.4±0.226.0±0.50.381
      Disease duration (year)9±19±18±10.808
      FEV1 (%)54±153±257±20.213
      IC (%)64±163±±162±20.743
      PaO2 (mmHg)74±273±276±20.159
      Anxiety (STAI score)39.4±0.638.5±0.741.9±1.40.024
      Anxiety prevalence (%)28.225.238.30.080
      Depression (SDS score)41.1±0.639.9±0.745.2±1.4<0.001
      Depression prevalence (%)18.812.938.3<0.001
      Prevalence of both anxiety and depression (%)10.96.525.5<0.001
      QoL (SGRQ total)45.1±1.745.3±1.944.2±3.40.781
      QoL (SGRQ symptoms)57.3±1.855.3±2.164.0±±3.80.047
      QoL (SGRQ activity)33.5±1.532.5±1.836.9±3.00.216
      QoL (SGRQ impact)42.7±1.541.8±1.745.7±2.90.272
      Dyspnea (MRC score)1.9±0.11.7±0.12.4±0.20.003
      Healthy subjects
      No. participants1148034
      Age (year)65±166±164±20.299
      Anxiety (STAI score)34.3±0.532.9±0.637.6±0.9<0.001
      Anxiety prevalence (%)6.13.811.80.103
      Depression (SDS score)32.5±0.730.9±0.836.3±1.60.001
      Depression prevalence (%)3.51.38.80.044
      Prevalence of both anxiety and depression (%)000
      P-value, male vs. female comparison. BMI, body-mass index; IC, inspiratory capacity; QoL, quality of life.
      The distribution of studied variables according to sex in the control group and in COPD patients (Table 1) revealed that women had a higher level of anxiety and depression and, in the COPD group only, a more severe degree of dyspnea and a worse symptom-related QoL. In light of this result, we analysed the correlation between dyspnea and depression in male and female patients; the correlation was stronger in the female group (r=0.541, P<0.001 for females and r=0.211, P<0.05 for males).
      The distribution of the studied variables according to disease severity is shown in Table 2. ANOVA found significant differences in terms of IC and QoL (total score and subgroups) with a worse ventilatory pattern and QoL in patients with more severe disease. No significant differences in anxiety or depression were found.
      Table 2Characteristics of COPD patients according to the GOLD
      • Pauwels R.A.
      • Buist A.S.
      • Calverley P.M.
      • et al.
      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.
      severity classification.
      Disease severityMildModerateSevereVery severeP-value
      FEV1⩾80%⩾50 FEV1<80⩾30 FEV1<50%FEV1<30%
      No. participants27875929
      Age (year)66±268±169±169±20.274
      No. male/female gender21/665/2248/1121/80.338
      BMI (kg/m2)25.9±0.526.4±0.326.8±0.625.4±0.50.291
      Disease duration (year)6±110±18±110±20.338
      IC (%)83±170±249±254±3<0.001
      PaO2 (mmHg)80±272±275±270±20.068
      Anxiety score (STAI)36.1±1.939.2±1.040.3±1.141.4±1.30.148
      Anxiety prevalence (%)18.533.322.034.50.256
      Depression score (SDS)40.2±1.640.2±1.142.1±1.142.7±1.10.428
      Depression prevalence (%)14.818.423.713.80.636
      Prevalence of both anxiety and depression (%)7.413.811.910.90.423
      QoL (SGRQ total)32.3±3.345.2±2.846.6±2.953.5±1.70.008
      QoL (SGRQ symptoms)44.01±5.050.3±2.965.0±2.974.9±3.4<0.001
      QoL (SGRQ activity)16.9±1.931.0±2.439.5±2.744.4±3.3<0.001
      QoL (SGRQ impact)27.6±2.639.1±2.348.6±2.555.7±3.2<0.001
      Dyspnea (MRC score)1.82±0.351.70±0.201.92±0.132.30±0.320.387
      BMI, body-mass index; IC, inspiratory capacity; QoL, quality of life. P-values are related to ANOVA for continuous variables and to χ2 test for qualitative variables. Significant post hoc differences between FEV1 stages were as follows. IC: all comparisons but not III–IV; SGRQ total score: I–IV; SGRQ symptoms: I–III, I–IV, II–III, II–IV; SGRQ activity: all comparisons but not II–III, III–IV; SGRQ impact: all comparisons but not III–IV.
      To evaluate the possible differences between patients with or without significant anxiety and depression levels, we analysed the distribution of all variables in the two groups (Table 3). Patients with a significant, high level of anxiety showed a higher level of depression and a worse QoL, while patients with a significant, high level of depression showed a worse QoL and a higher level of dyspnea. There were more depressive female patients than males (P<0.001). To evaluate the effect of the contemporary presence of significant high depression and anxiety levels on the studied variables, we compared the results of 22 patients (10.9% of the total COPD sample) with depression and anxiety scores higher than 50 and 45, respectively, with all other patients. Patients with a contemporary significant high score for depression and anxiety were more frequently females (P<0.001) and had worse QoL (SGRQ total score and three subgroups) (P<0.001); on the other hand, no statistically significant differences in lung function, dyspnea, and other demographic characteristics were detected.
      Table 3Differences between patients with or without significant high anxiety (STAI) or depression (SDS) score.
      CharacteristicsAnxiety (STAI score)Depression (SDS score)
      ⩾45<44P-value⩾50<50P-value
      No. participants5714538164
      No. male/female gender39/18116/290.08020/18135/29<0.001
      Age (year)67±169±10.40269±168±10.446
      BMI (kg/m2)26.5±0.326.2±0.30.52126.7±0.426.1±0.30.359
      Disease duration (year)9.8±1.58.2±0.60.47410.6±2.08.15±0.60.105
      FEV1 (% predicted)54±254±20.95454±354±10.799
      IC (% predicted)62±263±10.16259±364±10.146
      PaO2 (mmHg)72±275±20.33672±275±20.483
      Anxiety (STAI score)51.1±0.734.6±0.5<0.00146.6±1.737.6±0.6<0.001
      Depression (SDS score)48.0±1.038.4±0.7<0.00155.2±0.637.8±0.5<0.001
      QoL (SGRQ total)59.6±2.639.3±1.9<0.00156.4±3.442.4±1.80.001
      QoL (SGRQ symptoms)69.1±2.852.7±2.2<0.00170.4±4.054.3±2.00.001
      QoL (SGRQ activity)46.7±2.828.3±1.6<0.00150.4±3.429.6±1.6<0.001
      QoL (SGRQ impact)55.9±2.437.6±1.6<0.00157.4±3.139.3±1.6<0.001
      Dyspnea (MRC score)2.0±0.21.8±0.10.3192.6±0.31.7±0.1<0.001
      P-values, higher vs. lower anxiety and depression score. BMI, body-mass index; IC, inspiratory capacity; QoL, quality of life.
      Pearson correlations for all the variables evaluated in all COPD patients are given in Table 4. The patients’ psychological patterns were correlated with QoL and depression, but anxiety was not correlated with dyspnea. Both FEV1 and IC were significantly correlated with QoL, with a higher correlation for FEV1, except for the QoL symptoms subgroup. IC but not FEV1 was significantly correlated with dyspnea, and poorly correlated with both with anxiety and depression. Stepwise multiple regression analysis was used to identify variables that could best predict QoL, anxiety, and depression. The anxiety, depression scores, and the FEV1 value accounted for 20.9% of the variance in total score for the SGRQ; anxiety, QoL (symptoms subscale), dyspnea, and sex accounted for 43.0% of the score for depression, while depression and QoL (total score and activity subscale) accounted for 36.1% of the score for anxiety.
      Table 4Pearson correlations between variables.
      AnxietyDepressionQoL totalQoL symptomsQoL activityQoL impactDyspneaFEV1
      Anxiety0.550**0.612**0.654**0.669**0.676**NSNS
      Depression0.550**0.742**0.648**0.659**0.695**0.364**NS
      QoL total0.612**0.742**0.527**0.621**0.727**0.250*−220**
      QoL symptoms0.654**0.648**0.527**0.783**0.900**0.366**−0.425**
      QoL activity0.669**0.659**0.621**0.783**0.957**0.287**−0.394**
      QoL impact0.676**0.695**0.727**0.900**0.957**0.322**−0.426**
      DyspneaNS0.364**0.250*0.366**0.287**0.322**NS
      FEV1NSNS−0.220**−0.425**−0.394**−0.426**NS
      IC−0.163*−0.194**−0.157*−0.450**−0.352**−0.352**−0.505*−0.705**
      No consideration has been taken of the direction of correlation. NS, not significant; *P<0.05; **P<0.01. IC, inspiratory capacity; QoL, quality of life.

      Discussion

      Our study investigated the prevalence of both anxiety and depression disorders in a large population of male and female COPD outpatients with a wide range of disease severity. As previously stated, a recent study by Kunik et al.
      • Kunik M.E.
      • Roundy K.
      • Veazey C.
      • et al.
      Surprisingly high prevalence of anxiety and depression in chronic breathing disorders.
      investigated the prevalence of anxiety and depression in a large sample of patients with chronic breathing disorders, including COPD, but the authors enrolled only patients who reported a significant level of anxiety and depression in a telephone screening. The significant findings of our study are as follows: (1) the prevalences of anxiety and depression are very high in COPD, even when the disease is of mild or moderate degree; (2) female patients have higher levels of anxiety and depression and worse symptom-related QoL; (3) female patients report a higher level of dyspnea than males for the same level of ventilatory impairment; and (4) dyspnea is more strongly correlated with depression in females than in males.
      We found prevalences of anxiety and depression of 28.2% and 18.8%, respectively, in the COPD patients, which were significantly higher than those in the control group. A study aimed at estimating the prevalence of psychological distress in patients attending a cancer centre in Milan (Italy), found a 16% prevalence of major depressive disorders and generalized anxiety disorders, both evaluated through questionnaires,
      • Bredart A.
      • Didier F.
      • Robertson C.
      • et al.
      Psychological distress in cancer patients attending the European Institute of Oncology in Milan.
      while another study carried out in Scotland, also in lung cancer patients, found a higher prevalence of depression than anxiety (22% and 9%, respectively).
      • Montazeri A.
      • Milroy R.
      • Hole D.
      • et al.
      Anxiety and depression in patients with lung cancer before and after diagnosis: findings from a population in Glasgow, Scotland.
      This comparison stresses the importance of largely undiagnosed psychological factors in COPD, in comparison with neoplastic diseases, which are commonly regarded as severe conditions affecting psychological status. Our results are all the more impressive in light of the exclusion from our study of patients treated with long-term oxygen therapy, who are susceptible to greater psychological impairment than patients treated with standard medical therapy.
      The usefulness of evaluating the psychological status of patients with mild or moderate COPD is underlined by the comparison of the prevalences of anxiety and depression in patients with different levels of disease severity, even if a trend of anxiety and depression worsening emerged between patients with a more severe bronchial obstruction (Table 2). In fact, our study shows a stable, high prevalence of both anxiety and depression in all four stages of disease severity, with no significant difference between patients affected by mild and very severe disease. This result appears more relevant because of the clinically significant difference in QoL between mild vs. moderate and severe vs. very severe patients (SGRQ total score higher than 4 units).
      • Jones P.W.
      • Quirk F.H.
      • Baveystock C.M.
      • et al.
      A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire.
      In a review of the literature on the prevalence of depression in COPD patients, van Ede et al.
      • van Ede L.
      • Yzermans C.J.
      • Brouwer H.J.
      Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review.
      underlined the lack of studies having adequate sample sizes. Among all the reviewed studies, only one had a sample size of more than 200 patients, and it was limited to hypoxemic patients.
      • McSweeny A.J.
      • Grant I.
      • Heaton R.K.
      • et al.
      Life quality of patients with chronic obstructive pulmonary disease.
      In a study by van Manen et al.
      • van Manen J.G.
      • Bindels P.J.
      • Dekker F.W.
      • et al.
      Risk of depression in patients with chronic obstructive pulmonary disease and its determinants.
      on 162 COPD patients, depression was present in 21.6% of the whole cohort and in 25% of those subjects with an FEV1 of less than 50%. The authors stated that depression might have been more prevalent in their subjects than in others because they included patients with more severe airway obstruction. As previously reported, our results did not confirm this hypothesis, as the prevalence of depression was similar in all four COPD grades.
      We found that patients with a high level of anxiety, depression, or both have a worse QoL; the differences we found were always clinically significant (more than 4 units in SGRQ score—Table 3). Particularly significant is the correlation between depression and QoL, which is consistent with the results of Bosley et al.,
      • Bosley C.M.
      • Corden Z.M.
      • Rees P.J.
      • et al.
      Psychological factors associated with use of home nebulized therapy for COPD.
      who found that patients who report poor QoL are more likely to be depressed, feel unsupported by clinic staff, and be poorly adherent to treatment. A literature review on the prevalence of anxiety in COPD patients reported rates of anxiety ranging from 10% to 40%.
      • Brenes G.A.
      Anxiety and chronic obstructive pulmonary disease: prevalence, impact, and treatment.
      In our study, anxiety was significantly correlated with QoL but, unlike depression, not correlated with dyspnea.
      As emerged from a recent review, COPD in women is an understudied subject but is gaining attention as a significant public health threat.
      • Varkey A.B.
      Chronic obstructive pulmonary disease in women: exploring gender differences.
      In our study, the analysis of variable distribution according to sex revealed, among women, higher levels of depression, anxiety, dyspnea, and worse symptom-related QoL, without significant differences in lung function. A previous study of ours also found a higher prevalence of depression in female patients with chronic respiratory diseases.
      • Centanni S.
      • Di Marco F.
      • Castagna F.
      • et al.
      Psychological issues in the treatment of asthmatic patients.
      Antonelli-Incalzi et al.
      • Antonelli-Incalzi R.
      • Imperiale C.
      • Bellia V.
      • et al.
      Do GOLD stages of COPD severity really correspond to differences in health status?.
      stressed the greater susceptibility of females to the negative effects of COPD on health status (SGRQ total and impact scores), but no analysis of the influence of sex on depression has been carried out. A partial confirmation of this aspect could be the stronger association between depression and dyspnea in females than in males. A possible physiological explanation is suggested by the study of Weiner et al.,
      • Weiner P.
      • Magadle R.
      • Massarwa F.
      • et al.
      Influence of gender and inspiratory muscle training on the perception of dyspnea in patients with asthma.
      who showed that perception of dyspnea in asthmatic women was significantly higher than in men who had significantly higher maximal inspiratory pressure; interestingly, the difference in perception of dyspnea disappeared after inspiratory muscle training in women aimed at allowing them to reach the same level of muscle strength as asthmatic men.
      • Weiner P.
      • Magadle R.
      • Massarwa F.
      • et al.
      Influence of gender and inspiratory muscle training on the perception of dyspnea in patients with asthma.
      An interesting study by Yohannes et al.
      • Yohannes A.M.
      • Connolly M.J.
      • Baldwin R.C.
      A feasibility study of antidepressant drug therapy in depressed elderly patients with chronic obstructive pulmonary disease.
      in elderly, depressed patients with COPD found a low acceptance of antidepressant treatment with fluoxetine by the patients, and the authors concluded that offering antidepressants to COPD patients is not an effective strategy. In contrast, an approach based on cognitive behavioural therapy, carried out in a study on 56 patients, was able to reduce anxious and depressive symptoms.
      • Kunik M.E.
      • Roundy K.
      • Veazey C.
      • et al.
      Surprisingly high prevalence of anxiety and depression in chronic breathing disorders.
      We should mention some of the limitations of the present study. First, the use of a fixed cut-off to distinguish patients with or without anxiety and depression can be questioned. However, this a common limit of all questionnaires in which the cut-off with the best sensitivity and specificity is usually chosen. A study that used the STAI questionnaire in elderly patients found a cut-off higher than 45.
      • Kvaal K.
      • Ulstein I.
      • Nordhus I.H.
      • et al.
      The Spielberger state-trait anxiety inventory (STAI): the state scale in detecting mental disorders in geriatric patients.
      Another study
      • Bertolotti G.
      • Zotti A.M.
      • Michielin P.
      • et al.
      A computerized approach to cognitive behavioural assessment: an introduction to CBA-2.0 primary scales.
      found in general population a higher level of STAI score in females than in males, suggesting that a different cut-off score should be used according to gender. We performed a new analysis using a cut-off of 50 for females and of 45 for males. The prevalence of anxiety in females was 31.9%, with a prevalence in all COPD population of 26.7%. The 95th percentile of the STAI score in our control group was 48 in females and 44 in males, suggesting that a cut-off level between 45 and 50 should be used for females. Second, each questionnaire evaluates specific anxiety or depression symptoms factors.
      • Shafer A.B.
      Meta-analysis of the factor structures of four depression questionnaires: Beck, CES-D, Hamilton, and Zung.
      Therefore, the choice of the questionnaires can influence the results of the study. We chose the SDS and STAI questionnaires because they showed a good sensitivity and specificity.
      • Kvaal K.
      • Ulstein I.
      • Nordhus I.H.
      • et al.
      The Spielberger state-trait anxiety inventory (STAI): the state scale in detecting mental disorders in geriatric patients.
      • Okun A.
      • Stein R.E.
      • Bauman L.J.
      • et al.
      Content validity of the psychiatric symptom index, CES-depression scale, and State-Trait anxiety inventory from the perspective of DSM-IV.
      • Zung W.W.
      • Magruder-Habib K.
      • Velez R.
      • et al.
      The comorbidity of anxiety and depression in general medical patients: a longitudinal study.
      Third we evaluated anxiety and depression through questionnaires and not through a structured interview, due to the large size of the population evaluated (more than 300 subjects). However, it should be emphasized that STAI and SDS questionnaires have been used for many years, and they are highly sensitive and specific in detecting psychiatric disease as diagnosed by a complex psychiatric evaluation. Finally, as shown in Table 2, the distribution of anxiety and depression level did not reach the statistically significance although a trend emerged; one explanation of this result, which differs from some previous studies,
      • van Manen J.G.
      • Bindels P.J.
      • Dekker F.W.
      • et al.
      Risk of depression in patients with chronic obstructive pulmonary disease and its determinants.
      is the low number of enrolled patients with mild and very severe disease. However, also in a recent paper of Wagena et al.
      • Wagena E.J.
      • Arrindell W.A.
      • Wouters E.F.
      • et al.
      Are patients with COPD psychologically distressed?.
      did not emerge a significant or clinically relevant difference in psychological distress between patients with severe or very severe COPD and patients with mild or moderate COPD.
      In conclusion, anxiety and depressive symptoms are common in patients affected by COPD, even when their disease is mild in terms of FEV1 and respiratory symptoms. Both anxiety and depression correlate with QoL. Female patients appear to be more susceptible to psychological impairment, which correlates with some specific symptomatic aspects of the disease, such as dyspnea. These aspects have higher importance in light of the rising prevalence of COPD in females. Psychological aspects need to be carefully assessed in COPD patients, particularly in females.

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