The value of COPD Assessment Test in Screening Anxiety and Depression in stable COPD patients

doi:10.21203/rs.3.rs-1763790/v1

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Research Article

The value of COPD Assessment Test in Screening Anxiety and Depression in stable COPD patients

https://doi.org/10.21203/rs.3.rs-1763790/v1

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Background

Anxiety and depression are common comorbidities in COPD patients but are often under-diagnosed. We aimed to assess the value of the COPD Assessment Test (CAT) in identifying anxiety and depression from patients with COPD.

Methods

Stable COPD patients were recruited in this cross-sectional observational study between December 2016 and January 2021. The demographic characteristics and the CAT score were recorded. Anxiety was measured using Generalized Anxiety Disorder Questionnaire (GAD)-7. Depression was measured by Patient Health Questionnaire (PHQ)-9. Logistic regression analysis and receiver operating characteristic curve analysis were performed to identify factors associated with anxiety or depression and to calculate the predictive values.

Results

A total of 530 stable COPD patients were enrolled and of those the proportion of anxiety and depression were 17.0% and 21.5%, respectively. The CAT score correlated well with the GAD-7 score (r = 0.339, P < 0.001) and PHQ-9 score (r = 0.435, P < 0.001). The adjusted odds ratios of the CAT for the presence of anxiety and depression were 1.094 (95% CI: 1.057–1.131) and 1.143 (95% CI: 1.104–1.183), respectively. The CAT score demonstrated a good performance in identifying anxiety and depression with area under curves (AUCs) of 0.709 and 0.791, respectively. Among CAT items, analysis further showed that non-respiratory CAT components were superior to respiratory components in identifying both anxiety and depression.

Conclusions

The CAT score might be valuable in screening anxiety and depression in stable COPD patients. However, the screening value should be further evaluated using the diagnostic criteria for anxiety and depression in the future.

Trial registration:

Clinicaltrials.gov (NCT03044847); 07/02/2017.

Chronic obstructive pulmonary disease

COPD Assessment Test

Anxiety

Depression

Chronic obstructive pulmonary disease (COPD) is a high prevalent and complex respiratory disease [1], which often coexists with several comorbidities that may have a significant impact on morbidity and mortality [2]. Anxiety and depression are common comorbidities of COPD. The prevalence of anxiety ranged from 7–50%, and that of depression ranged from 10–57% among stable COPD patients in primary care settings [3]. Patients with anxiety and depression are prone to have a higher risk of exacerbations, hospitalization, rehospitalization, and subsequent mortality [4–8]. Therefore, early identification of anxiety and depression is of great importance.

Previous studies have identified several risk factors for anxiety and depression, including younger age, female sex, lower body mass index, tobacco exposure, and lower socioeconomic status [9–11]. The severity of airflow limitation described by FEV₁%predicted was recognized as a predictor of anxiety and depression in some studies [12, 13], but not in others [7, 9, 10]. Although anxious and depressive symptoms are found more commonly in patients with more severe airflow limitation [14], the relationship between anxiety/depression and FEV₁%predicted is still controversial.

On the other hand, COPD assessment test (CAT) has been recommended for the assessment of COPD impact beyond airflow limitation by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [15]. The CAT contains eight items including respiratory components (cough, phlegm, chest tightness, and breathlessness going up hills/stairs) and non-respiratory components (activity limitation at home, confidence leaving home, sleep, and energy) [16, 17]. Previous studies indicated that the CAT score was associated with anxiety and depression in COPD [18–21], but these studies just included a small sample size and limited confounders. Moreover, the value of CAT in screening anxiety and depression among COPD patients is unclear and which components of the CAT (respiratory components or non-respiratory components) had better abilities to identify anxiety and depression is not investigated.

The aim of this study is to investigate whether the CAT is superior to FEV₁%predicted in identifying anxiety and depression symptoms in COPD. Furthermore, we assessed the total CAT score and CAT components scores for the identification of anxiety and depression.

Study design and population

The Cohort Study for COPD in China (COMFORT study) is an ongoing multicenter prospective observational study to investigate the clinical characteristics of COPD subjects in China. Details of the study design were shown at http://www.chinacopd.com/#/hot (ClinicalTrials.gov ID: NCT03044847). We used baseline data between December 2016 and January 2021 from a single center (Beijing Chao-Yang Hospital) within the COMFORT study. Patients included in this analysis were: 1) 40-75 years old; 2) diagnosed with COPD by persistent respiratory symptoms, risk factors (e.g. cigarette smoking, biomass or occupational exposure) and post-bronchodilator forced expiratory volume in 1s/ forced vital capacity (FEV₁/FVC) less than 0.7 according to GOLD criteria [15]. The exclusion criteria were: 1) patients with acute exacerbation of COPD in the previous three months; 2) patients with other lung diseases such as uncontrolled tuberculosis or bronchiectasis; 3) patients having serious uncontrolled diseases and other confounding diseases. The study protocol was approved by the ethics Committee of Beijing Chao-Yang Hospital (NO.2016-KE-183) and all other participating hospitals in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients.

Data collection

Age, sex, smoking history, education level, annual household income, comorbidities, and the number of exacerbations in the past 12 months were collected based on patient reports. Ever-smokers were defined as current or former smokers with at least 10 pack-years of tobacco exposure. Exacerbations were defined as worsening of respiratory symptoms that result in a change of at least one of these medications (antibiotics, corticosteroid, and bronchodilator) or a visit to the emergency room or hospitalization [15]. Spirometry was performed using a MasterScreen spirometer (VIASYS Healthcare GmbN, Germany) and quality-control checks for the measurement results according to the ATS guideline [22]. COPD severity was categorized according to the GOLD criteria (GOLD 1: FEV₁≥ 80% predicted; GOLD 2: 50% ≤ FEV₁ < 80% predicted; GOLD 3: 30%≤ FEV₁ < 50% predicted; GOLD 4: FEV₁ < 30% predicted). Dyspnea was assessed by the modified Medical Research Council (mMRC) dyspnea scale [23].

Measurement of anxiety and depression

Anxiety was measured using the Generalized Anxiety Disorder Questionnaire (GAD) -7, which is a self-reported questionnaire that proved valid in both general populations and primary care centers [24, 25]. GAD contains seven items about generalized anxiety symptoms in the previous two weeks. GAD-7 scores range from 0 to 21, with scores of 0-4, 5-9, 10-14, and 15-21 were defined as minimal, mild, moderate, and severe anxiety, respectively. The Chinese version of GAD-7 has been well validated in general hospital outpatients [26]. We defined the GAD-7 score of ≥ 5 as clinical anxiety in the present study based on previous reports [27, 28].

Patient Health Questionnaire (PHQ)-9 was used to assess the presence of depression. It comprises nine items based on the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, 4^th edition (DSM-IV) for major depressive disorder in the previous 2 weeks. Each item rated on a 4-point Likert scale from 0 (not at all) to 3 (nearly every day), with a total score of 27. Depression symptoms were categorized into minimal (0–4), mild (5–9), moderate (10–14), moderately severe (15-19), and severe (20–27) [29]. The Chinese version of the PHQ-9 demonstrated applicability in screening depression with good sensitivity and specificity [30]. A PHQ score of ≥ 5 was defined as depression status in this study [29, 31].

COPD assessment test

The CAT is a valid disease-specific questionnaire to evaluate the health status among COPD individuals and is recommended by Chinese national guideline on COPD [17, 32]. It consists of eight items: cough, phlegm, chest tightness, breathlessness going up hills/stairs, activity limitation at home, confidence leaving home, sleep, and energy. Each item ranges from 0 to 5, presenting a total score of 0 to 40. Higher CAT scores indicate more COPD symptoms and poorer control of the disease [33]. The CAT score was classified into 0–10, 11–20, 21–30, and 31–40 for different symptom levels in this study.

Statistical analysis

Continuous variables were described as means and standard deviations (SDs) for normally distributed data, medians and interquartile ranges (IQRs) for non-normally distributed data. Categorical variables were expressed as number and percentage (%). The differences between two groups (anxiety vs. non-anxiety, depression vs. non-depression) were assessed by Student's t-test or Mann-Whitney U test for normally or non-normally distributed data, and Chi-square test or Fisher exact test for categorical variables. Group comparisons between CAT categories or GOLD stages were performed by Pearson’s chi-square test and linear-by-linear association. Due to the non-normally distribution of GAD-7 and PHQ-9 scores, Spearman rank correlation analysis was performed to assess the correlation between two quantitative variables. Univariate and multivariable logistic regression analyses were performed to identify the factors associated with anxiety or depression. Relevant factors that could affect the outcomes were included in the multivariable analyses: age, sex, BMI, smoking status, educated level, annual household income and exacerbation history. Odds ratios (ORs) were calculated with 95% confidence intervals (CIs). The receiver operating characteristic (ROC) curve was performed to analyze the predictive value of the total CAT score, CAT components and FEV₁%predicted for the presence of anxiety or depression. Operating characteristics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and Youden index, were shown for identifying the optimal cutoff value. The comparisons between the AUC of respiratory CAT components, non-respiratory CAT components, and the total CAT score were preformed using a nonparametric approach [34]. SPSS version 23.0 and MedCalc version 20.0 was used for the statistical analyses. P values < 0.05 were considered statistically significant.

Patient characteristics

A total of 530 patients were enrolled in this study with 88.7% were men (Table 1). The mean age was 64.9 ± 7.8 years and 87.7% were ever smokers. The mean FEV₁%predicted was 59.1 ± 21.1%, and the mean CAT score was 13.9 ± 8.2. A total of 250 (47.2%) patients experienced ≥ 1 exacerbations in the previous year. According to the GAD-7 score and PHQ-9 score, 90 patients (17.0%) had anxiety symptoms, while 114 patients (21.5%) had depression symptoms.

Table 1

Demographic and clinical characteristics of the enrolled patients
Characteristics	Data (n = 530)
Age, years (mean, SD)	64.9 ± 7.8
Men (n, %)	470 (88.7)
BMI, kg/m² (mean, SD)	24.5 ± 3.5
Smoking status
Ever smoker (n, %)	465 (87.7)
Pack-years history (median, IQR)	37.8 (18.6–50.0)
Educated level (n, %)
Middle school or below	270 (50.9)
High school or above	260 (49.1)
Annual household income^*, yuan (n, %)
< 100,000 yuan per year	308/501 (61.5)
≥ 100,000 yuan per year	193/501 (38.5)
Exacerbations in the previous year (n, %)
≥ 1	250 (47.2)
0	280 (52.8)
Comorbidities (n, %)
Cardiovascular disease	197 (37.2)
Diabetes Mellitus	47 (8.9)
Lung function (post-BD)
FEV₁, L (mean, SD)	1.61 ± 0.64
FEV₁%predicted (mean, SD)	59.1 ± 21.1
GOLD stage (n, %)
I	89 (16.8)
II	247 (46.6)
III	155 (29.2)
IV	39 (7.4)
mMRC (median, IQR)	2.0 (1.0–2.0)
CAT (mean, SD)	13.9 ± 8.2
Anxiety (GAD-7 ≥ 5) (n, %)	90 (17.0)
Depression (PHQ-9 ≥ 5) (n, %)	114 (21.5)
Data are presented as mean ± SD, median (IQR) or n (%).
^* A minority of the subjects (5%) refused to report their income.
BD: bronchodilator; BMI: body mass index; CAT: COPD Assessment Test; FEV₁: forced expiratory volume in 1 second; FVC: forced vital capacity; FEV₁%predicted: forced expiratory volume in 1 second in percent of the predicted value; GOLD: Global Initiative for Chronic Obstructive Lung Disease; mMRC: modified Medical Research Council dyspnea scale.

Characteristics of the patients categorized by anxiety and depression status

Clinical characteristics of patients classified by anxiety status or depression status were shown in Table 2. About half of the patients (50.9%) in depression group had concomitant anxiety, and more than half of the patients (64.4%) in anxiety group also had depression symptoms. Compared with the patients who had no depression symptoms, patients with depression symptoms had a higher proportion of women, lower FEV₁, higher CAT score, higher mMRC dyspnea score, and were more report of exacerbations in the preceding year. Similar results were showed in patients with anxiety symptoms compared with non-anxiety patients in terms of CAT, mMRC, and exacerbation history. FEV₁%predicted was lower in depression group compared with non-depression group (53.2 ± 23.5% vs. 60.7 ± 20.1%, P = 0.002), but not between anxiety group and non-anxiety group (58.2 ± 22.6% vs. 59.3 ± 20.8%, P = 0.658).

Table 2

Demographic and clinical characteristics of the patients categorized by anxiety or depression status
	Anxiety (n = 90)	No anxiety (n = 440)	P Value	Depression (n = 114)	No depression (n = 416)	P Value
Age, years (mean, SD)	64.4 ± 7.9	65.0 ± 7.8	0.520	64.5 ± 8.1	65.0 ± 7.7	0.559
Men (n, %)	70 (84.4)	394 (89.5)	0.164	95 (83.3)	375 (90.1)	0.042
BMI, kg/m²(mean, SD)	24.6 ± 3.8	24.4 ± 3.4	0.614	24.4 ± 4.0	24.5 ± 3.4	0.865
Ever smoker (n, %)	81 (90.0)	384 (87.3)	0.472	101 (88.6)	364 (87.5)	0.752
Pack-years history (median, IQR)	40.0 (18.0-51.5)	37.7 (19.0–50.0)	0.942	40.5 (20.0-51.3)	37.0 (18.0–50.0)	0.230
Annual household income ≥ 100,000 yuan (n, %)	27/82 (32.9)	166/419 (39.6)	0.255	34/108 (31.5)	159/393 (40.5)	0.090
Educated level to high school or above (n, %)	44 (48.9)	216 (49.1)	0.972	57 (50.0)	203 (48.8)	0.820
Exacerbations (≥ 1) in the previous year (n, %)	54 (60.0)	196 (44.5)	0.007	76 (66.7)	174 (41.8)	< 0.001
Cardiovascular disease history (n, %)	30 (33.3)	167 (38.0)	0.473	36 (31.6)	161 (38.8)	0.189
Lung function (post-BD)
FEV₁, L (mean, SD)	1.58 ± 0.73	1.61 ± 0.63	0.651	1.43 ± 0.74	1.65 ± 0.61	0.003
FEV₁%predicted (mean, SD)	58.2 ± 22.6	59.3 ± 20.8	0.658	53.2 ± 23.5	60.7 ± 20.1	0.002
GOLD stage (n, %)
I	12 (13.3)	77 (17.5)	0.360	15 (13.2)	74 (17.8)	< 0.001
II	44 (48.9)	203 (46.1)		39 (34.2)	208 (50.0)
III	24 (26.7)	131 (29.8)		39 (34.2)	116 (27.9)
IV	10 (11.1)	29 (6.6)		21 (18.4)	18 (4.3)
mMRC (median, IQR)	2.0 (1.0–3.0)	1.0 (1.0–2.0)	< 0.001	2.0 (2.0–3.0)	1.0 (0.0–2.0)	< 0.001
CAT (mean, SD)	18.8 ± 7.8	12.9 ± 8.0	< 0.001	20.7 ± 7.7	12.1 ± 7.4	< 0.001
Comorbid anxiety (n, %)	NA	NA	NA	58 (50.9)	32 (7.7)	< 0.001
Comorbid depression (n, %)	58 (64.4)	56 (12.7)	< 0.001	NA	NA	NA
Data are presented as mean ± SD, median (IQR) or n (%). Significant values were presented in bold.
BD: bronchodilator; BMI: body mass index; CAT: COPD Assessment Test; mMRC: modified Medical Research Council dyspnea scale; FEV₁: forced expiratory volume in 1 second; FEV₁%predicted: forced expiratory volume in one second in percent of the predicted value; GOLD: Global Initiative for Chronic Obstructive Lung Disease; NA: not applicable.

Correlations of the CAT and FEV₁%predicted with anxiety and depression

The proportions of anxiety and depression symptoms categorized by CAT groups and GOLD stages were shown in Fig. 1. The proportion of mild, moderate, and severe anxiety according to the GAD-7 score did not differ with different GOLD grades (x² = 11.3 P = 0.254 by chi-square test). However, among patients stratified by CAT score, the proportion of mild, moderate, and severe anxiety significantly increased with increasing CAT scores (x² = 46.2, P < 0.001 by chi-square test and P < 0.001 by linear-by-linear association). As for depression, the proportion of mild, moderate, and severe depression increased with increasing CAT scores (x² = 133.0, P < 0.001 by chi-square test and P < 0.001 by linear-by-linear association), and also increased with increasing GOLD stages (x² = 34.0, P < 0.001 by chi-square test and P < 0.001 by linear-by-linear association).

The GAD-7 anxiety score had a significant correlation with the CAT score (Spearman’s rho = 0.339, P < 0.001) but not with FEV₁%predicted (Spearman’s rho = -0.029, P = 0.506). Meanwhile, the PHQ-9 depression score had also a significant correlation with the CAT score (Spearman’s rho = 0.435, P < 0.001) and a weak negative correlation with FEV₁%predicted (Spearman’s rho = -0.124, P = 0.004). The correlation analysis between GAD-7, PHQ-9 and each CAT item were presented in Additional file 1: Table S1.

Comparison of the CAT and FEV₁%predicted as predictors of anxiety and depression

Univariate and multivariable logistic regression analyses were performed to identify factors associated with anxiety and depression (Table 3). In univariate analysis, a higher CAT score was associated with a greater risk of both anxiety and depression (OR = 1.089, 95% CI: 1.059–1.121, P < 0.001; OR = 1.148, 95% CI: 1.113–1.183, P < 0.001; respectively). These associations were still significant in multivariable analysis (OR = 1.094, 95% CI: 1.057–1.131, P < 0.001; OR = 1.143, 95% CI: 1.104–1.183, P < 0.001; respectively) after adjusting for potential confounders (age, sex, BMI, smoking status, educated level, annual household income, lung function and exacerbation history). However, lung function impairment defined by FEV₁%predicted showed no statistically significant relationship with anxiety (P > 0.05 in both univariate and multivariable analysis). And for depression, FEV₁%predicted was significantly associated with depression in the univariate analysis (OR = 0.983, 95% CI: 0.972–0.993, P < 0.001), but this relationship was not significant in multivariable analysis (OR = 1.000, 95% CI: 0.988–1.013, P = 0.952).

Table 3

Logistic regression analysis of the factors associated with anxiety and depression in patients with COPD
Factors	Anxiety			Depression
Factors	OR	95% CI	P-value	OR	95% CI	P-value
Univariate analysis
CAT score ^*	1.089	1.059–1.121	< 0.001	1.148	1.113–1.183	< 0.001
FEV₁%predicted ^*	0.998	0.987–1.008	0.657	0.983	0.972–0.993	0.001
Multivariable analysis
CAT score ^*	1.094	1.057–1.131	< 0.001	1.143	1.104–1.183	< 0.001
FEV₁%predicted ^*	1.012	1.000-1.025	0.071	1.000	0.988–1.013	0.952
Age (< 65 years vs ≥ 65 years)	1.758	1.045–2.958	0.034	1.687	1.021–2.787	0.041
Sex (women vs men)	3.594	1.231–10.489	0.019	4.332	1.485–12.635	0.007
BMI (< 21 kg/m ² vs ≥ 21 kg/m ²)	0.537	0.255–1.129	0.101	0.819	0.430–1.560	0.544
Smoking status (ever vs never)	3.324	1.006–10.980	0.049	2.730	0.861–8.652	0.088
Educated level (middle school or below vs high school or above)	0.862	0.513–1.448	0.574	0.768	0.464–1.270	0.303
Annual household income (< 100,000 yuan vs ≥ 100,000 yuan)	1.327	0.772–2.280	0.306	1.350	0.797–2.287	0.265
Exacerbations in the previous year (≥ 1 vs 0)	1.489	0.880–2.521	0.138	1.836	1.107–3.045	0.019
^* Entered as a continuous variable. Significant associations were presented in bold
BMI: body mass index; FEV₁%predicted: forced expiratory volume in one second in percent of the predicted value; CAT: COPD Assessment Test; OR: odds ratio; CI: confidence interval.

The ROC curve analysis indicated that the CAT score had a significant predictive value for the presence of anxiety (AUC = 0.709, 95% CI: 0.668–0.747, P < 0.001) (Fig. 2) as well as depression (AUC = 0.791, 95% CI: 0.754–0.825, P < 0.001) (Fig. 3). Whereas FEV₁%predicted showed a poor performance for identifying either anxiety or depression (AUC = 0.516, 95% CI: 0.473–0.559, P = 0.643; AUC = 0.607, 95% CI: 0.564–0.648, P = 0.001; respectively). The operating characteristics of the CAT for identifying anxiety and depression were shown in Table 4. The highest Youden index was achieved at a cutoff score of CAT ≥ 15 for both anxiety and depression. The sensitivity, specificity, PPV, NPV, and accuracy for screening anxiety was 70.0%, 63.4%, 28.1%, 91.2%, and 64.5% respectively. The same parameters were respectively 78.1%, 67.6%, 39.7%, 91.8% and 69.8% for depression.

Table 4

Operating Characteristics of the CAT for identifying anxiety and depression
Cutoff Score	Sensitivity (%)	Specificity (%)	Youden Index (%)	PPV (%)	NPV (%)	Accuracy (%)
Anxiety
≥ 11	84.4	43.4	27.8	23.4	93.2	50.4
≥ 13	77.8	54.1	31.9	25.7	92.2	58.1
≥ 15^*	70.0	63.4	33.4	28.1	91.2	64.5
≥ 17	61.1	69.6	30.7	29.1	89.7	68.1
≥ 19	54.4	77.5	31.9	33.1	89.3	73.6
≥ 21	43.3	83.0	26.3	34.2	87.7	76.2
Depression
≥ 11	90.4	46.6	37.0	31.7	94.6	56.0
≥ 13	82.5	57.2	39.7	34.6	92.2	62.6
≥ 15^*	78.1	67.6	45.7	39.7	91.8	69.8
≥ 17	69.3	73.6	42.9	41.8	89.7	72.6
≥ 19	61.4	81.3	42.7	47.3	88.5	77.0
≥ 21	50.9	86.5	37.4	50.9	86.5	78.9
^* Cutoff score with maximum Youden index.
CAT: COPD Assessment Test; PPV: positive predictive value; NPV: negative predictive value; Youden index: (sensitivity + specificity) -1.

Comparison of different CAT components to identify anxiety and depression

ROC curve analysis was performed on each CAT item to determine which component of the CAT can better identify anxiety and depression (Fig. 4). Among all items, sleep had the best predictive value for the presence of anxiety (AUC = 0.708, 95% CI: 0.667–0.746), whereas energy had the best predictive value for the presence of depression (AUC = 0.765, 95% CI: 0.727–0.801). Generally, non-respiratory CAT items (activity limitation at home, confidence leaving home, sleep, and energy) showed higher predictive value for the presence of anxiety and depression than respiratory related items (cough, phlegm, chest tightness, and breathlessness going up hills/stairs). Statistical comparisons of the predictive value of the total CAT score and the two components within CAT also showed that non-respiratory CAT components had a significantly higher predictive value than that of the respiratory components for both anxiety (AUC = 0.721 vs 0.651, P = 0.011) and depression (AUC = 0.805 vs 0.720, P < 0.001) (Additional file 1: Table S2).

In this cross-sectional study, we reported that the proportion of anxiety symptom and depression symptom were respectively 17.0% and 21.5% in stable COPD patients. The CAT score was significantly associated with anxiety and depression and had a good performance in identifying these symptoms. Furthermore, analysis of components within the CAT demonstrated that non-respiratory components can better identify anxiety and depression than respiratory related components.

COPD is currently considered as a complex disease with not only pulmonary symptoms but also systemic comorbidities. Mental health disorder, including anxiety and depression, are known to play an important role in the progression and prognosis of COPD [5]. In this study, we observed 17.0% of anxiety and 21.5% of depression among COPD outpatients using valid screening instruments of GAD-7 score and PHQ-9 score. High prevalence of comorbid anxiety and depression in COPD was reported in various world regions. A previous study using the GAD-7 questionnaire through a mobile monitoring system showed that the prevalence of anxiety was up to 35.1%-56.4% among COPD patients in the United Kingdom [35]. Another large COPD cohort study conducted in northern California found the prevalence of anxiety was 15% at baseline assessed by the Hospital Anxiety and Depression Scale (HADS) anxiety subscale [7]. The ECLIPSE study using the CES-D score identified 26% of depression in patients with COPD among 46 centers from 12 countries [10]. Lou et al. [9] found that stable COPD patients in rural China have a prevalence of 18.3% for anxiety symptoms and 35.7% for depression symptoms based on the HADS score. A Chinese multicenter study in tertiary hospitals showed that the prevalence of anxiety and depression were respectively 8.8% and 15.6%, which used moderate to severe symptoms assessed by the HADS to define anxiety and depression [36]. However, direct comparison between our findings and those studies was limited by differences in populations and screening questionnaires. The high prevalence rates in above studies all suggest identifying patients who are at high risk of anxiety and depression in clinic is warranted.

In the present study, no significant relationship was observed between FEV₁%predicted and anxiety, which is concordance with the report from Gudmundsson et al. [37], they found that the prevalence of anxiety status was not different among COPD patients with different GOLD stages. Another study of patients from the general public and pulmonary rehabilitation centers in the Netherlands showed that there was no significant increase in psychological distress between patients with severe or very severe COPD and patients with mild or moderate COPD [38]. However, an increased prevalence and severity of depressive symptoms was observed with increasing GOLD stages in this study. Some previous studies identified impaired lung function (FEV₁ or GOLD severity) as a risk factor for depression [12, 21, 39]. However, other studies showed that FEV₁%predicted was not independently associated with depression after adjusting for factors including respiratory symptoms and patient-reported outcomes [9, 10, 40–42]. Our results showed that the relationship between lung function and clinical depression is relatively weak, FEV₁%predicted was not associated with anxiety or depression after adjusting for CAT score and other confounders. These suggest that the relationship between COPD severity and anxiety/depression should be explained better by a clinical measure of disease symptoms rather than the physiologic assessment of lung function.

We found that the CAT score was significantly associated with anxiety and depression independent of age, sex, BMI, and other potential confounders. Previous studies have found that St George’s Respiratory Questionnaire (SGRQ) was strongly associated with anxiety and depression in COPD[9, 10, 20, 43]. However, the SGRQ questionnaire is too complex and time-consuming, which limits its utility in clinical practice. The CAT was developed as a brief tool to measure health status and to facilitate the communications between COPD patients and clinicians. It covers a wide range of respiratory symptoms and systemic symptoms for a reliable measure of disease impact among COPD patients. Hilmarsen et al. [19] reported from COPD patients referred for pulmonary rehabilitation that patients with anxiety and/or depression symptoms had a significantly higher CAT score than those without these symptoms. The present study also suggested that the CAT is valuable in screening both anxiety and depression among stable COPD outpatients.

Our study showed that the optimal cutoff score to identify both anxiety and depression was CAT ≥ 15, lower than a previous report from Harryanto et al. [18], which suggested a CAT score of ≥ 20 as an optimal cutoff to identify potential anxiety in Australia. It was also lower than a previous study in Korean [44] which recommended using a CAT score of ≥ 21 for screening depression in COPD patients. These discrepancies are probably partly due to different study population, different questionnaire scales and thresholds used for identifying clinical anxiety and depression in different studies. Although the accuracy was not high using our cutoff (64.5% for anxiety and 69.8% for depression), we recommend using a lower cutoff value in clinic so that patients with potential mental disorder can be identified as early as possible.

Furthermore, the association between anxiety, depression, and different CAT components were investigated. We found that all CAT items were associated with anxiety and depression while sleep and energy showed better correlations and higher AUCs than the other items, which is consistent with a previous study suggesting that CAT energy score was closely associated with clinical depression [44]. It is reasonable due to sleep disturbance and decreased energy were two main symptoms that often overlap between patients with COPD and patients with anxiety and depression [45]. In clinical practice, physicians always emphasized respiratory symptoms and overlook systemic symptoms when evaluating health status of patients with COPD. Our results show that non-respiratory CAT components were closer associated with anxiety and depression than respiratory related components. Thus, we suggest that more attentions should be draw to these systemic symptoms and an assessment of anxiety and depression should be performed in patients with prominent non-respiratory symptoms of the CAT.

There are several limitations in our study. First, this is a single-center study which may cause limitation in the generalizability of the results. Second, due to the cross-sectional design, anxiety and depression trajectories and follow up were not investigated. Third, we assessed anxiety and depression using self-reported questionnaires rather than the gold standard (Diagnostic and Statistical Manual of Mental Disorders-V). However, previous studies have shown the GAD-7 and PHQ-9 were valid in detecting psychiatric morbidities in primary care and among COPD patients [27, 46]. Moreover, the aim of this study was to screen anxiety and depression symptoms rather than to diagnose psychiatric disorders.

In the present study, we found that the CAT score was superior to FEV₁%predicted to explain anxiety and depression symptoms and might be valuable in screening anxiety and depression in stable COPD patients. And non-respiratory components among CAT items can better screen anxiety and depression than respiratory related components. This finding needs to be verified in a larger scale of COPD patients in the future.

ATS: American Thoracic Society; AUC: area under the curve; BMI: body mass index; CAT: COPD assessment test; CI: confidence interval; COPD: chronic obstructive pulmonary disease; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th edition; FEV₁: forced expiratory volume in 1 second; FEV₁%predicted: forced expiratory volume in one second in percent of the predicted value; FVC: forced vital capacity; GAD-7: Generalized Anxiety Disorder Questionnaire-7; GOLD: global initiative for chronic obstructive lung disease; HADS: Hospital Anxiety and Depression Scale; IQR: interquartile range; mMRC: modified Medical Research Council dyspnea scale; NPV: negative predictive value, OR: Odds ratio; PHQ-9: Patient Health questionnaire-9; PPV: positive predictive value, ROC: receiver operating characteristic; SD: standard deviation; SGRQ: St George respiratory questionnaire.

Ethics approval and consent to participate

The study design was approved by the Ethics Committee of Beijing Chao-Yang Hospital (NO. 2016-KE-183) in accordance with the Declaration of Helsinki. Informed consent was obtained from all patients.

Consent for publication

Not applicable.

Availability of data and materials

The datasets generated and analysed during the current study are not publicly available because other studies involving this data are in the progress, but are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was supported by the National Key R&D Program of China, Ministry of Science and Technology of China (2016YFC0901102), the Project of “Deng Feng” Talent Training, Beijing Municipal Administration of Hospitals (DFL20190301) and the National Natural Science Foundation of China (81870032), and AstraZeneca China (ESR-16-12485).

Authors' contributions

Study concept and design: ML, KH. Acquisition of data: ML, YL, DY, YW. Statistical analysis of data: ML. Drafting of the manuscript: ML. Critical revision of the manuscript for important intellectual content: TF, ZZ, CZ, KH. All authors agree with the article submission. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

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No competing interests reported.

Additionalfile0305.docx
Additional file 1. It provides a detailed correlation of CAT items with GAD-7 anxiety score or PHQ-9 depression score (Table S1), and the values of the total CAT score and CAT components for the presence of anxiety and depression (Table S2).

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The value of COPD Assessment Test in Screening Anxiety and Depression in stable COPD patients

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