Effectiveness of cognitive behavioural therapy for chronic obstructive pulmonary disease patients: A systematic review and meta‐analysis

Complementary Therapies in Clinical Practice 38 (2020) 101071

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Effectiveness of cognitive behavioural therapy for chronic obstructive pulmonary disease patients: A systematic review and meta-analysis Rui-Chen Ma, Ying-Ying Yin, Ya-Qing Wang, Xin Liu, Jiao Xie * School of Nursing, Jilin University, No. 965 Xinjiang Street, Changchun, Jilin Province, 130021, PR China

A R T I C L E I N F O

A B S T R A C T

Keywords: Anxiety Chronic obstructive pulmonary disease Cognitive behavioral therapy Depression Meta-analysis

Background: and purpose: Cognitive behavioural therapy (CBT) has gained increasing attention for the treatment of psychological disorders. This study aims to establish the effectiveness of CBT on psychological and physical outcomes in patients with chronic obstructive pulmonary disease (COPD). Methods: Two waves of electronic searches of the PubMed, Cochrane library, EMBASE, Web of Science and China National Knowledge Infrastructure databases were conducted. Statistical analyses were performed using Revman Manager 5.3 and Stata 12.0 software. Results: Sixteen randomized controlled trials were eligible. There were significant improvements in anxiety (SMD ¼ 0.23; 95% CI: 0.42 to 0.04; P ¼ 0.02), depression (SMD ¼ 0.29, 95% CI: 0.40 to 0.19, P < 0.01), quality of life (MD ¼ 5.21; 95% CI: 10.25 to 0.17; P ¼ 0.04), and mean visits to emergency de­ partments in the CBT groups. No statistically significant differences were observed in fatigue (SMD ¼ 0.88, 95% CI: 0.58 to 2.35, P ¼ 0.24), exercise capacity (MD ¼ 28.75, 95% CI: 28.30 to 85.80, P ¼ 0.32), self-efficacy (SMD ¼ 0.15, 95% CI: 0.05 to 0.34, P ¼ 0.14), or sleep quality (MD ¼ 1.21, 95% CI: 0.65 to 3.06, P ¼ 0.20). Conclusion: This meta-analysis suggests that CBT can serve as a complementary therapy to improve anxiety, depression, and quality of life in COPD patients and deserves more widespread application in clinical practice.

1. Introduction Chronic obstructive pulmonary disease (COPD) is a chronic pro­ gressive lung disease that is characterized by largely irreversible airway obstruction, which is associated with persistent respiratory symptoms, including dyspnoea, cough and excessive sputum production [1,2]. COPD has exhibited a rising trend in morbidity and mortality, and it is estimated that COPD will become the third leading cause of death in the world by 2020 [3]. Anxiety disorder and depressive disorder are the main comorbidities observed in COPD patients, and these disorders more commonly occur in COPD patients than in patients with other chronic diseases, such as cancer, diabetes or heart disease [4,5]. The prevalence rate of anxiety in patients with COPD is approximately 50% [6], and the rate of depression ranges from 10% to 42% in stable patients and up to 86% in patients with acute exacerbation [7,8]. The current focus tends to be on the physical symptoms experienced by those with COPD; thus, mental health symptoms could go unnoticed and therefore untreated. However, mental disorders seriously impair a patient’s adherence to treatment and can have a considerable impact on

health-related quality of life (HRQoL), exercise capacity, readmission rates and mortality [9–11]. The exact mechanism of the development of mental disorders is still unclear, but it likely involves many factors [12]. Pathophysiological factors are complex and may include hypoxemia and chronic inflam­ mation, while behavioural factors may include active smoking and to­ bacco addiction. Other factors include social isolation, comorbidities, reduced physical functioning and frequent rehospitalization. Further­ more, more than 70% of COPD patients have sleep disturbances [13], which are related to nocturnal oxygen desaturation and can, in turn, further aggravate anxiety and depressive symptoms [14]. In addition, the presence of psychological symptoms is often associated with a reduction in self-efficacy, which may lead to a decline in the ability to cope with diseases [15,16]. Increasing evidence has shown that the relationship between emotional disorders and COPD is bidirectional: the development of COPD exacerbates anxiety and depression, and the presence of mental disorders also worsens COPD outcomes [4,10,17]. The high prevalence of anxiety and depression in patients with COPD, as well as the adverse impacts of these mental disorders on the prognoses of

* Corresponding author. School of Nursing, Jilin University, No. 965 Xinjiang Street, Changchun, 130021, Jilin Province, PR China. E-mail address: [email protected] (J. Xie). https://doi.org/10.1016/j.ctcp.2019.101071 Received 20 April 2019; Received in revised form 11 November 2019; Accepted 11 November 2019 Available online 13 November 2019 1744-3881/© 2019 Elsevier Ltd. All rights reserved.

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Complementary Therapies in Clinical Practice 38 (2020) 101071

disease and patient-centred outcomes, prompted us to investigate effective therapies for the identification and management of patients’ mood disorders in clinical practice. Pharmacotherapy is the mainstream treatment for mental disorders among COPD patients, although there is some controversy regarding its effectiveness, and it is often accompanied by some side effects [9,18]. In addition, some studies have focused on the efficacy of non­ pharmacological interventions, such as yoga, exercises, and psycholog­ ical interventions, as complementary and alternative therapies in the treatment of anxiety and depression [19–21]. Cognitive behavioural therapy (CBT) is a type pf psychotherapy that is used for the treatment of psychiatric disorders [18] and is a collaborative psychological approach that is based on experimental and scientific psychology and neurosci­ ence [22]. CBT is a patient-centred and personalized therapy that is usually provided by psychologists or psychiatrists; the contents of the therapy vary and mainly include psychological education, cognitive reconstruction and behavioural activation [23]. The purpose of CBT is to teach patients skills to change their emotional state and behaviour in order to address their current dysfunctional thoughts, beliefs and negative behaviours [12,24]. This mode of psychotherapy emphasizes the effects of cognition on emotion and behaviour, and it theorizes that distorted thinking patterns can lead to "negative" emotions and mal­ adaptive behaviours [25]. Therefore, the treatment focuses on changing a patient’s cognitive pattern to improve psychological and physical outcomes. In recent years, CBT has attracted the attention of researchers who are investigating chronic diseases. Several studies have investigated the effect of CBT on COPD patients; however, the results have been incon­ sistent. For example, a randomized controlled trial (RCT) [26] showed that CBT reduced depressive disorders but did not reduce anxiety after an 8-week intervention. Conversely, another study showed that although patients exhibited a lesser degree of anxiety symptoms after CBT, there was no significant difference in the degree of depression between the two groups [27]. A direct comparison is hindered by many factors, such as the duration of the intervention, the different sample sizes, and the outcome assessment tools used. Previous systematic re­ views have investigated various psychological interventions within a single review, such as meditation, mindfulness, relaxation and CBT; the results showed that psychological therapies might be beneficial for reducing the severity of mental disorders [28–31]. However, due to the varying methodological qualities of the studies included in these re­ views, more high-quality studies in this area are clearly warranted. Furthermore, the results concerning CBT interventions presented in the current reviews are inconsistent. Some reviews showed that CBT is effective for improving psychological outcomes [28,29], while other reviews found no conclusive evidence of an effect [30–32]. Meanwhile, the outcomes of these reviews are not comprehensive; most of these studies have not focused on physical outcomes. It is worth noting that combining various psychological interventions in one review may mask or exaggerate the effects of each intervention included. Therefore, despite the similarities that exist among the different psychological therapies; there is still a need to examine the literature that has focused specifically on CBT. Considering the lack of a systematic review and meta-analysis that focuses solely on the efficacy of CBT regarding psychological and physical health outcomes in COPD patients, we believe it is necessary to quantify the effects of CBT alone. We did not include third-wave CBT methods, such as mindfulness-based cognitive therapy, because the components of the treatment and the overall aim of the interventions are different [33]. This study only included RCTs to further clarify the effectiveness of CBT for COPD pa­ tients, and to provide a reference for future research.

(PRISMA) guidelines [34]. 2.1. Search strategy To identify the relevant studies, two reviewers performed two waves of electronic literature searches of the PubMed, Web of Science, EMBASE, Cochrane library and China National Knowledge Infrastruc­ ture databases. An initial search was performed in January 2019, and an updated search was performed in July 2019. The electronic search was supplemented by browsing the reference lists of the relevant identified studies and previous related systematic reviews. The search strategies were customized for each database and were conducted by using a combination of medical subject headings (MESH). The search terms of each theme were combined with “OR”, and the search themes were then combined with “AND”. For the PubMed search, the search strategy used was as follows: (Cognitive Behavioural Therapy [Mesh]) AND (Pulmonary Disease, Chronic Obstructive [Mesh]). Similar methods were used to search the remaining databases. The detailed search strategy can be found in Supplementary File 1. 2.2. Study selection Studies were included if the following criteria were met: (1) Study design: RCTs; (2) Study population: individuals with an objective diagnosis of COPD according to pulmonary function or the Global Initiative for COPD criteria; (3) Interventions: the participants in the experimental group were treated with CBT; (4) Comparators: any other type of intervention, such as another intervention (active control group) or usual care (passive control group); (5) Outcomes: the primary out­ comes were anxiety and depression, and the secondary outcomes included HRQoL, fatigue, exercise capacity, self-efficacy, sleep quality, and the mean number of visits to emergency departments; the study had to have assessed at least one of the outcomes investigated in this metaanalysis; (6) Papers: full-text papers that were published in peerreviewed journals; and (7) Language: studies published in the English or Chinese languages. The exclusion criteria were as follows: (1) papers that were pro­ tocols, pilot studies, theses, unpublished studies or conference sum­ maries; (2) studies that utilized third-wave CBT (e.g. mindfulness-based cognitive therapy and meta-cognitive therapy); (3) the durations of the interventions were not reported and (4) detailed data could not be extracted from the articles for the meta-analysis. 2.3. Data extraction Each of the studies was independently checked by two authors (MRC and YYY), and any inconsistencies were resolved through discussion with the third author (LX). Finally, the authors reviewed the full text of all potentially relevant studies and further evaluated whether these studies met the inclusion criteria. From each included study, we extracted information including general study information (e.g. loca­ tion, language, year of publication), characteristics of participant (e.g. age, gender, diagnosis), details of the intervention (e.g. sessions, de­ livery method), and outcomes. 2.4. Quality assessment Two reviewers independently evaluated all included studies (MRC and YYY), and any inconsistencies were discussed with a third reviewer (WYQ). We used the Cochrane Collaboration ‘risk of bias’ tool [35], which included the following: (a) sequence generation; (b) allocation concealment; (c) blinding of participants and personnel; (d) blinding of outcome assessors; (e) incomplete outcome data; (f) selective outcome reporting; and (g) other biases. Each item was rated as ‘low risk’, ‘un­ clear’ or ‘high risk’ of bias. We did not exclude any studies due to methodological quality.

2. Methods This systematic review and meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2

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Complementary Therapies in Clinical Practice 38 (2020) 101071

Sensitive analysis: considering the fact that I2 values > 50% may represent substantial heterogeneity [40], a sensitivity analysis was conducted for the secondary outcomes to identify the source of the heterogeneity by omitting each of the included studies and to confirm that the effect sizes of the remaining studies did not significantly alter the outcomes.

2.5. Statistical analysis This meta-analysis was performed using Revman Manager 5.3 and Stata 12.0 software. We constructed forest plots in order to clarify the effect sizes. Considering that some of the included studies contained more than one follow-up time point, the data in the forest plot were selected from the first time point after the end of the interventions, because the effect sizes at the end of the intervention periods are considered to be the most relevant [36,37]. The results were reported as the mean difference (MD) or standard mean difference (SMD) with corresponding 95% confidence interval (CI). All data were presented as means and standard deviations. We set the low, moderate and high criteria to I2 values of 25%, 50% and 75%, respectively [38]. When I2 > 50%, we used a random effect model. Otherwise, a fixed-effect model was used. The results were determined to have statistical significance if the P-value < 0.05. Egger’s test (STATA 12.0) was performed to explore publication bias. The primary outcomes were tested by using Egger’s test in this paper, and P values < 0.10 were considered to have statistical publication bias [39].

3. Results 3.1. Study selection The process of study selection is illustrated in Fig. 1. A total of 663 articles were selected from the electronic databases. After excluding 154 duplicate documents, the remaining 509 articles were screened for further assessment. After browsing the headlines and abstracts, 43 studies remained for full-text review. Finally, sixteen RCTs (1974 par­ ticipants) were selected for the meta-analysis. One article in the Chinese database met the inclusion criteria [41], and fifteen articles in the En­ glish database met the inclusion criteria [26,27,42–54].

2.6. Additional analyses

3.2. Study characteristics

Subgroup analysis: the control groups were divided into active control groups and passive control groups. For the primary outcomes, subgroup analyses were conducted according to the control groups to investigate the effect of CBT when the control groups adopted different interventions.

The sample sizes ranged from 18 [47] to 279 [27] participants. Among the 1974 patients included in the studies, 1000 were assigned to the CBT groups, and 974 were assigned to the control groups. With the exception of one study that did not provide detailed data [41], most of the studies recruited more men. The male-female ratio was not similar,

Fig. 1. PRISMA 2009 flow diagram. 3

Singlecenter

Singlecenter

Guo (2015) China (Chinese) Kapella (2011) USA

4

Singlecenter

Singlecenter

Multicenter

Singlecenter

Singlecenter

Multicenter

Singlecenter

Jiang (2012) China

Hynnine (2010) Norway

Lamers (2010) Dutch

Kunik (2008) USA

de Godoy (2003) Brazil

Doyle (2017) Australia

Lee (2015) Korea

Multicenter

Singlecenter

14/4 IG: n ¼ 9 CG: n ¼ 9

Multicenter

Walters (2013) Australia

Livermore (2015) Australia Howard (2014) UK

NR IG: n ¼ 45 CG: n ¼ 45

Multicenter

Reen (2018) USA

38/72 IG: n ¼ 54 CG: n ¼ 56 138/13 IG: n ¼ 78 CG: n ¼ 73

22/8 IG: n ¼ 14 CG: n ¼ 16

226/9 IG: n ¼ 118 CG: n ¼ 120

112/75 IG: n ¼ 96 CG: n ¼ 91

25/26 IG: n ¼ 25 CG: n ¼ 26

67/29 IG: n ¼ 49 CG: n ¼ 47

16/15 IG: n ¼ 18 CG: n ¼ 13 85/115 IG: n ¼ 112 CG: n ¼ 110

96/86 IG: n ¼ 90 CG: n ¼ 92

161/14 IG: n ¼ 99 CG: n ¼ 76

128/151 IG: n ¼ 139 CG: n ¼ 140

Singlecenter

HeslopMarshall (2018) UK

Participants (M/ F)

Design


40–80

68.5 � 9.4/ 67.0 � 9.1

62.1 � 14.9/ 58.8 � 11.8

66.1 � 10.1/ 66.5 � 10.4

70.5 � 6.3/ 71.5 � 7.1

59.3 � 7.6/ 62.6 � 9.9

65.2 � 8.96/ 64.7 � 8.05

71.2 � 10.4/ 73.2 � 11.4

72.0 � 6

65 � 9/60 � 10

NR

68.2 � 7.9/ 67.3 � 7.6

65.8 � 8.4/ 67.4 � 8.1

66 � 10.2/ 67 � 9.6

Mean age (IG/ CG) Mean � SD

Table 1 Characteristics of the studies included in the meta-analysis.

GOLD II-IV

GOLD I-IV

GOLD I-III with depression

FEV1<70% predicted with anxiety and/or depression GOLD I-III

GOLD I-IV with depression

GOLD II-IV with anxiety and depression

GOLD II-III

GOLD II-III with FEV1<60% predicted GOLD I-IV with mMRC�3

GOLD I-III

GOLD I-IV with depression

GOLD I-IV (mMRC�3) with anxiety or depression GOLD II-III

GOLD I-IV with anxiety

Diagnosis

IG: problem-solving therapy based on CBT CG: usual care (PC)

IG: CBT þ pulmonary rehabilitation CG: pulmonary rehabilitation (AC) IG:CBT CG: befriending (AC)

IG:CBT CG:COPD education (AC)

IG: minimal psychological intervention based on CBT CG: routine care (PC)

IG: uncertainty management intervention based on CBT CG: usual care (PC) IG:CBT CG: standard care (PC)

IG:COPD manual based on CBT CG: information booklets (PC)

IG:CBT CG: routine care (PC)

IG: CBT CG: education (AC)

IG:CBT CG: routine follow-up (PC)

IG: Health mentoring based on CBT CG: usual care (PC)

IG:CBT CG: usual care (PC)

IG:CBT; CG: self-help leaflets (PC)

Intervention types

12 sessions; 6 months

8 sessions; 2 months

12 sessions; 3 months

8 sessions; 2 months

4 sessions; 3 months

7 sessions; 7 weeks

13 sessions; 10 months

35 sessions; 5 weeks

4 sessions; 1 month

6 sessions; 6 weeks

8 sessions; 6 months

16 sessions; 12 months

8 sessions; 4 months

22 sessions; 3 months

Total sessions; Duration of intervention

Baseline, 2 months, 4months Baseline, 6 months

Baseline, 3 months

Baseline, 1 week, 3 months, 9 months Baseline, 2 months, 14 months

Baseline, 7 weeks, 31 weeks

Baseline, 6 weeks, 6 months, 14 months Baseline, 10 months

Baseline, 7 months

Baseline, 3months, 6 months Baseline, 6 weeks

Baseline, 6 months, 12 months

Baseline, 3months, 6 months, 12 months Baseline, 4 months

Follow-ups

nurse

nurse

psychologists

NR

psychology interns and post-doctoral fellows

nurses

masters-level psychology student

intervention nurses

psychologists

experienced clinical psychologist

nurse

multi-disciplinary team

health nurses

mental health providers

respiratory nurses

Delivered by

telephone

telephone

group, face to face

group, face to face

individual, face to face

group, face to face

telephone

telephone þ face to face (individual)

individual, face to face

face to face, individual and group þ telephone group, face to face

telephone

face to face þ telephone

individual, face to face

Intervention format

(continued on next page)

Anxiety: BAI; Depression: PHQ-9; Selfefficacy: GSES Depression: CES-D; Selfefficacy: CSES

Anxiety: BAI; Depression: BDI-II; Fatigue: CRQ; 6MWD; Quality of life: SF-36 Anxiety: BAI; Depression: BDI; 6MWD

Anxiety: BAI; Depression: BDI-II; Quality of life: SGRQ; Sleep quality: PSQI Anxiety: SCL; Depression: BDI; Quality of life: SGRQ

Anxiety: STAI; Depression: HADS; Quality of life: SF-36

Anxiety: POMS-A; Depression: POMS-D; Sleep quality: PSQI; Fatigue: CRQ Anxiety: HADS; Depression: HADS; Quality of life: SGRQ Anxiety: HADS; Depression: HADS; Fatigue: CRQ-SR

Anxiety: HADS; Depression: HADS; Quality of life: SGRQ; Self-efficacy: SE MCD Depression: HAM-D

Quality of life: SF-12

Anxiety: HADS; Depression: HADS

Outcomes

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Complementary Therapies in Clinical Practice 38 (2020) 101071

Singlecenter Kunik (2001) USA

with a ratio of approximately 1.7:1. The participants across the studies were all over 40 years old and were at various stages of the disease. Among these studies, four were conducted in the United States [23,48, 49,53], three in Australia [26,52,54], two in England [27,44], and two in China [41,46], and the remaining five studies were conducted in Norway [45], the Netherlands [50], Korea [51], Denmark [42] and Brazil [43]. The contents of the CBT interventions were different, and most of the studies included psychoeducation, cognitive restructuring, behavioural activation, goal setting and problem-solving techniques. The durations of the intervention and the lengths of the follow-ups were significantly different among these studies. The durations of the inter­ vention varied from 3 weeks to 12 months, and the longest follow-up was up to 1 year. Twelve studies compared CBT with passive control groups: eleven studies used usual care, and one study [43] used co-intervention alone (the intervention group used CBT combined with co-intervention). The remaining four studies adopted active control groups: three studies [47–49] used COPD education, which was group-based, and the remaining study [26] used befriending. The main focus of this study was to examine the benefits of CBT for anxiety and depression. The included studies adopted different instruments to measure these two outcomes. Most of the studies used the Hospital Anxiety and Depression Scale (HADS). The HADS has been validated for use in COPD, with higher scores representing more severe symptoms. Further details of the base­ line characteristics and interventions are shown in Table 1.

Abbreviations: CBT: cognitive behavioural therapy; IG: intervention group; CG: control group; AC: active control; PC: passive control; NR: not reported; HADS: The Hospital Anxiety and Depression Scale; BAI: Beck Anxiety Inventory; SCL: the anxiety subscale of the Symptom Checklist-90; POMS-A: Profile of Mood States tension-anxiety subscale. HAM-D: The Hamilton Rating Scale for Depression; GDS: Geriatric Depression Scale; BDI: the Beck Depression Inventory; POMS-D: Profile of Mood States depression-dejection subscale; STAI: the State-Trait Anxiety Inventory; 6MWD: Six-minute walk distance; SGRQ: the Saint George’s Respiratory Questionnaire; CRQ: Chronic Respiratory Questionnaire; CRQ-SR: The Self-Reported Chronic Respiratory Questionnaire; CES-D: Center for Epidemiologic Studies Depression Scale; CSES: COPD Self-efficacy Scale; PHQ-9: Patient Health Questionnaire 9; GSES: General Self-Efficacy Scale; SE MCD: Self-Efficacy for Managing Chronic Disease; PSQI:, Pittsburgh Sleep Quality Index; SF-36: the Medical Outcomes Survey Short Form-36; SF-12: the Medical Outcomes Survey Short Form-12; GOLD: Global Organization for Lung Disease; FEV1: forced expiratory volume in 1 s; FEV: forced expiratory volume; mMRC: the Medical Research Council (MRC) dyspnoea scale; M: male; F: female; SD: standard deviation.

group, face to face þ telephone board-certified geropsychiatrist 1 session (þ6 phones); 6 weeks IG:CBT CG:COPD education (AC) 71.3 � 5.9

70.06 � 8.39/ 70.33 � 8.73 Singlecenter Bove (2016) Denmark

22/44 IG: n ¼ 33 CG: n ¼ 33 40/8 IG: n ¼ 21 CG: n ¼ 27

Design
Table 1 (continued )

Participants (M/ F)

Mean age (IG/ CG) Mean � SD

Diagnosis

FEV<0.75

1 session (þ1 phone); 3 weeks IG:CBT CG: usual care (PC)

Baseline, 7 weeks, 15 weeks Baseline, 6 weeks

Total sessions; Duration of intervention Intervention types

Delivered by

individual, face to face þ telephone

Anxiety: HADS; Depression: HADS; Fatigue: CRQ Anxiety: HADS; Depression: GDS; 6MWD

Complementary Therapies in Clinical Practice 38 (2020) 101071

Follow-ups

Intervention format

Outcomes

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3.3. Risk of bias assessment The bias risks of the included studies are shown in Table 2. Each study reported that the patients were randomly divided into an experi­ mental group and a control group, but five studies did not provide de­ tails of the randomization procedures. Only six studies clearly described the methods of allocation concealment. Due to the nature of the inter­ vention, the blinding of patients and personnel is hardly possible. In four studies, the outcome assessors were blinded to the allocation, while the remaining studies did not provide sufficient information to allow this judgment to be made. Intention-to-treat analyses were used in eight studies. There were only four studies whose study protocols were pub­ lished online, and the remaining studies were classified as having an “unclear” risk of bias. 3.4. Effects of CBT on primary outcomes Anxiety: Twelve included studies reported measures of anxiety in patients. There was moderate heterogeneity (I2 ¼ 62%) in the anxiety factor; therefore, we chose a random effects model (SMD ¼ 0.23; 95% CI: 0.42 to 0.04; P ¼ 0.02). The result indicated that the overall effect of CBT on anxiety was significant (Fig. 2). For the subgroup analysis, when the control groups adopted active comparisons, no statistically significant differences were observed in anxiety between the groups (SMD ¼ 0.01, 95% CI: 0.20 to 0.19, P ¼ 0.94). When the control groups adopted passive comparisons, the effect of CBT on symptoms of anxiety was statistically significant (SMD ¼ 0.38, 95% CI: 0.64 to 0.12, P ¼ 0.005) (Fig. 3). Depression: Fourteen studies investigated the efficiency of CBT for treating depression. The analysis of these studies demonstrated evidence of low heterogeneity (I2 ¼ 46%). The fixed effects model showed that the overall effect of CBT on depression was significant (SMD ¼ 0.29, 95% CI: 0.40 to 0.19, P < 0.001) (Fig. 4). For the subgroup analysis, no statistically significant differences were observed in depression between the groups when the control groups adopted active comparisons (SMD ¼ 0, 95% CI: 0.19 to 0.20, P ¼ 0.98). When the control groups adopted passive comparisons, there were significant differences be­ tween the groups (SMD ¼ 0.42, 95% CI: 0.54 to 0.29, P < 0.001) (Fig. 5). 5

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Table 2 Risk of bias assessment for the methodological quality.

Heslop-Marshall (2018) Reen (2018) Howard (2014) Hynnine (2010) Livermore (2015) Kunik (2001) Lamers (2010) Jiang (2012) Kunik (2008) de Godoy (2003) Walters (2013) Doyle (2017) Lee (2015) Guo (2015) Bove (2016) Kapella (2011)

Random sequence generation

Allocation concealment

Blinding of participants and personnel

Blinding of outcome assessors

Incomplete outcome data

Selective reporting

Other bias

Low

Low

Unclear

Low

Low

Low

Low

Unclear Low Low Unclear Low Low Low Low Unclear Low Low Unclear High Low Unclear

Unclear Low Low Unclear Unclear Low Unclear Unclear Unclear Low Unclear Unclear Unclear Low Unclear

Unclear Unclear High Unclear Unclear Unclear High Unclear Unclear High High High Unclear High Unclear

Unclear Unclear Unclear Unclear Unclear Unclear Unclear Low Unclear Low Low Uuclear Unclear High Unclear

Low Low High Low High Low Low Low Low Low Low High Low Low Low

Unclear Unclear Unclear Unclear Unclear Low Unclear Unclear Unclear Unclear Low Unclear Unclear High Unclear

Low Low Low Unclear Low Low Low Low Low Low High Low High Low Unclear

3.5. Effects of CBT on secondary outcomes

3.7. Publication bias

The results of the meta-analysis of all secondary outcomes are shown in Table 3, and the forest plots of the secondary outcomes are shown in Supplemental File 2. Four studies [45,50,52,54] assessed the benefits of CBT on HRQoL by using the Saint George’s Respiratory Questionnaire (SGRQ). The results showed that there was a significant difference be­ tween the groups (MD ¼ 5.21; 95% CI: 10.25 to 0.17; P ¼ 0.04). Three studies assessed the benefits of CBT on HRQoL by using the Medical Outcomes Survey Short Form-12 (SF-12) [53] and the Medical Outcomes Survey Short Form-36 (SF-36) [46,49]. All three studies showed that, compared with the scores at baseline, CBT significantly improved the mental component summary score (MCS), while the physical component summary score (PCS) did not show any improve­ ment (P > 0.05). Four studies reported data on fatigue [42,44,47,49]. No statistical improvements in fatigue were observed between the two groups (SMD ¼ 0.88, 95% CI: 0.58 to 2.35, P ¼ 0.24). Three studies [43,48, 49] assessed the effects of CBT on exercise capacity, with no significant improvement evident between groups (MD ¼ 28.75, 95% CI: 28.30 to 85.80, P ¼ 0.32). Three studies investigated the impact of intervention on self-efficacy [26,51,54] and showed that self-efficacy was not significantly different after the intervention (SMD ¼ 0.15, 95% CI: 0.05 to 0.34, P ¼ 0.14). Two studies [45,47] focused on sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI). There were no significant differences between the two groups (MD ¼ 1.21, 95% CI: 0.65 to 3.06, P ¼ 0.20). The mean number of emergency department visits were reported in two included studies. The first study [27] demonstrated that the patients in the CBT group had fewer mean emergency department visits than the patients in the control group at 12 months from baseline (0.37 versus 0.81; P ¼ not reported). The second study [44] also showed fewer mean visits to emergency departments in the study group at 12 months post-intervention compared to the control group (1.59 versus 1.98; P ¼ 0.047).

The results of Egger’s test did not reveal any evidence of publication bias (anxiety, P ¼ 0.193; depression, P ¼ 0.421). 4. Discussion The goal of the present study was to quantitatively evaluate the effect of CBT on psychological and physical outcomes in patients with COPD. Sixteen RCTs were included, and the results showed statistically signif­ icant decreases in anxiety, depression, and mean visits to emergency departments, as well as an improvement in HRQoL (SGRQ) in people with COPD. However, there were no significant improvements in fa­ tigue, exercise capacity, self-efficacy, or sleep quality. CBT, which is often performed in collaboration between patients and therapists, is a psychological therapy that aims to solve the thinking mode that leads to psychological disorders, thus changing the behav­ iours and emotional states of patients. The results showed that the overall effects of CBT on symptoms of anxiety and depression were significant. These results are somewhat comparable to those of a pub­ lished review showing that CBT can alleviate adverse psychological health outcomes [29]. Four of the included studies used active control groups, and eleven studies used passive control groups. The results of the subgroup analysis showed that compared with passive controls, CBT significantly improved anxiety and depressive disorders. However, when compared with active control groups, no significant differences in symptoms of anxiety and depression were evident between the groups after the intervention. Three studies [47–49] used COPD education as the active comparison. All of the COPD education sessions in these three studies were conducted in groups. The interaction and support provided by the group treatment may have had a unique impact on participants’ mental health. This result is consistent with a meta-analysis that showed that self-help groups are effective in treating emotional disorders [55]. One study [26] used befriending as an active comparison, wherein the clients in the control groups received telephone calls from volunteers once a week for eight weeks. The results showed that CBT reduced depression but not anxiety symptoms. Surprisingly, befriending pro­ duced significant reductions in anxiety, which is consistent with the finding of a meta-analytical review [56]. Perhaps the role of social support is different for COPD patients than for other populations. The findings of the subgroup analyses showed that CBT is effective, but it is not superior to some other active therapies, which is in line with the results of a previous meta-analysis [57]. The positive effects of CBT on mental health outcomes in this metaanalysis are also congruent with meta-analyses on patients with condi­ tions such as diabetes and breast cancer [58,59]. Among the studies that

3.6. Sensitivity analysis We conducted a sensitivity analysis to evaluate the stability of the outcomes. For HRQoL (SGRQ), when we removed Walter’s study [54], the heterogeneity significantly decreased (I2 ¼ 0), which indicated that this study was the source of the heterogeneity. However, the sensitivity analysis did not change the effect (MD ¼ 7.55; 95% CI: 11.28 to 3.83, P < 0.001). For fatigue, by omitting one study [44], the hetero­ geneity decreased (I2 ¼ 0), and the adjusted pooled estimates did not significantly change (MD ¼ 0.16, 95% CI: 0.06 to 0.38, P ¼ 0.16). The sensitivity analysis showed that the results were relatively robust. 6

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Complementary Therapies in Clinical Practice 38 (2020) 101071

Fig. 2. Forest plot of anxiety for overall analysis. Abbreviations: 95% CI: 95% confidence interval; SD: standard deviation.

Fig. 3. Forest plot of anxiety for subgroup analysis. Abbreviations: 95% CI: 95% confidence interval; SD: standard deviation.

used passive control groups, five [27,42,44,45,50] had more than one follow-up time point. Interestingly, when analysing the data from these five studies, four of the studies [27,44,45,50] showed that the psycho­ logical states of the patients were much better at the long-term follow-up than at the immediate, post-intervention time point, which may indicate that CBT will result in greater benefits as time progresses. However, this result is in contrast to a previous review [29] that showed that longer follow-up times reduced the effects of psychological therapies. One possible reason for this discrepancy could be that the quantitative analysis of this previous review included different types of psychological interventions, whereas our study quantified the effects of CBT alone.

Therefore, we suggest that future research should carry out follow-ups over longer time periods. Other psychological therapies, such as relax­ ation therapy (which includes a variety of techniques), mindfulness-based stress reduction (which mainly includes meditation), and mindfulness-based cognitive therapy (which is a combination of cognitive therapy and meditation), have shown good effects in treating generalized psychological disorders. Previous studies have shown that the effect of combined psychotherapy may be better than that of single therapy [21], and the effect of relaxation therapy may be better than the effect of CBT [60]. We suggest that future research should not only focus on the comparison between CBT and a passive control group but also 7

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Complementary Therapies in Clinical Practice 38 (2020) 101071

Fig. 4. Forest plot of depression for overall analysis. Abbreviations: 95% CI: 95% confidence interval; SD: standard deviation.

Fig. 5. Forest plot of depression for subgroup analysis. Abbreviations: 95% CI: 95% confidence interval; SD: standard deviation.

compare CBT with different kinds of psychotherapy in order to identify the best type of psychotherapy for COPD patients. CBT has been widely used to relieve symptoms of mental disorders, which indicates that there may be common neural mechanisms in the treatment process. The cognitive control network, which includes the prefrontal cortical regions, the dorsal anterior cingulate cortex, the

posterior parietal lobe, the thalamus and the striatum, is related to active cognitive behavioural changes and plays an important role in promoting mental health [61]. The neural mechanisms of psychological therapies show that the increased activity of this control system is related to the successful treatment of psychological diseases. One study demonstrated that CBT can effectively activate and enhance cognitive 8

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Table 3 Results of meta-analysis of secondary outcomes. Outcomes quality of life (SGRQ) fatigue exercise capacity (6MWD) self-efficacy sleep quality

Number of Studies 4 4 3 3 2

Number of Patients Study group

Control group

155 272 153 206 34

163 272 163 209 35

Pooled SMD/MD 5.21 0.88 28.75 0.15 1.21

95% CI of Pooled SMD/MD [-10.25, 0.17] [-0.58, 2.35] [-28.30, 85.80] [-0.05, 0.34] [-0.65, 3.06]

P Value 0.04 0.24 0.32 0.14 0.20

Heterogeneity I2 (%)

P value

56 98 0 11 25

0.08 <0.01 0.9 0.32 0.25

Abbreviations: CI: confidence interval; SMD: standard mean difference; MD: mean difference; SGRQ: the Saint George’s Respiratory Questionnaire; 6MWD: 6-min walk distance.

control regions, thus alleviating major depressive disorder and post-traumatic stress disorder [61]. One of the goals of chronic disease management is to improve the HRQoL of patients [62]. SGRQ is the most commonly used disease-specific questionnaire for evaluating the HRQoL of COPD patients, and it is a reliable tool that is sensitive to change [63]. The findings of our analysis showed that HRQoL improved significantly after the intervention. The SF-12 and SF-36 are two general question­ naires that can also be used in general populations, and these ques­ tionnaires have two sub-scales (PCS and MCS). Over the course of CBT, an improvement was ascertained in mental health-related quality of life, but not in the physical health-related quality of life. Considering that the included studies used different instruments to evaluate HRQoL, the re­ sults were difficult to integrate. Therefore, we suggest that future studies consider using the same instrument to measure HRQoL. One study has shown that anxious or depressed COPD patients make more annual emergency department visits than those who are not anxious or depressed [5]. One of the potential reasons for this finding is that the presence of chronic psychological stress disorders in COPD patients may weaken the function of the immune system, which could increase res­ piratory tract infections and exacerbate the incidence of disease [16]. Two included studies [27,44] showed that CBT can reduce the mean number of visits to emergency departments within 12 months after the intervention, which may be especially beneficial for individuals with anxiety and/or depression as well as for frequent visitors to emergency departments. In this meta-analysis, the results also showed that CBT could not improve fatigue or exercise capacity, which further indicates that CBT has no additional effects on physical health outcomes. These findings are also in line with a published review showing that for physical health outcomes, CBT could not reach a statistically significant effect [29]. Although we expect CBT to improve all clinical outcomes, COPD is a chronic and degenerative disease involving an irreversible airflow lim­ itation with persistent respiratory symptoms. Airflow limitation is due to the destruction of the lung parenchyma and narrowing of the small airways [64]. Given the characteristics of the disease, more frequent and longer CBT interventions are required to further explore the effect of CBT on physical outcomes. Self-efficacy is defined as confidence in one’s ability to engage in specific behaviours, and it plays an important role in the management of disease [26,65]. Interestingly, our results showed that CBT has no additional effect on self-efficacy. One study [51] showed that CBT failed to improve self-efficacy, which may be because the pa­ tients had relatively high levels of self-efficacy at baseline. Two studies [26,54] found that patients in the CBT groups showed improved self-efficacy compared with their baseline results, but the improvement did not reach statistical significance. Therefore, we speculate that it may take a longer follow-up period to observe the significant improvement in self-efficacy. PSQI is a tool with high diagnostic sensitivity that is used to distinguish poor sleepers from good sleepers [45]. However, in contrast to a meta-analysis investigating the effect of CBT on insomnia [66], our results showed that CBT did not improve sleep quality. The sleep problems of COPD patients may be related to underlying respiratory diseases; therefore, the improvement in mental disorders may not extend to sleep problems.

4.1. Issues requiring attention and suggestions for future research Mental health conditions among COPD patients have begun to receive more and more attention, mainly because an increasing number of individuals are being diagnosed with this disease, and a considerable amount of evidence has shown that mental disorders are more common in patients with COPD than in patients with other chronic diseases [67]. CBT, as one of the most extensively researched subjects, has not been fully used in patients with COPD [68]. It is plausible that, in clinical practice, it is very difficult to access psychologists who have received professional training. Fortunately, it has been demonstrated that rela­ tively inexperienced staff (such as nurses and other specialist staff in medical settings) can provide effective CBT after training [69]. Considering the fact that somatic symptoms of anxiety in COPD patients (such as breathlessness and sweating) are easily overlooked, as these symptoms can easily be attributed to lung disease rather than mental disorders, medical staff should be trained to better identify and effec­ tively treat psychological problems in COPD patients [4]. At the same time, as CBT is a cost-effective intervention [27,69] that can reduce the mean number of visits to emergency departments and the mean number of days spent in bed, it should be routinely added to clinical pathways. The content, number of sessions, and delivery format (group, indi­ vidual, face-to-face or telephone-based) of CBT varied among the included studies in this review, which highlights the lack of clear rec­ ommendations for CBT programmes. More studies should be carried out to investigate which form of CBT achieves the most promising results. Hospital health professionals could develop tailored CBT approaches for COPD patients to meet individual needs and preferences. In addition, it is worth noting that in the included studies, the proportion of males was significantly higher than that of females. Compared with men, women are more prone to mental disorders and emotional distress [70]. Therefore, special attention may need to be paid to women to identify and treat mental health problems in the future. Considering that some patients face transportation-related diffi­ culties, perhaps tele-delivered CBT can constitute an alternative approach. Telephone-delivered CBT has been used in COPD and appears to be viable [26,46]. With the advent of the Internet era, internet-based interventions may become a prioritized method. To the best of our knowledge, so far there has been an apparent lack of studies on the use of web-based CBT for COPD. Therefore, there is certainly scope to further investigate the effectiveness of Internet-based CBT for this patient population. Furthermore, the components of CBT can also be relatively easily added to rehabilitation programmes for COPD patients, which would be beneficial for all patients, regardless of whether they have a mental disorder [45]. 4.2. Strengths and limitations The strengths of this meta-analysis are that we only included RCTs and that the results yielded the highest quality of evidence; however, there are still some limitations. First, this systematic review was not a priori registered, but the review was conducted in accordance with the PRISMA guidelines and the recommendation of the Cochrane 9

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Collaboration. Second, owing to limited resources, the research studies were limited to Chinese and English publications. Relevant publications that were written in other languages were omitted. Third, data on the secondary results were insufficient, which may limit the strength of our evidence. Consequently, our findings need to be confirmed in welldesigned RCTs with larger sample sizes. Finally, due to the limited number of included studies, we did not conduct subgroup analyses ac­ cording to delivery format. Thus, the optimal intervention design for eliciting beneficial effects remains unclear; this aspect may be explored in future research.

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5. Conclusion In this review, CBT was demonstrated to have positive effects on anxiety, depression, HRQoL (SGRQ), and mean visits to emergency de­ partments, although potential beneficial effects on fatigue, exercise ca­ pacity, self-efficacy, and sleep quality were not observed. The current meta-analysis provides evidence regarding the use of CBT with pa­ tients with COPD and indicates that CBT could be a complementary therapy in clinical practice for COPD patients to improve their psycho­ logical outcomes and quality of life. Physicians and nurses, as well as other healthcare professionals, should cooperate with psychologists to improve the utilization rate of CBT in clinical settings. Future RCTs with high methodological quality and longer follow-up periods are needed to further confirm the outcome validity of this review and to investigate the long-term effects of CBT. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authorship statement We confirm that all listed authors meet the authorship criteria, and all authors are in agreement with the content of the manuscript. R.C.M and J.X designed the present study. R.C.M. and Y⋅Y.Y. identified and screened the included randomized controlled trials. X.L. and Y.Q.W analyzed and evaluated the data. R.C.M. wrote the first draft of the manuscript and YYY revised the manuscript. All authors approve the final version for submission. All authors are in agreement with the content of the manuscript. Declaration of competing interest None. Acknowledgements We acknowledge the staff of the School of Nursing, Jilin University, for all their valuable support. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.ctcp.2019.101071. References [1] R.A. Rabinovich, J. Vilaro, Structural and functional changes of peripheral muscles in chronic obstructive pulmonary disease patients, Curr. Opin. Pulm. Med. 16 (2) (2010) 123–133. [2] C.M. Riley, F.C. Sciurba, Diagnosis and outpatient management of chronic obstructive pulmonary disease: a review, Jama 321 (8) (2019) 786–797. [3] Gold, global strategy for prevention, diagnosis and management of copd, 2019. https://goldcopd.org/gold-reports/. (Accessed 6 February 2019). [4] S. Marsh, T.P. Guck, Anxiety and depression: easing the burden in COPD patients, J. Fam. Pract. 65 (4) (2016) 246–256.

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