Association between impairment of lung function and risk of anxiety and depression in patients with chronic obstructive pulmonary disease - A systematic review

doi:10.21203/rs.3.rs-4024678/v1

Background: This systematic review aims to evaluate the association between impairment of pulmonary function, anxiety and depression in patients with chronic obstructive pulmonary disease (COPD).

Methods: Literature search were performed using Embase and PubMed. Publications reporting association between forced expiratory volume in one second in percentage of expected value (FEV1(%)) and anxiety or depression in patients with COPD were included.

Results: 31 studies were included in the review, 15 allocated to anxiety group and 31 allocated to the depression group. Most were observational studies. Study population sizes ranged from 40 to 2147 patients. Three studies found a significant negative association between anxiety and FEV1(%), while five studies found a positive non-significant association between anxiety and FEV1(%). Fifteen studies found a significant negative association between FEV1(%) and depression. Especially the studies with larger study population sizes showed significant results.

Conclusion: This systematic review did not support an association between anxiety and impairment of pulmonary function as only 3/15 studies showed significant negative associations and some studies showed positive associations. This review indicated an association between depression and impairment pulmonary function in patients with COPD, as most studies with a larger study population size showed a significant negative association.

Registration: PROSPERO 2024 CRD42024506065

Pulmonary function

depression

anxiety

Forced Expiratory Volume

Chronic Obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is a common disease, and the third leading cause of death in the world [1]. In patients with COPD comorbidities are of great importance, and, among these, studies have shown a prevalence of anxiety in patients with COPD ranging from 13-46%, while the prevalence of depression is found to be 27%, in both cases higher than the general population [2,3]. Anxiety and depression in patients with COPD have been shown to both increase mortality, decrease quality of life and increase the risk of exacerbations [4, 5]. Therefore, the prevention, diagnosis, and treatment of anxiety disorders and depression in the COPD patient population is important from both an individual and societal point of view.

Several risk factors of anxiety and depression in patients with COPD have been suggested, even though there is inconsistency between studies. Some studies found a lower risk of anxiety with increasing age [6,7], while other studies found no association [8,9]. Previous studies found an association between female sex and anxiety [10,11], while a link between female sex and depressive were not significant [6,8,10].

It is not clear whether an increase in disease severity of COPD increases the risk of anxiety, especially because the definition of disease severity differs between studies. While some studies found a higher risk of anxiety with more severe Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and Medical Research Council Dyspnoea Scale (MRC) [6,12-13], other studies found no link between MRC scale, 6-minute walk test distance [6MWT] and anxiety risk [7,8].

Results are less conflicting in studies investigating the association between depression and COPD, yet also dependent on how disease severity of COPD was evaluated. There are strong associations between higher MRC-score and risk of depression [7-8,14-15], but inconsistent results were found between 6MWT and depression, as some studies found an association [7,14], but other studies found no association [7,12,15].

Many of the evaluation methods used above are subjective scores both for disease severity and for anxiety and depression. Although all scores are validated, subjective scores may be influenced by multiple factors [16,17]. Therefore, generalisability of the association between an objective measure and anxiety and depression could have higher impact, for example pulmonary function. The results from a 6MWT and Forced Expiratory Volume in one second [FEV1] have been found not to be directly comparable, as several factors affect the performance in the 6MWT [18]. The same applies to associations between MRC-score and FEV1 [19-21]. FEV1 is an objective and well-validated measure of pulmonary function in patients with COPD, although the measurement includes possible sources of error [22-24]

The primary aim of this systematic review is therefore to investigate whether there is an association between lung function impairment defined as FEV1 in relation to expected value and anxiety or depression in patients with COPD.

Search strategy

A literature search was conducted using PubMed and Embase. The keywords searched were “Chronic obstructive pulmonary disease” and “Forced Expiratory Volume” and either “depression” and/or “anxiety”, both as MeSH and Emtree-terms and as broad search. Common synonyms as such were also included in the search. All English studies published between January 1975 and January 2024 were included. The reference lists of eligible studies were searched to identify other relevant studies. The whole search string is available in Appendix 1. The search was conducted, and the review prepared according to the PRISMA-guidelines, adhering to the PRISMA-checklist [25].

The protocol was submitted to PROSPERO prior to conduction of search [26].

Selection criteria

Only studies exclusively including patients with spirometry verified COPD according to GOLD-recommendations were included in this review [27]. As FEV1 is influenced by sex, age, ethnicity, and height [22], only studies using FEV1 in percentage of expected value (FEV1(%)) or Z-score for calculations were included. Studies were eligible if they reported a numerical risk of anxiety or depression compared to measured FEV1(%) or Z-score, combined with a p-value. Studies were eligible if anxiety or depression were defined as follows: A verified depression or anxiety scale, the use of medication or hospital diagnosis. Studies concerning both anxiety and depression were included, but only if they differentiated between anxiety and depression as separate diagnosis in the analysis.

Exclusion criteria were other pulmonary diseases than COPD, either as only respiratory disease or in conjunction with COPD and studies of mixed populations, that is studies with both patients with COPD and healthy subjects within the study population. Studies only reporting e.g. health related quality of life or unspecified mental illness were excluded.

The titles and abstracts were screened by two independent reviewers. Any study evaluated to be eligible by any reviewer underwent full text review by one reviewer. In case of disagreement on inclusion a third reviewer was consulted. The number of excluded studies and the reason for exclusion were noted in PRISMA flow chart (Figure 1).

Every study was assessed regarding risk of bias with a version of Newcastle Ottawa Quality Assessment Scale (NOS) adapted for cross-sectional studies by one reviewer [28]. The main highlights of the bias assessment were discussed in the discussion chapter. Scale and results can be seen in Appendix 2-3.

Data extraction

Outcomes were either depression or anxiety compared to FEV1(%) or Z-score. The selected articles were divided into two groups, either concerning depression or anxiety, but could also be included in both groups if both outcomes were reported separately. For each study, study population, number of participants, study type and anxiety and depression definition and prevalence were recorded. Moreover, basic information consisting of first author and year were recorded. The findings of the studies were recorded using the statistical outcome measure presented in the article (e.g. relative risk, odds ratio, hazard ratio, mean difference) combined with p-value.

The studies were grouped according to size to evaluate the influence of study size on significance. They were also grouped according to publication year of inclusion to evaluate the influence on significance, and an investigation on the relationship between study size and year of inclusion were conducted in both groups.

Selection Process

A systematic search was conducted on the29^th of January 2024. The selection process is presented in figure 1. Twenty-two studies which only reported FEV1(L), had study populations that did not meet the inclusion criteria or did not report anxiety or depression in an appropriate way were excluded and are presented in Appendix 4. Of the 37 studies included, 15 were allocated to the anxiety group and 31 were allocated to the depression group, as 9 studies reported both outcomes. The studies were published between 2002 and 2023. None of the studies used Z-values to define FEV1 in relation to reference measures, so FEV1(%) will be as definition of pulmonary function onwards.

Study results

Anxiety

The studies allocated to the anxiety group are presented in table 1. Fifteen studies were included. Most studies (13/15) were observational, the remaining intervention studies, and study population sizes varied from 40 to 2147. The prevalence of anxiety in the studies were between 9.9% to 54.5%. Of the included studies twelve studies showed non-significant results.

Definitions of anxiety were The State Trait Anxiety Inventory (STAI) (N=5), Hospital Anxiety and Depression Scale Anxiety Inventory (HADS-A) (N=4), Anxiety Disorder Interview Schedule IV (ADIS IV) (N=2), Hamilton Anxiety Rating Scale (HAM-A) (N=1), Beck Anxiety Inventory (BAI) (N=1), Generalized Anxiety Disorder 7 item (GAD) (N=1) and Anxiety Inventory for Respiratory Disease (N=1). In all the rating scales, a higher score means a higher risk of anxiety.

The number of significant studies relative to the size of the study populations in the anxiety group is presented in figure 2.

There were no apparent association between year of publication and proportion of studies with significant results in the anxiety group, and there is no apparent pattern in study population size with increasing publication year, with one study with significant result in the small and two in the medium group respectively and none in the large group. Further elaboration of this is available in Appendix 5A-B.

Depression

The studies allocated to the depression group are presented in table 2. Thirty-one studies were included. Most studies were observational (29/31), the remaining were intervention studies. Study population sizes varied between 54 to 2147. The prevalence of depression in the studies were between 5.8% to 54.7%. One study [51] used two completely different study populations with two different sets of results, and therefore these results will be presented as two studies, meaning we will count the included studies as 32 in the further analysis. A significant association between FEV1(%) and depression was found in 15 studies.

Definitions of depression in included studies were Center for Epidemiologic Studies Depression Scale (CES-D) (N=4), Becks Depression Inventory (BDI) (N=7), Brief Assessment Schedule Depression Cards (BASDEC) (N=1), Geriatric Depression Scale (GDS) (N=4), Hospital anxiety and depression scale for depression (HADS-D) (N=5), Hamilton Depression Rating Scale (HAM-D) (N=3), Self-rating Depression Scale (SDS) (N=2), Medical history (N=1), Personal Health Questionnaire 9 (PHQ-9) (N=4) and Mini international neuropsychiatric interview plus (N=1). In all the rating scales, a higher score means a higher risk of depression.

There was a trend against significant outcome being dependant on study size in the depression group (figure 3). All but one (6/7, 85.7%) study with a large study population found a significant association between FEV1(%) and depression while four of the studies in the group of small studies (4/9, 44.4%) showed significant association. In the medium group every third study showed significant results (5/16, 31.3%)

There was a trend in number of studies with a significant outcome increasing gradually towards recent publication years in the depression group, with 0/2 in 2000-2004 to 7/9 in 2020-2024. Study sizes also generally increased with time. Further elaboration of this is available in Appendix 5C-D.

Risk of bias assessment

The scores of the risk assessment ranged between 3/8 and 7/8, with a median of 5. All studies scored the maximum of 2/2 in the ‘Outcome’ assessment. Seven studies obtained any points in the ‘Comparability’ assessment, and fourteen in the ‘non-respondents’ assessment. Further details about Risk of bias assessment are available in Appendix 3.

This study finds no association between anxiety and lung function impairment, defined by FEV1(%), in 12 out of 15 eligible studies. There are inconsistent findings about a potential association between depression and FEV1(%), as 15 out of 32 studies show a significant negative association. In general, the eligible studies vary regarding study size, prevalence and definition of anxiety or depression, which to some degree could explain the inconsistency. Only half as many studies were allocated to the anxiety group compared to the depression group.

Associations between anxiety and impairment of pulmonary function

Most studies show no association between anxiety and FEV1(%). There are even studies showing positive correlation coefficients or higher FEV1(%) in patients with anxiety compared to patients without anxiety [30,33-34,36,40].

Three studies by Funk et al 2009 [31], Livermore et al 2012 [32] and Allam et al 2017 [37] found a significant negative association between FEV1(%) and anxiety, while one study by Hieba et al 2021 [38] found a slightly significant association with GOLD stage 1-4 but not FEV1(%). These studies had small to medium study sizes (62-150), so the significant association cannot be explained by study size. The study population sizes in studies with significant associations did not differ from the studies showing a positive, but non-significant association between FEV1(%) and anxiety (30-291) [30,33-34,36,40]. The study population sizes of the anxiety group were generally small, as only one study with a large study population was included.

The prevalence of anxiety was relatively inconspicuous in the significant studies (22-54.5%) compared to the other studies in the anxiety group (Table 1), and comparable to the studies showing positive non-significant associations (11.3%-50%) [30,33-34,36,40]. The differences in anxiety prevalence could be due to the use of different rating scales in different study populations. However, there does not seem to be a pattern in the use of anxiety rating scales, as e.g. two of the significant studies and two of the studies obtaining positive, but non-significant associations used HADS-A, though cut-off varied between 8-11 [31-31,37,40]. Though, a study on patients with Parkinson’s disease found a high association among various anxiety scales [63]. In general, there is a great degree of heterogeneity between prevalence of anxiety in the studies, which might influence the results.

The three significant studies were all conducted in outpatient clinics in Australia, Egypt and Australia respectively. The study population in Livermore et al [32] included only patients in GOLD group II and III, whereas Allam et al [37] and Funk et al [31] included patients with stable COPD. Exclusion criteria (other unstable diseases) were not substantially different compared to the remaining studies in the anxiety group, as most studies excluded unstable patients in general. Livermore et al [32] specifically investigated panic disorder, which differs from the other studies. The patients in the study by Allam et al [37] had an average FEV1(%) of 76.6%, as such mild COPD [22]. This was a considerably higher average FEV1(%) compared to the studies by Livermore et al [32] with an average FEV1(%) of 52.9% and in one of the largest studies by Hernández-Pérez et al, with an average of 58.0% [40]. It is possible that the rating scales have a different sensitivity and specificity in patients with severe COPD compared to mild COPD, as anxiety often mimics somatic symptoms [64].

The two studies with the youngest average age of study populations found a significant association between anxiety and FEV1(%). The average age of the patients included in the study by Allam et al [37] was 50.3 years, comparable to the study by Hieba et al [38] with an average age of 57.2 years, while the average age of the patients in the remaining studies was 60-75 years (table 2). Previous studies have shown that younger people are better at describing their symptoms as anxiety, which might have an impact on the result of a study [65]. It is outside of the scope of this study to determine if the risk factors of anxiety might be different in a younger population than in an older population, and further studies would be needed to investigate this.

The percentage of females was 25%, 44% and 56% respectively in the studies with significant findings [31-32,37]. As the study populations in the studies with non-significant results consisted of 3% to 61% women this does not separate the studies with significant results from the non-significant (table 2). In this review there is no indications of specific gender differences in the association between FEV1(%) and anxiety.

Four studies used a direct comparison of average FEV1(%) between patients with and without anxiety. Three studies directly compared the prevalence of anxiety in GOLD group 1-4. Eight studies used different correlation coefficients. The studies showing significant results used both direct comparisons and correlation coefficients [31-32,37] and the same applies for the studies showing non-significant positive associations [30,33-34,36,40]. While this does not support significance implications of the statistical method, as long as it is appropriate, there are other studies that could indicate that choice of statistical method has influenced outcome: Hieba et al 2021 [38] found a significant association between GOLD group 1-4, i.e. FEV1(%) as a categorical value, but no significant association with FEV1(%) as a continuous value. Opposed to that, a significant association between FEV1(%) and anxiety severity were found, but no association with GOLD group 1-4 [38]. It is not unreasonable to think that the choice of continuous versus categorical values could influence the results.

The consequence of great heterogeneity in both outcome, exposure and statistical methods makes comparison between studies challenging.

With three studies indicating a negative association and five indicating a positive association this review does not indicate any association between anxiety and COPD. However, most studies are small and show a great heterogeneity in study population, statistic method and definition of anxiety.

Associations between depression and impairment of pulmonary function

The definition of depression varies greatly between studies. Nine different scales were used, with BDI, PHQ-9 and HADS-D being the most frequent. Even among studies using the same scale, cut-off values vary greatly. For the studies using GDS, cut off values of for example 6, 8 and 11 have been used [48-49,55]. GDS is meaningful in screening for depression in patients >65 years, as common somatic symptoms in elderly (Loss of appetite, sleep disturbances, tiredness) and possible symptoms of dementia are not included [66]. Some studies using GDS, only including patients over a certain age [48,55], but two had no age limit or even excluded older patients >65 years [46,49]. The use in younger populations is not validated. Sensitivity and specificity of GDS is comparable to the other scales (~80%) [66].

The scale yielding the highest proportion of significant studies is PHQ-9, as three out of four studies using this scale, showed significant results [58-59,62]. This might be due to the large sample sizes in those studies (630-1800). Studies have shown a specificity and sensitivity using PHQ-9, similar to the other scales [66]. Only one of the four studies using CES-D showed any significant results [43,45,50-51]. CES-D was invented for epidemiologic studies. A review by Smarr Kl et al showed that the use of CES-C yields a high degree of false positives at cut-off >16, which three of the studies in this review used, while one used >24 [43,45,50-51, 66]. On the other hand, CES-D is sensitive to anxiety and might misclassify somatic symptoms as symptoms of psychiatric disease, which have not been shown to be associated to FEV1(%) in this study [66]. Nonetheless, all four studies using CES-D had a small-medium sample size, and may therefore lack statistical power [43,45,50-51]. The heterogeneity in the definition of depression between the studies may be reflected in the prevalence of depression, ranging between 5.8%-75% (Table 2).

Common symptoms of depression include somatic symptoms such as sleep disturbances, appetite loss and weight loss [67]. Studies have shown that sleep disturbances and sedentary behaviour lead to depression in the elderly [68]. It has also previously been shown that 70% of patients with COPD have some degree of sleep disturbances [69]. Patients with COPD have a high degree of sedentary behaviour, which is even higher in case of comorbid depression [52,70]. Thus, symptoms of depression and burden of illness can be hard to distinguish in patients with COPD, possibly leading to bias or residual confounding. Most studies exclude patients with other severe comorbidities or cognitive impairment, and some exclude the oldest patients [34,40,46,57,60]. Age, comorbidities and cognitive impairment that is highly prevalent in COPD [71], also hold a risk of bias, misclassification and residual confounding. The scores used in the studies to define depression could possibly act as confounders in themselves, but it cannot be confirmed in this review.

The only large study without unambiguous significant results was Miravitlles et al [52]. Depression was here defined as BDI >10, which was the most commonly used cut-off value in the studies using BDI. Nevertheless, a prevalence of mild degree of depression of 74.6% and moderate to severe degree of depression of 51.1%, suggests a higher prevalence in this study than most studies in this review (table 2). In Miravitlles et al, the degree of depression as a continuous value, rather than categorical, was significantly correlated to FEV1(%). This suggests a significant association between depression and FEV1(%), after all. As most patients was allocated to the depression group, the heterogeneity of this group could be too big to obtain significant results when using categorical values for depression [52].

Studies have suggested that the increased mental health awareness in the last decade has led to overinterpretation of normal emotions as pathological by the individual [72]. Though the perception of depression and mental illness have changed over time, it is not clear whether time of publication was a significant confounder, as there is no apparent pattern with higher prevalence of anxiety and depression over time in this review.

Almost all of the large studies showed a significant association between FEV1(%) and depression, and even the remaining large study showed some significant results [52]. This indicates that a larger sample size is needed to obtain the power to carry studies in affective diseases in patients with COPD. All the studies with small to medium sized study populations, apart from one, show a trend of lower FEV1(%) in patients with depression, compared to patients without depression. Thus, this review suggests there may be an association between FEV1(%) and depression.

Limitations

As is the case with systematic reviews this review is susceptible to publication bias or outcome reporting bias [73]. Conference abstracts were not included, and it is possible that some data could have been retrieved from those.

Strict selection criteria increase the homogeneity and makes it possible to compare studies, but also increase the risk of exclusion-bias. Three studies mentioned FEV1(%) in a group of COPD patients with and without depression or anxiety but did not perform significance testing. FEV1(L) is not useful in this systematic review because it fluctuates with sex, age, ethnicity and height [22], and sixteen studies were excluded for only reporting FEV1(L). It could lead to bias if FEV1(%) was deliberately excluded from those studies because of non-significance or if demographic characteristics differ between groups or studies.

Many of the included studies had small to modest sample sizes, increasing the risk of lack of power, leading to an underestimation of the association between anxiety or depression and FEV1(%).

Quality assessments were done using NOS. As statistical analysis with p-value and appropriate definition of outcome were parts of selection criteria, all studies scored the maximum of two stars in the ‘Outcome’ evaluation. All studies also obtained the pulmonary function in an appropriate way, as spirometry verified COPD was a part of selection criteria. Therefore, all studies scored at least 3/8 points. The studies with smaller sample sizes would be susceptible to bias, which is also reflected in a lower NOS-score. At study level the greatest risks of bias would be the lack of control for confounders, especially symptoms, and unexplained non-respondents. Most studies (23/32) failed to inform about non-respondents, and even if they did, the risk of bias would not be completely eliminated. A previous study has found a greater risk of depressive symptoms in non-respondents [74] which could also be the case for these studies. Most studies did not control for confounders. The most important confounder would probably be symptoms of COPD, since previous studies have found a link between the symptom burden and both FEV1(%) and anxiety or depression [6-8,14,15,75].

Most studies included patients from outpatient clinics or rehabilitation. Whether this gives a satisfactory external validity depends on the access to these facilities (e.g waiting lists, referral criterions and payment), which would differ greatly from country to country. Most studies did not describe this. It is reasonable to believe that the prevalence of anxiety or depression could depend on whether patients in the study are stable or not, as a greater burden of symptoms earlier have shown to lead to anxiety and depression [6-8,14,15]. An influence on the results from selection bias on study level is definitely possible.

There was a great degree of heterogeneity between studies, which is especially evident when assessing the prevalence of depression and anxiety. It is possible that the risk of anxiety and depression differs between countries, as in the general population [76]. This review does not contain enough studies from each country, to enable evaluation of differences between nationalities.

Only three out of fifteen of studies investigating a correlation between anxiety and FEV1(%) showed significant results, while some even showed a reverse trend, which does not support an association between anxiety and impairment of pulmonary function. However, there may be indications of an association between anxiety and severe COPD.

The review indicates an association between depression and impairment of pulmonary function. However, investigation of any correlation should be investigated in large cohorts.

COPD: Chronic obstructive pulmonary disease

FEV1(%): Forced expiratory volume in one second in percentage of expected value

FEV1(L): Forced expiratory volume in one second in Liters

MRC: Medical Research Council Dyspnoea Scale

6MWT: 6 minute walk test

GOLD: Global Initiative for Chronic Obstructive Lung Disease

STAI: The State Trait Anxiety Inventory

HADS-A: Hospital Anxiety and Depression Scale Anxiety Inventory

ADIS IV: Anxiety Disorder Interview Schedule IV

HAM-A: Hamilton Anxiety Rating Scale

BAI: Beck Anxiety Inventory

GAD: Generalized Anxiety Disorder 7 item

AIR: Anxiety Inventory for Respiratory Disease

CES-D: Center for Epidemiologic Studies Depression Scale

BDI: Becks Depression Inventory

BASDEC: Brief Assessment Schedule Depression Cards

GDS: Geriatric Depression Scale

HADS-D: Hospital anxiety and depression scale for depression

HAM-D: Hamilton Depression Rating Scale (HAM-D)

SDS: Self-rating Depression Scale

PHQ-9: Personal Health Questionnaire 9

Sources of funding

Funding was received form the Danish Lung Association. The Danish Lung Association did only offer funding and did not take part in the conduction of this review or writing of manuscript.

Differences between protocol and review

Since submission of the protocol, the title of the project has been changed from ‘correlation between impairment of lung function and risk of depression and anxiety in patients with chronic obstructive pulmonary disease - A systematic review’ to ‘Association between impairment of lung function and risk of depression and anxiety in patients with chronic obstructive pulmonary disease - A systematic review’, as the team agreed that association was more fitting than correlation to describe the review.

As the use of Z-scores when describing pulmonary functions become more widespread in clinical settings, it was decided to include studies using Z-scores. Though, no studies using Z-scores were found.

It was decided to apply an official risk of bias tool, Newcastle Ottawa Risk Assessment Tool, to obtain an overview over, where the greatest challenges regarding bias were.

Competing interests

The authors declare that they have no competing interests

Ethics approval

Not applicable.

Consent for publication

Not applicable

Availability of data and materials

Entire search string for each publicly available database is available in appendix 1

Contributions of authors

Johanne Hermann Karlsen (JHK), Kirstine Hermann Jørgensen (KHJ) and Ulla Møller Weinreich (UMW) all contributed to the planning of the study. JHK wrote and submitted the final protocol to PROSPERO.

JHK conducted the search with help of a medical librarian and removed duplicates. JHK and KHJ conducted the screening of studies on title and abstract. JHK conducted the full text screening. UMW resolved discrepancies in the selection process as third part.

Primary draft for manuscript were prepared by JHK. KHJ and UMW contributed to the content and embodiment of the manuscript.

Acknowledgements

Anja Gamskjær Hansen, Medical librarian at the Library of Aalborg University Hospital, Denmark, assisted in creating the search string.

Organisation WH. The Top Ten Causes of Death 2024 [updated 9/12-2020; cited 2024 5/1-24 ]. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
Willgoss TG, Yohannes AM. Anxiety disorders in patients with COPD: a systematic review. Respir Care. 2013;58(5):858-66.
Matte DL, Pizzichini MM, Hoepers AT, Diaz AP, Karloh M, Dias M, et al. Prevalence of depression in COPD: A systematic review and meta-analysis of controlled studies. Respir Med. 2016;117:154-61.
Pooler A, Beech R. Examining the relationship between anxiety and depression and exacerbations of COPD which result in hospital admission: a systematic review. Int J Chron Obstruct Pulmon Dis. 2014;9:315-30.
Panagioti M, Scott C, Blakemore A, Coventry PA. Overview of the prevalence, impact, and management of depression and anxiety in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2014;9:1289-306.
Xiao T, Qiu H, Chen Y, Zhou X, Wu K, Ruan X, et al. Prevalence of anxiety and depression symptoms and their associated factors in mild COPD patients from community settings, Shanghai, China: a cross-sectional study. BMC Psychiatry. 2018;18(1):89.
Janssen DJ, Spruit MA, Leue C, Gijsen C, Hameleers H, Schols JM, et al. Symptoms of anxiety and depression in COPD patients entering pulmonary rehabilitation. Chron Respir Dis. 2010;7(3):147-57.
Di Marco F, Verga M, Reggente M, Maria Casanova F, Santus P, Blasi F, et al. Anxiety and depression in COPD patients: The roles of gender and disease severity. Respiratory Medicine. 2006;100(10):1767-74.
Lou P, Zhu Y, Chen P, Zhang P, Yu J, Zhang N, et al. Prevalence and correlations with depression, anxiety, and other features in outpatients with chronic obstructive pulmonary disease in China: a cross-sectional case control study. BMC Pulm Med. 2012;12:53.
Laurin C, Lavoie KL, Bacon SL, Dupuis G, Lacoste G, Cartier A, et al. Sex differences in the prevalence of psychiatric disorders and psychological distress in patients with COPD. Chest. 2007;132(1):148-55.
Eisner MD, Blanc PD, Yelin EH, Katz PP, Sanchez G, Iribarren C, et al. Influence of anxiety on health outcomes in COPD. Thorax. 2010;65(3):229-34.
Iyer AS, Holm KE, Bhatt SP, Kim V, Kinney GL, Wamboldt FS, et al. Symptoms of anxiety and depression and use of anxiolytic-hypnotics and antidepressants in current and former smokers with and without COPD - A cross sectional analysis of the COPDGene cohort. J Psychosom Res. 2019;118:18-26.
Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581-6.
Martinez Rivera C, Costan Galicia J, Alcázar Navarrete B, Garcia-Polo C, Ruiz Iturriaga LA, Herrejón A, et al. Factors Associated with Depression in COPD: A Multicenter Study. Lung. 2016;194(3):335-43.
Biswas D, Mukherjee S, Chakroborty R, Chatterjee S, Rath S, Das R, et al. Occurrence of anxiety and depression among stable COPD patients and its impact on functional capability. Journal of Clinical and Diagnostic Research. 2017;11(2):OC24-OC7.
Sunjaya A, Poulos L, Reddel H, Jenkins C. Qualitative validation of the modified Medical Research Council (mMRC) dyspnoea scale as a patient-reported measure of breathlessness severity. Respir Med. 2022;203:106984.
Pessoa BV, Arcuri JF, Labadessa IG, Costa JN, Sentanin AC, Di Lorenzo VA. Validity of the six-minute step test of free cadence in patients with chronic obstructive pulmonary disease. Braz J Phys Ther. 2014;18(3):228-36.
Borgmann M, Ivanda M, Hadizamani Y, Mohaupt M, Bals R, Lucas R, et al. Does the 6-minute walk test in hospitalized COPD patients exclusively correlate with lung function parameters or should psychological factors also be taken into account? PLoS One. 2020;15(5):e0232587.
Hayata A, Minakata Y, Matsunaga K, Nakanishi M, Yamamoto N. Differences in physical activity according to mMRC grade in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2203-8.
Huang WC, Wu MF, Chen HC, Hsu JY. Features of COPD patients by comparing CAT with mMRC: a retrospective, cross-sectional study. NPJ Prim Care Respir Med. 2015;25:15063.
Chai CS, Ng DL, Bt Mos S, Ibrahim MAB, Tan SB, Pang YK, et al. COPD exacerbations and patient-reported outcomes according to post-bronchodilator FEV(1) - a post-hoc analysis of pooled data. BMC Pulm Med. 2023;23(1):150.
Liou TG, Kanner RE. Spirometry. Clin Rev Allergy Immunol. 2009;37(3):137-52.
Han MZ, Hsiue TR, Tsai SH, Huang TH, Liao XM, Chen CZ. Validation of the GOLD 2017 and new 16 subgroups (1A-4D) classifications in predicting exacerbation and mortality in COPD patients. Int J Chron Obstructf Pulmon Dis. 2018;13:3425-33.
Antonelli-Incalzi R, Imperiale C, Bellia V, Catalano F, Scichilone N, Pistelli R, et al. Do GOLD stages of COPD severity really correspond to differences in health status? European Respiratory Journal. 2003;22(3):444-9.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
Johanne Karlsen, Kirstine Hermann Jørgensen, Ulla Møller Weinreich. Correlation between impairment in lung function and risk of depression and anxiety in patients with COPD. PROSPERO 2024 CRD42024506065 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506065
Terry PD, Dhand R. The 2023 GOLD Report: Updated Guidelines for Inhaled Pharmacological Therapy in Patients with Stable COPD. Pulmonary Therapy. 2023;9(3):345-57.
GA Wells BS, D O'Connell, J Peterson, V Welch, M Losos, P Tugwell. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.]
Livermore N, Butler JE, Sharpe L, McBain RA, Gandevia SC, McKenzie DK. Panic attacks and perception of inspiratory resistive loads in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;178(1):7-12.
Howard C, Hallas CN, Wray J, Carby M. The relationship between illness perceptions and panic in chronic obstructive pulmonary disease. Behaviour Research and Therapy. 2009;47(1):71-6.
Funk GC, Kirchheiner K, Burghuber OC, Hartl S. BODE index versus GOLD classification for explaining anxious and depressive symptoms in patients with COPD - a cross-sectional study. Respiratory Research. 2009;10.
Livermore N, Sharpe L, McKenzie D. Catastrophic interpretations and anxiety sensitivity as predictors of panic-spectrum psychopathology in chronic obstructive pulmonary disease. Journal of Psychosomatic Research. 2012;72(5):388-92.
Suh S, Ellis RJ, Sollers JJ, 3rd, Thayer JF, Yang HC, Emery CF. The effect of anxiety on heart rate variability, depression, and sleep in chronic obstructive pulmonary disease. J Psychosom Res. 2013;74(5):407-13.
Tselebis A, Bratis D, Pachi A, Moussas G, Ilias I, Harikiopoulou M, et al. A pulmonary rehabilitation program reduces levels of anxiety and depression in COPD patients. Multidisciplinary Respiratory Medicine. 2013;8(5).
Elassal G, Elsheikh M, Abu Zeid AG. Assessment of depression and anxiety symptoms in chronic obstructive pulmonary disease patients: A case-control study. Egyptian Journal of Chest Diseases and Tuberculosis. 2014;63(3):575-82.
Yohannes AM, Dryden S, Hanania NA. The Responsiveness of the Anxiety Inventory for Respiratory Disease Scale Following Pulmonary Rehabilitation. Chest. 2016;150(1):188-95.
Allam AH, Rawy AM, Abdeldayem OM, Mogahed MM, Abdelazeem E. Prevalence of anxiety and depression in patients with airway obstruction using hospital anxiety and depression scale (HADS) in different localities of Saudi Arabia. Egyptian Journal of Chest Diseases and Tuberculosis. 2017;66(4):617-22.
Hieba E, Rehab M, Noha A. Anxiety among Egyptian patients with stable chronic obstructive pulmonary disease and its effect on their functional assessment. Egyptian Journal of Chest Diseases and Tuberculosis. 2021;70(3):344-50.
Yoshida M, Hiramoto T, Moriwaki A, Osoreda H, Iwanaga T, Inoue H. Impact of extrapulmonary comorbidities on physical activity in chronic obstructive pulmonary disease in Japan: A cross-sectional study. PLoS ONE. 2022;17(7 July).
Hernández-Pérez A, Vargas-Núñez I, Moreno-Jiménez B, Pérez-Padilla R, Ramírez-Venegas A. Affective Comorbidity Associated with Symptoms, Lung Function, and Differences Between Patients with COPD for Biomass and Tobacco Smoke Exposure. Journal of Clinical Psychology in Medical Settings. 2022;29(2):310-7.
Hong YJ, Kim Y, Moon JY, Park S, Lee JK, Jung KS, et al. Associations between depression and anxiety index and frequency of acute exacerbation in chronic obstructive pulmonary disease. Therapeutic Advances in Respiratory Disease. 2023;17.
Liu M, Wang D, Fang J, Chang Y, Hu Y, Huang K. Validation of the Generalized Anxiety Disorder-7 in patients with COPD: a cross-sectional study. BMC Psychiatry. 2023;23(1).
Van Manen JG, Bindels PJE, Dekker FW, Ijzermans CJ, Van der Zee JS, Schadé E. Risk of depression in patients with chronic obstructive pulmonary disease and its determinants. Thorax. 2002;57(5):412-6.
Chavannes NH, Huibers MJH, Schermer TRJ, Hendriks A, van Weel C, Wouters EFM, et al. Associations of depressive symptoms with gender, body mass index and dyspnea in primary care COPD patients. Family Practice. 2005;22(6):604-7.
Al-shair K, Dockry R, Mallia-Milanes B, Kolsum U, Singh D, Vestbo J. Depression and its relationship with poor exercise capacity, BODE index and muscle wasting in COPD. Respiratory Medicine. 2009;103(10):1572-9.
Omachi TA, Katz PP, Yelin EH, Gregorich SE, Iribarren C, Blanc PD, et al. Depression and health-related quality of life in chronic obstructive pulmonary disease. Am J Med. 2009;122(8):778.e9-15.
De Voogd JN, Wempe JB, Koëter GH, Postema K, Van Sonderen E, Ranchor AV, et al. Depressive symptoms as predictors of mortality in patients with COPD. Chest. 2009;135(3):619-25.
Halabi S, Collins EG, Thorevska N, Tobin MJ, Laghi F. Relationship between depressive symptoms and hypogonadism in men with COPD. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2011;8(5):346-53.
Horita N, Kaneko T, Shinkai M, Yomota M, Morita S, Mengr BKR, et al. Depression in Japanese patients with chronic obstructive pulmonary disease: A cross-sectional study. Respiratory Care. 2013;58(7):1196-203.
Iguchi A, Senjyu H, Hayashi Y, Kanada R, Iwai S, Honda S, et al. Relationship between depression in patients with COPD and the percent of predicted FEV1, BODE index, and health-related quality of life. Respiratory Care. 2013;58(2):334-9.
Kim KU, Park HK, Jung HY, Ahn JJ, Moon E, Kim YS, et al. Association of depression with disease severity in patients with chronic obstructive pulmonary disease. Lung. 2014;192(2):243-9.
Miravitlles M, Molina J, Quintano JA, Campuzano A, Pérez J, Roncero C. Factors associated with depression and severe depression in patients with COPD. Respiratory Medicine. 2014;108(11):1615-25.
Battaglia S, Basile M, Scichilone N, Bellia V. Prevalence of Co-morbidities and severity of COPD. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2015;12(4):390-4.
Orlandi Lde C, Pinho JF, Murad MG, Rocha FL, Rodrigues-Machado MG. Depression diagnosed by the mini international neuropsychiatric interview plus (MINI) in patients with chronic obstructive pulmonary disease: relationship with functional capacity and quality of life. BMC Res Notes. 2016;9:65.
Tse HN, Tseng CZ, Wong KY, Ng LY, Lai TL, Yee KS. Frequent Exacerbator: The Phenotype at Risk of Depressive Symptoms in Geriatric COPD Patients. Lung. 2016;194(4):665-73.
Lee JH, Park MA, Park MJ, Jo YS. Clinical characteristics and related risk factors of depression in patients with early COPD. International Journal of COPD. 2018;13:1583-90.
Sharma K, Jain A, Goyal V, Goel N, Takhar R, Singh V, et al. Depression and physical activity impairment in COPD subjects. Journal of Clinical and Diagnostic Research. 2019;13(7):OC16-OC22.
Yang K, Wu Y, Chen D, Liu S, Chen R. The impact of lung function on extra-pulmonary diseases and all-cause mortality in us adult population with and without copd. Clinical Epidemiology. 2020;12:997-1005.
Choi JS, Kwak SH, Son NH, Oh JW, Lee S, Lee EH. Sex differences in risk factors for depressive symptoms in patients with COPD: The 2014 and 2016 Korea National Health and Nutrition Examination Survey. BMC Pulmonary Medicine. 2021;21(1).
Strollo HC, Nouraie SM, Hoth KF, Riley CM, Karoleski C, Zhang Y, et al. Association of Systemic Inflammation with Depressive Symptoms in Individuals with COPD. International Journal of COPD. 2021;16:2515-22.
Zhang T, Wang G, Li Q, Yan P, Sun J, Jin Y. Relationship between serum Th1/Th2 imbalance and depression in elderly patients with COPD and its clinical implications. Technology and Health Care. 2023;31(6):2047-58.
Horner A, Olschewski H, Hartl S, Valipour A, Funk GC, Studnicka M, et al. Physical Activity, Depression and Quality of Life in COPD - Results from the CLARA II Study. Int J Chron Obstruct Pulmon Dis. 2023;18:2755-67.
Mondolo F, Jahanshahi M, Granà A, Biasutti E, Cacciatori E, Di Benedetto P. Evaluation of anxiety in Parkinson's disease with some commonly used rating scales. Neurol Sci. 2007;28(5):270-5.
Organisation WH. Anxiety Disorders 2023 [Available from: https://www.who.int/news-room/fact-sheets/detail/anxiety-disorders. 23rd February 2024
Wetherell JL, Petkus AJ, McChesney K, Stein MB, Judd PH, Rockwell E, et al. Older adults are less accurate than younger adults at identifying symptoms of anxiety and depression. J Nerv Ment Dis. 2009;197(8):623-6.
Smarr KL, Keefer AL. Measures of depression and depressive symptoms: Beck Depression Inventory-II (BDI-II), Center for Epidemiologic Studies Depression Scale (CES-D), Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S454-66. doi: 10.1002/acr.20556. PMID: 22588766.
Poul Videbech KC, Maj Vinberg. Diagnosticering af Depressioner [updated 20 Feb 2023. Available from: https://pro.medicin.dk/Sygdomme/Sygdom/318201.
Luo Y, Li Y, Xie J, Duan Y, Gan G, Zhou Y, et al. Symptoms of depression are related to sedentary behavior and sleep duration in elderly individuals: A cross-sectional study of 49,317 older Chinese adults. J Affect Disord. 2022;308:407-12.
Miravitlles M, Ribera A. Understanding the impact of symptoms on the burden of COPD. Respir Res. 2017;18(1):67.
Lei Y, Zou K, Xin J, Wang Z, Liang K, Zhao L, Ma X. Sedentary behavior is associated with chronic obstructive pulmonary disease: A generalized propensity score-weighted analysis. Medicine (Baltimore). 2021;100(18):e25336.
Mahler DA, Halpin DMG. Consideration and Assessment of Patient Factors When Selecting an Inhaled Delivery System in COPD. Chest. 2024;165(2):323-32.
Foulkes L, Andrews JL. Are mental health awareness efforts contributing to the rise in reported mental health problems? A call to test the prevalence inflation hypothesis. New Ideas in Psychology. 2023;69:101010.
Drucker AM, Fleming P, Chan AW. Research Techniques Made Simple: Assessing Risk of Bias in Systematic Reviews. J Invest Dermatol. 2016;136(11):e109-e14.
Nwaru CA, Lövestad S, Gunnarsdóttir H, Sundh V, Hensing G. Determinants of non-response in a longitudinal study of participants in the Women and Alcohol in Gothenburg project. Women Health. 2021;61(5):452-60.
Zhou Y, Ampon MR, Abramson MJ, James AL, Maguire GP, Wood-Baker R, et al. Risk factors and clinical characteristics of breathlessness in Australian adults: Data from the BOLD Australia study. Chron Respir Dis. 2023;20:14799731231221820.
Luo J, Tang L, Kong X, Li Y. Global, regional, and national burdens of depressive disorders in adolescents and young adults aged 10–24 years from 1990 to 2019: A trend analysis based on the Global Burden of Disease Study 2019. Asian Journal of Psychiatry. 2024;92:103905.

Table 1. Studies allocated to the anxiety group

Name	Study type	Subjects	Patient population	Anxiety Prevalence	Anxiety definition	Results	Significant association?
Di Marco 2006 [8]	Observational	202	From a Respiratory Unit, Italy	28.2%	STAI >45	Anxiety prevalence compared in GOLD group 1-4. P-value 0,256.	No
Livermore N 2008 [29]	Case-Control	40	From an outpatient clinic, Australia	Unknown	ADIS-IV	FEV1 (%) compared between patients with panic disorder (80.1%) and no panic disorder (82.2%) (P-value 0.71)	No
Howard C 2009 [30]	Observational	59	From a cardiothoracic centre, UK	35%	HADS-A >11	Correlation coefficient between anxiety and FEV1(%) 0.005 (p-value >0.05)	No
Funk GC 2009 [31]	Observational	122	From an outpatient clinic, Austria, >18 years	49%	HADS-A >8	FEV1 (%) compared in patients with anxiety (40.5%) and no anxiety (48.3%) (p-value 0.025)	Yes
Livermore N 2012 [32]	Observational	62	From a Respiratory Medical Department, Australia, COPD stage GOLD II-III	40.3	ADIS-IV	FEV1 (%) correlation with panic, correlation coefficient β= -0.05 (p-value 0.04)	Yes
Suh S 2013 [33]	Observational study	30	From a pulmonary rehabilitation program, USA	50%	STAI	FEV1(%) compared between patients with anxiety (55.7%) and no anxiety (52.4%) (p-value >0.05)	No
Tselebis A 2013 [34]	Intervention study	101	From a rehabilitation program, Greece, <80 years	25-47.6%	STAI	Correlation coefficient between anxiety and FEV1 (%) r= 0.034 (p-value >0.05)	No
Elassal G 2014 [35]	Case-control	80	Out- and inpatients, Egypt	22.5%	HAM-A	Correlation coefficient between anxiety and FEV1(%) r = -0.182 (p-value 0.108)	No
Yohannes AM 2016 [36]	Observational	257	From a rehabilitation program, United Kingdom	29.2%	AIR >8	Correlation coefficient between FEV1 (%) and anxiety r=0.02 (p-value 0.82)	No
Allam AH 2017 [37]	Observational	150	From an outpatient clinic, Egypt, >18 years	22%	HADS-A >11	Correlation coefficient between FEV1 (%) and anxiety r=-0.66 (p-value 0.001)	Yes
Hieba E 2021 [38]	Observational	110	From an outpatient clinic, Egypt.	54.5%	STAI >38	Correlation coefficient between anxiety and FEV1 (%) r= −0.178 (p-value 0.063) Correlation coefficient between anxiety and GOLD stage (%) r= 0.194 (p-value 0.042)	No/Yes
Yoshida M 2022 [39]	Intervention study	60	From an outpatient clinic, Japan	9.9-10.2%	STAI	Distribution of subjects in GOLD 1-4 with anxiety (GOLD1 11.27% –GOLD 4 12.0%) compared with whole cohort (p-value 0.147)	No
Hernández-Pérez A 2022 [40]	Observational	291	From an outpatient clinic, Mexico, 60-85 years,	11.3%	HADS-A >8	Correlation coefficient between FEV1(%) and anxiety r=0.009 (p-value 0.873)	No
Hong YJ. 2023 [41]	Observational	2147	From a cohort study, Korea, >40 years,	19.3%	BAI >8	Distribution of subjects in GOLD 1-4 in patients with anxiety (GOLD1 13.1% –GOLD4 9.6%) and without (GOLD1 15.1% –GOLD4 6.2%) (p-value 0.319)	No
Liu M 2023 [42]	Observational	226	From a cohort study, China, >40 years old.	22.1%	GAD7 >5	FEV1 (%) compared in patients with anxiety (62.9%) and no anxiety (67.4) (p-value 0.204)	No

Table 2. Studies allocated to the depression group

Study	Study type	Subjects	Patient population	Prevalence of depression	Depression definition	Results	Significant?
van Manen JG 2002 [43]	Observational	163	From general practice, Netherlands	21.6%	CES-D >16	FEV1 <50% Adjusted OR 0.8 (CI 0.3-2.5) for depression compared to FEV1 >50%.	No
NH Chavannes 2005 [44]	Observational	147	From general practices, Netherlands	27.2%	BDI >10	OR 1.0 (CI 0.98-1.02) of average FEV1 (%) in patients with depressive symptoms compared to patients without (p-value >0.05)	No
Di Marco 2006 [8]	Observational	202	From an outpatient clinic, Italy	18.8%	SDS >50	Prevalence of depression in GOLD group 1-4, comparison between groups. P-value 0,636.	No
Al-shair K 2009 [45]	Observational	122	Recruited from media advertising, a Medicines Evaluation Unit, and Outpatient clinic, England.	1: 18.9% 2: 23.7%	1: BASDEC >7 or 2: CES-D Scale >16	1: Difference in FEV1(%) between patients with depression (50.1%) and without (52.3%) (p-value 0.56) 2: 1: Difference in FEV1(%) between patients with depression (50.4%) and without (52.4%) (p-value 0.59)	No
Omachi TA 2009 [46]	Observational	1202	From an ongoing cohort study, USA, 40-65 years of age.	27%	GDS >6	Multivariate analysis, OR between every 23% decrement in FEV1 (%) and risk of depression (p-value 0.03)	Yes
Howard C 2009 [30]	Observational	59	From a cardiothoracic centre, UK	19%	HADS-D >11	Correlation coefficient between depression and FEV1(%) -0.120 (p-value >0.05)	No
Funk GC 2009 [31]	Observational	122	From an outpatient clinic and a hospital ward, Austria, >18 years	52%	HADS-D >8	Difference in FEV1(%) between patients with depression (37.0%) and without (52.5%) (p-value 0.001)	Yes
de Voogd JN 2009 [47]	Observational	121	From pulmonary rehabilitation, the Netherlands.	16.5%	BDI >19 Highly depressed	Correlation coefficient between FEV1 (%) and depression r=–0.01 (p-value >0.05)	No
Halabi S 2011 [48]	Observational	104	From an outpatient clinic, England, Men, >55 years	34.6%	GDS >11	Difference in FEV1(%) between patients with depression (42%) and without (44%) (p-value 0.421)	No
Horita N 2013 [49]	Observational	84	From three hospitals, Japan, Saturation >90%. Able to perform 6MWT.	38.1%	GDS >6	Difference in FEV1(%) between patients with depression (38%) and without (51%) (p-value >0.001)	Yes
Iguchi A 2013 [50]	Observational	74	From pulmonary rehabilitations and in-patients from a pulmonary department, Japan	48.6%	CES-D >16	Correlation coefficient between FEV1(%) and depression r = -0.29 (p-value 0.01)	Yes
Tselebis A 2013 [34]	Intervention study	101	Patients from a rehabilitation program, Greece, <80 years old	47.5%	BDI	Correlation coefficient between depression and FEV1(%) 0.01 (p-value >0.05)	No
Kim KU 2014 [51]	Observational	245	From pulmonary outpatient clinic, Korea	17.6%	CES-D >24	Difference in FEV1(%) between patients with depression (60.6%) and without (60.4%) (p-value 0.959)	No
Elassal G 2014 [35]	Case-control	80	Out- and inpatients, Egypt	42.5%	HAM-D	Correlation coefficient between FEV1 (%) and depression r = -0.262 (p-value 0.019)	Yes
Miravitlles M 2014 [52]	Observational	836	From outpatient clinics, Spain, >40 years, >10 pack years.	51.1% moderate to severe	BDI >10	Difference in FEV1(%) between patients with depression 51.6%) and without (53.6%) (p-value 0.15) Difference in FEV1(%) between patients with mild depression (53.6%) and severe depression (48.9%) (p-value 0.01)	No
Battaglia S 2015 [53]	Observational	326	From an outpatient clinic, Italy	5.8%	Medical history	Prevalence of depression in GOLD 1 (4.3%), GOLD 2 (3.5%), GOLD 3 (5.7%) and GOLD 4 (8%) (p-value >0.05)	No
Martinez Rivera C 2016 [14]	Observational	115	From outpatient clinics, Spain, >40 years and >10 pack years.	24.3%	HADS-D >8	Difference in FEV1(%) between patients with depression (38.8%) and without (46.2%) (p-value 0.02)	Yes
Orlandi Le 2016 [54]	Observational	54	From an outpatient clinic, >40 years, Brazil	22.2%	Mini international neuropsychiatric interview plus	Difference in FEV1(%) between patients with depression (51.9%) and without (43.6%) (p-value 0.108)	No
Tse HN 2016 [55]	Observational	89	From a geriatric and COPD clinic, Hong-Kong, >60 years.	20.22%	GDS >8	Difference in FEV1(%) between patients with depression (38.7%) and without (46.1%) (p-value 0.15)	No
Allam AH 2017 [37]	Observational	150	From an outpatient clinic, Egypt, >18 years	14%	HADS-D >11	Correlation coefficient between FEV1 (%) and depression r=-0.57 (p-value 0.001)	Yes
Biswas D 2017 [15]	Observational	75	From an outpatient clinic, India	54.7%	HAM-D >8	Difference in FEV1(%) between patients with depression (47%) and without (54.5%) (p-value 0.178)	No
Lee JH 2018 [56]	Observational	211	From a registry, Korea, FEV1>50%, >40 years,	14.2%	PHQ-9 >27	Difference in FEV1(%) between patients with depression (77.7%) and without (80.1%) (p-value 0.35)	No
Sharma K 2019 [57]	Observational	120	From an outpatient clinic, India, 40-80 years.	75%	HAM-D >8	Difference in FEV1(%) between patients with depression (62.1%) and without (82.5%) (p-value >0.001)	Yes
Yang K 2020 [58]	Observational	1800	From an American registry	23.5%	PHQ-9 >4	Odds ratio of depression compared to FEV1 (%) OR=1.15 (p-value 0,004)	Yes
Choi JS 2021 [59]	Observational	877	From a Korean registry, >40 years	17.8%	PHQ-9 >5	Distribution of subjects in GOLD 1-4 in patients with depression (GOLD1 48.1% –GOLD 4 8.9%) and without (GOLD1 51.7% –GOLD 4 3.8%) (p-value 0.019)	Yes
Strollo HC 2021 [60]	Observational	1: 220 2: 745	1: From an American cohort,>40 years, >10 pack years. 2: From an American cohort, 2008-2011, 45-80 years, >10 pack years,	1: 21.4% 2: 13.0%	1,2: BDI >9	1: Distribution of subjects in GOLD 1-4 in patient with depression (GOLD1 17.0% –GOLD 4 4.3%) and without (GOLD1 34.1% –GOLD 4 0.1%) (p-value 0.01) 2: Distribution of patients in GOLD 1-4 with depression (GOLD1 11.3% –GOLD 4 19.6%) and without (GOLD1 24.4% –GOLD 4 9.6%) (p-value 0.002)	1: Yes 2: Yes
Hernández-Pérez A 2022 [40]	Observational	291	From an outpatient clinic, Mexico, 60-85 years,	30.9%	HADS-D >6	Correlation coefficient between FEV1(%) and depression r=-0.03 (p-value 0.592)	No
Yoshida M 2022 [39]	Intervention study	60	From an outpatient clinic, Japan	9.31%	SDS	Distribution of subjects in GOLD 1-4 in patients with depression (GOLD1 8.65% –GOLD 4 7.59%) compared to whole cohort (p-value 0.147)	No
Hong YJ 2023 [41]	Observational	2147	From a cohort study, >40 years, Korea	27.4%	BDI >10	Distribution of patients in GOLD 1-4 with depression (GOLD1 8.1% –GOLD 4 12.3%) and without (GOLD1 13.0% –GOLD 4 7.4%) (p-value 0.008)	Yes
Zhang T 2023 [61]	Observational	55	From a hospital ward, China	45.9%	SDS >50	Difference in FEV1(%) between patients with depression (50.2%) and without (61.8%) (p-value >0.01)	Yes
Horner A 2023 [62]	Observational	630	From multiple outpatient clinics, Austria >40 years,	46.2%	PHQ-9 >5	Regression coefficient between FEV1(%) and depression −0.06 (p-value < 0.001)	Yes

Association between impairment of lung function and risk of anxiety and depression in patients with chronic obstructive pulmonary disease - A systematic review

Status:

Version 1

Abstract

Figures

Introduction

Methods

Search strategy

Selection criteria

Data extraction

Results

Selection Process

Study results

Anxiety

Depression

Risk of bias assessment

Discussion

Associations between anxiety and impairment of pulmonary function

Limitations

Conclusion

Abbreviations

Declarations

References

Tables

Supplementary Files

Status:

Version 1