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

Association between impairment of lung function and risk of anxiety and depression in patients with chronic obstructive pulmonary disease - A systematic review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association between impairment of lung function and risk of anxiety and depression in patients with chronic obstructive pulmonary disease - A systematic review Johanne Hermann Karlsen, Kirstine Hermann Jørgensen, Ulla Møller Weinreich This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4024678/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Dec, 2024 Read the published version in Systematic Reviews → Version 1 posted 5 You are reading this latest preprint version Abstract 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 Figures Figure 1 Figure 2 Figure 3 Introduction 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. Methods 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. Results 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. Discussion 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. Conclusion 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. Abbreviations 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 Declarations 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. 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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, 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%. 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, 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 Supplementary Files Appendixreview.docx PRISMAchecklist.docx Cite Share Download PDF Status: Published Journal Publication published 04 Dec, 2024 Read the published version in Systematic Reviews → Version 1 posted Editorial decision: Major revision 24 May, 2024 Reviewers agreed at journal 06 May, 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4024678","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":298998436,"identity":"10d8723b-dcdd-4d1e-98fe-958cc9e0aa63","order_by":0,"name":"Johanne Hermann Karlsen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAlklEQVRIiWNgGAWjYBACxgYGxgMMFSBmGvFaGA4wnCFFCwgcYGwjRQtze/OBgz/n3ctjYE9LINJhPccSDvNuKy5m4Hl2gEgtM3IMDjNuS0hskEhvIF7LwZ9zSNVygLcBpCWNWIeB/MJzLCGxjedZAnFaDNubDz78UZOQ2M+eZkCklgYog4049UAgT7TKUTAKRsEoGLkAAH7NLwDFVrp0AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0007-2379-5626","institution":"Aalborg Hospital: Aalborg Universitetshospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Johanne","middleName":"Hermann","lastName":"Karlsen","suffix":""},{"id":298998437,"identity":"686497b0-769e-48f2-bfc9-4637893a1309","order_by":1,"name":"Kirstine Hermann Jørgensen","email":"","orcid":"","institution":"Aarhus University Hospital Skejby: Aarhus Universitetshospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kirstine","middleName":"Hermann","lastName":"Jørgensen","suffix":""},{"id":298998438,"identity":"4dcc4739-6176-40b7-973b-ae27148cbe85","order_by":2,"name":"Ulla Møller Weinreich","email":"","orcid":"","institution":"Aalborg University Hospital: Aalborg Universitetshospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ulla","middleName":"Møller","lastName":"Weinreich","suffix":""}],"badges":[],"createdAt":"2024-03-07 13:31:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4024678/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4024678/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13643-024-02720-z","type":"published","date":"2024-12-04T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":56411357,"identity":"253ba225-814e-4781-a923-d0ca65c99622","added_by":"auto","created_at":"2024-05-13 20:27:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":540738,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart describing selection process of eligible studies (25)\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4024678/v1/bd4837a0e218c992094d3294.jpg"},{"id":56411354,"identity":"362dbfc9-58c8-4e3a-bfad-51663981d2f4","added_by":"auto","created_at":"2024-05-13 20:27:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":4547,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of studies significant and non-significant results compared to sample sizes in the anxiety group. The light downward parts are studies showing non-significant results and the dark upward parts are the studies showing significant results.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4024678/v1/ddff7301cb2e65f5d978be59.png"},{"id":56412252,"identity":"c35890de-833a-47d9-9614-b0849963bfc8","added_by":"auto","created_at":"2024-05-13 20:35:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":4547,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of studies showing significant and non-significant results compared to sample sizes in the depression group. The light downward parts are studies with non-significant results and the dark upward parts are studies showing significant results.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4024678/v1/1b247b26bee3ca16c5b29dae.png"},{"id":70965286,"identity":"f88db676-c00c-4a55-88cc-bc7a812ff5c3","added_by":"auto","created_at":"2024-12-09 16:18:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1358681,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4024678/v1/7ec7f18e-40b4-4b53-a3a1-ccbd1e725d8b.pdf"},{"id":56411358,"identity":"5e8e813c-e624-4e01-b88e-666b2538fe8b","added_by":"auto","created_at":"2024-05-13 20:27:08","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":58848,"visible":true,"origin":"","legend":"","description":"","filename":"Appendixreview.docx","url":"https://assets-eu.researchsquare.com/files/rs-4024678/v1/cbe590857f814f5882715cae.docx"},{"id":56411359,"identity":"b2ae6eec-88d5-4b49-8bf7-29b5a28c92e2","added_by":"auto","created_at":"2024-05-13 20:27:08","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":32457,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAchecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-4024678/v1/135285246bb52537767dae46.docx"}],"financialInterests":"","formattedTitle":"Association between impairment of lung function and risk of anxiety and depression in patients with chronic obstructive pulmonary disease - A systematic review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic 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.\u003c/p\u003e\n\u003cp\u003eSeveral 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].\u003c/p\u003e\n\u003cp\u003eIt 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].\u003c/p\u003e\n\u003cp\u003eResults 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].\u003c/p\u003e\n\u003cp\u003eMany 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]\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch3\u003eSearch strategy\u003c/h3\u003e\n\u003cp\u003eA literature search was conducted using PubMed and Embase. The keywords searched were \u0026ldquo;Chronic obstructive pulmonary disease\u0026rdquo; and \u0026ldquo;Forced Expiratory Volume\u0026rdquo; and either \u0026ldquo;depression\u0026rdquo; and/or \u0026ldquo;anxiety\u0026rdquo;, 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].\u003c/p\u003e\n\u003cp\u003eThe protocol was submitted to PROSPERO prior to conduction of search [26].\u003c/p\u003e\n\u003ch3\u003eSelection criteria\u003c/h3\u003e\n\u003cp\u003eOnly 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.\u003c/p\u003e\n\u003cp\u003eExclusion 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.\u003c/p\u003e\n\u003cp\u003eThe 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.\u0026nbsp;The number of excluded studies and the reason for exclusion were noted in PRISMA flow chart (Figure 1).\u003c/p\u003e\n\u003cp\u003eEvery 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.\u003c/p\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003eOutcomes 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.\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e"},{"header":"Results","content":"\u003ch3\u003eSelection Process\u003c/h3\u003e\n\u003cp\u003eA systematic search was conducted on the29\u003csup\u003eth\u003c/sup\u003e 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.\u003c/p\u003e\n\u003ch3\u003eStudy results\u003c/h3\u003e\n\u003ch3\u003eAnxiety\u003c/h3\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\n\u003cp\u003eDefinitions 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.\u003c/p\u003e\n\u003cp\u003eThe number of significant studies relative to the size of the study populations in the anxiety group is presented in figure 2.\u003c/p\u003e\n\u003cp\u003eThere 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.\u003c/p\u003e\n\u003ch3\u003eDepression\u003c/h3\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\n\u003cp\u003eDefinitions 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.\u003c/p\u003e\n\u003cp\u003eThere 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%)\u003c/p\u003e\n\u003cp\u003eThere 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.\u003c/p\u003e\n\u003ch3\u003eRisk of bias assessment\u003c/h3\u003e\n\u003cp\u003eThe 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 \u0026lsquo;Outcome\u0026rsquo; assessment. Seven studies obtained any points in the \u0026lsquo;Comparability\u0026rsquo; assessment, and fourteen in the \u0026lsquo;non-respondents\u0026rsquo; assessment. Further details about Risk of bias assessment are available in Appendix 3.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis 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.\u003c/p\u003e\n\u003ch2\u003eAssociations between anxiety and impairment of pulmonary function\u003c/h2\u003e\n\u003cp\u003eMost 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].\u003c/p\u003e\n\u003cp\u003eThree 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\u0026nbsp;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.\u003c/p\u003e\n\u003cp\u003eThe 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\u0026rsquo;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.\u003c/p\u003e\n\u003cp\u003eThe 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 Hern\u0026aacute;ndez-P\u0026eacute;rez 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].\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\n\u003cp\u003eFour 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.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe consequence of great heterogeneity in both outcome, exposure and statistical methods makes comparison between studies challenging.\u003c/p\u003e\n\u003cp\u003eWith 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociations between depression and impairment of pulmonary function\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 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 \u0026gt;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 \u0026gt;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].\u003c/p\u003e\n\u003cp\u003eThe 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 \u0026gt;16, which three of the studies in this review used, while one used \u0026gt;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).\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCommon 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\u0026nbsp;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.\u003c/p\u003e\n\u003cp\u003eThe only large study without unambiguous significant results was\u0026nbsp;Miravitlles et al [52]. Depression was here defined as BDI \u0026gt;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].\u003c/p\u003e\n\u003cp\u003eStudies 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.\u003c/p\u003e\n\u003cp\u003eAlmost 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.\u003c/p\u003e\n\u003ch2\u003eLimitations\u003c/h2\u003e\n\u003cp\u003eAs 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.\u003c/p\u003e\n\u003cp\u003eStrict 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. \u0026nbsp;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.\u003c/p\u003e\n\u003cp\u003eMany 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(%).\u003c/p\u003e\n\u003cp\u003eQuality 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 \u0026lsquo;Outcome\u0026rsquo; 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].\u003c/p\u003e\n\u003cp\u003eMost 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.\u003c/p\u003e\n\u003cp\u003eThere 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.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOnly 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.\u003c/p\u003e\n\u003cp\u003eThe review indicates an association between depression and impairment of pulmonary function. However, investigation of any correlation should be investigated in large cohorts.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOPD: Chronic obstructive pulmonary disease\u003c/p\u003e\n\u003cp\u003eFEV1(%): Forced expiratory volume in one second in percentage of expected value\u003c/p\u003e\n\u003cp\u003eFEV1(L): Forced expiratory volume in one second in Liters\u003c/p\u003e\n\u003cp\u003eMRC: Medical Research Council Dyspnoea Scale\u003c/p\u003e\n\u003cp\u003e6MWT: 6 minute walk test\u003c/p\u003e\n\u003cp\u003eGOLD: Global Initiative for Chronic Obstructive Lung Disease\u003c/p\u003e\n\u003cp\u003eSTAI: The State Trait Anxiety Inventory\u003c/p\u003e\n\u003cp\u003eHADS-A: Hospital Anxiety and Depression Scale Anxiety Inventory\u003c/p\u003e\n\u003cp\u003eADIS IV: Anxiety Disorder Interview Schedule IV\u003c/p\u003e\n\u003cp\u003eHAM-A: Hamilton Anxiety Rating Scale\u003c/p\u003e\n\u003cp\u003eBAI: Beck Anxiety Inventory\u003c/p\u003e\n\u003cp\u003eGAD: Generalized Anxiety Disorder 7 item\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAIR: Anxiety Inventory for Respiratory Disease\u003c/p\u003e\n\u003cp\u003eCES-D: Center for Epidemiologic Studies Depression Scale\u003c/p\u003e\n\u003cp\u003eBDI: Becks Depression Inventory\u003c/p\u003e\n\u003cp\u003eBASDEC: Brief Assessment Schedule Depression Cards\u003c/p\u003e\n\u003cp\u003eGDS: Geriatric Depression Scale\u003c/p\u003e\n\u003cp\u003eHADS-D: Hospital anxiety and depression scale for depression\u003c/p\u003e\n\u003cp\u003eHAM-D: Hamilton Depression Rating Scale (HAM-D)\u003c/p\u003e\n\u003cp\u003eSDS: Self-rating Depression Scale\u003c/p\u003e\n\u003cp\u003ePHQ-9: Personal Health Questionnaire 9\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eSources of funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFunding 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDifferences between protocol and review\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSince submission of the protocol, the title of the project has been changed from \u0026lsquo;correlation\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ebetween impairment of lung function and risk of depression and anxiety in patients with chronic obstructive pulmonary disease - A systematic review\u0026rsquo; to \u0026lsquo;Association between impairment of lung function and risk of depression and anxiety in patients with chronic obstructive pulmonary disease - A systematic review\u0026rsquo;, as the team agreed that association was more fitting than correlation to describe the review.\u003c/p\u003e\n\u003cp\u003eAs 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.\u003c/p\u003e\n\u003cp\u003eIt 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEntire search string for each publicly available database is available in appendix 1\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions of authors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJohanne Hermann Karlsen (JHK), Kirstine Hermann J\u0026oslash;rgensen (KHJ) and Ulla M\u0026oslash;ller Weinreich (UMW) all contributed to the planning of the study. JHK wrote and submitted the final protocol to PROSPERO.\u003c/p\u003e\n\u003cp\u003eJHK 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.\u003c/p\u003e\n\u003cp\u003ePrimary draft for manuscript were prepared by JHK. KHJ and UMW contributed to the content and embodiment of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnja Gamskj\u0026aelig;r Hansen, Medical librarian at the Library of Aalborg University Hospital, Denmark, assisted in creating the search string.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrganisation WH. The Top Ten Causes of Death 2024 [updated 9/12-2020; cited 2024 5/1-24 ]. 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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.\u003c/li\u003e\n\u003cli\u003eChoi 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).\u003c/li\u003e\n\u003cli\u003eStrollo 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.\u003c/li\u003e\n\u003cli\u003eZhang 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.\u003c/li\u003e\n\u003cli\u003eHorner 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.\u003c/li\u003e\n\u003cli\u003eMondolo F, Jahanshahi M, Gran\u0026agrave; A, Biasutti E, Cacciatori E, Di Benedetto P. Evaluation of anxiety in Parkinson\u0026apos;s disease with some commonly used rating scales. Neurol Sci. 2007;28(5):270-5.\u003c/li\u003e\n\u003cli\u003eOrganisation WH. Anxiety Disorders 2023 [Available from: https://www.who.int/news-room/fact-sheets/detail/anxiety-disorders. 23rd February 2024\u003c/li\u003e\n\u003cli\u003eWetherell 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.\u003c/li\u003e\n\u003cli\u003eSmarr 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.\u003c/li\u003e\n\u003cli\u003ePoul Videbech KC, Maj Vinberg. Diagnosticering af Depressioner [updated 20 Feb 2023. Available from: https://pro.medicin.dk/Sygdomme/Sygdom/318201.\u003c/li\u003e\n\u003cli\u003eLuo 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.\u003c/li\u003e\n\u003cli\u003eMiravitlles M, Ribera A. Understanding the impact of symptoms on the burden of COPD. Respir Res. 2017;18(1):67.\u003c/li\u003e\n\u003cli\u003eLei 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.\u003c/li\u003e\n\u003cli\u003eMahler DA, Halpin DMG. Consideration and Assessment of Patient Factors When Selecting an Inhaled Delivery System in COPD. Chest. 2024;165(2):323-32.\u003c/li\u003e\n\u003cli\u003eFoulkes 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.\u003c/li\u003e\n\u003cli\u003eDrucker AM, Fleming P, Chan AW. Research Techniques Made Simple: Assessing Risk of Bias in Systematic Reviews. J Invest Dermatol. 2016;136(11):e109-e14.\u003c/li\u003e\n\u003cli\u003eNwaru CA, L\u0026ouml;vestad S, Gunnarsd\u0026oacute;ttir 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.\u003c/li\u003e\n\u003cli\u003eZhou 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.\u003c/li\u003e\n\u003cli\u003eLuo J, Tang L, Kong X, Li Y. Global, regional, and national burdens of depressive disorders in adolescents and young adults aged 10\u0026ndash;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.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Studies allocated to the anxiety group\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eName\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubjects\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient population\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnxiety Prevalence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnxiety definition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignificant association?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eDi Marco 2006 [8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a Respiratory Unit, Italy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e28.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eSTAI \u0026gt;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eAnxiety prevalence compared in GOLD group 1-4. P-value 0,256.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eLivermore N 2008 [29]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eCase-Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Australia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eADIS-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eFEV1 (%) compared between patients with panic disorder (80.1%) and no panic disorder (82.2%) (P-value 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eHoward C 2009 [30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a cardiothoracic centre, UK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e35%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-A \u0026gt;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between anxiety and FEV1(%) 0.005 (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eFunk GC 2009 [31]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Austria, \u0026gt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e49%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-A \u0026gt;8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eFEV1 (%) compared in patients with anxiety (40.5%) and no anxiety (48.3%) (p-value 0.025)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Yes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eLivermore N 2012 [32]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a Respiratory Medical Department, Australia, COPD stage GOLD II-III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e40.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eADIS-IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eFEV1 (%) correlation with panic, correlation coefficient \u0026beta;= -0.05 (p-value 0.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eSuh S 2013 [33]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a pulmonary rehabilitation program, USA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eSTAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eFEV1(%) compared between patients with anxiety (55.7%) and no anxiety (52.4%) (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eTselebis A 2013 [34]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eIntervention study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a rehabilitation program, Greece, \u0026lt;80 years\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e25-47.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eSTAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between anxiety and FEV1 (%) r= 0.034 (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eElassal G 2014 [35]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eOut- and inpatients, Egypt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e22.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eHAM-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between anxiety and FEV1(%) r = -0.182 (p-value 0.108)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eYohannes AM 2016 [36]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a rehabilitation program, United Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e29.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eAIR \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1 (%) and anxiety r=0.02 (p-value 0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eAllam AH 2017 [37]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Egypt, \u0026gt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e22%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-A \u0026gt;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1 (%) and anxiety r=-0.66 (p-value 0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eHieba E 2021\u003c/p\u003e\n \u003cp\u003e[38]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Egypt.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e54.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eSTAI \u0026gt;38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between anxiety and FEV1 (%) r= \u0026minus;0.178 (p-value 0.063)\u003c/p\u003e\n \u003cp\u003eCorrelation coefficient between anxiety and GOLD stage (%) r= 0.194 (p-value 0.042)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo/Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eYoshida M 2022 [39]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eIntervention study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Japan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e9.9-10.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eSTAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eDistribution of subjects in GOLD 1-4 with anxiety (GOLD1 11.27% \u0026ndash;GOLD 4 12.0%) compared with whole cohort (p-value 0.147)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eHern\u0026aacute;ndez-P\u0026eacute;rez A 2022 [40]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Mexico, 60-85 years,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e11.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-A \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1(%) and anxiety r=0.009 (p-value 0.873)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eHong YJ. 2023 [41]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e2147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a cohort study, Korea, \u0026gt;40 years,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e19.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eBAI \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eDistribution of subjects in GOLD 1-4 in patients with anxiety (GOLD1 13.1% \u0026ndash;GOLD4 9.6%) and without (GOLD1 15.1% \u0026ndash;GOLD4 6.2%) (p-value 0.319)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.799136069114471%\" valign=\"top\"\u003e\n \u003cp\u003eLiu M 2023 [42]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.991360691144709%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.559395248380129%\" valign=\"top\"\u003e\n \u003cp\u003e226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.30669546436285%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a cohort study, China, \u0026gt;40 years old.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.44708423326134%\" valign=\"top\"\u003e\n \u003cp\u003e22.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.259179265658748%\" valign=\"top\"\u003e\n \u003cp\u003eGAD7 \u0026gt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.885529157667385%\" valign=\"top\"\u003e\n \u003cp\u003eFEV1 (%) compared in patients with anxiety (62.9%) and no anxiety (67.4) (p-value 0.204)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.751619870410368%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eTable 2. Studies allocated to the depression group\u003c/strong\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubjects\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient population\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrevalence of depression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDepression definition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignificant?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003evan Manen JG\u003cem\u003e\u0026nbsp;\u003c/em\u003e2002 [43]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom general practice, Netherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e21.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eCES-D \u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eFEV1 \u0026lt;50% Adjusted OR 0.8 (CI 0.3-2.5) for depression compared to FEV1 \u0026gt;50%.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eNH Chavannes 2005 [44]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom general practices, Netherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e27.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eBDI \u0026gt;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eOR 1.0 (CI 0.98-1.02) of average FEV1 (%) in patients with depressive symptoms compared to patients without (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eDi Marco 2006 [8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Italy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e18.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eSDS \u0026gt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003ePrevalence of depression in GOLD group 1-4, comparison between groups. P-value 0,636.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eAl-shair K 2009 [45]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eRecruited from media advertising, a Medicines Evaluation Unit, and Outpatient clinic, England.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e1: 18.9%\u003c/p\u003e\n \u003cp\u003e2: 23.7%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003e1: BASDEC \u0026gt;7 or 2: CES-D Scale \u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e1: Difference in FEV1(%) between patients with depression (50.1%) and without (52.3%) (p-value 0.56)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2: 1: Difference in FEV1(%) between patients with depression (50.4%) and without (52.4%) (p-value 0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eOmachi TA 2009 [46]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e1202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an ongoing cohort study, USA, 40-65 years of age.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e27%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eGDS \u0026gt;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eMultivariate analysis, OR between every 23% decrement in FEV1 (%) and risk of depression (p-value 0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eHoward C 2009 [30]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a cardiothoracic centre, UK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e19%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-D \u0026gt;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between depression and FEV1(%) -0.120 (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eFunk GC 2009 [31]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic and a hospital ward, Austria, \u0026gt;18 years\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e52%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-D \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (37.0%) and without (52.5%) (p-value 0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003ede Voogd JN 2009 [47]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom pulmonary rehabilitation, the Netherlands.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e16.5%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eBDI \u0026gt;19\u003c/p\u003e\n \u003cp\u003eHighly depressed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1 (%) and depression r=\u0026ndash;0.01 (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eHalabi S 2011 [48]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, England, Men, \u0026gt;55 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e34.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eGDS \u0026gt;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (42%) and without (44%) (p-value 0.421)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eHorita N 2013 [49]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom three hospitals, Japan, Saturation \u0026gt;90%. Able to perform 6MWT.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e38.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;GDS \u0026gt;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (38%) and without (51%) (p-value \u0026gt;0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eIguchi A 2013 [50]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom pulmonary rehabilitations and in-patients from a pulmonary department, Japan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e48.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eCES-D \u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1(%) and depression r = -0.29 (p-value 0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eTselebis A 2013 [34]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eIntervention study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003ePatients from a rehabilitation program, Greece, \u0026lt;80 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e47.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eBDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between depression and FEV1(%) 0.01 (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eKim KU 2014\u003c/p\u003e\n \u003cp\u003e[51]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom pulmonary outpatient clinic, Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e17.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eCES-D \u0026gt;24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (60.6%) and without (60.4%) (p-value 0.959)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eElassal G 2014 [35]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eOut- and inpatients, \u0026nbsp;Egypt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e42.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHAM-D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1 (%) and depression r = -0.262 (p-value 0.019)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eMiravitlles M 2014 [52]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e836\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom outpatient clinics, Spain, \u0026gt;40 years, \u0026gt;10 pack years.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e51.1% moderate to severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eBDI \u0026gt;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression 51.6%) and without (53.6%) (p-value 0.15)\u003c/p\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with mild depression (53.6%) and severe depression (48.9%) (p-value 0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eBattaglia S 2015 [53]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Italy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e5.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eMedical history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003ePrevalence of depression in GOLD 1 (4.3%), GOLD 2 (3.5%), GOLD 3 (5.7%) and GOLD 4 (8%) (p-value \u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eMartinez Rivera C 2016 [14]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom outpatient clinics, Spain, \u0026gt;40 years and \u0026gt;10 pack years.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e24.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-D \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (38.8%) and without (46.2%) (p-value 0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eOrlandi Le 2016 [54]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, \u0026gt;40 years, Brazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e22.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eMini international neuropsychiatric interview plus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (51.9%) and without (43.6%) (p-value 0.108)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eTse HN 2016 [55]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a geriatric and COPD clinic, Hong-Kong, \u0026gt;60 years.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e20.22%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eGDS \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (38.7%) and without (46.1%) (p-value 0.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eAllam AH 2017 [37]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Egypt, \u0026gt;18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e14%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-D \u0026gt;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1 (%) and depression r=-0.57 (p-value 0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eBiswas D 2017 [15]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, India\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e54.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHAM-D \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (47%) and without (54.5%) (p-value 0.178)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eLee JH 2018 [56]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a registry, Korea, FEV1\u0026gt;50%, \u0026gt;40 years,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e14.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003ePHQ-9 \u0026gt;27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (77.7%) and without (80.1%) (p-value 0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eSharma K 2019 [57]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, India, 40-80 years.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e75%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHAM-D \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (62.1%) and without (82.5%) (p-value \u0026gt;0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eYang K 2020 [58]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e1800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an American registry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e23.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003ePHQ-9 \u0026gt;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eOdds ratio of depression compared to FEV1 (%) OR=1.15 (p-value 0,004)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eChoi JS 2021 [59]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e877\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a Korean registry, \u0026gt;40 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e17.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003ePHQ-9 \u0026gt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDistribution of subjects in GOLD 1-4 in patients with depression (GOLD1 48.1% \u0026ndash;GOLD 4 8.9%) and without (GOLD1 51.7% \u0026ndash;GOLD 4 3.8%) (p-value 0.019)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eStrollo HC 2021 [60]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e1: 220\u003c/p\u003e\n \u003cp\u003e2: 745\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003e1: From an American cohort,\u0026gt;40 years, \u0026gt;10 pack years.\u003c/p\u003e\n \u003cp\u003e2: From an American cohort, 2008-2011, 45-80 years, \u0026gt;10 pack years,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e1: 21.4%\u003c/p\u003e\n \u003cp\u003e2: 13.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003e1,2: BDI \u0026gt;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003e1: Distribution of subjects in GOLD 1-4 in patient with depression (GOLD1 17.0% \u0026ndash;GOLD 4 4.3%) and without (GOLD1 34.1% \u0026ndash;GOLD 4 0.1%) (p-value 0.01)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2: Distribution of patients in GOLD 1-4 with depression (GOLD1 11.3% \u0026ndash;GOLD 4 19.6%) and without (GOLD1 24.4% \u0026ndash;GOLD 4 9.6%) (p-value 0.002)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003e1: Yes\u003c/p\u003e\n \u003cp\u003e2: Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eHern\u0026aacute;ndez-P\u0026eacute;rez A 2022 [40]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Mexico, 60-85 years,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e30.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eHADS-D \u0026gt;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eCorrelation coefficient between FEV1(%) and depression r=-0.03 (p-value 0.592)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eYoshida M 2022 [39]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eIntervention study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom an outpatient clinic, Japan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e9.31%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eSDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDistribution of subjects in GOLD 1-4 in patients with depression (GOLD1 8.65% \u0026ndash;GOLD 4 7.59%) compared to whole cohort (p-value 0.147)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eHong YJ 2023 [41]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e2147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a cohort study, \u0026gt;40 years, Korea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e27.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eBDI \u0026gt;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDistribution of patients in GOLD 1-4 with depression (GOLD1 8.1% \u0026ndash;GOLD 4 12.3%) and without (GOLD1 13.0% \u0026ndash;GOLD 4 7.4%) (p-value 0.008)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eZhang T 2023 [61]\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom a hospital ward, China\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e45.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003eSDS \u0026gt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eDifference in FEV1(%) between patients with depression (50.2%) and without (61.8%) (p-value \u0026gt;0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.267241379310345%\" valign=\"top\"\u003e\n \u003cp\u003eHorner A 2023 [62]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.866379310344827%\" valign=\"top\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.711206896551724%\" valign=\"top\"\u003e\n \u003cp\u003e630\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814655172413794%\" valign=\"top\"\u003e\n \u003cp\u003eFrom multiple outpatient clinics, Austria \u0026gt;40 years,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.051724137931034%\" valign=\"top\"\u003e\n \u003cp\u003e46.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452586206896552%\" valign=\"top\"\u003e\n \u003cp\u003ePHQ-9 \u0026gt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.525862068965516%\" valign=\"top\"\u003e\n \u003cp\u003eRegression coefficient between FEV1(%) and depression \u0026minus;0.06 (p-value \u0026lt; 0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.310344827586207%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary function, depression, anxiety, Forced Expiratory Volume, Chronic Obstructive pulmonary disease","lastPublishedDoi":"10.21203/rs.3.rs-4024678/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4024678/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThis systematic review aims to evaluate the association between impairment of pulmonary function, anxiety and depression in patients with chronic obstructive pulmonary disease (COPD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e31 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis 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.\u003c/p\u003e\n\u003cp\u003eRegistration: PROSPERO 2024 CRD42024506065\u003c/p\u003e","manuscriptTitle":"Association between impairment of lung function and risk of anxiety and depression in patients with chronic obstructive pulmonary disease - A systematic review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-13 20:27:03","doi":"10.21203/rs.3.rs-4024678/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2024-05-24T22:54:11+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-05-06T04:37:36+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-06T01:36:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-15T04:26:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Systematic Reviews","date":"2024-03-07T08:31:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4a7b6f7f-1e68-4594-8831-45a7afd223d5","owner":[],"postedDate":"May 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-09T16:11:10+00:00","versionOfRecord":{"articleIdentity":"rs-4024678","link":"https://doi.org/10.1186/s13643-024-02720-z","journal":{"identity":"systematic-reviews","isVorOnly":false,"title":"Systematic Reviews"},"publishedOn":"2024-12-04 15:57:45","publishedOnDateReadable":"December 4th, 2024"},"versionCreatedAt":"2024-05-13 20:27:03","video":"","vorDoi":"10.1186/s13643-024-02720-z","vorDoiUrl":"https://doi.org/10.1186/s13643-024-02720-z","workflowStages":[]},"version":"v1","identity":"rs-4024678","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4024678","identity":"rs-4024678","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}