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Abstract
Objectives Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms.
Methods This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen’s kappa. Two multivariable logistic regressions were built.
Results According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression.
Conclusion At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.
- asthma
- anxiety disorders
- depression & mood disorders
Data availability statement
Data are available upon reasonable request. Please contact the corresponding author to arrange access to study data.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This study is a secondary analysis of a multicentric study that recruited both adults and adolescents with asthma from primary and secondary care.
A comprehensive set of individual-level characteristics was analysed, which allowed us to explore the impact of sociodemographic factors and cofactors such as quality of life and asthma control on the presence of anxiety/depression symptoms.
A possible source of bias was the recruitment strategy based on convenience sampling.
The frequency of distressing symptoms and the relationships with associated factors could not be established overtime.
Introduction
Asthma affects approximately 300 million people worldwide.1 In Portugal, asthma affects 695 000 Portuguese, with a general prevalence of 6.8%.2 In Spain, asthma affects more than 3 million people, with an estimated prevalence of 5% in adults.3 Asthma is primarily related to chronic inflammation of the lower respiratory tract, variable airflow obstruction and bronchial hyper-responsiveness.4 Yet, this disease is often accompanied by multiple associated comorbidities, such as chronic rhinosinusitis, nasal polyposis, allergic rhinitis, gastro-oesophageal reflux disease, obstructive sleep apnoea syndrome,5 and also anxiety and depression.6
In two systematic reviews, the average reported prevalence of any anxiety disorder among patients with asthma was 24%7 and 34%.8 Regarding depression, a pragmatic literature review found that 1%–45% of patients with asthma suffer from depression or depressive symptoms.9 In severe asthma, a study reported an average prevalence of 27% for emotional distress (mainly due to anxiety and depression).10 Currently, most studies about emotional distress focus essentially on adult patients with more severe asthma.11 There is a lack of data regarding other asthma subgroups, namely adolescents and those with mild or moderate persistent asthma.
Anxiety and depression are associated with significantly lower quality of life, poor asthma control, higher frequency of exacerbations and increased use of healthcare resources.12 Moreover, anxiety is associated with greater perceived dyspnoea intensity and may shape the quality and intensity of this symptom at a given respiratory load.13 However, it is still uncertain whether other factors can affect the patient’s psychological state. It is important to have a more sophisticated understanding of the interplay between emotional distress and asthma.14
Despite these negative impacts, anxiety and depression in patients with asthma is not routinely assessed during clinical visits and thus there is a lack of information about its real-world frequency. One of the most used tools for psychological screening is the Hospital Anxiety and Depression Scale (HADS). HADS is a self-report questionnaire designed to screen anxiety and depression symptoms15 and it was already used in adolescents and adults with asthma in previous studies.16 17 However, this scale has 14 items and although it takes around 5 min to complete,18 it is not always feasible to administer in a busy clinic setting.19 20 European Quality of Life Five Dimension Questionnaire (EQ-5D) is a generic measure of health status that provides a simple descriptive profile and a single index value that can be used for the clinical and economic evaluation of healthcare,21 but also emotional distress screening.22 Currently, EQ-5D is being widely used in a variety of conditions, where asthma is integrated.23 Some studies compared HADS and EQ-5D in patients with other diseases and showed that EQ-5D can be responsive to different degrees of HADS-assessed distress.24 Yet, there is no published data comparing HADS and EQ-5D in patients with asthma.
With the present study, we aimed to assess (1) the frequency of symptoms of anxiety and depression in patients with asthma as assessed by HADS and EQ-5D questionnaires; (2) the level of agreement between the two questionnaires and (3) the factors associated with the presence of these symptoms.
Methods
Patient and public involvement
No patient involved.
Study design
Data from the baseline face-to-face visit from five prospective observational studies of the INSPIRERS project were analysed.25 This project addresses the topic of adherence to asthma inhalers among adolescents and adults with persistent asthma. Convenience samples were recruited between November 2017 and October 2020 at 32 allergy, pulmonology and paediatric secondary care outpatient clinics (30 from Portugal and 2 from Spain) and 30 primary care centres from Portugal. The studies were approved by the ethics committees of all participating centres. Eligible patients were approached by physicians during medical visits. Adult patients signed a consent form. Adolescents signed an assent form, and a parental consent form was also obtained. The studies had similar inclusion criteria and methods. The study is reported according to Strengthening the Reporting of Observational Studies in Epidemiology guidelines.26
Patients
Patients were included in the analysis if they had a previous medical diagnosis of persistent asthma, were at least 13 years old (13–17 years adolescents; ≥18 years adults) and had an active prescription for an inhaled controller medication for asthma. All inhaled controller treatments were allowed, and there was no change in any prescribed medication regarding the participation in these studies. Patients were excluded if they had a diagnosis of a chronic lung disease other than asthma or a diagnosis of another significant chronic condition with possible interference with the study aims.
Data collection
During the baseline face-to-face visit, data were collected from both physicians and patients in an attempt to improve the quality of the information obtained. Physicians answered a questionnaire including the asthma treatment plan and comorbidities. Information about the healthcare setting (primary, secondary) was obtained based on the centre where patients were recruited.
Demographic data (age, gender, educational level, marital status and current occupation) and clinical data (weight, height, smoking habits and age of asthma diagnosis) were collected from patients.
Two asthma control questionnaires were used to gather the perspectives of the physician and the patient. Physicians answered the Global Initiative for Asthma (GINA) assessment of symptom control,26 which is recommended to be used at every opportunity in adolescents and adults. Patients answered the Control of Allergic Rhinitis and Asthma Test (CARAT). CARAT is a self-report questionnaire with a total score (CARAT-T) calculated by summing up the score of each of the 10 questions, resulting in a range of 0–30 points. A score >24 indicates good disease control.27 This questionnaire has been widely used in clinical practice and in scientific research, being translated/culturally adapted in >27 languages and used in >15 different countries.28
The Portuguese version of the HADS was used to assess the presence of symptoms of anxiety and depression.29 HADS contains 14 items related to the past week, 7 of which assess anxiety symptoms (HADS-A) and the other 7 depression symptoms (HADS-D). HADS-A and HADS-D are scored separately. The item response scale varies between 0 and 3 points, with total scores ranging from 0 (minimum symptomatic load) up to 21 (maximum symptomatic load) for HADS-A and HADS-D. A score ≥8 on HADS-A or HADS-D was considered as the presence of symptoms of anxiety or depression, respectively.30
The EQ-5D three-level version was filled in by the patients to assess their overall quality of life. The item 5 ‘Anxiety and Depression’ could be a useful tool in screening for anxiety and depressive symptoms in hospital and community settings.31 Therefore, this item, with its three response options (‘I am not anxious or depressed’, ‘I am moderately anxious or depressed’, ‘I am extremely anxious or depressed’) was additionally used to assess the presence of these symptoms.32 Patients were considered to have anxiety/depression when answering ‘I am moderately anxious or depressed’ or ‘I am extremely anxious or depressed’. The EQ-5D summary index score was calculated to characterise the sample. It ranges from less than 0 (where 0 is a health state equivalent to death) to 1 (perfect health).33 The EQ-5D visual analogue scale (VAS) was also used to assess patients’ perception of their general health (from 0 ‘the worst health you can imagine’ to 100 ‘the best health you can imagine’).
Statistical analyses
Descriptive statistics were used to characterise the sociodemographic variables, clinical characteristics, the HADS score and EQ-5D responses. Absolute and relative frequencies were used to characterise the categorical variables. Means and SD or medians and IQRs were used, according to data distribution, to characterise the numerical variables.
To determine the agreement between HADS and EQ-5D questionnaires for the presence of symptoms of anxiety/depression, the percentage of agreement and weighted Cohen’s kappa were used. Cohen’s kappa values were interpreted as follows: <0, no agreement; 0–0.20, slight; 0.21–0.40, fair; 0.41–0.60, moderate; 0.61–0.80, substantial and 0.81–1.0, almost perfect agreement.34
To explore associations between variables related to the presence of symptoms of anxiety and depression, patients with and without symptoms of anxiety and depression were compared using independent t-tests for normally distributed data, Mann-Whitney U tests for non-normally distributed continuous data and ordinal data, and χ2 tests for categorical data. In the case of χ2 tests, when a statistically significant difference was found for a categorical variable with more than two categories, χ2 multiple comparison tests with Bonferroni correction were performed to explore which categories differed from each other. The variables that were statistically different (p<0.05) between the two groups were selected to further explore their relationship with the presence of anxiety and depression and to adjust for possible confounders in two stepwise multivariable logistic regression models. The dependent variable in each multivariable logistic regression was the presence of symptoms of anxiety or depression based on HADS (0=absent, 1=present). The overall models were evaluated using the goodness-of-fit tests and Nagelkerke’s R2 and the final model was selected based on the best combination of these results. The level of significance considered was 0.05. Statistical analyses were performed using IBM SPSS Statistics V.26.0 (IBM Corporation).
Results
Patient’s characteristics
A total of 614 participants with asthma (mean age 32.6±16.9 years) were included in this study. There were 447 (72.8%) adults and 397 (64.7%) women. Forty per cent of the participants had completed primary school (n=244), 47.4% were employed (n=289) and 65.1% were prescribed only one inhaler (n=396). According to the GINA assessment of symptom control, 296 (48.7%) patients had well-controlled asthma. Table 1 shows the sociodemographic and clinical characteristics of the study participants.
Sociodemographic and clinical characteristics of the participants (n=614)
Symptoms of anxiety and depression
According to HADS, 221 (36.0%) participants had symptoms of anxiety, 73 (11.9%) had symptoms of depression, 59 (9.6%) both symptoms and 235 (38.3%) participants had symptoms of anxiety or depression. Both anxiety (41.4% vs 21.6%) and depression (14.1% vs 6%) symptoms were more frequent in adults than adolescents. According to EQ-5D, 223 (36.3%) participants had anxiety or depression problems, 32.6% were moderately anxious or depressed and 3.7% extremely anxious or depressed. The agreement between these two questionnaires was moderate for anxiety (k=0.54 (95% CI 0.47 to 0.61)); fair for depression (k=0.23 (95% CI 0.17 to 0.30)) and moderate for anxiety/depression (k=0.55 (95% CI 0.48 to 0.62)).
Predictors of anxiety and depression
In the multivariable logistic regression (table 2), being an adolescent (OR 0.43, 95% CI 0.27 to 0.68), having a better asthma control (CARAT-T score) (OR 0.98, 95% CI 0.94 to 1.00) and a perception of better health (OR 0.97, 95% CI 0.95 to 0.98) were significantly associated with lower odds for the presence of anxiety symptoms. In contrast, being a female was significantly associated with a higher odd for the presence of anxiety symptoms (OR 1.75, 95% CI 1.56 to 2.64). Having better health-related quality of life (OR 0.97, 95% CI 0.95 to 0.99) and perception of better health (OR 0.97, 95% CI 0.96 to 0.99) were associated with a lower odd for the presence of depression. While asthma diagnosis at a later age (OR 1.03, 95% CI 1.01 to 1.05) and the presence of a higher number of comorbidities (OR 1.31, 95% CI 1.05 to 1.64) were associated with an increase in the likelihood of exhibiting symptoms of depression. The univariate analyses are presented in online supplemental table 1.
Supplemental material
Multivariable logistic regression analyses to explain anxiety and depression
Discussion
This study showed that more than 1/3 of participants with asthma experienced symptoms of anxiety and/or depression. Asthma diagnosis at a later age, presence of comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of better health were factors associated with lower odds for anxiety/depression. In this study, the agreement between HADS and EQ-5D questionnaires in identifying anxiety and depression was sufficient to moderate.
According to HADS and EQ-5D questionnaires, more than 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression (38.3% and 36.3%, respectively). Therefore, the percentages of participants with one of these symptoms detected by HADS and EQ-5D were similar. With HADS, it was possible to detect the percentages of patients with persistent asthma that had only symptoms of anxiety (36.0%) or had only symptoms of depression (11.9%). The proportions found in the present study were similar to the ones found among patients with asthma in previous reviews,8 9 analysing studies that included only, or mostly, adults with asthma. A study from the UK found similar frequencies of anxiety and depression using HADS, although a slightly higher cut-off has been used (HADS-A/HADS-D≥10).35 We found a lower frequency for depression as compared with a study in patients with severe asthma, where 25% reported depression.36 This difference might be explained by the role of poorer physical functioning on symptoms of depression.37 Patients with severe asthma experience more physical disability. Other studies reported that patients with severe asthma have more often emotional distress as compared with patients with mild-moderate asthma.38 39
This study includes both adolescents and adults with persistent asthma, which is rarely found in previous articles. However, anxiety and depression were only assessed at one time point. Analysing emotional distress in the long run could be important as suggested in previous cohort studies that followed adolescents with asthma to young adulthood, showing that there was a persistence or recurrence of anxiety and depression in adulthood.40 41 In our study, adults with persistent asthma presented an increased frequency of anxiety/depression symptoms (vs adolescents), which is in accordance with a population-based study that reported that having asthma and older age were independent risk factors for the presence of anxiety disorders, in participants above the age of 15 years.42 Therefore, emotional distress seems to be associated with age differences in patients with persistent asthma.
Age at asthma onset has emerged as a critical factor in distinguishing the phenotypes of asthma.43 Adult-onset asthma differs from asthma that first occurs in childhood since it usually is less well controlled, is associated with a faster decline in lung function and with more comorbidities.44 45 Moreover, worse asthma control and the presence of more comorbidities might be associated with an increased risk of emotional distress.46 These results contribute to explaining our finding that asthma diagnosis at a later age and number of physician-reported comorbidities were associated with a higher frequency of depression. Female patients were more likely to have anxiety symptoms. This was previously observed in other studies in asthma but also other respiratory diseases, such as chronic obstructive pulmonary disease (COPD). Possibly these gender differences are more than a specificity of respiratory diseases, but a reflection of the known gender differences in the general population.47 48
In our study, the perception of better health was associated with a lower odd for the presence of anxiety symptoms. In a previous study with patients with COPD, the perceived severity of COPD symptoms was predictive of depression and anxiety.49 These findings are in line with our study, although coming from a different disease. The close correlation between asthma control, quality of life, anxiety and depression has been also confirmed in other studies.50 51 Consequently, in patients with poor asthma control, physicians should ask about the symptoms of anxiety/depression or screen it using simple tools like EQ-5D or HADS before making adjustments on asthma treatment strategy.17
EQ-5D questionnaire could be useful in clinical practice.52 The EQ-5D anxiety or depression domain had a greater agreement with the HADS score in identifying cases with both symptoms, as expected, than in identifying anxiety or depressive symptoms. In general, the percentages of patients with anxiety/depression detected by HADS and EQ-5D were similar. Furthermore, it is expected that remarkably less time consumption is needed for the EQ-5D item 5 assessment compared with HADS.18 53 Therefore, EQ-5D score appears to have value as a screening tool for anxiety or depression in patients with asthma. In a previous study, this questionnaire also seemed to be reasonably valid and moderately responsive in patients with anxiety disorders.54 This could be important in clinical practice because a generic health instrument like the EQ-5D, with few and quick questions, could be used to easily raise awareness of a possible emotional distress in patients with asthma. A limitation of EQ-5D is that anxiety and depression are two separate emotional disorders and their combination in a single item in this questionnaire could lead to inconsistencies in responses.55 Nevertheless, EQ-5D could be used as a first screening questionnaire and, in patients reporting anxiety or depression symptoms, a more specific questionnaire, such as HADS, could be used to better characterise their symptoms. Actually, emotional distress screening is very important in clinical practice because physicians can use targeted interventions to improve patients’ symptoms.56 Studies about psychological interventions in adults with asthma suggest that education and simple psychological interventions namely relaxation techniques and biofeedback or a stepped care approach could produce significant positive healthcare outcomes.57 58
This study has some strengths that should be acknowledged: it is a multicentric study that recruited both adults and adolescents with asthma from primary and secondary care. A comprehensive set of individual-level characteristics was collected and analysed, which allowed us to explore the impact of a range of sociodemographic factors, health literacy and cofactors such as quality of life and asthma control. Therefore, includes a sample from different healthcare contexts and with different clinical presentations, contributing to the robustness of these findings.
Nevertheless, it also has some limitations. A possible source of bias was the recruitment strategy of using a convenience sampling. Future studies using other sampling strategies could be important to generalise the results of our study. A control group of healthy individuals with similar sociodemographic characteristics should also be included in further research to increase the validity of these findings. In the absence of a control group it would have been useful to compare anxiety/depression frequencies with normative data from Portugal and Spain, but we did not find it neither for HADS nor EQ-5D. Moreover, the impact of the presence of specific comorbidities, such as rhinitis, which is closely associated both with asthma and anxiety/depression, was not assessed.59 Another limitation of the present study is related to its cross-sectional nature. The frequency of distressing symptoms and the relationships with associated factors could not be established along the progression of the disease. Also, patients were not recruited at the same time point, as recruitment in the INSPIRERS studies occurred across four different years (from 2017 to 2020), and the last 15% of the sample was recruited during COVID-19 pandemic. Longitudinal studies following a cohort of patients with asthma would address these issues and identify other predictors of symptoms of anxiety and depression.
This study shows that more than 30% of the patients with persistent asthma experience symptoms of anxiety/depression, which supports the relevance of emotional distress screening in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. Late asthma diagnosis, presence of comorbidities and female gender were positively associated with the presence of emotional distress, while better asthma control, health-related quality of life and perception of better health presented a negative association. These factors need to be further investigated in future long-term studies.
Data availability statement
Data are available upon reasonable request. Please contact the corresponding author to arrange access to study data.
Ethics statements
Patient consent for publication
Ethics approval
The studies were approved by the ethics committees of all participating centres. For example, the study was approved by the Ethics Committee of Centro Hospitalar de S. João—EPE (protocol code 258-17 and date of approval: 5 January 2018).
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Twitter @luismonteiro140, @Daniela
Contributors All authors contributed to the selection of bibliography, revision and final approval of the manuscript. AMP, RAmaral, MA-C, RAlmeida, JAF and CJ were responsible for study conception and design. RAmaral, AMP, RAlmeida, MA-C, CCL, CLopes, JC, CR, CVidal, DA-A, DP, MF-M, MJV, CLozoya, NS, FC, LT-B, RF, PMS, TMF, RC, ES, DB, CG, MJC, SdS, MLM, AM, CN, CVieira, RP, AA, JVM, BR, LM, RM, MC, BV, DSC, SF, PM, MAA, ARM, JAF and CJ participated in the data collection. CJ and AMP performed the data analysis and MSC prepared the first draft. All authors contributed to the interpretation of data, to the critical revision of the manuscript for important intellectual content. JAF and CJ act as guarantors for study.
Funding This study is a secondary analysis from the mINSPIRE project financed by national funds through the Foundation for Science and Technology (PTDC/MEC-OUT/29130/2017) and cofinanced by Operational Programme ‘Competitiveness and Internationalization’ (COMPETE 2020), PORTUGAL 2020 from European Regional Development Fund - FEDER (POCI-01-0145-FEDER-029130).This article was supported by National Funds through FCT - Fundação para a Ciência e a Tecnologia,I.P., within CINTESIS, R&D Unit (reference UIDP/4255/2020).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.