Hostname: page-component-74656f9884-8r8nv Total loading time: 0 Render date: 2026-11-08T00:35:58.632Z Has data issue: false hasContentIssue false
  • English
  • Français

Anxiety in asthma: a systematic review and meta-analysis

Published online by Cambridge University Press:  12 January 2021

Gang Ye ,
David S. Baldwin  and
Ruihua Hou Open the ORCID record for Ruihua Hou [Opens in a new window]
Gang Ye
Affiliation:
Suzhou Guangji Hospital, Suzhou, Jiangsu, China
David S. Baldwin
Affiliation:
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK University Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
Ruihua Hou*
Affiliation:
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK
*
Author for correspondence: Ruihua Hou, E-mail: r.hou@soton.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Background

Background: Growing evidence from observational studies indicates a high prevalence of anxiety in asthma. However, prevalence rates of coexisting anxiety symptoms and comorbid anxiety disorders vary widely across studies. We aimed to evaluate the associations between anxiety and asthma and provide more precise comorbidity estimates.

Methods

We systematically reviewed the literature from case-controlled studies and conducted a meta-analysis to evaluate the pooled prevalence estimates and risks of anxiety symptoms and anxiety disorders in asthma individuals. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis. A random-effects model was used to calculate pooled prevalence rates. Meta-analysis was conducted using Review Manager 5.3. Multiple databases including PubMed, ScienceDirect, PsychINFO, and PsycARTICLES were searched for publications before 1 December 2019. The review protocol was registered on PROSPERO (ref: CRD42020176028).

Results

In total, 19 studies involving 106813 participants were included. The pooled prevalence of anxiety symptoms and anxiety disorders in individuals with asthma was 0.32 (95% CI 0.22–0.43) and 0.24 (95% CI 0.13–0.41), respectively. The risks of coexisting anxiety symptoms and comorbid anxiety disorders were significantly higher in asthma patients than in non-asthma controls indicated by OR 1.89 (95% CI 1.42–2.52; Z = 4.37; p < 0.001) and OR 2.08 (95% CI 1.70–2.56; Z = 6.97; p < 0.001), respectively. Anxiety symptoms and anxiety disorders occur at increased frequency among patients with asthma.

Conclusions

Our findings highlight the need for appropriate assessments for these comorbid conditions, which may help to identify a subgroup of patients who might benefit from interventions designed to reduce anxiety and enhance the quality of life.

Keywords

Anxietyasthmaprevalencereviewmeta-analysis

Information

Type
Review Article
Information
Psychological Medicine , Volume 51 , Issue 1 , January 2021 , pp. 11 - 20
Check for updates
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Background

Asthma is a major chronic health problem affecting over 300 million worldwide, which causes significant social and financial burdens (Del Giacco et al. Reference Del Giacco, Cappai, Gambula, Cabras, Perra, Manconi and Pinna2016). It is a complex multifactorial illness involving interactions between neural, endocrine, immune, behavioural and psychological processes (Di Marco, Santus, & Centanni, Reference Di Marco, Santus and Centanni2011; Mrazek, Reference Mrazek2003). Anxiety is the strongest predictor of breathlessness in asthma (Spinhoven, van Peski-Oosterbaan, Van der Does, Willems, & Sterk, Reference Spinhoven, van Peski-Oosterbaan, Van der Does, Willems and Sterk1997) and has a stronger association with asthma-related health condition than does lung function (Laveneziana et al. Reference Laveneziana, Lotti, Coli, Binazzi, Chiti, Stendardi and Scano2006). Anxiety can enhance symptom perception (Thomas, Bruton, Moffat, & Cleland, Reference Thomas, Bruton, Moffat and Cleland2011; von Leupoldt et al. Reference von Leupoldt, Sommer, Kegat, Baumann, Klose, Dahme and Buchel2009) and negatively impact cognition and coping behaviour (Lavoie et al. Reference Lavoie, Bouthillier, Bacon, Lemiere, Martin, Hamid and Ernst2010). Recent reviews have demonstrated that asthma diagnoses significantly increase the risk of psychological conditions (Goodwin et al. Reference Goodwin, Olfson, Shea, Lantigua, Carrasquilo, Gameroff and Weissman2003b; Su et al. Reference Su, Ren, Li, Zhao, Kong and Kang2016). Generalized anxiety disorder, panic disorder and agoraphobia, including anxiety related to symptoms, anxiety related to asthma-triggers, and anxiety related to medical treatment (ten Thoren & Petermann, Reference ten Thoren and Petermann2000). Observational surveys show the high prevalence of anxiety in asthma patients: up to 30% in children and adolescents and 34% in adults (Katon, Richardson, Lozano, & McCauley, Reference Katon, Richardson, Lozano and McCauley2004; Weiser, Reference Weiser2007; Wong, Hunter Rowe, Douwes, & Senthilselvan, Reference Wong, Hunter Rowe, Douwes and Senthilselvan2013). Such comorbidity can cause adverse outcomes, such as poor asthma control, symptomatic exacerbation, lower quality of life and increased utilization of emergency services (McCauley, Katon, Russo, Richardson, & Lozano, Reference McCauley, Katon, Russo, Richardson and Lozano2007; Richardson et al. Reference Richardson, Lozano, Russo, McCauley, Bush and Katon2006).

However, previous research has produced highly disparate findings and little consensus. Most studies did not include a valid control group and used different sample sources and outcome measures (Arif & Korgaonkar, Reference Arif and Korgaonkar2016; Han, Forno, Marsland, Miller, & Celedon, Reference Han, Forno, Marsland, Miller and Celedon2016; Lehto, Pedersen, Almqvist, Lu, & Brew, Reference Lehto, Pedersen, Almqvist, Lu and Brew2019; Lu et al. Reference Lu, Ho, Lim, Kuan, Goh, Mahadevan and van Bever2014; Martinez-Rivera, Vennera, Canete, Bardagi, & Picado, Reference Martinez-Rivera, Vennera, Canete, Bardagi and Picado2011; Ortega, Huertas, Canino, Ramirez, & Rubio-Stipec, Reference Ortega, Huertas, Canino, Ramirez and Rubio-Stipec2002). The current study aimed to systematically evaluate current evidence and conduct a meta-analysis to provide more precise estimates of prevalence and risks of this comorbid condition. We reviewed and synthesized data from studies reporting anxiety symptoms and anxiety disorders separately.

Methods

The current review and meta-analysis were conducted following PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis (Moher, Liberati, Tetzlaff, Altman, & The PRISMA Group, Reference Moher, Liberati, Tetzlaff and Altman2009; Moher et al. Reference Moher, Shamseer, Clarke, Ghersi, Liberati and Petticrew2015). The protocol was registered on PROSPERO (Ref: CRD42020176028).

Search strategy

The electronic databases of PubMed, ScienceDirect (Elsevier), PsychINFO and PsycARTICLES were used to select relevant publications before 1 December 2019. The search terms used included ‘asthma’, intersected with ‘anxiety’, ‘generalized anxiety disorder’, ‘panic disorder’, ‘phobias’, ‘social phobia’, ‘social anxiety’, ‘agoraphobia’, ‘separation anxiety disorder’, ‘posttraumatic stress disorder’ and ‘obsessive compulsive disorder’. We also examined reference lists of appropriate articles in order to identify additional relevant studies. Two investigators (GY and RH) independently assessed the literature included in the review. Any discrepancies were discussed and a consensus was reached.

Inclusion and exclusion criteria for study selection

Studies were included if they met the following criteria: (1) published in English in peer-reviewed journals; (2) used a case-controlled study design, which comprised a sample with asthma and a non-asthma control group; (3) included both cross-sectional and prospective studies, with baseline data of prospective studies extracted; (4) fulfilled the diagnostic criteria for anxiety disorders based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD); or had symptomatology measures of anxiety; (5) provided sufficient data (including numbers in both groups) allowing the computation of an effect size. Exclusion criteria included: (1) non-English language studies; (2) review papers or full papers not accessible; (3) no valid anxiety diagnosis or anxiety symptom measures. Eligibility criteria were applied during two phases: (a) title and abstract screening and (b) full-text screening. We also scrutinized and hand-searched the reference lists of all the relevant publications identified to check for any additional studies. Disagreements were resolved by discussions between GY and RH to reach a consensus.

Data extraction

Data were extracted using a pre-piloted structured form. In addition to bibliographic information, extraction processes sought the following data: population, study design, sample size, sex (female %), age (Mean or Median or Range), outcome measures, and key results (see details in Table 1).

Table 1.

Characteristics of studies reporting anxiety symptoms and anxiety disorders in asthma and non-asthma controls

Note: −, data not reported; YSR, Youth Self-Report; STAI, State-Trait Anxiety Inventory; HADS, Hospital Anxiety and Depression Scale; PRIME-MD PHQ, PRIME-MD Patient Health Questionnaire (PHQ) (DSM-IV version); PAQ, Panic Attack Questionnaire; SCID-I, Structured Clinical Interview for DSM-IV diagnosis of Axis I disorders; SCID-II, Structured Clinical Interview for DSM-IV diagnosis of Axis II disorders; ICD-9, International Classification of Disease, Ninth revision; GMHAT/PC, Global Mental Health Assessment Tool-Primary Care and General Health version; DIA-X/M-CIDI, Munich Composite International Diagnostic Interview; DIS, Diagnostic Interview Survey from the Diagnostic and Statistical Manual of the American Psychiatric Association, 3rd Revision (DSM-III); DISC 2.3, Diagnostic Interview Schedule for Children; K-SADS, Schedule for Affective Disorders and Schizophrenia for School-Age Children.

Quality assessment

After reviewing recommendations for observational studies (Mueller et al. Reference Mueller, D'Addario, Egger, Cevallos, Dekkers, Mugglin and Scott2018), the approach developed by Hawker, Payne, Kerr, Hardey, & Powell (Reference Hawker, Payne, Kerr, Hardey and Powell2002) was adopted to assess the methodological quality of individual studies included in this review. Nine components were assessed including the title and abstract, introduction and objectives, method and data, sampling, data analysis, ethical aspects of the research process, the results, transferability or generalizability of the information that emerged, and the implications and usefulness of the study using a four-point Likert scale: from good (4) to very poor (1), thus yielding a maximum score of 36. Overall quality ratings were then assigned as follows: high quality (H), 30–36 points; medium quality (M), 24–29 points; low quality (L), 9–24 points.

Statistical analysis

Random effects meta-analysis was used to synthesize individual study effect sizes and generate an overall effect size due to the clinical and methodological variation across studies. The pooled prevalence of anxiety symptoms and anxiety disorders in patients with asthma was calculated using the random effects model via Comprehensive Meta-Analysis version 2.0. Meta-analysis of odds ratio (OR) was conducted using Review Manager 5.3 software. I2 test was used to indicate the percentage of variance in a meta-analysis that is attributable to study heterogeneity, with 25, 50, and 75% considered to indicate low, medium, and high heterogeneity, respectively. Funnel plot of standard error by Hedges'g was used to indicate any potential publication bias.

Results

Search results and study characteristics

The PRISMA flow chart (see Fig. 1) illustrates how studies were selected in this review and meta-analysis. Our search strategy yielded an initial total of 19 905 articles. In total, 13 359 potentially relevant articles remained after duplicates were removed. The titles and abstracts of these articles were then screened and 13 121 articles were excluded. A total of 238 full-length articles were then reviewed. Finally, 19 articles which met both inclusion and exclusion criteria were included. Among these, 10 articles reported self-report anxiety symptoms and nine articles reported clinically diagnosed anxiety disorders; all of which had both an asthma group and a non-asthma control group.

Fig. 1.

PRISMA flow chart of study selection.

Anxiety symptoms and asthma

There were 10 studies involving 52 929 participants (including 6224 asthma patients) reporting anxiety symptoms included in this meta-analysis (Arif & Korgaonkar, Reference Arif and Korgaonkar2016; Centanni et al. Reference Centanni, Di Marco, Castagna, Boveri, Casanova and Piazzini2000; Cooper et al. Reference Cooper, Parry, Saul, Morice, Hutchcroft, Moore and Esmonde2007; Dorhofer & Sigmon, Reference Dorhofer and Sigmon2002; Ferro et al. Reference Ferro, Van Lieshout, Scott, Alati, Mamun and Dingle2016; Goodwin et al. Reference Goodwin, Olfson, Shea, Lantigua, Carrasquilo, Gameroff and Weissman2003b; Han et al. Reference Han, Forno, Marsland, Miller and Celedon2016; Lehto et al. Reference Lehto, Pedersen, Almqvist, Lu and Brew2019; Lu et al. Reference Lu, Ho, Lim, Kuan, Goh, Mahadevan and van Bever2014; Ryu, Chun, Lee, & Chang, Reference Ryu, Chun, Lee and Chang2010). The characteristics of these studies are presented in Table 1. The random effects model was used to calculate the pooled prevalence of anxiety symptoms in asthma patients and in non-asthma controls which were 0.32 (95% CI 0.22–0.43) and 0.21 (95% CI 0.16–0.26), respectively. Meta-analysis using Review Manager 5.3 indicated that the risk of coexisting anxiety symptoms was significantly higher in patients with asthma than that of non-asthma controls (OR 1.89; 95% CI 1.42–2.52; Z = 4.37; p < 0.001), as shown in the forest plot in Fig. 2.

Fig. 2.

Forest plot of comparison of anxiety symptoms (2a) and anxiety disorders (2b) in asthma and non-asthma controls. The black diamond at the bottom of the effect size plot represents the overall pooled odds ratio. Odds ratio>1 represents anxiety prevalence higher in the asthma group than in the non-asthma control group.

Anxiety disorders and asthma

There were nine studies involving 53 884 participants (including 24144 asthma patients) reporting anxiety disorders in asthma patients (Bussing, Burket, & Kelleher, Reference Bussing, Burket and Kelleher1996; Caccappolo-van Vliet, Kelly-McNeil, Natelson, Kipen, & Fiedler, Reference Caccappolo-van Vliet, Kelly-McNeil, Natelson, Kipen and Fiedler2002; Del Giacco et al. Reference Del Giacco, Cappai, Gambula, Cabras, Perra, Manconi and Pinna2016; Goodwin, Jacobi, & Thefeld, Reference Goodwin, Jacobi and Thefeld2003a; Lee, Lee, Lai, Chen, & Stewart, Reference Lee, Lee, Lai, Chen and Stewart2016; Martinez-Rivera et al. Reference Martinez-Rivera, Vennera, Canete, Bardagi and Picado2011; Ortega et al. Reference Ortega, Huertas, Canino, Ramirez and Rubio-Stipec2002; Ortega, McQuaid, Canino, Goodwin, & Fritz, Reference Ortega, McQuaid, Canino, Goodwin and Fritz2004; Sharma et al. Reference Sharma, Singh, Sharma, Choudhary, Singh, Lane and Copeland2013). The characteristics of these studies were extracted and shown in Table 1. The pooled prevalence of anxiety disorders in asthma patients and controls without asthma was 0.24 (95% CI 0.13–0.41) and 0.11 (95% CI 0.05–0.22), respectively. The risk of comorbid anxiety disorders was significantly higher in patients with asthma than those of non-asthma controls (OR 2.08; 95% CI 1.70–2.56; Z = 6.97; p < 0.001), as shown in the forest plot in Fig. 2.

Assessment of heterogeneity

The meta-analysis revealed significantly different degrees of heterogeneity across studies reporting anxiety symptoms (τ 2 = 0.15, χ2 = 117.34, df = 9, p < 0.00001; I 2 = 92%) and anxiety disorders (τ 2 = 0.04, χ2 = 16.83, df = 8, p = 0.03; I 2 = 52%), respectively. Studies reporting anxiety symptoms had a higher degree of heterogeneity than studies reporting anxiety disorders, possibly due to larger asthma patient populations and higher quality in studies of anxiety disorders. For more details and different weighting of individual study see Table 2 and Fig. 2. Due to the high heterogeneity, random-effects model was used for analysis. The funnel plots (see Fig. 3) indicated a tendency towards reporting positive findings. The underlying causes of the asymmetry include (1) chance due to a relatively small number of studies included; (2) heterogeneity across studies such as differences in methodology including settings, types of outcome measures; and (3) a few smaller studies with higher OR seen in studies conducted by Bussing et al. (Reference Bussing, Burket and Kelleher1996) and Caccappolo-van Vliet et al. (Reference Caccappolo-van Vliet, Kelly-McNeil, Natelson, Kipen and Fiedler2002) known as ‘small study effects’ also contributing asymmetry in the funnel plot.

Fig. 3.

Funnel plot of standard error by Hedges'g for studies reporting anxiety symptoms (3a) and anxiety disorders (3b). Asymmetry indicates a potential publication bias.

Table 2.

Quality assessment of studies

Note: A/T, Abstract and Title; I/A, Introduction and Aims; M/D, Methods and Data; S, Sampling; A, Analysis; E/B, Ethics and Bias; R, Results; T, Transferability; I, Implications. H: high quality, 30–36 points; M: medium quality, 24–29 points; L: low quality, 9–24 points.

Discussion

This up-to-date review of evidence from 19 case-controlled studies involving 106 813 participants includes 30 368 asthma patients and systematically evaluates the association between anxiety and asthma. Prevalence rates of anxiety in asthma varied widely between studies, possibly due to methodological issues including differences in definitions and diagnostic criteria used to define anxiety and in selections of control groups. Meta-analysis provides precise estimates of the prevalence rates and the risks of anxiety symptoms and anxiety disorders, respectively, and indicates significantly elevated comorbidity when compared with the general population.

Anxiety symptoms were reviewed from 10 studies involving 6224 participants, with over one-third of asthma individuals reporting anxiety symptoms measured by psychometric questionnaires. The meta-analysis revealed a significant 1.89 times higher risk of developing anxiety symptoms in asthmatic individuals than in non-asthmatic controls. In contrast, evidence from nine studies involving 24 144 participants revealed that a quarter of asthma individuals developed anxiety disorders, with a significant 2.08 times higher risk than non-asthma controls.

An earlier meta-analysis of 15 studies involving 1494 asthmatic adults suggested that the prevalence of any anxiety disorder was 34% (Weiser, Reference Weiser2007), which is much higher than the figure of 24% reported in our meta-analysis. This is possibly due to the stricter inclusion criteria adopted in our review where only studies with a case-controlled design were selected to remove any confounding factors (most studies included in the earlier review did not include a control group). In addition, most studies in the earlier review examined participants recruited from clinical settings (such as hospitals and outpatient clinics), where comorbidity conditions are usually more burdensome. The inclusion of both clinical and non-clinical populations and matched controls in our review can limit such bias (Berkson, Reference Berkson1946). Another review of evidence across 17 countries suggested the pooled estimate of odds ratio for anxiety disorders was 1.5 (95% CI 1.4–1.7) (Scott et al. Reference Scott, Von Korff, Ormel, Zhang, Bruffaerts, Alonso and Haro2007) which is lower than the figure of 2.08 (95% CI 1.70–2.56) indicated in our meta-analysis: possibly because the earlier review examined only community populations.

It is important to consider to what extent the results of the studies are consistent. I 2 test results derived from our meta-analyses revealed substantial heterogeneity across the 10 studies reporting anxiety symptoms in asthma, and moderate heterogeneity across the nine studies reporting anxiety disorders in asthma. Reasons for heterogeneity, other than characteristics and size of study populations, include different methodological issues such as recruitment pathways, measurement tools and diagnostic criteria, asthma severity and duration, other comorbid physical conditions, settings and countries where each study was carried out, as well as publication bias as indicated in the funnel plots. It should be noted that the effects of these potential sources of heterogeneity were not examined, due to the relatively small numbers of studies included in this review, however, sub-group analysis and meta-regression should be conducted when there are adequate numbers of studies in future meta-analysis. Although the consideration of risk and protective factors linked to comorbid anxiety in asthma is not within the scope of our review, factors like gender, marital status, educational years, urbanization levels, residential areas, levels of care, other comorbid physical conditions (such as cardiovascular disease and diabetes), childhood trauma and negative life events have all been found to be associated with anxiety in asthma (Goodwin, Fergusson, & Horwood, Reference Goodwin, Fergusson and Horwood2004; Grigsby, Anderson, Freedland, Clouse, & Lustman, Reference Grigsby, Anderson, Freedland, Clouse and Lustman2002; Lu, Feng, Lim, & Ng, Reference Lu, Feng, Lim and Ng2013; Roy-Byrne et al. Reference Roy-Byrne, Davidson, Kessler, Asmundson, Goodwin, Kubzansky and Stein2008; Scott et al. Reference Scott, Von Korff, Alonso, Angermeyer, Benjet, Bruffaerts and Posada-Villa2008), whereas socioeconomic advantage, younger age and oral prednisolone usage may be protective factors (Protsiuk et al. Reference Protsiuk, Yablon, Protsiuk, Bykovska, Herasymova and Kapitan2019; Tzeng et al. Reference Tzeng, Chang, Chung, Kao, Chang, Yeh and Chien2018).

The mechanisms underlying comorbid anxiety in asthma remain unclear. One biological theory suggests that repetitive experiences with hypoxia and hypercapnia due to asthma may sensitize neural circuits that control fear responses, such as neurons in the amygdala and locus coeruleus, to overreact and to enhance fearful perceptions of conditioned stimuli such as the sensation of breathlessness (Katon et al. Reference Katon, Richardson, Lozano and McCauley2004). Evidence from adults and adolescents support this theory (Goodwin et al. Reference Goodwin, Olfson, Shea, Lantigua, Carrasquilo, Gameroff and Weissman2003b; Perna, Ieva, Caldirola, Bertani, & Bellodi, Reference Perna, Ieva, Caldirola, Bertani and Bellodi2002; Pine et al. Reference Pine, Klein, Coplan, Papp, Hoven, Martinez and Gorman2000). Another potential biological mechanism is linked to complex psycho-neuro-immunological pathways involving mainly pro-inflammatory cytokines and imbalance towards the Th2 T-cell response (Del Giacco et al. Reference Del Giacco, Cappai, Gambula, Cabras, Perra, Manconi and Pinna2016). Castillo and colleagues (Castillo, Zheng, & Yang, Reference Castillo, Zheng and Yang2018) found that pro-inflammatory cytokines played an important role in the pathogenesis of allergy-related diseases, such as asthma. Studies have shown that cytokines such as interleukin (IL)-6, tumour necrosis factor-alpha, IL-10, and monocyte chemoattractant protein-1/CCL2 might be associated with emotional disorders, including anxiety disorders (Kohler et al. Reference Kohler, Freitas, Stubbs, Maes, Solmi, Veronese and Carvalho2018; Rosenblat & McIntyre, Reference Rosenblat and McIntyre2017). Another recent study showed that pro-inflammatory cytokines, salivary cortisol and alpha-amylase were potentially implicated in the development of generalized anxiety disorder in asthma patients (Yang, Liu, Xu, Shi, & Du, Reference Yang, Liu, Xu, Shi and Du2017). Genetic studies suggest shared genes and potential causal links between asthma and anxiety disorders (Zhu et al. Reference Zhu, Zhu, Liu, Shi, Shen, Yang and Liang2019). A locus is significantly associated with both asthma and anxiety disorders (sentinel SNP: rs1709393) and the NR3C1 gene substantially modifies the level of trait anxiety in asthma sufferers (Panek, Pietras, Szemraj, & Kuna, Reference Panek, Pietras, Szemraj and Kuna2014). Cognitive theory can be used to explain the psychosocial mechanisms underlying the comorbidity of anxiety with asthma (Katon et al. Reference Katon, Richardson, Lozano and McCauley2004): it suggests that long periods and unpredictable experiences with asthma may generate fearful or uncontrollable beliefs about respiratory symptoms which can provoke panic attacks (Carr, Lehrer, Rausch, & Hochron, Reference Carr, Lehrer, Rausch and Hochron1994; Roy-Byrne & Stein, Reference Roy-Byrne and Stein2001). Some individuals may misinterpret normal occurrences of breathlessness as indicative of an asthma attack and if they then respond to these normal bodily sensations in the same way as if they were asthma symptoms, anxiety may increase. Subsequently, avoidance or escape behaviours may appear, which would lead to long-term anxiety (Dudeney, Sharpe, Jaffe, Jones, & Hunt, Reference Dudeney, Sharpe, Jaffe, Jones and Hunt2017).

A high prevalence of anxiety also occurs in a range of other physical illnesses including gastrointestinal disease, pulmonary disease, cardiovascular disease, and chronic pain (Bordoni, Marelli, Morabito, & Sacconi, Reference Bordoni, Marelli, Morabito and Sacconi2017; Celano, Daunis, Lokko, Campbell, & Huffman, Reference Celano, Daunis, Lokko, Campbell and Huffman2016; Meuret, Tunnell, & Roque, Reference Meuret, Tunnell and Roque2020; Neuendorf, Harding, Stello, Hanes, & Wahbeh, Reference Neuendorf, Harding, Stello, Hanes and Wahbeh2016; Ortego et al. Reference Ortego, Villafañe, Doménech-García, Berjano, Bertozzi and Herrero2016). While a medical condition can be sufficient enough to be a stressor for an individual to develop anxiety, some shared underlying biological mechanism may also contribute to anxiety and comorbid physical illness. Growing evidence also suggests neurotransmitter disturbances, hypothalamic-pituitaryadrenal axis dysfunction, and neuroplasticity may also contribute to these comorbid conditions. Future work is warranted to identify potential shared underlying pathological mechanisms between anxiety and asthma as this could offer novel intervention targets and optimize clinical outcome.

Conclusions

The current study provides precise comorbidity and risk estimates of coexisting anxiety symptoms and comorbid anxiety disorders in individuals with asthma. It highlights the need for early and appropriate assessment for anxiety symptoms and disorders in individuals with asthma. This could help to stratify a subgroup of patients who may benefit from interventions targeted at anxiety which might lead to better overall health and quality of life. Further research is warranted to examine underlying mechanisms and identify modifiable risk factors which may offer new intervention approaches to benefit asthma patients with comorbid anxiety.

Acknowledgements

This work was supported by an award from Jiangsu Commission of Health International Exchange Programme grant (Ref: JSH-2019-015).

Conflicts of interest

None.

References

Arif, A. A., & Korgaonkar, P. (2016). The association of childhood asthma with mental health and developmental comorbidities in low-income families. Journal of Asthma, 53(3), 277–281. doi:10.3109/02770903.2015.1089277.CrossRefGoogle ScholarPubMed
Berkson, J. (1946). Limitations of the application of fourfold table analysis to hospital data. Biometrics Bulletin, 2(3), 47–53.CrossRefGoogle ScholarPubMed
Bordoni, B., Marelli, F., Morabito, B., & Sacconi, B. (2017). Depression, anxiety and chronic pain in patients with chronic obstructive pulmonary disease: The influence of breath. Monaldi Archives for Chest Disease, 87(1),811. doi:10.4081/monaldi.2017.811.CrossRefGoogle Scholar
Bussing, R., Burket, R. C., & Kelleher, E. T. (1996). Prevalence of anxiety disorders in a clinic-based sample of pediatric asthma patients. Psychosomatics, 37(2), 108–115. doi:10.1016/S0033-3182(96)71576-1.CrossRefGoogle Scholar
Caccappolo-van Vliet, E., Kelly-McNeil, K., Natelson, B., Kipen, H., & Fiedler, N. (2002). Anxiety sensitivity and depression in multiple chemical sensitivities and asthma. Journal of Occupational and Environmental Medicine, 44(10), 890–901. doi:10.1097/00043764-200210000-00006.CrossRefGoogle ScholarPubMed
Carr, R. E., Lehrer, P. M., Rausch, L. L., & Hochron, S. M. (1994). Anxiety sensitivity and panic attacks in an asthmatic population. Behaviour Research and Therapy, 32(4), 411–418. doi:10.1016/0005-7967(94)90004-3.CrossRefGoogle Scholar
Castillo, E. F., Zheng, H., & Yang, X. O. (2018). Orchestration of epithelial-derived cytokines and innate immune cells in allergic airway inflammation. Cytokine & Growth Factor Reviews, 39,19–25. doi:10.1016/j.cytogfr.2017.11.004.CrossRefGoogle ScholarPubMed
Celano, C. M., Daunis, D. J., Lokko, H. N., Campbell, K. A., & Huffman, J. C. (2016). Anxiety disorders and cardiovascular disease. Current Psychiatry Reports, 18(11),101. doi:10.1007/s11920-016-0739-5.CrossRefGoogle ScholarPubMed
Centanni, S., Di Marco, F., Castagna, F., Boveri, B., Casanova, F., & Piazzini, A. (2000). Psychological issues in the treatment of asthmatic patients. Respiratory Medicine, 94(8), 742–749. doi:10.1053/rmed.1999.0766.CrossRefGoogle ScholarPubMed
Cooper, C. L., Parry, G. D., Saul, C., Morice, A. H., Hutchcroft, B. J., Moore, J., & Esmonde, L. (2007). Anxiety and panic fear in adults with asthma: Prevalence in primary care. BMC Family Practice, 8(1), 62. doi:10.1186/1471-2296-8-62.CrossRefGoogle ScholarPubMed
Del Giacco, S. R., Cappai, A., Gambula, L., Cabras, S., Perra, S., Manconi, P. E., … Pinna, F. (2016). The asthma-anxiety connection. Respiratory Medicine, 120,44–53. doi:10.1016/j.rmed.2016.09.014.CrossRefGoogle ScholarPubMed
Di Marco, F., Santus, P., & Centanni, S. (2011). Anxiety and depression in asthma. Current Opinion in Pulmonary Medicine, 17(1), 39–44. doi:10.1097/MCP.0b013e328341005f.CrossRefGoogle ScholarPubMed
Dorhofer, D. M., & Sigmon, S. T. (2002). Physiological and psychological reactivity in women with asthma: The effects of anxiety and menstrual cycle phase. Behaviour Research and Therapy, 40(1), 3–17. doi:10.1016/s0005-7967(00)00110-8.CrossRefGoogle ScholarPubMed
Dudeney, J., Sharpe, L., Jaffe, A., Jones, E. B., & Hunt, C. (2017). Anxiety in youth with asthma: A meta-analysis. Pediatric Pulmonology, 52(9), 1121–1129. doi: 10.1002/ppul.23689.CrossRefGoogle ScholarPubMed
Ferro, M. A., Van Lieshout, R. J., Scott, J. G., Alati, R., Mamun, A. A., & Dingle, K. (2016). Condition-specific associations of symptoms of depression and anxiety in adolescents and young adults with asthma and food allergy. Journal of Asthma, 53(3), 282–288. doi:10.3109/02770903.2015.1104694.CrossRefGoogle Scholar
Goodwin, R. D., Fergusson, D. M., & Horwood, L. J. (2004). Asthma and depressive and anxiety disorders among young persons in the community. Psychological Medicine, 34(8), 1465–1474. doi:10.1017/s0033291704002739.CrossRefGoogle Scholar
Goodwin, R. D., Jacobi, F., & Thefeld, W. (2003a). Mental disorders and asthma in the community. Archives of General Psychiatry, 60(11), 1125–1130. doi:10.1001/archpsyc.60.11.1125.CrossRefGoogle Scholar
Goodwin, R. D., Olfson, M., Shea, S., Lantigua, R. A., Carrasquilo, O., Gameroff, M. J., & Weissman, M. M. (2003b). Asthma and mental disorders in primary care. General Hospital Psychiatry, 25(6), 479–483. doi:10.1016/s0163-8343(03)00071-9.CrossRefGoogle Scholar
Grigsby, A. B., Anderson, R. J., Freedland, K. E., Clouse, R. E., & Lustman, P. J. (2002). Prevalence of anxiety in adults with diabetes: A systematic review. Journal of Psychosomatic Research, 53(6), 1053–1060. doi:10.1016/s0022-3999(02)00417-8.CrossRefGoogle ScholarPubMed
Han, Y. Y., Forno, E., Marsland, A. L., Miller, G. E., & Celedon, J. C. (2016). Depression, asthma, and bronchodilator response in a nationwide study of US adults. The Journal of Allergy and Clinical Immunology: In Practice, 4(1), 68-73 e1. doi:10.1016/j.jaip.2015.10.004.Google Scholar
Hawker, S., Payne, S., Kerr, C., Hardey, M., & Powell, J. (2002) Appraising the evidence: Reviewing disparate data systematically. Qualitative Health Research, 12(9), 1284–1299. doi: 10.1177/1049732302238251.CrossRefGoogle ScholarPubMed
Katon, W. J., Richardson, L., Lozano, P., & McCauley, E. (2004). The relationship of asthma and anxiety disorders. Psychosomatic Medicine, 66(3), 349–355. doi:10.1097/01.psy.0000126202.89941.ea.Google ScholarPubMed
Kohler, C. A., Freitas, T. H., Stubbs, B., Maes, M., Solmi, M., Veronese, N., … Carvalho, A. F. (2018). Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: Systematic review and meta-analysis. Molecular Neurobiology, 55(5), 4195–4206. doi:10.1007/s12035-017-0632-1.Google ScholarPubMed
Laveneziana, P., Lotti, P., Coli, C., Binazzi, B., Chiti, L., Stendardi, L., … Scano, G. (2006). Mechanisms of dyspnoea and its language in patients with asthma. European Respiratory Journal, 27(4), 742–747. doi:10.1183/09031936.06.00080505.CrossRefGoogle ScholarPubMed
Lavoie, K. L., Bouthillier, D., Bacon, S. L., Lemiere, C., Martin, J., Hamid, Q., … Ernst, P. (2010). Psychologic distress and maladaptive coping styles in patients with severe vs moderate asthma. Chest, 137(6), 1324–1331. doi:10.1378/chest.09-1979.CrossRefGoogle ScholarPubMed
Lee, Y. C., Lee, C. T., Lai, Y. R., Chen, V. C., & Stewart, R. (2016). Association of asthma and anxiety: A nationwide population-based study in Taiwan. Journal of Affective Disorders, 189,98–105. doi:10.1016/j.jad.2015.09.040.CrossRefGoogle ScholarPubMed
Lehto, K., Pedersen, N. L., Almqvist, C., Lu, Y., & Brew, B. K. (2019). Asthma and affective traits in adults: A genetically informative study. European Respiratory Journal, 53(5), 1802142. doi:10.1183/13993003.02142-2018.CrossRefGoogle ScholarPubMed
Lu, Y., Feng, L., Lim, L., & Ng, T. P. (2013). Asthma, life events and psychiatric disorders: A population-based study. Social Psychiatry and Psychiatric Epidemiology, 48(8), 1273–1282. doi:10.1007/s00127-013-0655-5.CrossRefGoogle ScholarPubMed
Lu, Y., Ho, R., Lim, T. K., Kuan, W. S., Goh, D. Y., Mahadevan, M., … van Bever, H. P. (2014). Psychiatric comorbidities in Asian adolescent asthma patients and the contributions of neuroticism and perceived stress. Journal of Adolescent Health, 55(2), 267–275. doi:10.1016/j.jadohealth.2014.01.007.CrossRefGoogle ScholarPubMed
Martinez-Rivera, C., Vennera, M. D. C., Canete, C., Bardagi, S., & Picado, C. (2011). Psychological profile of patients with bronchial asthma and functional dyspnea: A comparison with a non-asthmatic population and impact on the disease. Archivos De Bronconeumologia, 47(2), 73–78. doi:10.1016/j.arbres.2010.10.003.CrossRefGoogle ScholarPubMed
McCauley, E., Katon, W., Russo, J., Richardson, L., & Lozano, P. (2007). Impact of anxiety and depression on functional impairment in adolescents with asthma. General Hospital Psychiatry, 29(3), 214–222. doi:10.1016/j.genhosppsych.2007.02.003.CrossRefGoogle ScholarPubMed
Meuret, A.E., Tunnell, N., & Roque, A. (2020). Anxiety disorders and medical comorbidity: Treatment implications. Advances in Experimental Medicine and Biology 1191 237–261. doi: 10.1007/978-981-32-9705-0_15.CrossRefGoogle ScholarPubMed
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D.G., & The PRISMA Group. (2009) Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Medicine, 6(7), e1000097. doi: 10.1371/journal.pmed.1000097.CrossRefGoogle ScholarPubMed
Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., & Petticrew, M., … PRISMA-P Group. (2015). Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews, 4(1), 1. doi:10.1186/2046-4053-4-1.CrossRefGoogle ScholarPubMed
Mrazek, D. A. (2003). Psychiatric symptoms in patients with asthma causality, comorbidity, or shared genetic etiology. Child and Adolescent Psychiatric Clinics of North America, 12(3), 459–471. doi:10.1016/s1056-4993(03)00028-2.CrossRefGoogle ScholarPubMed
Mueller, M., D'Addario, M., Egger, M., Cevallos, M., Dekkers, O., Mugglin, C., & Scott, P. (2018). Methods to systematically review and meta-analyse observational studies: A systematic scoping review of recommendations. BMC Medical Research Methodology, 18(1), 44. doi:10.1186/s12874-018-0495-9.CrossRefGoogle ScholarPubMed
Neuendorf, R., Harding, A., Stello, N., Hanes, D., & Wahbeh, H. (2016) Depression and anxiety in patients with inflammatory bowel disease: A systematic review. Journal of Psychosomatic Research, 87,70–80. doi:10.1016/j.jpsychores.2016.06.001.CrossRefGoogle ScholarPubMed
Ortega, A. N., Huertas, S. E., Canino, G., Ramirez, R., & Rubio-Stipec, M. (2002). Childhood asthma, chronic illness, and psychiatric disorders. Journal of Nervous & Mental Disease, 190(5), 275–281. doi:10.1097/00005053-200205000-00001.CrossRefGoogle ScholarPubMed
Ortega, A. N., McQuaid, E. L., Canino, G., Goodwin, R. D., & Fritz, G. K. (2004). Comorbidity of asthma and anxiety and depression in Puerto Rican children. Psychosomatics, 45(2), 93–99. doi:10.1176/appi.psy.45.2.93.CrossRefGoogle ScholarPubMed
Ortego, G., Villafañe, J.H., Doménech-García, V., Berjano, P., Bertozzi, L., & Herrero, P. (2016). Is there a relationship between psychological stress or anxiety and chronic nonspecific neck-arm pain in adults? A systematic review and meta-analysis. Journal of Psychosomatic Research, 90,70–81. doi:10.1016/j.jpsychores.2016.09.006.CrossRefGoogle ScholarPubMed
Panek, M., Pietras, T., Szemraj, J., & Kuna, P. (2014). Association analysis of the glucocorticoid receptor gene (NR3C1) haplotypes (ER22/23EK, N363S, BclI) with mood and anxiety disorders in patients with asthma. Experimental & Therapeutic Medicine, 8(2), 662–670. doi:10.3892/etm.2014.1734.CrossRefGoogle ScholarPubMed
Perna, G., Ieva, A., Caldirola, D., Bertani, A., & Bellodi, L. (2002). Respiration in children at risk for panic disorder. Archives of General Psychiatry, 59(2), 185–186. doi:10.1001/archpsyc.59.2.185.CrossRefGoogle ScholarPubMed
Pine, D. S., Klein, R. G., Coplan, J. D., Papp, L. A., Hoven, C. W., Martinez, J., … Gorman, J. M. (2000). Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group. Archives of General Psychiatry, 57(10), 960–967. doi:10.1001/archpsyc.57.10.960.CrossRefGoogle ScholarPubMed
Protsiuk, T. L., Yablon, O. S., Protsiuk, L. O., Bykovska, O. А., Herasymova, О. V., & Kapitan, T. V. (2019). Features of clinical manifestations of disease and psychological status of adolescents with bronchial asthma of various levels of control and the influence of risk factors. Wiadomoci Lekarskie, 72(5 cz 1), 795–801.CrossRefGoogle ScholarPubMed
Richardson, L. P., Lozano, P., Russo, J., McCauley, E., Bush, T., & Katon, W. (2006). Asthma symptom burden: Relationship to asthma severity and anxiety and depression symptoms. Pediatrics, 118(3), 1042–1051. doi:10.1542/peds.2006-0249.CrossRefGoogle ScholarPubMed
Rosenblat, J. D., & McIntyre, R. S. (2017). Bipolar disorder and immune dysfunction: Epidemiological findings, proposed pathophysiology and clinical implications. Brain Sciences, 7(11), 144. doi:10.3390/brainsci7110144.CrossRefGoogle ScholarPubMed
Roy-Byrne, P. P., Davidson, K. W., Kessler, R. C., Asmundson, G. J., Goodwin, R. D., Kubzansky, L., … Stein, M. B. (2008). Anxiety disorders and comorbid medical illness. General Hospital Psychiatry, 30(3), 208–225. doi:10.1016/j.genhosppsych.2007.12.006.CrossRefGoogle ScholarPubMed
Roy-Byrne, P., & Stein, M. B. (2001). Inspiring panic. Archives of General Psychiatry, 58(2), 123–124. doi:10.1001/archpsyc.58.2.123.CrossRefGoogle ScholarPubMed
Ryu, Y. J., Chun, E. M., Lee, J. H., & Chang, J. H. (2010). Prevalence of depression and anxiety in outpatients with chronic airway lung disease. Korean Journal of Internal Medicine, 25(1), 51–57. doi:10.3904/kjim.2010.25.1.51.CrossRefGoogle ScholarPubMed
Scott, K. M., Von Korff, M., Alonso, J., Angermeyer, M. C., Benjet, C., Bruffaerts, R., … Posada-Villa, J. (2008). Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma. Psychosomatic Medicine, 70(9), 1035–1043. doi:10.1097/PSY.0b013e318187a2fb.CrossRefGoogle ScholarPubMed
Scott, K. M., Von Korff, M., Ormel, J., Zhang, M. Y., Bruffaerts, R., Alonso, J., … Haro, J. M. (2007). Mental disorders among adults with asthma: Results from the world mental health survey. General Hospital Psychiatry, 29(2), 123–133. doi:10.1016/j.genhosppsych.2006.12.006.CrossRefGoogle ScholarPubMed
Sharma, B. B., Singh, S., Sharma, V. K., Choudhary, M., Singh, V., Lane, S., … Copeland, J. (2013). Psychiatric morbidity in chronic respiratory disorders in an Indian service using GMHAT/PC. General Hospital Psychiatry, 35(1), 39–44. doi:10.1016/j.genhosppsych.2012.09.009.CrossRefGoogle Scholar
Spinhoven, P., van Peski-Oosterbaan, A. S., Van der Does, A. J., Willems, L. N., & Sterk, P. J. (1997). Association of anxiety with perception of histamine induced bronchoconstriction in patients with asthma. Thorax, 52(2), 149–152. doi:10.1136/thx.52.2.149.CrossRefGoogle ScholarPubMed
Su, X., Ren, Y., Li, M., Zhao, X., Kong, L., & Kang, J. (2016). Prevalence of comorbidities in asthma and nonasthma patients: A meta-analysis. Medicine (Baltimore), 95(22), e3459. doi:10.1097/MD.0000000000003459.CrossRefGoogle ScholarPubMed
ten Thoren, C., & Petermann, F. (2000). Reviewing asthma and anxiety. Respiratory Medicine, 94(5), 409–415. doi:10.1053/rmed.1999.0757.CrossRefGoogle ScholarPubMed
Thomas, M., Bruton, A., Moffat, M., & Cleland, J. (2011). Asthma and psychological dysfunction. Primary Care Respiratory Journal, 20(3), 250–256. doi:10.4104/pcrj.2011.00058.CrossRefGoogle ScholarPubMed
Tzeng, N. S., Chang, H. A., Chung, C. H., Kao, Y. C., Chang, C. C., Yeh, H. W., … Chien, W. C. (2018). Increased risk of psychiatric disorders in allergic diseases: A nationwide, population-based, cohort study. Frontiers in Psychiatry, 9 133. doi:10.3389/fpsyt.2018.00133.CrossRefGoogle ScholarPubMed
von Leupoldt, A., Sommer, T., Kegat, S., Baumann, H. J., Klose, H., Dahme, B., & Buchel, C. (2009). Dyspnea and pain share emotion-related brain network. Neuroimage, 48(1), 200–206. doi:10.1016/j.neuroimage.2009.06.015.CrossRefGoogle ScholarPubMed
Weiser, E. B. (2007). The prevalence of anxiety disorders among adults with asthma: A meta-analytic review. Journal of Clinical Psychology in Medical Settings, 14(4), 297–307. doi:10.1007/s10880-007-9087-2.CrossRefGoogle Scholar
Wong, K. O., Hunter Rowe, B., Douwes, J., & Senthilselvan, A. (2013). Asthma and wheezing are associated with depression and anxiety in adults: An analysis from 54 countries. Pulmonary Medicine, 2013, 929028. doi:10.1155/2013/929028.CrossRefGoogle ScholarPubMed
Yang, C. J., Liu, D., Xu, Z. S., Shi, S. X., & Du, Y. J. (2017). The pro-inflammatory cytokines, salivary cortisol and alpha-amylase are associated with generalized anxiety disorder (GAD) in patients with asthma. Neuroscience Letters, 656,15–21. doi:10.1016/j.neulet.2017.07.021.CrossRefGoogle ScholarPubMed
Zhu, Z., Zhu, X., Liu, C. L., Shi, H., Shen, S., Yang, Y., … Liang, L. (2019). Shared genetics of asthma and mental health disorders: A large-scale genome-wide cross-trait analysis. European Respiratory Journal, 54(6), 1901507. doi:10.1183/13993003.01507-2019.CrossRefGoogle ScholarPubMed
Figure 0

Table 1. Characteristics of studies reporting anxiety symptoms and anxiety disorders in asthma and non-asthma controls

Figure 1

Fig. 1. PRISMA flow chart of study selection.

Figure 2

Fig. 2. Forest plot of comparison of anxiety symptoms (2a) and anxiety disorders (2b) in asthma and non-asthma controls. The black diamond at the bottom of the effect size plot represents the overall pooled odds ratio. Odds ratio>1 represents anxiety prevalence higher in the asthma group than in the non-asthma control group.

Figure 3

Fig. 3. Funnel plot of standard error by Hedges'g for studies reporting anxiety symptoms (3a) and anxiety disorders (3b). Asymmetry indicates a potential publication bias.

Figure 4

Table 2. Quality assessment of studies